MX2008006653A - Thrombopoietin activity modulating compounds and methods - Google Patents

Abstract

Disclosed herein are amide containing heterocyclic compounds, pharmaceutical compositions comprising the compounds, methods of modulating the activity a thrombopoietin receptor using the compounds, methods of identifying compounds as thrombopoietin receptor modulators, and methods of treating disease by administering the compounds to a patient in need thereof.

Description

COMPOUNDS AND METHODS THAT MODULATE THE ACTIVITY OF TROMBOPOYETINE FIELD OF THE INVENTION The present invention relates to compounds and methods in the fields of chemistry and medicine. More specifically, the present invention relates to compounds that modulate one or more of the thrombopoietin activity and / or the binding to thrombopoietin receptors and methods for making and using such a compound.

BACKGROUND Thrombopoietin (TPO), also referred to as c-Mpl ligand, mpl ligand, megapoietin and growth factor and megakaryocyte development, is a glycoprotein that has been shown to be involved in the production of platelets. See, e.g., Wendling F., et al., Biotherapy 10 (4): 269-77 (1998); Kutter D.J. et al., The Oncologist, 1: 98-106 (1996); Metcalf, Nature 369: 519-520 (1994), all of which are incorporated herein by reference in their entirety. The TPO has been cloned and its amino acid sequence and the cDNA sequence encoding it have been described. See, e.g., E.U. 5,766,581; Kuter D.J. et al., Proc. Nati Acad. Sci. , 91: 11104-11108 (1994); of Sauvage F.V. et al., Nature, 369: 533-538 (1994); Lok S. et al., Nature 369: 565-568 (1994); Wending F. et al., Nature, 369: 571-574 (1994), all of which are incorporated in the present by reference in its entirety.

In certain cases, TPO activity results from the TPO link to the TPO receptor (also called MPL). The TPO receptor has been cloned and its amino acid sequence has been described. See, e.g., Vigon et al., Proc. Nati Acad. Sci., 89: 5640-5644 (1992), which is incorporated herein by reference in its entirety. In certain cases, TPO modulators may be useful in the treatment of a variety of hematopoietic conditions, including, but not limited to, thrombocytopenia. See, e.g., Baser et al., Blood 89: 3118-3128 (1997); Fanucchi et al., New Engl. J. Med. 336: 404-409 (1997), both of which are incorporated herein by reference in their entirety. For example, patients who experience certain chemotherapies, including but not limited to chemotherapy and / or radiation therapy for the treatment of cancer, may have reduced levels of platelets. In certain cases, the treatment of such patients with a selective TPO modulator increases platelet levels. In certain cases, selective TPO modulators stimulate the production of glial cells, which can result in the repair of damaged nerve cells. SUMMARY OF THE INVENTION In certain embodiments, the present invention or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisoster; each R2 is selected independently of hydrogen, halogen, OR, NR R, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, x-C6 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted C! -C10 alkyl, an optionally substituted Ci-Ci0 haloalkyl and an optionally substituted Ci-Ci0 heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is selected from (CH2) mR18, C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, (CH2) mR18 / and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R is selected from hydrogen, halogen, oxo, OR, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C3 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-Cg haloheteroalkyl; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and Ci-C4 haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, CX-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and C1-C6 heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form a C3- ring C8 optionally substituted; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, Ci-C3 alkyl, Ci-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; W is selected from O, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C3 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Ci0 aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted heterocycle or non-aromatic carbocycle, and a 1-5 atoms selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-Ce haloalkyl, each optionally fused with an optionally substituted C6-Cio aryl; m is 0, 1, 2, or 3; and n is 0 or 1; each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, 0-thiocarbamyl, N-thiocarbamyl, C-amido, N- amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = 0, = S, amino, and protected derivatives of amino groups; whenever, if Y is found oriented in the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) D is not naphthyl if X is N and W is NH, (ii) D is not phenyl if X is CH, W is NH, Z is phenyl and R10 or R11 is - (CH2) 0-6OH, (iii) 1 ^ 10 is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl; and (iv) U is not NH; further provided that, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and is NH in the compounds of Formulas III or IV, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisostere. In certain embodiments, the present invention provides a compound of Formula I, II or III as described earlier: or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisoster; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Cx-Cg alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted C6-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl and C! -C6 haloheteroalkyl; R6 is selected from an optionally substituted Ci-C10 alkyl, an optionally substituted C1-C10 haloalkyl, an optionally substituted C1-C10 heteroalkyl, (CH2) mR18, C (0) NHR18, C = CR18, CR3 = CRR18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, CH2) mR18, and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C8 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and CI-CQ haloheteroalkyl; R is selected from hydrogen, Ci-C3 alkyl, Ci-C6 haloalkyl, C6-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci-C6 alkyl, C6-C6 haloalkyl, C6-C6 heteroalkyl, and C1-C6 heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C3 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-Cs heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, C1-C3 haloalkyl x-C3 alkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from O, NR4, CR3R4 f CO, and null; W is selected from O, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Cx-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a spacer of 2-5 atoms selected from an optionally substituted C6-Cio aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused to a heterocycle or non-aromatic carbocycle optionally substituted, and a 1-5 atom spacer selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted C, L-C6 haloalkyl, each optionally fused with an optionally substituted C6-Cio aryl; m is 0, 1, 2, or 3; and n is 0 or 1; each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, 0-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, 0-carboxy, isocyanate, thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, = 0, = S, amino, and protected derivatives of amino groups; whenever, if Y is found oriented in the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) D is not naphthyl if X is N and W is NH, (ii) D is not phenyl if X is CH, W is NH, Z is phenyl and R10 or R11 is - (CH2) 0-6OH, (iii) Rii is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl; and (iv) U is not H; further provided that, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and is NH in the compound of Formula III, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisoster. In certain embodiments, the present invention provides a compound of Formula I, II or III as described above; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein; R1 is selected from halogen, OR14, N02, CN, NR14R15, Ci-C4 alkyl, Ci-C haloalkyl, an optionally substituted Ci-C4 heteroalkyl, C02R14, CONR1 R15, S03R14, S02NR14R15 and a carboxylic acid bioisosterole selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (0) NR1 R15, and wherein A, B, and C are each independently selected from 0, S, and NR20; each R2 is independently selected from hydrogen, halogen, OR14, NR1 R15, C1-C4 alkyl, haloalkyl Ci-C4, C1-C4 heteroalkyl and Ci-C4 heterohaloalkyl; R3 and R4 are independently selected from hydrogen, C1-C4 alkyl, Ci-C4 haloalkyl and an optionally substituted Ci-C heteroalkyl; R5 is selected from hydrogen, OR14, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C heteroalkyl and Ci-C4 haloheteroalkyl; R6 is selected from Ci-C10 alkyl, Ci-halo haloalkyl, an optionally substituted C1-C10 heteroalkyl, (CH2) mR18, C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (O) NR14R15, and wherein A, B, and C are each independently selected from O, S, and N; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, Ci-C4 alkyl, Ci-C4 haloalkyl, an optionally substituted Ci-C4 heteroalkyl, (CH2) mR18 and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, Ci-C4 alkyl, Ci-C4 haloalkyl and a Ci-C4 heteroalkyl optionally substituted; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R 12 is selected from hydrogen, halogen C 1 -C 4 alkyl, Ci-C 4 haloalkyl, Ci-C 4 heteroalkyl, and Ci-C 4 haloheteroalkyl; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, and Cx- ^ haloheteroalkyl; R 14 is selected from hydrogen, C 1 -t alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl, and C 1 -C 4 heterohaloalkyl; R15 is selected from hydrogen, S02R19, CX-C4 alkyl, C1-C4 haloalkyl, and Ci-C4 heteroalkyl; R16 and R17 are each independently selected from hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C4-C7 ring; R19 is selected from. hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; G is selected from O, S and NR14; J is selected from 0, S, NR14 and CR14R15; K is 0 or S; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; it is selected from 0, NR4, CR3R4, CO, and null; X is N or CR5; And it is selected from: Z is selected from: null, a spacer of 2-5 atoms selected from an optionally substituted C6-Cio aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted heterocycle or non-aromatic carbocycle, and a 1-5 atom spacer selected from an optionally substituted C1-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused to a C6-Cio aryl optionally substituted; m is 0, 1, 2, or 3; Y oriented in the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) D is not naphthyl if X is N and W is NH, (ii) D is not phenyl if X is CH, W is NH, Z is phenyl and R10 or R11 is - (CH2) 0-6OH, (iii) R11-D-R10 is not optionally substituted pyrazolyl or 5-hydroxypyrazolyl; and (iv) U is not NH; further provided that, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and W is NH in the compound of Formula III, then R6, R10 and R11 do not contain a carboxyl, amido, ester or sulfurate functionality or a carboxylic acid bioisoster. In certain embodiments, the present invention provides a compound of Formula IV, V or VI as described above: or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR1 R15, an optionally substituted Ci-C3 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl and Ci-C3 haloheteroalkyl; R6 is selected from an optionally substituted Ci-Ci0 alkyl, an optionally substituted Ci-C10 haloalkyl, an optionally substituted CÍ-CIO heteroalkyl, (CH2) mR18, C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisoster; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, (CH2) mR18 and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R 10 is selected from hydrogen, halogen, oxo, OR 16, NR 16 R 17, SR 16, an optionally substituted C 1 -C 6 alkyl, an optionally substituted Ci-C 6 haloalkyl and an optionally substituted Ci-C 6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, C6-C6 heteroalkyl, and haloheteroalkyl Ci ~ C6; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl, and C 1 -C 4 haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci-Cs alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-Cg heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; W is selected from O, NR4, CR3R4, CO, and null; X is N or CR5; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Cio aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted non-aromatic heterocycle or carbocycle, and a 1-5 atom spacer selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is 0, 1, 2, or 3; and n is 0 or 1; each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanate, thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, = 0, = S, amino, and protected derivatives of amino groups; provided, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and it is NH in the compounds of Formula IV, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisoster.

In certain embodiments, the present invention provides a compound of Formula IV, V or VI or a pharmaceutically acceptable salt, ester, amide or prodrug the, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C3 haloalkyl, an optionally substituted C6-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere selected from tetrazole, NHS02R19, OC ( S) NR14R15, SC (O) NR1R15, and wherein A, B, and C are each independently selected from O, S, and N; R2 is selected from hydrogen, halogen, OR14, NR1R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R7 is selected from C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (0) NR14R15, and wherein A, B, and C are each independently selected from 0, S, and N; In certain embodiments, the present invention provides a compound of Formula I, II, III, IV, V, or VI: (IV) (V) (VI) or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-Cs heteroalkyl, C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, a Ci-C6 alkyl optionally substituted, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Cx-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted C6-C6 haloalkyl and a heteroalkyl Ci-C3 optionally substituted; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, C6-C6 haloalkyl Ci-C6 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted Ci-Cio alkyl, an optionally substituted Ci-C10 haloalkyl and an optionally substituted Ci-Ci0 heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is selected from (CH2) mR18 , C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisoster; each R8 and each R9 is independently selected from hydrogen, OR16, NR1SR17, an optionally substituted Ci-C6 alkyl, an optionally substituted Cx-C6 haloalkyl, an optionally substituted Ci-Cg heteroalkyl, (CH2) mR18 and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR R, SR, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce heteroalkyl, and Ci-Ce haloheteroalkyl; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and Ci-C4 haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C3 heteroalkyl, and Ci-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C3 heteroalkyl, and Ci-Cg heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, C1-C3 alkyl, Ci-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; W is selected from O, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted Ce-Ci0 aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted heterocycle or non-aromatic carbocycle, and a 1-5 atoms selected from an optionally substituted Ci-C6 alkyl, an optionally substituted C6-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is 0, 1, 2, or 3; and n is 0 or 1; provided that, if X is N, W is NH, and Y is not found -N = CR12- oriented to form a dihydropyrazole, and Z or R6 are not an optionally substituted non-aromatic ring fused to an optionally substituted aromatic ring; or if X is N, is NH, R6 is alkoxy, an alkyl optionally substituted, an optionally substituted aryl or an optionally substituted heteroaryl, and -N = CR12-oriented to form a dihydropyrazole, and Z is not an optionally substituted non-aromatic ring fused with an optionally substituted aromatic ring, then D is not a phenyl; provided, if X is N, W is NH and Y is -N = CR12- oriented to form a dihydropyrazole, then D is not a naphthyl; whenever, if U is NH; or if D and one of R10 and R11 form a 5-hydroxypyrazole, X is N and W is NH; or if E and one of R10 and R11 form a 5-hydroxypyrazole and X is N, and W is NH: or if E is phenyl, one of R10 or R11 is - (CH2) 0-6OH, X is C, W is NH, R6 is optionally substituted aryl or an optionally substituted heteroaryl, and Z is zero, an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted heteroaryl; or if E is phenyl, one of R10 or R11 is - (CH2) 0-6OH, X is N, W is NH, Z is zero, an optionally substituted alkyl, aryl optionally substituted an optionally substituted heteroaryl, and R6 is Ci alkyl. -C6, Ci-C6 alkoxy, - (CH2) o -sOR20, an optionally substituted aryl, an optionally substituted heteroaryl, NR21R22 or a heterocyclic methylene substituent represented by Formula VII; or if D is phenyl, one of R10 or R11 is - (CH2) 0_6OH, X is C, W is NH, Z is aromatic, and R6 is alkoxy, an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted heteroaryl; then Y is not found -N = CR12- oriented to form a dihydropyrazole; R20 is selected from hydrogen, a substituted alkyl, a substituted aryl, and a substituted heteroaryl; R21 and R22 are each independently selected from hydrogen, alkyl and aryl; or R21 and R22 taken together with the nitrogen to which they are attached represent a 5 or 6 membered saturated ring containing up to another heteroatom selected from oxygen and nitrogen; wherein A, B, C and V are each independently selected from 0, S and NR20. In certain embodiments, the invention provides a compound selected from: 3 '- Acid. { [1- (3, 5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-yldenomethyl] amino} -2 '-hydroxybiphenyl-3-carboxylic acid (Compound 101); 2, 4-dihydroxybenzoic acid N '-. { 1- [1- (3, 5-dimethylphenyl) -2- ??? -6-trifluoromethyl-1,2-dihydroindol -3-ethylhene] ethyl} hydrazide (Compound 102); Acid 3-. { 3- [(5-chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl) -3-yl) hydrazono] -2-oxo-2,3-dihydroindol-l-yl} benzoic (Compound 103); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 104); 3 'acid. { [1- (3, 5-dimethylphenyl) -2-??? - 6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -4-fluoro-2 '-hydroxybiphenyl-3-carboxylic acid (Compound 105); 2- (3'-. {[[1- (3, 5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -2'-hydroxybiphenyl-3 acid -yl) -2-methylpropionic (Compound 106); 3 'acid. { [1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -2 '-hydroxybiphenyl-3-carboxylic acid (Compound 107); 4- Acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 108); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-yl-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 109); Methyl ester of 3 - acid. { 3 - [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 110); Methyl ester of 3- acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol- 1- il} benzoic (Compound 111); Acid 3-. { 3- [(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 112); Acid 3-. { 3- [1- (3 ', 5'-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-1-ylideneamino] 2-oxo-2,3-dihydrobenzooxazol-7-yl} benzoic (Compound 113); Acid 3-. { 3- [(2-hydroxy-3, 3 ', 4' -trimethylbiphenyl -3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 114); 3-Hydroxybenzoic acid N '-. { 1- [1- (3, 5-dimethylphenyl) -2-??? - 6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 115); 1- (3,5-dimethylphenyl) -3-. { 1- [2- (4-hydroxyphenyl) -2-oxo-ethylamino] ethylidene} -6-trifluoromethyl-1,3-dhydroindol-2 -one (Compound 116). Acid 3.. { 3- [(5-Fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 117); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 118); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 119); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 120); 4- Acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl} butyric (Compound 121); 2-Chloro-3- (4. {[[(3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -3-hydroxyphenyl acid acrylic) (Compound 122); 4-hydroxybenzoic acid N '-. { l- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 123); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 124); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 125); Acid 3-. { 3- [(2-hydroxy-5, 3 ', 5' -trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 126); 4-aminobenzoic acid N '-. { l- [1- (3,5-Dimethylphenyl) -2 -oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 127); 3- (7- {? '- [1- (3,5-dimethylphenyl) -2-OXO-6- acid trifluoromethyl-1,2-dihydroindol-3-ylidene] hydrazino} -1H-indol-3-yl) ropionic (Compound 128); 4- Acid. { 3- [N '- (4-methylbenzoyl) hydrazinomethylidene] -2-OXO-2, 3-dihydroindol-1-yl} benzoic (Compound 129); Acid 3-. { 2-??? - 6-trifluoromethyl-3- [4- (3-trifluoromethyl-phenyl) -lH-pyrrol-2-ylmethylidene] -2,3-dihydroindol-1-yl} benzoic (Compound 130); 3- (7- { N '- [l- (3,4-dimethylphenyl) -3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene] hydrazino-1H-indole-3-yl acid ) propionic (Compound 131); 3- (3 { [4- (3, 4-Dimethylphenyl) thiazol-2-ylamino] methylidene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) benzoic acid ( Compound 132); 3- (3 { [4- (4-Methoxyphenyl) thiazol-2-ylamino] methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) benzoic acid (Compound 133 ); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylene] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 134); Acid 3-. { 3- [(4- (4-methylphenyl) -2-thiazolylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 135); Acid 3 -. { 3 - [(3,4-dimethylbenzoylhydrazino) methylidene] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 136); Acid 3-. { 3- [(4-Chlorobenzoylhydrazino) methylidene] -2-??? - 6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 137); Acid 3-. { 3- [(4-methoxybenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 138); Acid 3-. { 3- [(3,4-dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl} benzoic (Compound 139); 1- (3,4-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 140); 1- (3,4-Dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 141); 1- (3,4-dimethylphenyl) -3- [(2,4-dihydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 142); 1- (3, 5-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 143); 1- (3,5-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 144); 1- (3, 5-dimethylphenyl) -3- [(2,4- dihydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 145); 1- (3, 5-dimethylphenyl) -3 - [(4-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 146); 3- (3- [1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid (Compound 147); 1- (3, 4-dimethylphenyl) -3 - [(4-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 148); 1- (3,4-dimethylphenyl) -3 - [(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 149); 1- (3, 5-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 150); 2- (3,4-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 151); 3- (6-Chloro-3- [(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindol-1-yl) benzoic acid (Compound 152); 1- (3,4-dimethylphenyl) -3- [1- (2,5-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 153); 1- (3,4-dimethylphenyl) -3- [1- (3-nitro-4- hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 154); 1- (3, 4-dimethylphenyl) -3- [1- (3-aminosulfonyl-4-chlorobenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 155); 1- (3, 4-dimethylphenyl) -3- [l-3-amino-4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 156); 1- (3,4-dimethylphenyl) -3- [1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 157); Acid 3-. { 3- (1- (3,5-dimethylphenyl) -2 -oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl} benzoic (Compound 158); Acid 3-. { 3- (3, 5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2 -oxo-2,3-dihydro-1-indolyl} benzoic (Compound 159); Acid 3-. { 3- (1- (3, 4-dimethylphenyl) -2 -oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl} benzoic (Compound 160); 4- Acid. { 1- (6-Fluoro-2-oxo-2,3-dihydro-3- (2- (3,5-dimethylphenyl) -aminocarbonylphenyl) aminomethylidene) indolyl} butanoic (Compound 161); 4- Acid. { l- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) -aminomethylidene) indolyl Jbutanoic (Compound 162); Acid 3-. { l- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl J-benzoic acid (Compound 163); 4- Acid. { l. (5-fluoro-2-oxo-2,3-dihydro-3- (2-hydroxo) -3- (3, 5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} butanoic (Compound 164); Acid 3-. { 3- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indolidene) ethylamino) -2-hydroxyphenyl-benzoic acid (Compound 165); Acid 3-. { 3- (1- (3, -dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indolidene) ethylamino) -2-hydroxyphenyl} benzoic (Compound 166); Acid 3-. { 1- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazone) indolyl} benzoic (Compound 167); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3-cyclohexylphenyl) amino) ethylidene) indolyl} benzoic (Compound 168); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) aminomethylidene) indolyl J-benzoic acid (Compound 169); 4- Acid. { 2-Hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminophenyl} butanoic (Compound 170); 4- Acid. { 2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylaminophenyl} butanoic (Compound 171); Acid 3-. { 3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolidene) methylamino) indolyl} propanic (Compound 172); Acid 3-. { 3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3-indolidene) methylamino) indolyl} propanic (Compound 173); 4- Acid. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (3, 5-dimethylphenyl) indolidene) methylaminophenyl Jbutanoic (Compound 174); 2-chloro-3- acid. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propionic (Compound 175); 2-chloro-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl} propionic (Compound 176); 2-ethyl-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl} propionic (Compound 177); 2-ethyl-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic (Compound 178); 2-ethyl-3- acid. { 3-hydroxy-4- (2-0x0-2, 3-dihydro-l- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic (Compound 179); 4- Acid. { 2-hydroxy-3- (4- (2- (3,4-dimethylphenyl) -3-oxo-3,4-dihydro-5-methyl) pyrazolidene) methylaminophenyl} butanoic (Compound 180); Acid (Z) -4-. { l- (2,5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl Jbutanoic (Compound 181); Acid (E) -4-. { l- (2, 5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl Jbutanic (Compound 182); Acid (Z) -3-. { 1- (2, 5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl} benzoic (Compound 183); Acid (E) -3-. { l- (2, 5-dioxo-3 - (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl} benzoic (Compound 184); 4- Acid. { 3- (4-Oxo-2-thioxo-5- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) hydrozono) thiazolidinyl Jbutanoic (Compound 185); Acid 3-. { 2- (3- (1- (3,5-dimethylphenyl) -6-chloro-2-oxo-2,3-dihydroindolidene) methylamino) phenylaminobenzoic acid (Compound 186); Acid 3-. { 2- (3- (1- (3,5-dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydroindolidene) methylamino) phenylamino} benzoic (Compound 187); Acid 3-. { 2- (4- (2- (3,5-dimethylphenyl) -5-methyl-3-oxo-3,4-dihydropyrazolidene) methylamino) phenylamino} benzoic (Compound 188); Acid (+) - 3-methyl-5-. { 2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) phenyl} pentanoic (Compound 189); Acid (+) - 3 - (1- (6-chloro-2-oxo-2,3-dihydro-3- (3- (1- (3,5-dimethylphenyl) -2-oxo-2,3-dihydro) ) indolyl) aminomethylidene) indolyl} benzoic acid (Compound 190); 3- ({4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-acid) dihydro-1- (3, 5-dimethylphenyl) indolyl) hydrazono) iridinyl} benzoic acid (Compound 191); 3- {4- (3-hydroxy-6-methyl-2- (3- (6- trifluoromethyl-2-oxo-2, 3-dihydro-1- (3, 5-dimethylphenyl) indolidene) methylamino) pyridinyl} benzoic acid (Compound 192); 3- (4- (3-hydroxy-2-) acid (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) pyridinyl} benzoic acid (Compound 193); 3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) pyridinyl} benzoic acid (Compound 194); (5- (4-hydroxo-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) pyridinyl} benzoic acid (C omitted 195); Acid 3-. { 5- (4-Hydroxo-3 - (3- (6-trifluoromethyl-2-yl) -2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) iridinyl} benzoic acid (Compound 196 ); 3- ({5- (4-hydroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4-dimethylphenyl) pyrazolyl) hydrazono) pyridinyl acid. Benzoic acid (Compound 197): 4- {2- (3-Oxo-3,4-dihydro-5-methyl-4- (3- (3,4-dimethylphenyl) phenyl) hydrozono) pyrazolyl}. butanoic acid (Compound 198): 3- { 2-amino-5-methyl-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-l- (3,5-dimethylphenyl) indolidene) methylamino phenyl) benzoic acid (Compound 199); 3- ({I-l- (5-fluoro-2-oxo-2,3-dihydro-3- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) indolyl Jbenzoic (Compound 200); 4- ({2- (5-Methyl-2-oxo-2,3-dihydro-4- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic acid (Compound 201); Acid (3- (5-fluoro-2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylam ino) -1-pyrazolyl) acetic acid (Compound 202); Acid (3- (5-fluoro-2-hydroxy-3- (3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) -1-pyrazolyl) acetic acid (Compound 203); 4- ({2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy)) acid; 3 - . 3- (2-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 204); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 205); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2 - (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 206); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxo-3 - (2- (3-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 207); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2 - (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 208); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxo-3- (2- (1-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 209); Acid 3-. { l- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxo-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 210); Acid 3-. { l- (5-Nitro-2-oxo-2,3-dihydro3- (5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 211); 2-hydroxy-3- acid. { 3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminobenzoic acid (Compound 212); 2-hydroxy-3- acid. { 3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino} benzoic (Compound 213); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) aminomethylidene) pyrazolyl} butanoic (compound 214); 4- Acid. { 2- (5-Methyl-3-oxo-3, -dihydro-4- (2-hydroxy-3-heptaylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 215); 4- Acid. { 2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2,4-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 216); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2 - (3-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 217); 4- Acid. { 1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl Jbutanoic (Compound 218); Acid 2-. { 1- (2-??? -2,3-Dihydro-3 - (2-hydroxo-3- (3,5-dimethylphenyl) phenyl) hydrazone) indolyl} acetic (Compound 219); Acid 2-. { l. (2 -oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl Jacético (Compound 220); 4- Acid. { 4- (2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylamino) thiazolyl}. benzoic (Compound 221); Acid 3-. { 1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-5-methyl-3- (1-adamantane) phenyl) aminomethylidene) indolyl} benzoic acid (Compound 222): Acid 3-. { l- (6-trifluoromethyl-2-oxo-2,3-dihydro-3) (4-hydroxo-5- (3, 4-dimethylphenyl) pyridinyl) hydrazone) indolyl} benzoic acid (Compound 223); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxo-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethylidene) pyrazolyl} butanoic (Compound 224); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy 3- (2- (2-fluoro) phenyl) -ethylphenyl) aminomethylidene) pyrazolyl} butanoic (Compound 225); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (1-naphthyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 226); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (3, 5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compounds 227); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 228); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 229); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxo-3- (2- (2-fluoro-3-methyl-phenyl) ethyl) phenyl) aminomethylidene) irazolyl } butanoic (Compound 230); 4- Acid. { 2- (5-Methyl-3-oxo-3, -dihydro- (Z) - (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 231); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-cyanophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 232); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 233); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 234); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 235): Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 236); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 237); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3, 4-dihydro- 4 (Z) - (2-hydroxy-3- (2, (2,5-dimethyl-phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 238); 3- ({2- (5-trifluoromethyl-3) acid -oxo-3, 4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic acid (Compound 239); Acid 3-. { 2- (5-phenyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 240); Acid 3-. { 2- (5-tert-Butyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 241); Acid 3-. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 242); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 243); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 244); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 245); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanico (Compound 246); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 247); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethyl-phenyl) -ethyl) -phenyl) -hydrazono) -pyrazolyl} butanoic (Compound 248); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyanophenyl) ethyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 249); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-chlorophenyl) ethyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 250); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2 - (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 251); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 252); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 253); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazone) prazolyl Jbutanoic (Compound 254); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-6-trifluoromethylphenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 255); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 256); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 257); Acid (+) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 258); Acid (+) -3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 259); Acid 3 -. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (2-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 260); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2 - (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 261); Acid 3-. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-phenyl) -ethyl) -phenyl) -hydrazono) -pyrazolyl} benzoic (Compound 262); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 263); Acid 3 -. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxo-3- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 264); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl-6-trifluoromethylphenyl) ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 265); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} Benzoic (Compound 266); Acid 3-. { 2- (5-methyl-3 -oxo-2, 3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 267); Acid (E) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 268); Acid 3-. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 269); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} butanoic (Compound 270); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 271); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3, 5-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 272); Acid 3-. { 1- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazone) indolyl} Benzoic (Compound 273); 4- Acid. { 2- (5-methyl-3-oxo-2, 3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl} butanoic (Compound 274); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 275); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-phenylpropyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 276); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) rovyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 277); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 278); Acid (E) -4-. { 2- (5-Methyl-3-oxo-2, 3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 279); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro- (Z) - (2- hydroxy-3- (2- (2,6-dimethylphenyl) - (Z) -ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 280); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 281); Acid (Z) -4-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-bromoethenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 282); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 283); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2-cyclopropyletenyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 284); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 285); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fluoro-3- (3,5-dimethylphenyl) phenyl) hydrazono) pyrazolyl butanoic acid (Compound 286); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3, 4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 287); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl Jbutanóico (Compound 288); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3, 5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 289); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 290); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 291); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3, 4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 292); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 293); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 294); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-fluorophenyl) propyl) -phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 295); Acid 3-. { 2- (5-methyl-3 -oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) irazolyl} benzoic (Compound 296); Acid 3-. { 2. (5-Rethyl-3-oxo-3f-4-dihydro-4 (Z) - (2-hydroxy-3- (3, 5-dimethylphenyl) -phenyl) aminomethylidene) irazolyl} benzoic (Compound 297); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 298); Acid 3-. { 1- (2-??? -2,3-Dihydro-3 - (2-hydroxy-3 - (3,5-dimethylphenyl) -phenyl) hydrazone) indolyl} propionic (Compound 299); Acid 3-. { 1 - (2 - ??? - 2, 3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazone) -indolyl} benzoic (Compound 300); Acid 3-. { 1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl} propionic (Compound 301); Acid 3-. { 1- (6-chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) aminomethylidene) indolyl} benzoic (Compound 302); Acid (+) -3-. { 1- (6-chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (1,2-dihydro-1-methyl-2-indolylphenyl) aminomethylidene) indolyl. benzoic (Compound 303); 4- ({2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl acid butanoic acid (Compound 304); 4- ({2- (5-methyl-3-oxo-3,4-dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenyl)} carbonylamino) phenyl) hydrazone) pyrazolyl} butanoic (Compound 305); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2- (2-fluorophenyl) ethyl) indolidene) -hydrazinophenyl-benzene (Compound 306); Acid 3-. { 2-hydroxy-3- (2-OXO-2,3-dihydro-1- (2- (2-chlorophenyl) ethyl) indolylidene) -hydrazinophenyl-benzene (Compound 307); Acid 3-. { 3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridyl} Benzoic (Compound 308); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 309); Acid 3-. { 3-hydroxy-2- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolylidene-hydrazino) -4-pyridyl} benzoic (Compound 310); Acid 3-. { 1 - (2 - ??? - 2,3-dihydro-3 - (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazino) indolyl J-benzoic acid (Compound 311); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 312); Acid 3-. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino) -2-pyridyl-benzoic acid (Compound 313); 4- Acid. { 2-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3, 5-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl Jbutanoic (Compound 314); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 315); Acid 3-. { 3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -4-pyrazolidene) hydrazino-5-benzothienyl} benzoic (Compound 316); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 317); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3,5-diisopropylphenyl) -carbonylhydrazinomethylidene) pyrazolyl Jbutanoic acid (Compound 318); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -aminomethylidene) pyrazolyl} butanoic (Compound 319); Acid (+) -4-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-1-methyl-2-oxo-3-indolyl) methyl) phenyl) hydrazone Jubuntuic pyrazolyl (Compound 320); Acid 3-. { 1- (2-OXO-2, 3-dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl} propionic (Compound 321); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3- (2- (2, 5-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 322); Acid (+) -3-. { 2- (5-methyl-3-oxo-2,3-dihydro- - (2-hydroxy-3- (2,3-dihydro-l-methyl-2-oxo-3-indolyl) methyl) phenyl) hydrazone) pyrazolyl} benzoic (Compound 323); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-l-methyl-2-yl-3-indolylidene) methyl) phenyl hydrazone) pyrazolyl} benzoic (Compound 324); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 325); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (E) - (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 326); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} benzoic (Compound 327); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-l-methyl-2-oxo-3-indolylidene) methyl) phenyl) hydrazonopyrazole } butanoic (Compound 328); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 329); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-difluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 330); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-dimethylphenyl) -ethenyl) phenyl) hydrazono) irazolyl} butanoic (Compound 331); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-methylphenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 332); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 333); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z) - (2- (5-fluoro-2-methyl) phenyl) ethenyl) phenyl) hydrazone) pyrazolyl Jbutanóico (Compound 334); 4- Acid. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 335); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 336); 4- Acid. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 337); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2-phenylethenyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 338); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3- (2-phenylethynyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 339); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 340); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -etinyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 341); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) ethynyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 342); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -etinyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 343); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-phenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 344 ); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (l-methyl-1-indenyl-2-phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 345); 4- ({2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,3-dimethyl-2-indenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 346); 4- {2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) -hydrazono) -pyrazolyl acid Jbutanóico (Compound 347); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-dimethyl) -2-indenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 348); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 349); Acid 3-. { 2-hydroxy -3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolylidene) methylaminophenyl} benzoic (Compound 350); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) -indolylidene) methylaminophenyl-benzene (Compound 351); Acid (+) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (1,2,3,4-tetrahydro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 352); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 353); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (1-indanylidene) -methylphenyl) hydrazono) pyrazolyl} butanoic (Compound 354); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-trifluoromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 355); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (6-fluoro-2-trifluoro-methylphenyl) ethenyl) phenyl) hydrazone) irazolil } butanoic (Compound 356); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (6-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 357); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 358); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 359); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 360); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2, 5-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 361); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-trifluoro-methylphenyl) ethenyl) phenyl) hydrazone) irazolil } butanoic (Compound 362); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -etinyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 363); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3 (E) - (1,2,3,4-tetrahydro) -naphthylidene) methylphenyl) hydrazono) pyrazolyl} butanoic (Compound 364); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-5-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 365); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3,5-dimethyl-4-isoxazolyl) ethenyl) phenyl) hydrazone) pyrazolyl } butanoic (Compound 366); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,5-dimethyl-4-isoxazolyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 367); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E) - (2-methylphenyl) ethenyl) -3 (Z) -indolylidene) methylaminophenyl-benzene (Compound 368); Acid 3-. { 2-hydroxy-3- (2-OXO-2,3-dihydro-1- (2 (E) - (2,4-difluorophenyl) ethenyl) -3 (Z) -indolylidene) methylaminophenyl} benzoic (Compound 369); Acid 3-. { 2-hydroxy-3- (2-γ-2,3-dihydro-1- (2-indenyl) -3 (Z) -indolylidene) methyl-aminophenyl} benzoic (Compound 370); Acid 3-. { 2-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 371); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} butanoic (Compound 372); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 373); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 374); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2 - (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 375); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 376); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 377); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (2-fluoro-6-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 378); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,3-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 379); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,3-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 380); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3 (E) - (2- (2-fluoro-4-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 381); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 382); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-dichlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 383); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-chlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 384); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2, 5-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 385); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chloro-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 386); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 387); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (2,4-dichlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 388); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chloromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazone) pyrazolyl} benzoic (Compound 389); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,4-dichloromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 390); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro) -naphthyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 353); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-8-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 392); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-8-methyl) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 393); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-7-methyl) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 394); 4- Acid. { 2- (5-Methyl-3-oxo-2, 3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 395); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-6-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 396); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (3,4-dihydro-5-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 397); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-8-chloro) -naphthyl) phenyl) hydrazono) irazolyl} butanoic (Compound 398); Acid 3 -. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 399); and a pharmaceutically acceptable salt, ester, or prodrug of any of those compounds. In certain embodiments, a compound of Formula I, II, III, IV, V or VI is a selective TPO modulator. In certain such embodiments, a compound of Formula I, II, III, IV, V or VI is a TPO mimic. In certain embodiments, the invention provides methods for modulating the activity of TPO. Certain such methods comprise contacting a cell with one or more compounds of the present invention. Such methods include, but are not limited to, contacting the TPO or the TPO receptor with one or more compounds of the present invention. In certain embodiments, the invention provides a method for identifying a compound capable of modulating TPO activity, comprising: a) contacting a cell capable of TPO activity with a compound of the present invention; and b) monitor the effect on the cell. In certain such modalities, the cell expresses a TPO receptor.

In certain embodiments, the invention provides methods for treating a patient, which comprise administering to the patient a compound of the present invention. In certain embodiments, such a patient suffers from thrombocytopenia. In certain embodiments, one or more compounds of the present invention are administered to a patient, before, during or after chemotherapy, bone marrow transplantation and / or radiation therapy. In certain embodiments, one or more compounds of the invention are administered to a patient suffering from aplastic anemia, bone marrow failure and / or idiopathic thrombocytopenia. In certain embodiments, one or more compounds of the present invention are administered to a patient suffering from a disease of the nervous system. In certain embodiments, one or more compounds of the present invention are administered to a patient suffering from amyotrophic lateral sclerosis, multiple sclerosis, or multiple dystrophy. In certain embodiments, one or more compounds of the present invention are administered to a patient with a nerve injury, including, but not limited to, a spinal cord injury. In certain embodiments, the invention provides pharmaceutical compositions comprising: i) a physiologically acceptable carrier, diluent or excipient or a combination thereof; and ii) one or more compounds of the present invention.

In certain embodiments, the invention provides a selective TPO modulator. In certain embodiments, the invention provides a selective TPO receptor agonist. In certain embodiments, the invention provides a selective TPO receptor antagonist. In certain embodiments, the invention provides a partial selective TPO agonist. In certain embodiments, the invention provides a selective TPO receptor binding compound. In certain embodiments, the invention provides a TPO mimic. DETAILED DESCRIPTION It should be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and not restrictive of the claimed invention. In this application, the use of the singular includes the plural unless otherwise defined. In this application, the one "o" means "and / or" unless otherwise defined. In addition, the use of the term "including" as well as other forms, such as "includes" and "included", is not limiting.

The section headers used here are for organizational purposes only and should not be construed as limiting the subject matter described. All documents, or portions of documents, cited in the application, including, but not limited to, Patents, patent applications, articles, books, manuals and treatises are hereby expressly incorporated by reference in their entirety for all purposes. Definitions Unless specific definitions are provided, the nomenclatures used in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein, are those known in the art. The standard chemical symbols are used interchangeably with the complete names represented by such symbols. Thus, for example, it is understood that the terms "hydrogen" and "H" have an identical meaning. Standard techniques can be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation and delivery, and patient treatment. Standard techniques for recombinant DNA, oligonucleotide synthesis, and culture and transformation of the tides (e.g., electroporation, lipofection) can be used. Reactions and purification techniques can be effected e.g., using equipment according to the manufacturer's specifications or as is commonly accomplished in the art or as described herein. The above techniques and procedures may be carried out generally in accordance with conventional methods well known in the art. technique and as described in the various general and more specific references that are cited and discussed throughout this specification. See, eg, Sambrook et al., Molecular Cloning: A Laboratory Manual (2nd ed. Cold Spring Harbor Press, Cold Spring Harbor, NY, (1989)), which is incorporated herein by reference in its entirety for any purpose .

As used herein, the following terms are defined with the following meanings, unless expressly defined otherwise. The term "selective binding compound" refers to a compound that selectively binds to any protein of one or more targets. The term "selective TPO receptor binding compound" refers to a compound that selectively binds to any portion of a TPO receptor. The term "selectively binds" refers to the ability of a selective binding compound to bind to a target receptor with higher affinity than to which it binds to a non-target receptor. In certain embodiments, selective binding refers to the link to a target with an affinity that is at least 10, 50, 100, 250, 500 or 1000 times greater than the affinity for a non-target. The term "target receptor" refers to a receptor or a portion of a receiver capable of being linked by a selective binding compound. In certain modalities, a target receptor is a TPO receptor. The term "modulator" refers to a compound that alters an activity. For example, a modulator can cause an increase or decrease in the magnitude of a certain activity compared to the magnitude of the activity in the absence of the modulator. In certain embodiments, a modulator is an inhibitor, which decreases the magnitude of one or more activities. In certain embodiments, an inhibitor completely prevents one or more biological activities. In certain embodiments, a modulator is an activator, which increases the magnitude of at least one activity. In certain embodiments, the presence of a modulator results in an activity that does not occur in the absence of the modulator. The term "selective modulator" refers to a compound that selectively modulates a target activity. The term "selective TPO modulator" refers to a compound that selectively modulates at least one TPO activity. The term selective TPO modulator includes, but is not limited to, "TPO mimic" which refers to a compound, whose presence results in at least one TPO activity. The TPO mimics are described in O 03 / 103686A1 and O 01/21180, both of which are incorporated herein by reference in their entirety.

The term "modulates selectively" refers to the ability of a selective modulator to modulate a target activity to a greater degree than it modulates a non-target activity. The term "target activity" refers to the biological activity capable of being modulated by a selective modulator. Certain exemplary target activities include, but are not limited to, binding affinity, signal transduction, enzymatic activity, the proliferation and / or differentiation of progenitor cells, the generation of platelets and the alleviation of the symptoms of a disease or condition. The term "TPO activity" refers to a biological activity that results either directly or indirectly from the presence of TPO. Exemplary TPO activities include, but are not limited to, proliferation and / or differentiation of progenitor cells to produce platelets; hematopoiesis; growth and / or development of glial cells; repair of nerve cells; and relief of thrombocytopenia. The term "thrombocytopenia" refers to a condition in which the concentration of platelets in a patient's blood is below what is considered normal for a healthy patient. In certain modalities, thrombocytopenia is a platelet count less than 450,000, 400,000, 350,000, 300,000, 250,000, 200,000, 150,000, 140,000, 130,000, 120,000, 110,000, 100,000, 75,000, or 50,000 platelets per microliter of blood. The term "receptor-mediated activity" refers to any biological activity that results, either directly or indirectly, from the binding of a ligand to a receptor. The term "agonist" refers to a compound, the presence of which results in a biological activity of a receptor that is the same as the biological activity resulting from the presence of a ligand of natural origin for the receptor. The term "partial agonist" refers to a compound, the presence of which results in a biological activity of a receptor that is of the same type as that resulting from the presence of in ligand of natural origin for the receptor, but of a smaller magnitude. The term "antagonist" refers to a compound whose presence results in a decrease in the magnitude of a biological activity of a receptor. In certain embodiments, the presence of an antagonist results in the complete inhibition of a biological activity of a receptor. The term "alkyl" refers to an aliphatic hydrocarbon group. An alkyl can be an "alkyl" "saturated", which means that it does not contain any alkene or alkyne group An alkyl group can be an "unsaturated alkyl", which means that it comprises at least one alkene or alkyne group. An alkyl, whether saturated or unsaturated, can be branched or straight chain. The alkyls may be cyclic or non-cyclic. Cyclic alkyls may include multicyclic systems including fused alkyl rings. The alkyls can be substituted or unsubstituted. Alkyls include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, of which each one may be optionally substituted. In certain embodiments, an alkyl comprises from 1 to carbon atoms (when it appears in the present, a number range such as "1 to 20" refers to each integer in the given range, eg, "1 to 20 carbon atoms" means that an alkyl group can comprise only 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although the term "alkyl" also includes examples where no numerical range of carbon atoms is designated) . The term "lower alkyl" refers to an alkyl comprising from 1 to 5 carbon atoms. The term "middle alkyl" refers to an alkyl comprising from 5 to 10 carbon atoms. An alkyl can be designated as "Ci-C4 alkyl" or similar designations. By way of example only, "Ci-C4 alkyl" denotes an alkyl having one, two, three or four carbon atoms, eg, the alkyl is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec -butyl, t-butyl, ethenyl, propenyl, butenyl, ethynyl, propynyl and butynyl. The term "alkenyl" refers to an alkyl group comprising at least one carbon-carbon double bond. The term "alkynyl" refers to an alkyl group comprising at least one triple carbon-carbon bond. The term "haloalkyl" refers to an alkyl in which at least one hydrogen atom is replaced with a halogen atom. In certain embodiments in which two or more hydrogen atoms are replaced by halogen atoms, the halogen atoms are all the same as the others. In certain such embodiments, the halogen atoms are not all the same as the others. The term "heteroalkyl" refers to a group comprising an alkyl and one or more heteroatoms. Certain heteroalkyls are acylalkyl, in which the one or more heteroatoms are within an alkyl chain.

Examples of heteroalkyls include, but are not limited to, CH3C (= 0) CH2-, CH3C (= 0) CH2CH2-, CH3CH2C (= 0) CH2CH2-, CH3C (= 0) CH2CH2CH2-, CH3OCH2CH2-, CH3NHCH2- and the like. The term "straight chain alkoxy" refers to a group comprising the formula: - (CH2) 0-, where p is any integer. Straight chain alkoxy does not include substituted or branched alkoxy groups. The term "non-straight-chain alkoxy-heteroalkyl" refers to any heteroalkyl which is not a straight-chain heteroalkyl alkoxy. Thus, for example, non-straight chain heteroalkyls include, but are not limited to: 2,2-isopropyloxy; 1,2-propyloxy; 1, 1-ethyloxy; methylamino; ethylamino; propylamino; methylpyrrolidino and methylpiperidino. The term "olefin" refers to a C = C bond. The term "heterohaloalkyl" refers to a heteroalkyl in which at least one hydrogen atom is replaced with a halogen atom. The term "carbocycle" refers to a group comprising a covalently closed ring in which each of the atoms forming the ring is a carbon atom. The carbocyclic rings can be formed by three, four, five, six, seven, eight, nine or more than nine carbon atoms. The carbocycles can be optionally substituted.

The term "heterocycle" refers to a group comprising a covalently closed ring in which at least one atom forming the ring is a heteroatom. Heterocyclic rings can be formed by three, four, five, six, seven, eight, nine or more than nine atoms. Any number of those atoms may be heteroatoms (i.e., a heterocyclic ring may comprise one, two, three, four, five, six, seven, eight, nine or more than nine heteroatoms). In heterocyclic rings comprising two or more heteroatoms, those two or more heteroatoms may be the same or different from each other. The heterocycles can be optionally substituted. The bond to a heterocycle can be found in a hetero atom or by means of a carbon atom. For example, the bond for derivatives fused to benzo can be by means of a carbon of the benzenoid ring. Examples of heterocycles include, but are not limited to the following: wherein D, E, F and G independently represent a heteroatom. Each of D, E, F and G can be the same or different from each other. The term "heteroatom" refers to an atom other than carbon or hydrogen. Heteroatoms are typically independently selected from oxygen, sulfur, nitrogen and phosphorus, but are not limited to those atoms. In embodiments in which two or more heteroatoms are present, the two or more heteroatoms may all be the same as the others, or some or all of the two or more heteroatoms may be different from the others. The term "aromatic" refers to a group comprising a covalently closed ring having a delocalized pi-electron system. The aromatic rings can be formed by five, six, seven, eight, nine or more than nine atoms. The aromatics may be optionally substituted. Examples of aromatic groups include, but are not limited to, phenyl, naphthalenyl, phenanthrenyl, anthracenyl, tetralinyl, fluorenyl, indenyl, and indanyl. The term "aromatic" includes, for example, benzenoid groups, connected by one of the ring-forming carbon atoms, and optionally contains one or more substituents selected from an aryl, a heteroaryl, a cycloalkyl, a non-aromatic heterocycle, a halo, a hydroxy, an amino, a cyano, a nitro, an alkylamido, an acyl, a Ci-6 alkoxy, a Ci_6 hydroxyalkyl, a Ci-6 aminoalkyl, an Ci_ 6 alkylamino, an alkylsulfenyl, an alkylsulfinyl, an alkylsulfonyl, a sulfamoyl, or a trifluoromethyl. In certain embodiments, an aromatic group is substituted in one or more of the para, meta and / or other positions. Examples of aromatic groups comprising substitutions include, but are not limited to, phenyl, 3-halophenyl, 4-halophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3-aminophenyl, 4-aminophenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4 - . 4-trifluoromethoxyphenyl, 3-cyano-phenyl, 4-cyanophenyl, dimethylphenyl, naphthyl, hydroxynaphthyl, hydroxymethylphenyl, (trifluoromethyl) phenyl, alkoxyphenyl, 4-morpholin-4-ylphenyl, 4-pyrrolidin-1-ylphenyl, 4-pyrazolylphenyl, 4-triazolfenyl and 4- (2-oxopyrrolidin-1-yl) phenyl. The term "aryl" refers to an aromatic group in which each of the atoms forming the ring is a carbon atom. The aryl rings can be formed by five, six, seven, eight, nine or more than nine carbon atoms. The aryl groups can be optionally substituted. The term "heteroaryl" refers to an aromatic group in which at least one atom that forms the aromatic ring is a heteroatom. Heteroaryl rings can be formed by three, four, five, six, seven, eight, nine or more than nine atoms. Heteroaryl groups can be optionally substituted. Examples of heteroaryl groups include, but are not limited to, aromatic C3.8 heterocyclic groups comprising an oxygen or sulfur atom or up to four nitrogen atoms, or a combination of an oxygen or sulfur atom and up to two nitrogen atoms, and its substituted derivatives as well as fused to benzo and pyrido, for example, connected by one of the ring-forming carbon atoms. In certain embodiments, heteroaryl groups are optionally substituted with one or more substituents, independently selected from halo, hydroxy, amino, cyano, nitro, alkylamido, acyl, Ci-6 alkoxy, Ci-6 alkyl / Ci-6 hydroxyalkyl, aminoalkyl Ci_6, Ci-6 alkylamino, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, sulfamoyl, or trifluoromethyl. Examples of heteroaryl groups include, but are not limited to, unsubstituted and mono- and di-substituted derivatives of furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole, oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, benzothiazole, isothiazole, imidazole , benzimidazole, pyrazole, indazole, tetrazole, quinoline, isoquinoline, pyridazine, pyrimidine, purine and pyrazine, furazan, 1, 2, 3-oxadiazole, 1, 2, 3-thiadiazole, 1, 2,4-thiadiazole, triazole, benzotriazole , pteridine, phenoxazole, oxadiazole, benzopyrazole, quinolizine, cinnoline, phthalazine, quinazoline and quinoxaline. In some embodiments, the substituents are halo, hydroxy, cyano, or Ci_ 6-alkyl, C 1-6 alkyl, hydroxy Ci-6-alkyl, and amino-1-6-alkyl. The term "non-aromatic ring" refers to a group comprising a covalently closed ring that does not have a delocalised pi-electron system. The term "cycloalkyl" refers to a group comprising a non-aromatic ring wherein each of the atoms that form the ring is a carbon atom. Cycloalkyl rings can be formed by three, four, five, six, seven, eight, nine or more than nine carbon atoms. Cycloalkyls may include multicyclic systems (e.g., fused ring systems). Cycloalkyls may be optionally substituted. In certain embodiments, a cycloalkyl comprises one or more unsaturated bonds. Examples of cycloalkyls include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclopentadiene, cyclohexane, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, cycloheptane, and cycloheptene. The term "non-aromatic heterocycle" refers to a group comprising a non-aromatic ring in which one or more of the atoms forming the ring is a heteroatom. Non-aromatic heterocyclic rings can be formed by three, four, five, six, seven, eight, nine or more than nine atoms. Non-aromatic heterocycles can be optionally substituted. In certain embodiments, the non-aromatic heterocycles comprise one or more carbonyl or thiocarbonyl groups such as, for example, oxo- and thio-containing groups. Examples of non-aromatic heterocycles include, but are not limited to, lactams, lactones, cyclic imides, cyclic thioimides, cyclic carbamates, tetrahydrothiopyran, 4H-pyran, tetrahydropyran, piperidine, 1,3-dioxin, 1,3-dioxane, 1, 4-dioxin, 1,4-dioxane, piperazine, 1,3-oxathiane, 1,4-oxathiane, 1,4-oxathiane, tetrahydro-1,4-thiazine, 2H-1, 2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hindantoin, dihydrouracil, morpholine, trioxane, hexahydro-1,3,5-triazine, tetrahydrothiophene, tetrahydrofuran, pyrroline, pyrrolidine, pyrrolidone, pyrrolidione, pyrazoline, pyrazolidine, imidazoline, imidazolidine, 1,3- dioxol, 1,3-dioxolane, 1,3-dithiol, 1,3-dithiolane, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine and 1,3-oxathiolane. The term "arylalkyl" refers to a group comprising an aryl group linked to an alkyl group. The term "carbocycloalkyl" refers to a group comprising a carbocyclic cycloalkyl ring. The carbocycloalkyl rings can be formed by three, four, five, six, seven, eight, nine or more than nine atoms of carbon. The carbocycloalkyl groups can be optionally substituted. The term "ring" refers to any covalently closed structure. The rings include, for example, carbocycles (e.g., aryls and cycloalkyl), heterocycles (e.g., heteroaryls and non-aromatic heterocycles), aromatics (e.g., aryls and heteroaryls) and non-aromatics (e.g., cycloalkyls and non-aromatic heterocycles). The rings may be optionally substituted. The rings can be part of a ring system. The term "ring system" refers to either a single ring or two or more rings, where, if two or more rings are present, the two or more rings are fused together. The term "merged" refers to structures in which two or more rings share one or more links. The term "carboxylic acid bioisostere" refers to a group that is biologically equivalent to a carboxylic acid. For example, carboxylic acid bioisosteres include, but are not limited to, tetrazole, NHS02R15, OC (S) NR10R11, SC (O) NR ^ R11, thiazolidinedione, oxazolidinedione, and l-oxa-2,4-diazolidin-3, 5-dione. In certain embodiments, a carboxylic acid bioisostere comprises the following structure: where A, B and C are each independently selected from O, S and N. The term "spacer" refers to an atom or group of atoms that separate two or more groups from each other by a desired number of atoms. For example, in certain embodiments, it may be desirable to separate two or more groups by one, two, three, four, five, six, or more than six atoms. In such embodiments, any atom or group of atoms can be used to separate those groups by the selected number of atoms. The spacers are optionally replaced. In certain embodiments, a spacer comprises saturated or unsaturated alkyls, heteroalkyls and / or haloalkyls. In certain embodiments, a spacer comprises atoms that are part of a ring. For illustration purposes only, and without limiting the above definition, some examples of spacers are provided. Examples of 1-atom spacers include, but are not limited to, the following: where A and B represent groups that are separated by the desired number of atoms. Examples of 2-atom spacers include, but are not limited to, the following: where A and B represent groups that are separated by the desired number of atoms. Examples of 3-atom spacers include, but are not limited to, the following: where A and B represent groups that are separated by the desired number of atoms. As is evident from the previous examples, the atoms that create the desired separation can by themselves be part of a group. That group can be, for example, an alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, or substituted alkyl, all of which are optionally substituted. Thus, the term "1-5 atom spacer" refers to a spacer that separates two groups by 1, 2, 3, 4 or 5 atoms and does not indicate the total size of the group that constitutes the spacer.

As used herein, the term "bound to form a ring" refers to cases in which two atoms are linked either to a single atom or to atoms that are themselves finally bound, and each linked to a linking group, in such a way that the resulting structure forms a ring. That resulting ring comprises the two atoms that are bonded to form a ring, the atom (or atoms) that were previously bound to those atoms, and the linker. For example, if A and B below are "linked to form a ring" the resulting ring includes A, B, C, and a linker group. Unless indicated otherwise, that link group may be of any length and may optionally be substituted. With reference to the previous example, the resulting structures include, but are not limited to: In certain embodiments, the two substituents that together form a ring are not immediately linked to the same atom. For example, if A and B, below, are linked to form a ring: the resulting ring comprises A, B, the two atoms that already bind to A and B and a linking group. Examples of the resulting structures include, but are not limited to: and the similar. In certain embodiments, the atoms that together form a ring are separated by three or more atoms. For example, if A and B, below, are linked to form a ring: »The resulting ring comprises A, B, 3 atoms that already link to A and B and a linking group. Examples of the resulting structures include, but are not limited to: > and the similar. As used herein, the term "jointly forming a bond" refers to the case in which two substituents for neighboring atoms are null, the bond between neighboring atoms becomes a bond double. For example, if A and B below "jointly form a link" The resulting structure is: The term "null" refers to a group that is absent from a structure. For example, in the structure, / \. , where in certain cases X is N, if X is N, one of R 'or R "is null, which means that only three groups are linked to N. The substituent" R "that appears by itself and without a designated number, it refers to a substituent selected from alkyl, cycloalkyl, aryl, heteroaryl (linked by a ring carbon) and non-aromatic heterocycle (linked by a ring carbon). The term "O carboxy" refers to a group of the formula RC (= 0) 0-. The term "C carboxy" refers to a group of the formula -C (= 0) OR. The term "acetyl" refers to a group of the formula -C (= 0) CH3. The term "trihalomethanesulfonyl" refers to a group of the formula X3CS (= 0) 2- where X is a halogen.

The term "cyano" refers to a group of the formula -CN. The term "isocyanate" refers to a group of the formula -NCO. The term "thiocyanate" refers to a group of the formula -CNS. The term "isothiocyanate" refers to a group of the formula -NCS. The term "sulfonyl" refers to a group of the formula -S (= 0) -R. The term "S-sulfonamido" refers to a group of the formula -S (= 0) 2NR. The term "N-sulfonamido" refers to a group of the formula RS (= 0) 2NH-. The term "trihalomethanesulfonamido" refers to a group of the formula X3CS (= 0) 2NR-. The term "O-carbamyl" refers to a group of the formula -0C (= 0) -NR. The term "N-carbamyl" refers to a group of the formula R0C (= 0) NH-. The term "0-thiocarbamyl" refers to a group of the formula -0C (= S) -NR. The term "N-thiocarbamyl" refers to a group of the formula R0C (= S) NH-. The term "C-amido" refers to a group of the Formula -C (= 0) -NR2. The term "N-amido" refers to a group of the formula RC (= 0) NH-. The term "oxo" refers to a group of the formula = 0. The term "dihydropyrazolylene" refers to a di radical of an optionally substituted dihydropyrazole ring, wherein the dihydropyrazole ring has the structure: and wherein the two radicals can be in any position on the ring. The term "pyrazolyl" refers to a radical of a pyrazole ring, wherein the pyrazole ring has the structure: and where the radical can be found in any position on the ring. The term "ester" refers to a chemical residue with the formula - (R) n-C00R ', wherein R and R' are independently selected from alkyl, cycloalkyl, aryl, heteroaryl (linked by a ring carbon) and a non-aromatic heterocycle (bound by a carbon of ring), where n is 0 or 1. The term "amide" refers to a chemical residue with the formula - (R) nC (0) NHR 'or - (R) n -NHC (0) R', in where R and R 'are independently selected from alkyl, cycloalkyl, aryl, heteroaryl (linked by a ring carbon) and heteroalicyclic (linked by a ring carbon), wherein n is 0 or 1. In certain embodiments, an amide may be be an amino acid or a peptide. The terms "amine", "hydroxy", and "carboxyl" include such groups that have been esterified or amidated. The specific procedures and groups used to achieve esterification and amidation are known to those skilled in the art and can be easily found in reference sources such as Greene and Wuts, Protective Groups in Organic Synthesis (Protective Groups in Organic Synthesis), 3a Ed., John iley & Sons, New York, NY, 1999, which is incorporated in the present in its entirety. Unless otherwise indicated, the term "optionally substituted" refers to a group in which, none, one or more of one of the hydrogen atoms has been replaced with one or more groups individually and independently selected from: alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, 0-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, and amino, including mono and di-substituted amino groups, and protected derivatives of amino groups. Such protecting derivatives (and protecting groups that can form such protective derivatives) are known to those skilled in the art and can be found in references such as Greene and Wuts, supra. In embodiments in which two or more hydrogen atoms have been substituted, the substituent groups can together form a ring. Throughout the specification, the groups and substituents thereof may be selected by those skilled in the art, to provide stable residues and compounds. The term "vehicle" refers to a compound that facilitates the incorporation of another compound into cells or tissues. For example, dimethyl sulfoxide (DMSO) is a vehicle commonly used to improve the incorporation of certain organic compounds within cells or tissues. The term "pharmaceutical agent" refers to a chemical compound or composition capable of inducing a desired therapeutic effect in a patient. In certain modalities, A pharmaceutical agent comprises an active agent, which is the agent that induces the desired therapeutic effect. In certain embodiments, a pharmaceutical agent comprises a prodrug. In certain embodiments a pharmaceutical agent comprises inactive ingredients such as vehicles, excipients and the like. The term "therapeutically effective amount" refers to an amount of a pharmaceutical agent sufficient to achieve a desired therapeutic effect. The term "prodrug" refers to a pharmaceutical agent that is converted in a less active form into a corresponding more active form in vivo. The term "pharmaceutically acceptable" refers to "a formulation of a compound that does not significantly abrogate biological activity, a pharmacological activity and / or other properties of the compound, when the formulated compound is administered to a patient. In certain embodiments, a pharmaceutically acceptable formulation does not cause significant irritation in a patient. The term "co-administer" refers to the administration of more than one pharmaceutical agent to a patient. In certain embodiments, the co-administered pharmaceutical agents are co-administered in a single dose unit. In certain embodiments, the co-administered pharmaceutical agents are administered separately.

In certain embodiments, the co-administered pharmaceutical agents are administered at the same time. In certain embodiments, the co-administered pharmaceutical agents are administered at different times. The term "patient" includes human and animal subjects. The term "substantially pure" means an objective species (e.g., compound) which is the predominant species present (i.e., on a molar basis it is more abundant than the other individual species in the composition). In certain embodiments, a substantially purified fraction is a composition wherein the target species comprises at least about 50 percent (on a molar basis) of all species present. In certain embodiments, a substantially pure composition will comprise more than about 80%, 85%, 90%, 95% or 99% of all species present in the composition. In certain embodiments, the target species is purified to essential homogeneity (the contaminant species can not be detected in the composition by conventional detection methods) wherein the composition consists essentially of a single species. The term "tissue selective" refers to the ability of a compound to modulate a biological activity in a tissue to a greater or lesser degree than it modulates a biological activity in another tissue. Biological activities in different tissues can be mediated by the same type of target receptor. For example, in certain embodiments, a tissue-selective compound can modulate the biological activity mediated by the receptor in a tissue and fail to modulate, or modulate to a lesser degree, the biological activity mediated by the receptor in another type of tissue. The term "monitor" refers to observing the effect or absence of some effect. In certain embodiments, the cells are monitored after contacting those cells with a compound of the present invention. Examples of effects that can be monitored include, but are not limited to, changes in the cellular phenotype, cell proliferation, receptor activity, or the interaction between a receptor and a compound known to bind to the receptor. The term "cell phenotype" refers to physical or biological characteristics. Examples of characteristics that constitute the phenotype include, but are not limited to, cell size, cell proliferation, cell differentiation, cell survival, apoptosis (cell death) or the utilization of a metabolic nutrient (e.g., glucose uptake). Certain changes or the absence of changes in the cell phenotype are easily monitored using techniques known in the art. The term "cell proliferation" refers to the rate at which cells divide. In certain modalities, cells are found in situ in an organism. In certain embodiments, the cells are cultured in vitro in a container. The number of cells that are grown in a container can be quantified by the person skilled in the art (e.g., counting the cells in a defined area using a microscope or using latory apparatus that measures the density of the cells in an appropriate medium). The person skilled in the art can calculate the cell proliferation by determining the number of cells in two or more times. The term "contacting" refers to placing two or more materials in close enough proximity so that they can interact. In certain embodiments, contact can be achieved in a package such as a test tube, a petri dish, or the like. In certain modalities, contact can be made in the presence of additional materials. In certain embodiments, contact can be made in the presence of cells. In certain such embodiments, one or more of the materials contacted may be within a cell. The cells can be alive or dead. The cells may or may not be intact.

Certain Compounds Certain compounds that modulate one or more TPO activities and / or that bind to TPO receptors play a role in health. In certain modalities, the compounds of the present invention are useful for treating any of a variety of diseases or conditions. In certain embodiments, the present invention provides selective TPO modulators. In certain embodiments, the invention provides selective TPO receptor binding agents. In certain embodiments, the invention provides methods for preparing and methods for using selective TPO modulators and / or selective TPO receptor binding agents. In certain embodiments, selective TPO modulators are agonists, partial agonists and / or antagonists for the TPO receptor. In certain embodiments, the present invention relates to compounds of Formula I, II, III, IV, V or VI: (IV) (V) (VI) or a pharmaceutically acceptable salt, ester, amide or prodrug thereof. In certain embodiments, R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci_C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere. In certain such embodiments, the carboxylic acid bioisostere is selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (0) NR14R15, and wherein A, B, and C are each independently selected from O, S, and N; In certain embodiments, each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Cx-C6 alkyl, an optionally substituted haloalkyl i ~ Cs, and an optionally substituted x-Ce heteroalkyl. In certain embodiments, R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, and an optionally substituted Ci-C6 heteroalkyl. In certain embodiments, R5 is selected from a group of hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl and Ci-C6 haloheteroalkyl; In certain modalities, R6 is selected from alkyl Ci-Cio optionally substituted, an optionally substituted Ci-Ci0 haloalkyl or an optionally substituted Ci-Ci0 heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is (CH2) mR18, or C (0) NHR18. In certain embodiments, R6 is selected from an optionally substituted Ci-Cio alkyl, an optionally substituted Ci-Ci0 haloalkyl or an optionally substituted Ci-Cio heteroalkyl, each optionally fused to a substituted aryl or a substituted heteroaryl, or R6 is selected from (CH2) mR18, or C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18. In certain embodiments, R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere. In certain such embodiments, the carboxylic bioisostere is selected from tetrazole, NHS02R19, OC (S) NR1 R15, SC (0) NR14R15, and wherein A, B, and C are each independently selected from O, S, and N; In certain embodiments, each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted -i-C6 heteroalkyl, (CH2) mR18 and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; In certain embodiments, R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl. In certain embodiments, R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR1. In certain modalities, R11 and R4 are linked to form a heterocycle optionally substituted. In certain embodiments, R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C3 heteroalkyl, and Ci-C6 haloheteroalkyl. In certain embodiments, R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl > C1-C4 haloalkyl, C1-C4 heteroalkyl, and Ci-C4 haloheteroalkyl. In certain embodiments, R14 is selected from hydrogen, Ci-Ce alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and C6-C6 heterohaloalkyl. In certain embodiments, R15 is selected from hydrogen, S02R19, Ci-C6 alkyl, C-halo haloalkyl, Ci-C6 heteroalkyl and heterohaloalkyl Ci-Ce. In certain embodiments, R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and (CH2) mR18. In certain embodiments, one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null. In certain embodiments, R16 and R17 are linked to form an optionally substituted C3-C8 ring. In certain embodiments, R18 is selected from a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally is fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either on the heterocycle or non-aromatic carbocycle or on the aromatic ring system. In certain embodiments, R19 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and optionally substituted aryl. In certain embodiments, D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused to a heterocycle or non-aromatic carbocycle. In certain embodiments, E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fusing with a heterocycle or non-aromatic carbocycle. In certain modalities, L is NH or null. In certain embodiments, Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle. In certain embodiments, U is selected from 0, NR4, CR3R4, CO, and null. In certain embodiments, W is selected from 0, NR4, CR3R4, CO, and null. In certain modalities, X is N or CR5.

In certain embodiments, Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl. In certain modalities, if Y is found oriented in the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) S is not naphthyl if X is N and W is NH, (ii) D is not phenyl if X is CH, W is NH, Z is phenyl, and R10 or R11 is - (CH3) 0-6OH, (iii) -D- 10 is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl, and (iv) U is not NH. In certain embodiments, if C is N and W is NH, then D is not phenyl. In certain embodiments, Z is selected from null, a spacer of 2-5 atoms selected from an optionally substituted C6 -Ci0 aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted non-aromatic heterocycle or carbocycle, and a spacer of 1-5 atoms selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C3 haloalkyl, each optionally fused with an optionally substituted Ce-Cio aryl. In certain modalities, m is 0, 1 or 2 In certain modalities, m is 0, 1, 2 or 3. In certain embodiments, n is 0 or 1. In certain embodiments, if X is N and is NH in the compounds of formulas II or VI, then R6, R10 and R11 do not they contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisoster. In modalities in which two or more of a particular group are present, the identities of those two or more particular groups are independently selected and, therefore, may be the same or different from the other. For example, certain compounds of the invention comprise two or more R14 groups. The identities of those two or more groups R14 are each independently selected. Therefore, in certain modalities, those R14 groups are all the same as the others; in certain modalities those R14 groups are all different from each other; and in certain modalities some of those R14 groups are the same as the others and some are different from the others. This independent selection applies to any group that is present in a compound more than once. In certain embodiments, a compound of Formula I, II, III, IV, V or VI is a selective TPO modulator. In certain embodiments, a compound of Formula I, II, III, IV, V, VI is a selective TPO receptor agonist. In certain embodiments, a compound of Formula I, II, III, IV, V or VI is a selective TPO receptor antagonist. In certain embodiments, a compound of Formula I, II, III, IV, V or VI is a partial agonist of the selective TPO receptor. In certain embodiments, a compound of Formula I, II, III, IV, V or VI is a tissue-specific selective TPO modulator. In certain embodiments, a compound of Formula I, II, III, IV, V or VI is a selective TPO receptor binding compound. In certain embodiments, a compound of Formula I, II, III, IV, V or VI is a TPO mimic. In certain embodiments, the invention provides compounds selected from: 3 '- Acid. { [1- (3, 5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-yldenomethyl] amino} -2 '-hydroxybiphenyl-3-carboxylic acid (Compound 101); 2, 4-dihydroxybenzoic acid N '-. { 1- [1- (3, 5-dimethylphenyl) -2-??? - 6-trifluoromethyl-1,2-dihydroindol-3-yldene] ethyl} hydrazide (Compound 102); Acid 3-. { 3- [(5-chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 103); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 104); 3 'acid. { [1- (3, 5-dimethylphenyl) -2-OXO-6- trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -4-fluoro-2'-hydroxybiphenyl-3-carboxylic acid (Compound 105); 2- (3 '- { [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenomethyl] amino} -2'-hydroxybiphenyl-3 acid -yl) -2-methylpropionic (Compound 106); 3 'acid. { [1- (3, -dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -2 '-hydroxybiphenyl-3-carboxylic acid (Compound 107); 4- Acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 108); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 109); Methyl ester of 3- acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 110); Methyl ester of 3- acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-ylbenzoic acid (Compound 111); Acid 3-. { 3 - [(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl -3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 112); Acid 3-. { 3- [1- (3 ', 5'-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-l-ylideneamino] 2-oxo-2, 3- dihydrobenzooxazol-7-yl} benzoic (Compound 113); Acid 3-. { 3- [(2-hydroxy-3,3 ', 4'-trimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 114); 3-hydroxybenzoic acid N '-. { 1- [1- (3, 5-dimethylphenyl) -2 -oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 115); 1- (3, 5-dimethylphenyl) -3-. { 1- [2- (4-hydroxyphenyl) -2-oxo-ethylamino] ethylidene} -6-trifluoromethyl-1,3-dohydroindol-2-one (Compound 116). Acid 3.. { 3- [(5-Fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 117); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 118); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 119); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 120); 4- Acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl} butyric (Compound 121); 2-Chloro-3- (4. {[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -3-hydroxyphenyl acid acrylic) (Compound 122); 4-hydroxybenzoic acid N '-. { l- (3,5-Dimethylphenyl) -2- ??? -6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 123); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 124); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 125); Acid 3-. { 3- [(2-hydroxy-5, 3 ', 5'-trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 126); 4-aminobenzoic acid N '-. { l- [1- (3, 5-dimethylphenyl) -2- ??? -6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 127); 3- (7- {? '- [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene] hydrazino} -1H-indole- 3 -yl) propionic (Compound 128); 4- Acid. { 3- [N '- (4-methylbenzoyl) hydrazinomethylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 129); Acid 3-. { 2-oxo-6-trifluoromethyl-3 - [4- (3- trifluoromethylphenyl) -lH-pyrrol-2-ylmethylidene] -2,3-dihydroindol-1-yl} benzoic (Compound 130); 3- (7- { N '- [l- (3,4-dimethylphenyl) -3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene] hydrazino-lH-indol-3-yl acid ) propionic (Compound 131); 3- (3 { [4- (3, 4-Dimethylphenyl) thiazol-2-ylamino] methylidene} -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) benzoic acid ( Compound 132); 3- (3 { [4- (4-Methoxyphenyl) thiazol-2-ylamino] methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) benzoic acid (Compound 133) ); Acid 3 -. { 3 - [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 134); Acid 3-. { 3- [(4- (4-methylphenyl) -2-thiazolylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 135); Acid 3-. { 3 - [(3,4-dimethylbenzoylhydrazino) methylidene] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 136); Acid 3-. { 3- [(4-chlorobenzoylhydrazino) methylidene] -2-??? - 6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 137); Acid 3-. { 3- [(4-methoxybenzoylhydrazino) methylidene] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 138); Acid 3-. { 3- [(3,4-dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl} benzoic (Compound 139); 1- (3,4-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 140); 1- (3,4-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 141); 1- (3,4-dimethylphenyl) -3- [(2,4-dihydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 142); 1- (3,5-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 143); 1- (3,5-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 144); 1- (3, 5-dimethylphenyl) -3 - [(2,4-dihydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 145); 1- (3, 5-dimethylphenyl) -3- [(4-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 146); 3- (3- [1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid (Compound 147); 1- (3,4-dimethylphenyl) -3- [(4-hydroxybenzoylhydrazino) methylidene] -2-oxo-2,3-dihydroindole (Compound 148); 1- (3,4-dimethylphenyl) -3- [(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 149); 1- (3,5-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 150); 2- (3,4-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 151); 3- (6-Chloro-3- [(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl) benzoic acid (Compound 152); 1- (3,4-dimethylphenyl) -3- [1- (2,5-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 153); 1- (3,4-dimethylphenyl) -3- [1- (3-nitro-4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 154); 1- (3,4-dimethylphenyl) -3- [1- (3-aminosulfonyl-4- chlorobenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 155); 1- (3, -dimethylphenyl) -3- [1-3-amino-4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 156); 1- (3, 4-dimethylphenyl) -3- [1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 157); Acid 3-. { 3- (1- (3,5-dimethylphenyl) -2 -oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl} benzoic (Compound 158); Acid 3-. { 3- (3, 5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2-oxo-2,3-dihydro-l-indolyl} benzoic (Compound 159); Acid 3-. { 3- (1- (3, 4-dimethylphenyl) -2 -oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl-benzoic acid (Compound 160); 4- Acid. { 1- (6-Fluoro-2-oxo-2,3-dihydro-3- (2- (3,5-dimethylphenyl) -aminocarbonylphenyl) aminomethylidene) indolyl Jbutanoic (Compound 161); 4- Acid. { l- (6-chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) -aminomethylidene) indolyl Jbutanoic (Compound 162); Acid 3-. { l- (6-chloro-2-oxo-2,3-dihydro-3 - (2-hydroxy) 3 - . 3- (3, 5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} benzoic (Compound 163); 4- Acid. { l. (5-Fluoro-2-oxo-2,3-dihydro-3- (2-hydroxo-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} butanoic (Compound 164); Acid 3-. { 3- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indolidene) ethylamino) -2-hydroxyphenyl-benzoic acid (Compound 165); Acid 3-. { 3- (1- (3, -dimethylphenyl) -6-trifluoromethyl-2-OXO-2,3-dihydro-3-indolidene) ethylamino) -2-hydroxyphenyl} benzoic (Compound 166); Acid 3-. { l- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazono) indolylbenzoic acid (Compound 167); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3-cyclohexylphenyl) amino) ethylidene) indolyl J-benzoic acid (Compound 168); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) aminomethylidene) indolylbenzoic acid (Compound 169); 4- Acid. { 2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminophenyl-J-tatanoic (Compound 170); 4- Acid. { 2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylaminophenyl-J-tatanoic (Compound 171); Acid 3-. { 3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolidene) methylamino) indolyl} propanic (Compound 172); Acid 3-. { 3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3-indolidene) methylamino) indolyl} propanic (Compound 173); 4- Acid. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminophenyl Jbutanoic (Compound 174); 2-chloro-3 acid. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl-J-propionic (Compound 175); 2-chloro-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl-J-propionic acid (Compound 176); 2-ethyl-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl-J-propionic acid (Compound 177); 2-ethyl-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2- oxo-2, 3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic (Compound 178); 2-ethyl-3- acid. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic (Compound 179); 4- Acid. { 2-hydroxy-3- (4- (2- (3,4-dimethylphenyl) -3-oxo-3,4-dihydro-5-methyl) pyrazolidene) methylaminophenyl} butanoic (Compound 180); Acid (Z) -4-. { 1- (2,5-dioxo-3- (3- (3,5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl} butanoic (Compound 181); Acid (E) -4-. { 1- (2, 5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl} butanoic (Compound 182); Acid (Z) -3-. { 1- (2, 5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl} benzoic (Compound 183); Acid (E) -3-. { 1- (2, 5-dioxo-3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl} benzoic (Compound 184); 4- Acid. { 3- (4-Oxo-2-thioxo-5- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) hydrozono) thiazolidinyl Jbutanoic (Compound 185); Acid 3-. { 2- (3- (1- (3, 5-dimethylphenyl) -6-chloro-2 -oxo- 2. 3-dihydroindolidene) methylamino) phenylaminobenzoic acid (Compound 186); Acid 3-. { 2- (3- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydroindolidene) methylamino) phenylaminobenzoic acid (Compound 187); Acid 3-. { 2- (4- (2- (3, 5-dimethylphenyl) -5-methyl-3-oxo-3,4-dihydropyrazolidene) methylamino) phenylaminobenzoic acid (Compound 188); Acid (+) - 3-methyl-5-. { 2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) phenyl Jpentanoic (Compound 189); Acid (+) - 3 - (1- (6-chloro-2-oxo-2,3-dihydro-3 - (3- (1- (3,5-dimethylphenyl) -2-oxo-2,3-dihydro) ) indolyl) aminomethylidene) indolyl Jbenzoic (Compound 190); Acid 3-. { 4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) pyridinyl J-benzoic acid (Compound 191); Acid 3-. { 4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) pyridinyl J-benzoic acid (Compound 192); Acid 3-. { 4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-yl) -2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) iridinyl J-benzoic acid (Compound 193); 3- { 4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) pyridinyl J-benzoic acid (Compound 194 ); 3- ({5- (4-hydroxo-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-l- (3,5-dimethylphenyl) indolidene) methylamino) pyridinyl acid} benzoic (Compound 195); 3- ({5- (4-hydroxo-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-l- (3,5-dimethylphenyl)} indolyl) hydrazone) pyridinyl J-benzoic acid (Compound 196); 3- ({5- (4-hydroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4)} -dimethylphenyl) pyrazolyl) hydrazono) pyridinyl J-benzoic acid (Compound 197); 4- ({2- (3-phenyl) -3,4-dihydro-5-methyl-4- (3- (3,4-dimethylphenyl)} phenyl) hydrozono) pyrazolyl Jbutanoic (Compound 198); 3- {2-amino-5-methyl-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-l- (3, 5- dimethylphenyl) indolidene) methylamino) phenyl} benzoic (Compound 199); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (3- (3, 4-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 200); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 201); Acid (3- (5-fluoro-2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylamino) -1-pyrazolyl ) acetic (Compound 202); Acid (3- (5-fluoro-2-hydroxy-3- (3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) - 1-pyrazolyl) acetic acid (Compound 203); 4- ({2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) ) aminomethylidene) pyrazolyl Jbutanoic (Compound 204); 4- ({2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl} ) hydrazono) pyrazolyl Jbutanoic (Compound 205); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 206); 4- Acid. { 2- (5-methyl-2-oxo-2, 3-dihydro-4- (2-hydroxo- 3- (2- (3-methyl) phenyl) ethyl) phenyl) hydrazone) irazolyl} butanoic (Compound 207); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 208); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxo-3- (2- (1-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 209); Acid 3-. { l- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxo-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 210); Acid 3-. { l- (5-Nitro-2-oxo-2,3-dihydro3- (5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 211); 2-hydroxy-3- acid. { 3 - (2-Oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino} benzoic (Compound 212); 2-hydroxy-3- acid. { 3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino} benzoic (Compound 213); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) aminomethylidene) irazolyl} butanoic (compound 214); 4- Acid. { 2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy) 3 - . 3-heptanylphenyl) hydrazono) pyrazolyl} butanoic (Compound 215); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2,4-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl} butanoic (Compound 216); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl} butanoic (Compound 217); 4- Acid. { 1 - (2 - ??? - 2, 3-dihydro-3- (2-hydroxy-3 - (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} butanoic (Compound 218); Acid 2-. { 1 - (2 - ??? - 2, 3-dihydro-3- (2-hydroxy-3 - (3,5-dimethylphenyl) phenyl) hydrazone) indolyl} acetic (Compound 219); Acid 2-. { l. (2-OXO-2, 3-dihydro-3 - (2-hydroxy-3 - (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} acetic (Compound 220); 4- Acid. { 4 - (2 - (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylamino) thiazolyl J-benzoic acid (Compound 221); - (2- (3 - (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylamino) thiazolyl J-benzoic acid (Compound 221); 3- Acid. (5-nitro-2-oxo-2,3-dihydro-3- (2-hydroxy) -methyl-3- (1-adamantane) phenyl) aminomethylidene) indolyl} benzoic (Compound 222): Acid 3-. { 1- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (4-hydroxo-5- (3,4-dimethylphenyl) pyridinyl) hydrazono) indolyl} benzoic (Compound 223); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxo-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethylidene) pyrazolyl} butanoic (Compound 224); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-fluoro) phenyl) -ethylphenyl) aminomethylidene) pyrazolyl Jbutanoic acid (Compound 225); and a pharmaceutically acceptable salt, ester or prodrug of any of these compounds. In certain embodiments, the invention provides a compound selected from: 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (1-naphthyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 226); 4- Acid. { 2- (5-methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (3,5-dimethylphenyl) - ethyl) phenyl) aminomethylidene) irazolyl Jbutanoic (Compounds 227); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 228); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanóico (Compound 229); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxo-3- (2- (2-fluoro-3-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanóico (Compound 230); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 231); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-cyanophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 232); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 233); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 234); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} benzyl (Compound 235): Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 236); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 237 ); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2, (2,5-dimethyl-phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 238); 3- ({2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethyl-phenyl) -ethyl) -phenyl} acid ) aminomethylidene) pyrazolyl J-benzoic acid (Compound 239); 3- ({2- (5-phenyl-3-oxo-3,4-dihydro-4 (Z) - (2-) acid) hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) irazolyl} benzoic (Compound 240); Acid 3-. { 2- (5-tert-Butyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 241); Acid 3-. { 2- (5-Methyl-3-oxo-3, -dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 242); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 243); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dimethylphenyl) -ethyl) phenyl) hydrazono) irazolyl Jbutanico (Compound 244); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 245); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 246); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) - ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 247); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 248); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyanophenyl) ethyl) -phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 249); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-chlorophenyl) ethyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 250); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 251); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 252); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 253); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2, 5-dimethylphenyl) -ethyl) phenyl) hydrazone) prazolyl Jbutanoic (Compound 254); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (2-fluoro-6-trifluoro-methylphenyl) ethyl) phenyl) hydrazone) irazolyl Jbutanóico (Compound 255); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 256); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 257); Acid (+) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 258); Acid (+) -3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyrazolyl J-benzoic acid (Compound 259); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 260); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 261 ); Acid 3-. { 2- (5-methy1 -oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-phenyl) -ethyl) -phenyl) -hydrazono) -pyrazolyl-J-benzoic acid (Compound 262); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 263); Acid 3 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro- - (2-hydroxy-3- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazone) irazolyl} benzoic (Compound 264); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl-6-trifluoromethylphenyl) ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 265); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 266); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) irazolyl} benzoic (Compound 267); Acid (E) -4-. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 268); Acid 3-. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3, 4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 269); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} butanoic (Compound 270); Acid 3 -. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 271); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 272); Acid 3-. { l- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazone) indolyl} benzoic (Compound 273); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl} butanoic (Compound 274); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 275); Acid 4 -. { 2 - (5-methyl-3 -oxo-2,3-dihydro-4 - (2-hydroxy-3- (3-phenylpropyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 276); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 277); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 278); Acid (E) -4-. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 279); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4 (Z) - (2- hydroxy-3- (2- (2,6-dimethylphenyl) - (Z) -ethenyl) phenyl) hydrazono) irazolyl} butanoic (Compound 280); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 281); Acid (Z) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-bromoethenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 282); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 283); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2-cyclopropyletenyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 284); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 285); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fluoro-3- (3,5-dimethylphenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 286); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 287); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (5-chloro-2- hydroxy-3-cyclohexylphenyl) -hydrazono) irazolyl Jbutanoic (Compound 288); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3, 5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 289); Acid 3-. { 2- (5-Methyl-3-oxo-2; 3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) irazolyl} benzoic (Compound 290); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 291); Acid 3 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 292); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 293); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 294); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-fluorophenyl) propyl) -phenyl) hydrazono) pyrazolyl-jbutanoic acid (Compound 295); Acid 3-. { 2- (5-methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,4-dimethylphenyl) - phenyl) aminomethylidene) irazolyl} benzoic (Compound 296); Acid 3-. { 2. (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 297); 4- Acid. { 2- (5-methyl-3-oxo-3, -dihydro-4 (Z) - (2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 298); Acid 3-. { 1 - (2 - ??? - 2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) -hydrazono) -indolyl-J-propionic acid (Compound 299); Acid 3-. { 1- (2-OXO-2,3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazono) -indolyl J-benzoic acid (Compound 300); Acid 3-. { 1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl Jpropionic (Compound 301); Acid 3-. { 1- (6-chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) aminomethylidene) indolyl J-benzoic (Compound 302); Acid (+) -3-. { l- (6-chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (1,2-dihydro-l-methyl-2-indolylphenyl) aminomethylidene) indolyl Jbenzoic (Compound 303); 4- ({2- (5-methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 304); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenyl-carbonylamino) phenyl) hydrazono) pyrazolyl} butanoic (Compound 305); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2- (2-fluorophenyl) ethyl) indolidene) -hydrazinophenyl-benzene (Compound 306); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2- (2-chlorophenyl) ethyl) indolylidene) -hydrazinophenyl-benzene (Compound 307); Acid 3-. { 3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridyl-benzoic acid (Compound 308); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 309); Acid 3-. { 3-hydroxy-2- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolylidene-hydrazino) -4-pyridyl-J-benzoic acid (Compound 310); Acid 3 -. { 1- (2 -oxo-2, 3-dihydro-3 - (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazino) indolyl J-benzoic acid (Compound 311); Acid 3-. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl J-benzoic acid (Compound 312); Acid 3-. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino) -2-pyridyl} benzoic (Compound 313); 4- Acid. { 2-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3, 5-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl Jbutanoic (Compound 314); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl-jbutanoic acid (Compound 315); Acid 3-. { 3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -4-pyrazolidene) hydrazino-5-benzothienyl} benzoic (Compound 316); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 317); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3,5-diisopropylphenyl) -carbonylhydrazinomethylidene) pyrazolyl jbutanoic acid (Compound 318); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3, 5-dimethylphenyl) phenyl) -aminomethylidene) pyrazolyl jbutanoic acid (Compound 319); Acid (+) -4-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-l-methyl-2-oxo-3-indolyl) methyl) phenyl) hydrazone ) Jubathanoic pyrazolyl (Compound 320); Acid 3-. { l- (2-??? -2,3-Dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl} propionic (Compound 321); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 322); Acid (+) -3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2,3-dihydro-1-methyl-2-oxo-3 -indolyl) methyl) phenyl) hydrazone ) pyrazolyl} benzoic (Compound 323); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-1-methyl-2-oxo-3-indolylidene) methyl) phenyl) hydrazone ) pyrazolyl} benzoic (Compound 324); Acid 3 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolylbenzoic acid (Compound 325); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4 (E) - (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 326); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} benzoic (Compound 327); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-l-methyl-2-oxo-3-) indolylidene) methyl) phenyl) hydrazone) irazolyl} butanoic (Compound 328); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 329); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-difluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 330); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-dimethylphenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 331); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-methylphenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 332); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 333); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z) - (2- (5-fluoro-2-methyl) phenyl) ethenyl) phenyl) hydrazone) irazolil } butanoic (Compound 334); 4- Acid. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanico (Compound 335); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 336); 4- Acid. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluorophenyl) -ethenyl) phenyl) -hydrazono) -pyrazolyl-J-tatanoic (Compound 337); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (E) - (2-phenylethenyl) -phenyl) -hydrazono) -pyrazolyl-Jbutanic (Compound 338); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenylethynyl) -phenyl) hydrazono) irazolyl Jbutanoic (Compound 339); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy 3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) irazolyl Jbutanoic (Compound 340); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy 3- (2- (2,6-dimethylphenyl) -etinyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 341); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy 3- (2- (2-fluorophenyl) ethynyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 342); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy 3- (2- (2-trifluoromethylphenyl) - ethynyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 343); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-phenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 344 ); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (l-methyl-l-indenyl-2-phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 345); 4- ({2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3, 3-dimethyl-2-indenyl) phenyl) hydrazono) irazolyl Jbutanóico (Compound 346); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) -hydrazono) -pyrazolyl acid Jbutanóico (Compound 347); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-dimethyl) -2-indenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 348); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 349); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolylidene) methylaminophenyl-benzene (Compound 350); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) - indolylidene) methylaminophenyl} benzoic (Compound 351); Acid (+) -4-. { 2- (5-methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (1, 2, 3, 4-tetrahydro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 352); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 353); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (1-indanylidene) -methylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 354); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-trifluoromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanóic or (Compound 355); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (6-fluoro-2-trifluoro-methylphenyl) ethenyl) phenyl) hydrazone) pyrazolyl Jbutanóico (Compound 356); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (6-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 357); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 358); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 359); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 360); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2, 5-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 361); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-trifluoro-methylphenyl) ethenyl) phenyl) hydrazone) pyrazolyl Jbutanóico (Compound 362); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -etinyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 363); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (1,2,3,4-tetrahydro) -naphthylidene) methylphenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 364); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-5-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 365); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3,5-dimethyl-4-isoxazolyl) ethenyl) phenyl) hydrazone) pyrazolyl } butanoic (Compound 366); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,5-dimethyl-4-isoxazolyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 367); Acid 3 -. { 2-Hydroxy -3- (2-oxo-2,3-dihydro-1- (2 (E) - (2-methylphenyl) ethenyl) -3 (Z) -indolylidene) methylaminophenyl-benzene (Compound 368); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E) - (2,4-difluorophenyl) ethenyl) -3 (Z) -indolylidene) methylaminophenyl-benzene (Compound 369); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2-indenyl) -3 (Z) -indolylidene) methyl-aminophenyl-benzene (Compound 370); Acid 3-. { 2-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 371); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl Jbutanoic acid (Compound 372); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3 - . 3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 373); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 374); Acid 3 -. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl J-benzoic (Compound 375); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 376); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl J-benzoic acid ( Compound 377); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-6-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl J benzoic ( Compound 378); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,3-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 379); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,3-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 380); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-4-methylphenyl) ethenyl) phenyl) hydrazone) irazolyl Jbutanoic ( Compound 381); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 382); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-dichlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 383); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-chlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 384); Acid 3 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2, 5-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 385); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chloro-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 386); Acid 3 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 387); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3 (E) - (2- (2,4-dichlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 388); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chloromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazono) irazolyl} benzoic (Compound 389); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,4-dichloromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 390); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2 - (3,4-dihydro) -naphthyl) phenyl) hydrazono) irazolyl} benzoic acid (Compound 353); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 392); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-methyl) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 393); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-methyl) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 394); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 395); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-6-fluoro) -naphthyl) phenyl) hydrazono) irazolyl Jbutanoic ( Compound 396); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-5-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 397); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-8-chloro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 398); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl J-benzoic acid ( Compound 399); and a pharmaceutically acceptable salt, ester, or prodrug of any of those compounds. In certain embodiments, such compounds are selective TPO modulators. Certain compounds of the present invention can exist as stereoisomers including optical isomers. The present disclosure is intended to include all stereoisomers and both racemic mixtures of such stereoisomers and individual enantiomers that can be separated according to methods known in the art or that can be excluded by synthetic schemes known in the art designed to predominantly produce an enantiomer with relationship to another.

Certain Methods of Synthesis In certain embodiments, certain compounds of the present invention can be synthesized using the following Schemes.

Scheme I The process of Scheme I is a multistage synthetic sequence that begins with the cross-coupling of catalysed palladium from a phenylboronic acid such as structure 2 and an aryl bromide such as structure 1 to form the biaryl 3 structure. To the deprotection of the methyl ester follows nitration and hydrogenation to provide the biphenyl amino acid such as structure 4. The amino group is then diazotized under standard conditions and treated with the appropriate coupling partner to provide the final product of structure 6. "R" may be present 0, 1, 2 or 3 times and each R is independently selected from the groups in the definition of "optionally substituted" given above. Scheme II The process of Scheme II is a multistage synthetic sequence that begins with the catalyzed copper cross coupling of an oxindole such as structure 7 and an aryl or alkyl bromide to provide the N-substituted oxindole of structure 8. A this then follows the coupling of the N-substituted oxindole with the diazonium salt of the biphenyl amino acid such as structure 4 to provide the final product of structure 9. "R- can be present 0, 1, 2 or 3 times and each R is independently selected from the groups in the definition of "optionally substituted" given above.

X = OEt, or N (CHS) 2 The process of Scheme III is a multistage synthetic sequence that begins with the catalyzed copper cross coupling of an oxindole such as structure 7 and an aryl or alkyl bromide to provide the N-substituted oxindole of structure 8.

This is then converted to the structure 10 by a reaction with either dimethylformamide dimethylacetal (or equivalent) or with triethyl ortoformate. This is then reactivated with an amine to provide the structure 11. "R" may be present 0, 1, 2 or 3 times and each R is independently selected from the groups in the definition of "optionally substituted" given above. Scheme IV The process of Scheme IV is a single synthetic step joining the arylated oxindole 8 of Scheme I and an appropriately substituted pyrrolocarboxaldehyde 12 in the presence of a base to provide 13. "R" may be present 0, 1, 2 or 3 times and each R is independently selected from the groups in the definition of "optionally substituted" given above.

Scheme V The process of Scheme V is a single synthetic step that reacts with the pathogen, or some synthetic equivalent, to produce 15. "R" may be present 0, 1, 2 or 3 times and each R is independently selected from the groups in the definition of "optionally substituted" given above. Scheme VI R = e or R7 The process of Scheme VI is a multistage synthetic sequence that begins with the formation of benzothiophene from aryl thioether 16. This is then converts to structure 19 by reaction with diazonium salt 18. Scheme VII The process of Scheme VII is a multistage synthetic sequence that begins with Wittig olefinination of a benzaldehyde such as structure 20 and a phosphonium bromide such as structure 21 to form olefin 22. Reduction of the nitro group (and / or olefin) provides the phenyl amine such as structure 23. The amino group is then diazotized under standard conditions and treated with the appropriate coupling partner to provide the final product of structure 24. "R" is selected from the groups in the definition of "optionally substituted" given above Scheme VIII Q = Re or -Z-R7 O! V = OEt or N (CH,) 2 27 25 eC (OEt) 3 26 The process of Scheme VIII is a multistage synthetic sequence that begins with the formation of enamine or enol ether of an N-substituted oxindole of structure 25 or its analogues. This is then converted to structure 27 by reaction with an amine partner. "R" may be present 0, 1, 2 or 3 times and each R is independently selected from the groups in the definition of "optionally substituted" given above.

Scheme IX The general process of Scheme IX begins with the diazotization of the amino compounds 28 under standard conditions followed by a coupling reaction with the compounds of structure 25 to produce the hydrazone products of structure 29. "R" may be present. , 1, 2 or 3 times and each R is independently selected from the groups in the definition of "optionally substituted" given above. The person skilled in the art will recognize that analogous synthesis schemes can be used to synthesize similar compounds. The person skilled in the art will recognize that the compounds of the present invention can be synthesized using other synthetic schemes. In certain embodiments, the invention provides a salt corresponding to any of the compounds provided herein. In certain embodiments, the invention provides a salt corresponding to a selective TPO modulator. In certain embodiments, the invention provides a salt corresponding to a selective TPO receptor binding agent. In certain embodiments a salt is obtained by reactivating a compound with an acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. In certain embodiments, a salt is obtained by reactivating a compound with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a sodium or potassium salt, an alkaline earth metal salt, such as a calcium or magnesium salt, a salt of organic bases such as choline, dicyclohexylamine, N-methyl-D-glucamine, tris (hydroxymethyl) methylamine, 4- (2-hydroxyethyl) -morpholine, 1- (2-hydroxyethyl) -pyrrolidine, ethanolamine and salts with amino acids such as arginine, lysine and the like. In certain embodiments, a salt is obtained by reactivating a free acid form of a selective TPO modulator or a selective TPO binding agent with multiple molar equivalents of a base, such as bis-sodium, bis-ethanolamine and the like.

Similary. In certain embodiments, a salt corresponding to a compound of the present invention is selected from salts of acetate, ammonium, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, choline, clauvulanate , citrate, dihydrochloride, diphosphate, edetate, edisilate, estolate, esilate, fumarate, gluceptate, gluconate, glutamate, glycolylaminosanilate, hexylresorcinate, hydrabanin, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, magnesium, malate, maleate , mandelato, mucato, napsilate, nitrate, N-methylglucamine, oxalate, pamoate (embonate), palmitate, pantothenate, phosphate, polygalacturonate, potassium, salicylate, sodium, stearate, subacetate, succinate, sulfate, tannate, tartrate, theoclate, tosylate, treithioiodide, tromethamine, trimethylammonium and valerate. In certain embodiments, one or more carbon atoms of a compound of the present invention are replaced with silicone. See, e.g., WO 03/037905 Al; Tacke and Zilch, Endeavor, New Series, 10, 191-197 (1986); Bains and Tacke, Curr. Opin. Drug. Discov. Devel. , Jul: 6 (4) 526-43 (2003), all of which are incorporated herein by reference in their entirety. In certain embodiments, the compounds of the present invention comprising one or more silicone atoms, possess certain desired properties, including, but not limited to, greater stability and / or longer half-life in a patient, when compared to the same compound in which no carbon atom has been replaced with a silicone atom . Certain Assays In certain embodiments, assays may be used to determine the level of TPO modulating activity of the compounds of the present invention. For example, the potency of the compounds of the present invention as selective TPO modulators can be determined in a luciferase assay, such as those described in Lamb et al., Nucleic Acids Research, 23: 3283-3289 (1995) and / or Seidel et al., Proc. Nati Acad. Sci. USA 92: 3041-3045 (1995), both of which are incorporated herein by reference in their entirety.

In vitro proliferation and / or differentiation assays can also be used, such as those described by Barley et al., Cell 77: 1117-1124 (1994) and / or Cwirla et al., Science, 276: 1696-1699 (1997). , both of which are incorporated herein by reference in their entirety. Certain Pharmaceutical Agents In certain embodiments, at least one selective TPO modulator, or a salt, ester, amide and / or prodrug Pharmaceutically acceptable thereof, either alone or in combination with one or more pharmaceutically acceptable carriers, forms a pharmaceutical agent. Techniques for the formulation and administration of the compounds of the present invention can be found, for example, in "Remington's Pharmaceutical Sciences", Mack Publishing Co., Easton, PA. , 18th edition, 1990, which is incorporated herein by reference in its entirety.

In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is prepared using known techniques, including, but not limited to, mixing, dissolving, granulating, pelletizing, levigating, emulsifying, encapsulating, entrapping processes. or making tablets. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is a liquid (e.g., a suspension, elixir and / or solution). In certain such embodiments, a liquid pharmaceutical agent comprising one or more compounds of the present invention is prepared using ingredients known in the art including, but not limited to, water, glycols, oils, alcohols, flavoring agents, preservatives and coloring agents . In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is a solid (e.g., a powder, tablet and / or capsule). In certain such embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is prepared using ingredients known in the art, including, but not limited to, starches, sugars, diluents, granulating agents, lubricants, binders and disintegration agents. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is formulated as a depot preparation. Certain such deposit preparations are typically longer acting than non-deposit preparations. In certain embodiments, such preparations are administered by implantation (e.g., subcutaneously or intramuscularly) or by intramuscular injection. In certain embodiments, deposit preparations are prepared using suitable polymeric or hydrophobic materials (for example, an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention, comprises a delivery system. Examples of delivery systems include, but are not limited to, liposomes and emulsions. Certain delivery systems are useful for preparing certain pharmaceutical agents including those comprising hydrophobic compounds. In certain embodiments, certain organic solvents such as dimethyl sulfoxide are used. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention, comprises one or more tissue-specific delivery molecules designated to deliver the pharmaceutical agent to specific tissues or cell types. For example, in certain embodiments, pharmaceutical agents include liposomes coated with a tissue-specific antibody. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention comprises a co-solvent system. Certain such co-solvent systems comprise, for example, benzyl alcohol, a non-polar surfactant, an organic polymer mixable in water, and an aqueous phase. In certain embodiments, such co-solvent systems are used for hydrophobic compounds. A non-limiting example of such co-solvent systems is the VPD co-solvent system, which is an absolute ethanol solution comprising 3% w / v of benzyl alcohol, 8% w / v of the non-polar surfactant Polisorbate 80 ™ , and 65% weight / volume of polyethylene glycol 300. The proportions of such co-solvent systems can vary considerably without significantly alter its solubility and toxicity characteristics. In addition, the identity of the co-solvent components may vary: for example, other surfactants may be used instead of Polysorbate 80 ™; the size of the polyethylene glycol fraction may vary; other biocompatible polymers can replace polyethylene glycol, e.g., polyvinyl pyrrolidone; and other sugars or polysaccharides can be substituted for dextrose. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention comprises a sustained release system. A non-limiting example of such a sustained release system is a semi-permeable matrix of solid hydrophobic polymers. In certain modalities, sustained release systems, depending on their chemical nature, can release compounds over a period of hours, days, weeks or months. Certain compounds used in the pharmaceutical agent of the present invention can be provided as pharmaceutically acceptable salts with pharmaceutically compatible counterions. The pharmaceutically acceptable salts can be formed with many acids, including, but not limited to, hydrochloric, sulfuric, acetic, lactic, tartaric, malic, succinic, etc. In certain modalities, a pharmaceutical agent that comprises one or more compounds of the present invention, comprises an active ingredient in a therapeutically effective amount. In certain embodiments, the therapeutically effective amount is sufficient to prevent, alleviate or ameliorate the symptoms of a disease or to prolong the survival of the subject being treated. The determination of a therapeutically effective amount is within the ability of those skilled in the art. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is formulated as a prodrug. In certain modalities, prodigies are useful because they are easier to administer than the corresponding active form. For example, in certain cases, a prodrug may be more bioavailable (e.g., by oral administration) than the corresponding active form. In certain cases, a prodrug may have a better solubility compared to the corresponding active form. In certain modalities, a prodrug is an ester. In certain embodiments, such prodrugs are less soluble in water than the corresponding active form. In certain cases, such prodrugs have a superior transmission through the cell membranes, where the solubility in water is harmful to mobility. In certain embodiments, the ester in such prodrugs is hydrolyzed metabolically to the carboxylic acid. In certain cases, the compounds containing carboxylic acid is the corresponding active form. In certain embodiments, a prodrug comprises a short peptide (polyamino acid) linked to an acid group. In certain such embodiments, the peptide is metabolized to form the corresponding active form. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is useful for treating a condition or disorder in a mammal, and particularly in a human patient. Suitable routes of administration include, but are not limited to, oral, rectal, transmucosal, intestinal, enteral, topical, suppository, by inhalation, intrathecal, intraventricular, intraperitoneal, intranasal, intraocular and parenteral (eg, intravenous, intramuscular, intramedullary and subcutaneous). In certain modalities, intrathecal pharmaceuticals are administered to achieve local rather than systemic exposures. For example, the pharmaceutical agents can be injected directly into the desired area of effect (e.g., in the renal or cardiac area). In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is administered in the form of a dosage unit (e.g., tablet, capsule, bolus, etc.). In certain embodiments, such dose units comprise a selective TPO modulator in a dose of about 1 ug / kg of body weight to about 50 mg / kg of body weight. In certain embodiments, such dose units comprise a selective TPO modulator in a dose of about 2 ug / kg of body weight to about 25 mg / kg of body weight. In certain embodiments, such dose units comprise a selective TPO modulator in a dose of about 10 ug / kg of body weight to about 5 mg / kg of body weight. In certain modalities, pharmaceutical agents are administered as needed, once a day, twice a day, three times a day, or four times or more a day. It is recognized by those skilled in the art that the particular dose, frequency and duration of administration depend on a number of factors including, without limitation, the desired biological activity, the condition of the patient and the tolerance for the pharmaceutical agent. In certain embodiments, a pharmaceutical agent comprising one or more compounds of the present invention is prepared for oral administration. In certain such embodiments, a pharmaceutical agent is formulated by combining one or more compounds of the present invention with one or more pharmaceutically acceptable carriers. Certain of such vehicles allow the compounds of the invention to be formulated as tablets, pills, pills, capsules, liquids, gels, syrups, mixtures, suspensions and the like, for their oral ingestion by a patient. In certain embodiments, pharmaceutical agents for oral use are obtained by mixing one or more compounds of the present invention and one or more solid excipients. Suitable excipients include, but are not limited to fillers, such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methyl cellulose, hydroxypropylmethyl cellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP). In certain embodiments, such a mixture is optionally comminuted and auxiliaries are optionally added. In certain embodiments, pharmaceutical agents are formed to obtain tablets or pellet cores. In certain embodiments, disintegrating agents (e.g., cross-linked polyvinyl pyrrolidone, agar or alginic acid or a salt thereof, such as sodium alginate) are added. In certain embodiments, the pellet cores are provided with coatings. In certain such embodiments, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol and / or titanium dioxide, lacquer solutions, and organic solvents or solvent mixtures. adequate. May dyes or pigments are added to tablets or tablet coatings. In certain embodiments, pharmaceutical agents for oral administration are soft-fit capsules made of gelatin. Certain such soft-fit capsules comprise one or more compounds of the present invention in admixture with one or more fillers such as lactose, binders such as starches and / or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In certain embodiments, pharmaceutical agents for oral administration are soft sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. In certain soft capsules, one or more compounds of the present invention are dissolved or suspended in suitable liquids such as fatty oils, liquid paraffin or liquid polyethylene glycols. In addition, stabilizers can be added. In certain embodiments, pharmaceutical agents are prepared for buccal administration. Certain such pharmaceutical agents are tablets or lozenges formulated in a conventional manner. In certain embodiments, a pharmaceutical agent is prepared for administration by injection (e.g., intravenous, subcutaneous, intramuscular, etc.). In certain such embodiments, a pharmaceutical agent comprises a vehicle and formulated in aqueous solution, such as water or physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological saline buffer. In certain embodiments other ingredients are included (e.g., ingredients that aid in solubility or that serve as preservatives). In certain embodiments, injectable suspensions are prepared using appropriate liquid carriers, suspending agents, and the like. Certain pharmaceutical agents are presented in unit dosage form, e.g., in ampoules or in multi-dose containers. Certain pharmaceutical agents for injection are suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and / or dispersing agents. Certain solvents suitable for use in pharmaceutical agents for injection include, but are not limited to, lipophilic solvents and fatty oils, such as sesame oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides and liposomes. Aqueous suspensions for injection may contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran. Optionally, such suspensions may also contain stabilizers or suitable agents that increase the solubility of the compounds to allow preparation of highly concentrated solutions. In certain embodiments, a pharmaceutical agent is prepared for transmucosal administration. In certain such embodiments the appropriate penetrants to permeate the barrier are used in the formulation. Such penetrants are generally known in the art. In certain embodiments, a pharmaceutical agent is prepared for administration by inhalation. Certain such pharmaceutical inhalation agents are prepared in the form of an aerosol spray in a pressurized pack or a nebulizer. Certain such pharmaceutical agents comprise a propellant, e.g., dichlorodifluromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In certain embodiments using a pressurized aerosol, the dose unit can be determined with a valve that supplies a measured quantity. In certain embodiments, capsules and cartridges may be formulated for use in an inhaler or insufflator. Certain such formulations comprise a powder mixture of a compound of the invention and a suitable powder base such as lactose or starch. In certain embodiments, a pharmaceutical agent is prepared for rectal administration, such as suppositories or retention enema. Certain such pharmaceutical agents comprise known ingredients such as cocoa butter and / or other glycerides. In certain embodiments, a pharmaceutical agent is prepared for topical administration. Certain such pharmaceutical agents comprise soft moisturizing bases such as ointments or creams. Exemplary suitable ointment bases include, but are not limited to, petrolatum, petrolatum plus volatile silicones, lanolin, and oil-in-water emulsions such as Eucerin ™, available from Beiersdorf (Cincinnati, Ohio). Exemplary suitable cream bases include, but are not limited to, Nivea ™ cream, available from Beiersdorf (Cincinnati, Ohio), cold cream (USP), Purpose Cream ™ available from Johnson & Johnson (New Brunswick, New Jersey), hydrophilic ointment (USP) and Lubriderm ™ available from Pfizer (Morris Plain, New Jersey). In certain embodiments, the formulation, route of administration and dosage for a pharmaceutical agent of the present invention may be selected in view of the particular condition of the patient. (See e.g., Fingí et al., 1975, in "The Pharmacological Basis of Therapeutics," Chapter 1, p.1, which is incorporated herein by reference in its entirety). In certain embodiments, a pharmaceutical agent is administered in a single dose. In certain embodiments, a pharmaceutical agent is administered as a series of two or more doses administered for one or more days.

In certain embodiments, a pharmaceutical agent of the present invention is administered to a patient between about 0.1% and 500%, 5% and 200% $, 10% and 100%, 15% and 85%, 25% and 75% or 40%. % and 60% of an established human dose. When no human dose is established, an appropriate human dose can be inferred from the ED50 or ID50 values, or other appropriate values derived from in vitro or in vivo studies. In certain embodiments, a daily dose regimen for a patient comprises an oral dose of between 0.1 mg and 2000 mg, 5 mg and 1500 mg, 10 mg and 1000 mg, 20 mg and 500 mg, 30 mg and 200 mg or 40 mg and 100 mg of a compound of the present invention. In certain embodiments, a daily dose regimen is administered as a single daily dose. In certain embodiments, a daily dose regimen is administered as two, three, four or more than four doses. In certain embodiments, a pharmaceutical agent of the present invention is administered by continuous intravenous infusion. In certain such embodiments, 0.1 mg to 500 mg of a composition of the present invention is administered per day. In certain embodiments, a pharmaceutical agent of the invention is administered during a period of continuous therapy. For example, a pharmaceutical agent of the present invention can be administered over a period of days, weeks, months or years. The amount of dose, the interval between doses, and the duration of treatment can be adjusted to achieve a desired effect. In certain embodiments, the amount of dose and the interval between the doses are adjusted to maintain a desired concentration of the compound in a patient. For example, in certain embodiments, the amount of dose and the interval between doses are adjusted to provide the plasma concentration of a compound of the present invention in an amount sufficient to achieve a desired effect. In certain such embodiments, the plasma concentration is maintained above the minimum effective concentration (MEC). In certain embodiments, the pharmaceutical agents of the present invention are administered at a dose rate designed to maintain a concentration above the MEC for 10-90% of the time, between 30-90% of the time or between 50-90% weather. In certain embodiments in which the pharmaceutical agent is administered locally, the dosage regimen is adjusted to achieve a desired local concentration of a compound of the present invention. In certain embodiments, a pharmaceutical agent may be present in a package or dispensing device that may contain one or more dosage unit forms containing the active ingredient. The packaging it may comprise, for example, sheet metal or plastic, such as a blister pack. The packaging or dispensing device may be accompanied by instructions for administration. The package or dispenser may also be accompanied by information associated with the container in the form prescribed by the government agency that regulates the manufacture, use or sale of pharmacists, whose information reflects the approval, by the agency, of the form of drug for human or veterinary administration. Such information, for example, may be the label approved by the U.S. Food and Drug Administration for the prescription of drugs, or the insert of the approved product. Compositions can also be prepared comprising a compound of the invention formulated in a compatible pharmaceutical carrier, placed in an appropriate container and labeled for the treatment of an indicated condition. In certain embodiments, a pharmaceutical agent is in the form of powders for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use. Certain Combination Therapies In certain embodiments, one or more pharmaceutical agents of the present invention are co-administered with one or more different pharmaceutical agents. In certain embodiments, such one or more different pharmaceutical agents they are designed to treat the same disease or condition as the one or more pharmaceutical agents of the present invention. In certain embodiments, such one or more other pharmaceutical agents are designed to treat a disease or condition different from the one or more pharmaceutical agents of the present invention. In certain embodiments, such one or more other pharmaceutical agents are designed to treat an undesired effect of one or more pharmaceutical agents of the present invention. In certain embodiments, one or more pharmaceutical agents of the present invention are co-administered with another pharmaceutical agent to treat an undesired effect of that other pharmaceutical agent. In certain embodiments, one or more pharmaceutical agents of the present invention and one or more other pharmaceutical agents are administered at the same time. In certain embodiments, one or more pharmaceutical agents of the present invention and one or more other pharmaceutical agents are administered at different times. In certain embodiments, one or more pharmaceutical agents of the present invention and one or more other pharmaceutical agents are prepared together in a single formulation. In certain embodiments, one or more pharmaceutical agents of the present invention and one or more other pharmaceutical agents are prepared separately.

Examples of pharmaceutical agents that can be administered with a pharmaceutical agent of the present invention, include, but are not limited to anti-cancer treatments, including, but not limited to, chemotherapy and radiation treatment; corticosteroids, including, but not limited to prednisone; immunoglobulins, including but not limited to, intravenous immunoglobulin (IVIg); analgesics (e.g., acetaminophen); anti-inflammatory agents, including, but not limited to, non-steroidal anti-inflammatory drugs (e.g., ibuprofen, COX-1 inhibitors, and COX-2 inhibitors); salicylates; antibiotics; antivirals; antifungal agents; antidiabetic agents (e.g., biguanides, glucosidase inhibitors, insulins, sulfonylureas and thiazolidenediones); adrenergic modifiers; diuretics; hormones (e.g., anabolic steroids, androgen, estrogen, calcitonin, progestin, somatostan, and thyroid hormones); immunomodulators; muscle relaxants; antihistamines; osteoporosis agents (e.g., bisphosphonates, calcitonin and estrogens); prostaglandins, antineoplastic agents; psychotherapeutic agents; sedatives; Toxic oak or toxic sumac products; antibodies; and vaccines. Certain Indications In certain embodiments, the invention provides methods for treating a patient, comprising administering one or more compounds of the present invention. In certain embodiments, such a patient suffers from thrombocytopenia. In certain of such modalities, thrombocytopenia results from chemotherapy and / or radiation treatment. In certain embodiments, thrombocytopenia results in failure of the spinal cord resulting from spinal cord transplantation and / or aplastic anemia. In certain modalities, thrombocytopenia is idiopathic. In certain embodiments, one or more compounds of the present invention are administered to a patient in conjunction with peripheral blood progenitor cell harvest and / or in conjunction with platelet apheresis. Such administration may be carried out before, during and / or after such harvest. In certain embodiments, one or more compounds of the present invention are administered to a patient suffering from a condition that affects the nervous system, including, but not limited to, diseases that affect the nervous system and damage to the nervous system. Such diseases include, but are not limited to, amyotrophic lateral sclerosis, multiple sclerosis, and multiple dystrophy. Damage to the central nervous system includes, but is not limited to, spinal cord damage or damage to peripheral nerves, including, but not limited to, damage resulting from trauma or shock. In certain embodiments, one or more compounds of the present invention are used to promote the growth or development of glial cells. Such glial cells can repair nerve cells. In Certain embodiments, the compounds of the present invention are used to treat psychological disorders including, but not limited to, cognitive disorders.

EXAMPLES The following examples, including the experiments and results achieved, are provided for illustrative purposes only and are not constructed to limit the present invention. Where the chemical structures represent the atoms that have an unfilled valence, it must be understood that the valence is satisfied with one or more hydrogen atoms. Example 1 3 'acid. { [1- (3, 5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3 (Z) -yldenomethyl] -2'-hydroxybiphenyl-3-carboxylic acid (Compound 101) This compound was prepared as it is described in Scheme VIII. ¾ NR (500 MHz, DMSO-d6) 13.05 (s, 1H), 11.35 (d, .7 = 13.3 Hz, 1H), 9.40 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.97 (d, J = 7.9 Hz, 1H), 7.95 (ddd, J = l .1, 1.6, 1.3 Hz, 1H), 7.81-7.78 (m, 2H), 7.60 (t,, 7 = 7.7 Hz, 1H) , 7.44 (dq, J = 7.9, 0.9 Hz, 1H), 7.14 (t, J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.11 (m, 2H), 7.07 (dd, .7 = 7.8, 1.5 Hz, 1H), 6.94 (q, J = 0.9 Hz, 1H), 2. 36 (s, 6H). Example 2 2,4-dihydroxybenzoic acid -. { l- [1- (3, 5-Dimethylphenyl) -2- ??? -6-trifluoromethyl-1,2-dihydroindol-3 (Z) -ylidene] ethyl} hydrazide (Compound 102) This compound was prepared as described in Scheme VIII. ¾ MR (500 MHz, CD3OD) d 8.49 (s, 1H), 7.71 (m, 1H), 7.67 (m, 1H), 7.34 (m, 1H), 7.16 (s, 1H), 7.04 (s, 2H) , 6.93 (s, 1H), 6.39 (m, 1H), 6.34 (s, 1H), 2.64 (s, 3H), 2.41 (s, 6H). Example 3 Acid 3-. { 3- [(5-Chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) -hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 103) This compound was prepared as described in Scheme II. XH NMR (500 MHz, DMSO-ds) d 13.29 (s, 1H), 12.95 (s, 1H), 9.36 (s, 1H), 8.08 (t, J = ll Hz, 1H), 8.04 (ddd, .7 = 7.7, 1.7, 1.2 Hz, 1H), 7.82 (m, 2H), 7.74 (t, J = 7.7 Hz, 1H), 7.65 (d, J = 2.6 Hz, 1H), 7.34 (m, 1H), 7.33 (td, J = 7.6, 1.3 Hz, 1H), 7.27 (dd, J = 8.0, 1.8 Hz, 1H), 7.23 (d, J = 8.0, Hz, 1H), 7.22 (td, J = 7.6, 0.9 Hz , 1H) 6.94 (dm, J = 7.6 Hz, 1H), 6.93 (d, J = 2.6 Hz, 1H), 2.28 (s, 3H), 2.27 (s, 3H). Example 4 Acid 3-. { 3- [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) -hydrazono] -2-OXO-2,3-dihydroindol-1-yl} benzoic (Compound 104) This compound was prepared as described in Scheme II. H NMR (500 MHz, DMSO-dff) 13.29 (s, 1H), 13.04 (s, 1H), 9.11 (s, 1H), 8.08 (t, J = J = 1.8 Hz, 1H), 8.04 (ddd, J = J = 7.7, 1.8, 1.2 Hz, 1H), 7.83 (ddd, J = 7.7, 1.8, 1.2 Hz, 1H), 7.75 (m, 1H), 7.74 (t, J "= 7.7 Hz, 1H), 7.69 (dd, J = 7.7, 1.6 Hz, 1H), 7.31 (td, J = 7.6, 1.3 Hz, 1H), 7.22 (td, J = 7.6, 0.9 Hz, 1H), 7.15 (m, 2H), 7.06 ( t, J = 7.7, 1H) 7.00 (m, 1H), 6. 95 (m, 1H), 6.94 (dd, .7 = 7.7, 1.6 Hz, 1H), 2.33 (s, 6H). Example 5 3 'acid. { [1- (3, 5-Dimethylphenyl) -2-oxo-6-trifluoromet-dihydroindol-3 (Z) -yldenomethyl] amino} -4-fluoro-2'-hydroxybiphenyl-3-carboxylic acid (Compound 105) This compound was prepared as described in Scheme VIII. ? NMR (500 MHz, DMS0-d6) d 13.35 (s, 1H), 11.34 (d, J = 13.3 Hz, 1H), 9.41 (s, 1H), 9.08 (d, .7 = 13.3 Hz, 1H), 8.01 (dd,, 7 = 7.2, 2.3, Hz, 1H), 7.96 (d , J = 7.9 Hz, 1H), 7.79 (dd, J = 7.9, 1.5 Hz, 1H), 7.78 (ddd, J = 8.4, 4.4, 2.3 Hz, 1H), 7. 44 (dq, J = 7.0, 0.9 Hz, 1H), 7.42 (dd, J = 10.6, 8.4 Hz, 1H), 7.13 (t, J = 7.9 Hz, 1H), 7.12 (m, 1H), 7.10 (m , 2H) 7.06 (dd, J = 7.9, 1.5, Hz, 1H), 6.94 (m, 1H), 2.36 (s, 6H). Example 6 2- (3 '- { [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3 (Z) -ylidenemethyl] amino} -2'- acid hydroxybiphenyl-3-yl) -2-methylpropionic (Compound 106) This compound was prepared as described in Scheme VIII. XH NMR (500 MHz, DMSO-de) d 12.39 (s, 1H), 11.36 (d, J = 13.3 Hz, 1H), 9.32 (s, 1H), 9.08 (d, J = 13.3 Hz, 1H), 7.97 (d, J = 7.9, Hz, 1H), 7.76 (dd, J = 7.9, 1.5 Hz, 1H), 7.54 (m, 1H), 7.45-7.42 (m, 3H), 7.35 (m, 1H), 7.12 (t, J = 7.9, Hz, 1H), 7.12 (m, 1H), 7.11 (m, 2H), 7.02 (dd, .7 = 7.9, 1.5 Hz, 1H) 6.95 (q, J = 0.8 Hz, 1H ), 2.37 (s, 6H), 1.52 (s, 6H). Example 7 3 'acid. { [1- (3, 4-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3 (Z) -ylidenemethyl] amino} 2'-Hydroxybiphenyl-3-carboxylic acid (Compound 107) This compound was prepared as described in Scheme VIII. XH NMR (500 MHz, DMSO-de) d 13.03 (s, 1H), 11.31 (d, J = 13.7 Hz, 1H), 9.38 (s, 1H), 9.06 (d, J = 13.7 Hz, 1H), 8.09 (t, .7 = 1.5 Hz, 1H), 7.91-7.95 (m, 2H), 7.77 (m, 2H), 7.58 (t, J = 7.3 Hz), 7.41 (dd, J = 7.8, 1.0 Hz, 1H ), 7.34 (d, «7 = 7.8, Hz, 1H), 7.26 (d,, 7 = 2.0, Hz, 1H), 7.19 (dd, .7 = 7.8, 2.0, Hz, 1H), 7.11 (t, J = 7.8, Hz, 1H) 7.04 (dd , .7 = 7.8, 1.5, Hz, 1H), 6.90 (d, J = 1.5 Hz, 1H), 2.29 (s, 3H), 2.28 (s, 3H). Example 8 4- Acid. { 3- [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) -hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 108) This compound was prepared as described in Scheme II. X H NMR (500 MHz, DMSO-d 6) d 13.18 (s, 1 H), 13.05 (s, 1 H), 9.13 (s, 1 H), 8.14 (d, J = 8.5 Hz, 2 H), 7.75 (m, 1 H) , 7.70 (m, 2H), 7.69 (dd, J = 7.8, 1.6 Hz, 1H), 7.32 (t, .7 = 7.6, 1.2 Hz, 1H), 7.23 (td, J = 7.6, 0.7 Hz, 1H) , 7.15 (s, 2H), 7.06 (t, .7 = 7.8 Hz, 1H), 7.03 (m, 1H), 7.00 (s, 1H) 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 2.33 ( s, 6H). Example 9 Acid 3-. { 3- [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) -hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 109) This compound was prepared as described in Scheme II. H NMR (500 MHz, DMSO-d6) d 13.30 (s, 1H), 13.20 (s, 1H), 9.27 (s, 1H), 8.11 (t, J = 1.78 Hz, 1H), 8.07 (ddd, J = 7.8, 1.8, 1.2 Hz, 1H), 7.94 (d, J = 7.9, Hz, 1H), 7.86 (ddd, J = 7.8, 1.8, 1.2 Hz, 1H), 7.77 (t, .7 = 7.8 Hz, 1H ), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.56 (dq, J = 7.9, 0.7 Hz, 1H), 7.15 (m, 2H), 7.09 (t, J = 7.8, Hz, 1H), 7.08 (m, 1H) 7.01 (m, 1H), 6.99 (dd, J = 7.8, 1.6 Hz, 1H), 2.33 (s, 6H). Example 10 Methyl ester of 3- acid. { 3- [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) -hydrazono] -2-yl-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 110) This compound was prepared as described in Scheme II. XH NMR (500 MHz, DMSO-de) d 13.20 (s, 1H), 9.27 (s, 1H), 8.15 (dd, J = 2.1, 1.6 Hz 1H), 8.10 (ddd, J = 7.9, 1.6, 1.1 Hz, 1H), 7.94 (d, J = 7.79 Hz, 1H), 7.90 (ddd) , J = 7.9, 2.1, 1. 1 Hz, 1H), 7.80 (t, J = 7.9 Hz, 1H), 7.74 (dd, J = 7.9, 1.6 Hz, 1H), 7.57 (dq, J = 7.9, 0.8 Hz, 1H), 7.15 (m, 2H), 7.09 (t, J = 7.9 Hz, 1H), 7.08 (m, 1H), 7.01 (m, 1H) 7.00 (dd, J = 7.9, 1.6 Hz, 1H), 3.90 (s, 3H), 2.33 (s, 6H). Example 11 Methyl ester of 3 - acid. { 3 - [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) -hydrazono] -2-oxo-2,3-dihydroindol-1-yl} methylbenzoic acid (Compound 111) This compound was prepared as described in Scheme II. ¾ NMR (500 MHz, DMSO-dff) d 13.04 (s, 1H), 9.11 (s, 1H), 8.12 (m, 1H), 8.06 (ddd, .7 = 7.8, 1.6, 1.2 Hz, 1H), 7.87 (ddd, J = 7.8, 2.2, 1.2 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.75 (m, 1H), 7.69 (dd, J = 7.8, 1.6 Hz, 1H), 7.31 ( td, J = 7.6, 1.2 Hz, 1H), 7.22 (td, J = 7.6, 0.9 Hz 1H), 7.15 (m, 2H), 7.06 (t, J = 7.8 Hz, 1H), 7.00 (m, 1H) 6.95 (m, 1H), 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 3.90 (s, 3H), 2.33 (s, 6H). Example 12 Acid 3-. { 3- [(5-Fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) -hydrazono] -2-oxo-2,3-dihydroindol-1-yl} Benzoic (Compound 112) This compound was prepared as described in Scheme II. XH NMR (500 MHz, DMSO-de) d 13.29 (s, 1H), 12.97 (s, 1H), 9.06 (s, 1H), 8.08 (m, 1H), 8.04 (ddd, J = 7.8, 2.2, 1.1 Hz, 1H), 7.83 (m, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.45 (dd, J = 9.5, 3.0 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.19 (s, 2H), 7.02 (s, 1H) 6.94 (d, .7 = 7.6 Hz, 1H), 6.75 (dd, J = 9.5, 3.0 Hz, 1H), 2.33 (s, 6H). Example 13 Acid 3-. { 3 - [1- (3, 5-Dimethylphenyl) -2 -oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylideneamino] -2-oxo-2,3-dihydrobenzooxazol-7-yl} benzoic (Compound 113) As described in Scheme V, a biphasic 3 'mixture. { ? ' - [1- (3, 5-Dimethyl-phenyl) -2 -oxo-6-trifluoromethyl-1, 2-dihydro-indole-3-ylidene] -hydrazine} -2 '-hydroxy-biphenyl-3-carboxylic acid (153 mg, 0.20 mmol, 0.1 equiv.) In dichloromethane (6 mL) and added 1: 1 saturated aqueous sodium bicarbonate / 2.0 M aqueous sodium hydroxide ( 6 ml) triphosgene (83 mg, 0.28 mmol, 3.0 equiv) at room temperature. The mixture was stirred for 4 h and then acidified with 6N HC1. The organic layer was removed and the aqueous layer was extracted twice with dichloromethane. The combined organics were washed once with water and once with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (gradient: 9: 1 hexanes / EtOAc to 3: 2 hexanes / EtOAc to 59.9: 40: 0.1 hexanes / EtOAC / HOAc), then triturated with methanol to provide the Compound 113. 1H MR (500 MHz, DMSO-de) d 13.25 (s, 1H), 8.45 (dd, J = 2.0, 1.5 Hz, 1H), 8.09 (ddd, J "= 7.8, 2.0, 1.0 Hz 1H), 8.05 (ddd, J = 8.3, 1.5, 1.0 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.73 (dd, J = 7.8, 7.8, Hz, 1H), 7.64 (dd, J = 8.0 , 1.2 Hz, 1H), 7.46 (m, 2H), 7.367 (dd, .7 = 7.8, 1.2 Hz, 1H), 7.21 (s, 3H), 6.86 (d, J = 1.6 Hz, 1H), 2.38 (s, 6H). Example 14 Acid 3-. { 3- [(2-Hydroxy-5,3 ', 4'-trimethylbiphenyl-3-yl) -hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 114) This compound was prepared as described in Scheme II. XH NMR (500 MHz, DMSO-de) d 13.28 (s, 1H), 13.03 (s, 1H), 8.81 (s, 1H), 8.08 (dd, J = 1.5, 1.0 Hz, 1H), 8.04 (ddd, J = 7.8, 1.5, 1.5 Hz, 1H), 7.83 (ddd, .7 = 7.9, 2.2, 1.2 Hz, 1H), 7.75 (m, 2H), 7.51 (d, J = 2.1 Hz, 1H), 7.30 ( m, 2H), 7.23 (m, 3H), 6.94 (d, J = 7.9 Hz, 1H), 6.76 (dd, J = 2.1, 0.7 Hz, 1H), 2.34 (s, 3H) 2.27 (s, 3H) , 2.26 (s, 3H). Example 15 3-hydroxybenzoic acid N '-. { l- [1- (3,5-dimethylphenyl) -2-oxo-6- trifluoromethyl-1,2-dihydroindol-3 (Z) -ylidene] ethyl} hydrazide (Compound 115) This compound was prepared as described in Scheme VIII. X H NMR (500 MHz, DMSO-d 6) d 11.76 (s, 1 H), 11.08 (s, 1 H), 9.84 (s, 1 H), 7.70 (d, J = 8.3 Hz, 1 H), 7.35 (m, 4 H) , 7.13 (S, 1H), 7.07 (s, 2H), 7.02 (dt, .7 = 5.2, 3.7 Hz, 1H), 6.92 (d, J = 1.5 Hz, 1H), 2.58 (s, 3H), 2.36 (s, 6H). Example 16 1- (3, 5-Dimethylphenyl) -3 (Z) -. { l- [(2-Hydroxyphenyl-2-oxo-ethylamino] -ethylidene] -6-trifluoromethyl-1,3-dihydroindol-2-one (Compound 116) This compound was prepared as described in Scheme VIII. ¾ NMR (500 MHz, Methanol-d4) d 8.54 (s, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.65 (d, J "= 8.3 Hz, 1H), 7.32 (d, J = 7.8 Hz, 1H), 7.15 (s, 1H), 7.03 (s, 2H), 6.93 (s, 1H), 6.90 (d, J = 8.3 Hz, 2H), 5.14 (s, 2H), 2.67 (s, 3H) 2.41 (s, 6H) Example 17 Acid 3-. { 3- [(5-Fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 117) This compound was prepared as described in Scheme II. X H NMR (500 MHz, DMSO-d 6) d 13.28 (s, 1 H), 13.09 (s, 1 H), 9.18 (s, 1 H), 8.09 (d, J = 2 Hz, 1 H), 8.07 (m, 1 H) , 8.0 (d, J = 7.8 Hz, 1H), 7.87 (m, 1H), 7.77 (t, J = 7.9 Hz, 1H), 7.58 (d, J "= 7.8 Hz, 1H), 7.52 (dd, J = 9.4, 3.1 Hz, 1H), 7.19 (s, 2H), 7.07 (s, 1H), 7.03 (s, 1H) 6.82 (dd, J = 9.5 Hz, 1H), 2.33 (s, 6H) Example 18 Acid 3-. { 3- [(2-Hydroxy-3 ', 4' -dimethylbiphenyl-3-yl) hydrazono] 2-??? - 6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 118) This compound was prepared as described in Scheme II. X H NMR (500 MHz, DMSO-d 6) d 13.28 (s, 1 H), 13.18 (s, 1 H), 9.23 (s, 1 H), 8.11 (t, J = ll Hz, 1 H), 8.07 (dd, J = 7.6, 1.2 Hz, 1H), 7.94 (d, J = 1.8 Hz, 1H), 7.85 (m, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.73 (m, 1H), 7.57 ( t, J = 8.8 Hz, 1H), 7.33 (s, 1H), 7.24 (dd, J = 13.9, 4.9 Hz, 2H), 7.09 (m, 1H), 6.99 (dd, J = 1.7, 1.6 Hz , 1H), 2.26 (s, 3H), 2.25 (s, 3H). Example 19 Acid 3-. { 3- [(2-Hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 119) This compound was prepared as described in Scheme II. ± ?? NMR (500 MHz, DMSO-de) d 13.28 (s, 1H), 13.04 (s, 1H), 9.09 (s, 1H), 8.08 (m, 1H), 8.04 (dt, .7 = 7.8, 1.4 Hz, 1H), 7.83 (ddd, J = 8.0, 2.2, 1.2 Hz, 1H), 7.74 (t, J = 7.7 Hz, 2H), 7.68 (dd, J = 7.8, 1.5Hz, 1H), 7.31 (m, 2H ), 7.23 (m, 3H), 7.06 (t, J = 7.9 Hz, 1H), 6.94 (dt, J "= 5.9, 3.9 Hz, 1H), 2.26 (s, 3H) 2.25 (s, 3H). twenty Acid 3-. { 3 (Z) - [(2-Hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 120) This compound was prepared as described in Scheme III. XH NR (500 MHz, DMSO-d5) d 13.23 (s, 1H), 11.15 (d, J- = 13.2 Hz 1H), 9.08 (s, 1H), 8.88 (dd, J = 13.18 Hz, 1H), 8.04 (m, 1H), 7.99 (m, 1H), 7.81 (m, 2H), 7.70 (m, 2H), 7.33 (s, 1H), 7.24 (m, 2H), 7.09 (m, 3H), 6.93 ( m, 2H) 2.27 (s, 3H), 2.26 (s, 3H). Example 21 4- Acid. { 3 (Z) - [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} Butyric (Compound 121) This compound was prepared as described in Scheme III. XH MR (500 MHz, DMSO-de) d 13.02 (s, 1H), 12.14 (s, 1H), 9.06 (s, 1H), 7.63 (dd, J = 7.8, 1.5 Hz, 2H), 7.33 (td, J = 1.1, 1.1 Hz, 1H), 7.21 (t, 1H), 7.13 (m, 3H), 7.03 (t, J = 7.8 Hz, 1H), 7.00 (s, 1H), 6.91 (m, 1H) ), 3.85 (t, J = 6.8 Hz, 2H), 2.33 (m, 8H), 1.88 (t, J = 6.8 Hz, 2H). Example 22 2-Chloro-3- (4-. {L- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3 (Z) -ylidenemethyl] amino} -3 acid -hydroxyphenyl) acrylic (Compound 122) This compound was prepared as described in Scheme VIII. XH NMR (500 MHz, DMSO-d6) d 11.20 (d, J = 14.2 Hz, 1H), 10.6 (br s, 1H), 9.06 (d, J = 12.7 Hz 1H), 7.94 (d, J = 8.3 Hz , 1H), 7.75 (d, .7 = 8.8 Hz, 1H), 7.63 (s, 2H), 7.43 (d, J = 8.8 Hz, 1H), 7.45-7.29 (m, 1H), 7.13 (s, 1H) ), 7.11 (s, 2H), 6.94 (s, 1H), 2.37 (s, 6H). Example 23 4-Hydrobenzoic acid -. { l- [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3 (Z) -ylidene] ethyl} hydrazide (Compound 123) This compound was prepared as described in Scheme VIII. 1H R (500 MHz, DMSO-de) d 12.04 (s, 1H), 10.92 (s, 1H), 10.11 (s, 1H), 7.82 (dt, J = 6.0, 4.8 Hz, 2H), 7.66 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.06 (s, 2H), 6.91 (s, 1H), 6.85 (d, J = 8.3 Hz, 2H), 2.60 (s, 3H), 2. 36 (s, 6H). Example 24 Acid 3-. { 3- [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) -hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 124) This compound was prepared as described in Scheme II. X H NMR (500 MHz, DMSO-d 6) d 13.29 (s, 1 H), 13.11 (s, 1 H), 9.27 (s, 1 H), 8.52 (d, J = 2.4 Hz, 1 H), 8.20 (dd, J = 8.8, 2.4 Hz, 1H), 8.10 (m, 2H), 7.84 (m, 2H), 7.78 (dd, J = 7.8, 7.8 Hz, 1H), 7.15 (d, J = 0.9 Hz, 2H), 7.10 ( m, 2H), 7.01 (dd, J = 7.6, 1.6 Hz, 2H), 2.33 (s, 6H). Example 25 Acid 3-. { 3 (Z) - [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) -methylidene] -2-oxo-2,3-dihydroindol-1-yl} Benzoic (Compound 125) This compound was prepared as described in Scheme III. XH NMR (500 MHz, DMSO-dff) d 13.2 (s, 1H), 11.17 (d, J = 13.7 Hz 1H), 9.11 (s, 1H), 8.89 (d, J = 13.2 Hz, 1H), 8.04 ( t, .7 = 1.8 Hz, 1H), 7.99 (m, 1H), 7.80 (m, 2H), 7.71 (m, 2H), 7.14 (m, 2H), 7.10 (m, 2H), 7.06 (m, 1H), 7.00 (s, 1H) 6.94 (m, 2H), 2.32 (s, 6H). Example 26 Acid 3-. { 3- [(2-Hydroxy-5,3 ', 5'-trimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 126) This compound was prepared as described in Scheme II. XH NMR (500 MHz, CD3OD-d4) d 8.10 (m, 2H), 7.75 (d, J = 6.B Hz, 1H), 7.68 (m, 2H), 7.54 (d, J = 2.0 Hz, 1H) , 7.26 (ddd, J = 7.8, 7.3, 1.0 Hz, 1H), 7.19 (dd, J = l .3, 7.3 Hz, 1H), 7.10 (s, 2H), 6.99 (s, 1H), 6.93 (d , J = l.8 Hz, 1H), 6.74 (d, J = 2.0 Hz, 1H), 2.36 (s, 3H), 2.35 (s, 6H). Example 27 4-Aminobenzoic acid -. { l- [1- (3,5-dimethylphenyl-2-oxo-6-trifluoromethyl-1,2-dihydroindol -3 (Z) -ylidene] ethyl] hydrazide (Compound 127) This compound was prepared as described in Scheme VIII. H NMR (500 MHz, DMSO-d6) d 11.83 (s, 1H), 10.71 (s, 1H), 7.67 (m, 3H), 7.35 (d, J = 1. 8 Hz, 1H), 7.12 (s, 1H), 7.06 (s, 2H), 6.91 (s, 2H), 6.60 (d, J = 8.8 Hz, 2H), 5.84 (s, 2H), 2.57 (s, 3H), 2.36 (s, 6H). Example 28 3- (7- {? '- [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromet-1,2-dihydroindol-3-ylidene] hydrazino} - lH-indol-3 acid -yl) propionic (Compound 128) This compound was prepared as described in Scheme II. ¾ NMR (500 MHz, DMSO-d6) d 13.48 (s, 1H), 12.11 (s, 1H), 10.78 (s, 1H), 8.39 (d,, 7 = 8.3 Hz, 1H), 7.56 (d, j = 8.1 Hz, 1H), 7.39 (d, J "= 7.8 Hz, 1H), 7.27 (d, J" = 2.7 Hz, 1H), 7.18 (s, 2H), 7.11 (m, 1H), 7.05 (t , J = 1.7 Hz, 1H), 7.00 (s, 1H), 2.98 (t, J "= 7.32 Hz, 2H), 2.63 (t, J = 7.8 Hz, 2H), 2.37 (s, 6H). Example 29 rut 4- Acid. { 3 (Z) - [? ' - (4-methylbenzoyl) -hydrazinomethylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 129) This compound was prepared as described in Scheme III. XH NMR (500 MHz, D SO-d d 13.8 (s, 1H), 8.17 (d, J "= 8.3 Hz, 1H), 7.82 (d, J = 7.8 Hz, 2H), 7.78 (d, J = l .8 Hz, 1H), 7.70 (J "= 8.3 Hz, 2H), 7.46 (dd, .7 = 7.8, 7.8 Hz, 1H), 7.43 (d, J = 8.3 Hz, 2H), 7.28 (dd, J = 1.8, 7.8 Hz, 1H), 7.00 (d, 7 = 7.8 Hz, 1H), 2.40 (s, 3H) Example 30 Acid 3-. { 2-Oxo-6-trifluoromethyl-3 (Z) - [4- (3-trifluoromethyl-phenyl) -lH-pyrrol-2-ylmethylidene] -2,3-dihydroindol-1-yl} Benzoic (Compound 130) This compound was prepared as described in Scheme IV. XH NR (500MHz, Acetone-de) 6 13.70 (s, 1H), 8.27 (s, 1H), 8.2 (d, J = 7.8 Hz, 1H), 7.91 (m, 5H), 7.82 (m, 5H), 7.59 (s, 1H), 7.47 (d, J = 1.8 Hz, 1H), 7.13 (s, 1H), 6.74 (m, 1H). Example 31 3- (7- {? '- [1- (3, 4-Dimethylphenyl) -3-methyl-5-oxo-l, 5-dihydropyrazol-4-ylidene] hydrazino] -lH-indole 3-yl) propionic (Compound 131) This compound was prepared as described in Scheme II. H NMR (500MHz, DMSO-de) d 12.10 (s, 1H), 10.62 (s, 1H), 7.75 (s, 1H), 7.67 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H), 7.22 (d, J = 8.3 Hz, 1H), 7.09 (t, J = 7.8 Hz, 1H), 2.97 (t, J = 7.4 Hz, 1H), 2.62 (t, J = 7.8Hz, 1H), 2.43 (s, 3H), 2.28 (s, 3H), 2.24 (s, 3H). Example 32 3- (3 (?) - { [4- (3, 4-Dimethylphenyl) thiazol-2-ylamino] methylidene} -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl. ) benzoic (Compound 132) This compound was prepared as described in Scheme III. ¾ NMR (500 MHz, acetone-d6) d 68.98 (s, 1H), 8.24 (s, 1H), 8.16 (d, J = 1 .8 Hz, 1H), 7.99 (d, J = 1 .8 Hz, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.79 (m, 2H), 7.74 (d, J = 1.8 Hz, 1H), 7.48 (s, 1H), 7.47 (d, J = 9.0 Hz, 1H), 7.21 (m, 2H), 2.33 (s, 3H), 2.29 (s, 3H). Example 33 3- (3 (Z) - { [4- (4-Methoxyphenyl) thiazol-2-ylamino] methylene} -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl) benzoic acid (Compound 133) This compound was prepared as described in Scheme III. XH NMR (500 MHz, acetone-de) d 8.98 (s, 1H), 8.24 (s, 1H), 8.16 (dt, .7 = 7.8, 1.2 Hz, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 9.3 Hz, 2H), 7.88 (d, J = 1.8 Hz, 1H), 7.79 (t, J = 7.8 Hz, 1H), 7.46 (d, J = 1. 3 Hz, 1H), 7.41 (s, 1H), 7.19 (s, 1H), 7.01 (d, J = 8.8 Hz, 2H), 3.85 ( s, 3H). Example 34 Acid 3-. { 3 (Z) - [(2-Hydroxy-3 ', 5' -dimethylbiphenyl-3-ylamino) methylene] -2-??? - 6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 134) This compound was prepared as described in Scheme III. ¾ NMR (500 MHz, DMSO-d6) d 11.35 (d, J = 13.4 Hz, 1H), 9.24 (s, 1H), 9.10 (d, J = 13.2 Hz, 1H), 8.00 (m, 2H), 7.99 (d, J = 8.3 Hz, 1H), 7.74 (m, 2H), 7.68 (t, J = 7.6 Hz, 1H), 7.46 (d, J = 7.3 Hz, 1H), 7.14 (s, 2H), 7.08 (t, J = 7.9 Hz, 1H), 7.03 (s, 1H), 6.99 (m, 2H), 2.32 (s, 6H). Example 35 Ac 4- (4-Methylphenyl) -2-thiazolylamino) methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 135) This compound was prepared as described in Scheme III. ?? NMR (500 MHz, DMSO-de) 13.25 (s, 2H), 11.81 (d, "7 = 12.1, 1H), 11.41 (d, J = 13.0, 1H), 8.96 (d, .7 = 12.1, 1H) , 8.59 (d, «7 = 13.0, 1H), 8.35 (ra, 1H), 8.11-8.00 (m, 5H), 7.93 (d, J = 8.2, 2H), 7.84 (d,« 7 = 8.2, 2H ), 7.84 (m, 1H), 7.81-7.72 (m, 3H), 7.67 (m, 1H), 7.65 (s, 1H), 7.55 (m, 1H), 7.47 (dq, «7 = 7.9, 0.7, 1H), 7.27 (d, "7 = 8.1, 4H), 7.04 (s, 1H), 6.98 (s, 1H), 2.35 (s, 3H), 2.34 (s, 3H).

Acid 3-. { 3 (Z) - [(3,4-dimethylbenzoylhydrazino) methylidene] ??? - 6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 136) This compound was prepared as described in Scheme III. XH NMR (500 MHz, SO-de D) 13.24 (br s, 1H), 11.30 (d, J = 13.0, 1H), 10.28 (d,, 7 = 13.0, 1H), 8.42 (br s, 1H), 8.10-7.96 (ra, 2H), 7.82-7.64 (m, 4H), 7.38 (d, J = 8.1, 1H), 7.31 (d, J = 7.6, 1H), 7.01 (s, 1H), 6.95 (br s, 1H), 2.31 (s, 6H). Example 37 Acid 3-. { 3 (Z) - [(4-Chlorobenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 137) This compound was prepared as described in Scheme III. 1 H NMR (500 MHz, DMSO-d 6) 15.42 (s, 1 H), 13.24 (s, 1H), 11.47 (s, 1H), 8.43 (s, 1H), 8.10-7.89 (m, 4H), 7.84-7.70 (m, 3H), 7.65 (d, J = 8.4, 2H), 7.38 (d, J = 7.7, 1H), 7.01 (s, 1H). Example 38 3- (3 (Z) - [(4-methoxybenzoylhydrazino) methylidene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 138) This compound was prepared as described in Scheme III XH NMR (500 MHz, DMSO-de) 11.32 (s, 1H), 11.30 (d, J = 12.2, 1H), 10.27 (d, J = 12.2, 1H), 8.43 (s, 1H), 8.11-7.65 (m, 7H), 7.38 (d, J = 8.1, 1H), 7.09 ( d, J = 8.5, 2H), 7.01 (s, 1H), 3.85 (s, 3H).

Acid 3-. { 3 (Z) - [(3,4-dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl} benzoic (Compound 139) This compound was prepared as described in Scheme III. ?? NMR (500 MHz, DMS0-de) 13.22 (s, 1H), 11.20 (br, 2H), 8.25 (s, 1H), 8.05-7.93 (m, 4H), 7.88 (m, 1H), 7.78 (m, 1H), 7.74-7.69 (m, 5H), 7.68-7.64 (m, 3H), 7.60 (m, 2H), 7.54 (s, 1H), 7.32-7.29 (m, 2H), 7.14 (m , 1H), 7.07 (dd, J = 8.2, 1.9, 1H), 6.83 (d, J = 1.9, 1H), 6.78 (M, 1H), 2.30 (s, 12H). Example 40 1- (3, 4-Dimethylphenyl) -3 (Z) - [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2-OXO-2,3-dihydroindole (Compound 140) This compound was prepared as described in Scheme VIII. ? R (300 MHz, DMSO-d6) 11.76 (s, 1H), 11.43 (s, 1H), 10.73 (s, 1H), 10.25 (s, 1H), 7.73 (d, J = 8.6, 1H), 7.51 ( m, 1H), 7.32 (d, J = 8.1, 1H), 7.21 (d, J = 2.0, 1H), 7.14 (dd, J = 8.1, 2.0, 1H), 7.07-6.99 (m, 2H), 6.79 (m, 1H), 6.38 (dd, J "= 8.6, 2.4, 1H), 6.34 (d, J = 2.4, 1H), 2.47 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H) Example 41 1- (3, 4-Dimethylphenyl) -3 (Z) - [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-OXO-2,3-dihydroindole (Compound 141) This compound was prepared as described in Scheme VIII . 1 H NMR (300 MHz, DMSO-d 6) 11.44 (s, 1 H), 10.75 (s, 1 H), 10.21 (s, 1 H), 7.81 (d, J = 8.8, 2 H), 7.51 (m, 1 H), 7.32 (d, J = 8.2, 1H), 7.21 (d, J = 2.0, 1H), 7.14 (dd, J = 8.2, 2.0, 1H), 7.07-6.99 (m, 2H), 6.88 (d, J = 8.8 , 2H), 6.79 (m, 1H), 2.47 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H). Example 42 1- (3, 4-Dimethylphenyl) -3 (Z) - [(2,4-dihydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 142) This compound was prepared as described in Scheme VIII . NMR (300 MHz, DMS0-d6) 12.04 (s, 1H), 11.94 (s, 1H), 11.02 (s, 1H), 10.28 (s, 1H), 10.25 (s, 1H), 9.64 (d, J "= 11.5, 1H), 8.11 (s, 1H), 7.80 (m, 1H), 7.76-7.70 (m, 2H), 7.58 (d, J = 10.4, 1H), 7.55-7.50 (m, 2H), 7.42 (d, J- = 11.5f 1H), 7.34-7.27 (m, 2H), 7.23 (d, J = 1.6, 1H), 7.18-6.96 (m, 7H), 6.79-6.71 (m, 2H), 6.40-6.31 (m, 4H), 2.29 (s, 6H), 2. 28 (s, 3H), 2.27 (s, 3H). Example 43 1- (3, 5-Dimethylphenyl) -3 (Z) - [1- (2,4-dihydroxybenzoylhydrazino) ethylidenoj -2 -oxo-2,3-dihydroindole (Compound 143) This compound was prepared as described in the Scheme VIII. 1 H NMR (300 MHz, DMSO-d 11.77 (s, 1 H), 11.44 (s, 1 H), 10.73 (s, 1 H), 10.26 (s, 1 H), 7.73 (d, J "= 8.8, 1 H), 751 (m, 1H), 7.09-7.01 (m, 5H), 6.82 (m, 1H), 6.38 (dd, .7 = 8.8, 2.3, 1H), 6.34 (d, J = 2.3, 1H), 2.47 (s) , 3H), 2.35 (s, 6H) Example 44 1- (3, 5-Dimethylphenyl) -3 (Z) -. { 1- (4-hydroxybenzoylhydrazino) ethylidene) -2-OXO-2,3-dihydroindole (Compound 144) This compound was prepared as described in Scheme VIII. XU NMR (300 MHz, DMSO-d6) 11.45 (s, 1H), 10.76 (s, 1H), 10.22 (s, 1H), 7.81 (d, J = 8.8, 2H), 7.51 (ra, 1H), 7.09-6.97 (m, 5H), 6.88 (d, J "= 8.8, 2H ), 6.82 (m, 1H), 2.48 (s, 3H), 2.35 (s, 6H). 1- (3, 5-Dimethylphenyl) -3 (Z) - [(2,4-dihydroxybenzoylhydrazino) methylidenoj -2 -oxo-2,3-dihydroindole (Compound 145) This compound was prepared as described in Scheme VIII. ¾ NMR (300 MHz, DMSO-de) 11.98 (m, 2H), 11.02 (s, 2H), 10.28 (s, 1H), 10.26 (s, 1H), 9.65 (d, J = 11.6, 1H), 8. 12 (s, 1H), 7.80 (m, 1H), 7.77-7.70 (m, 2H), 7.56-7.50 (m, 2H), 7.42 (d, J "= 11.6, 1H), 7.08-6.96 (m, 10H), 6.83-6.72 (m, 2H), 6.40-6.31 (m, 4H), 2.35 (s, 6H), 2.33 (s, 6H) Example 46 1- (3, 5-Dimethylphenyl) -3 (Z) - [(4-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 146) This compound was prepared as described in Scheme VIII. ¾ MR (300 MHz, DMSO-d6) 11.00 (s, 2H), 10.20 (s, 1H), 10.19 (s, 1H), 9.65 (ra, 1H), 8.10 (s, 1H), 7.84-7.74 (m , 5H), 7.54 (m, 1H), 7.40 (d, .7 = 10.3, 1H), 7.10-6.95 (m, 10H), 6.91-6.84 (m, 4H), 6.78 (m, 1H), 3.18 ( s, 1H), 3.16 (s, 1H), 2.35 (s, 6H), 2.33 (s, 6H). Example 47 3- (3 (Z) - [1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2-oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid (Compound 147) This compound was prepared as it is described in Scheme III. HNR (500 MHz, DMS0-d6) 11.55 (s, 1H), 8.02 (dt, J = 7.6, 1.5, 1H), 7.98 (t, J = 1.5, 1H), 7.78-7.65 (m, 4H), 7.53 (d, J = 8.2, 1H), 7.30 (d, J = 8.2, 1H), 7.10 (dd, J = 8.2, 2.0, 1H), 6.84 (d.J = 2.0, 1H), 2.52 (s, 3H) ), 2.30 (s, 6H). Example 48 1- (3, 4-Dimethylphenyl) -3 (Z) - [(4-hydroxybenzoylhydrazino) methylidene] -2-??? -2,3-dihydroindole (Compound 148) This compound was prepared as described in Scheme VIII . ?? NMR (500 MHz, DMS0-d6) 10.99 (s, 2H), 10.19 (s, 1H), 10.18 (s, 1H), 9.64 (d, J = 12.0, 1H), 8.09 (s, 1H), 7.83- 7.74 (m, 5H), 7.54 (m, 1H), 7.40 (m, 1H), 7.31 (d, J = 8.0, 1H), 7.29 (d, J "= 8.0, 1H), 7.23 (m, 1H) , 7.18-7.14 (m, 2H), 7.10 (dd, J = 8.0, 2.0, 1H), 7.07-7.02 (m, 2H), 7.00-6.97 (m, 3H), 6.89-6.84 (m, 4H), 6.77 (m, 1H), 6.73 (m, 1H), 2.30 (s, 3H), 2.29 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H), Example 49 1- (3, 4-Dimethylphenyl) -3 ()) - [(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 149) This compound was prepared as described at Scheme VIII. ¾ NR (500 MHz, DMSO-d6) 12.29 (s, 1H), 12.22 (s, 1H), 11.52 (s, 2H), 9.71 (d,, 7 = 10.6, 1H), 8.14 (s, 1H), 7.82 (m, 1H), 7.68-7.58 (m, 2H), 7.54-7.48 (m, 2H), 7.34-7.23 (m, 5H), 7.19-7.16 (m, 2H), 7.13-6.96 (m, 5H) ), 6.78 (m, 1H), 6.74 (m, 1H), 3.27 (m, 2H), 2.86 (m, 2H), 2.31 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H) , 2.28 (s, 3H), 1.23 (d, J = 6.8, 6H), 1.23 (d, J = 6.8, 6H), 1.20 (d, J = 6.8, 6H), 1.20 (d, J = 6.8, 6H ). Example 50 1- (3, 5-Dimethylphenyl) -3 (Z) - [1- (3,4-dihydroxybenzoylhydrazine) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 150) This compound was prepared as described in Scheme VIII. HNR (500 MHz, DMSO-d6) 11.47 (s, 1H), 7.51 (m, 1H), 7.35 (d, J = 1.5, 1H), 7.30 (dd, J = 8.3, 1.5, 1H), 7.10 -7.01 (m, 5H), 6.86-6.80 (m, 2H), 2.47 (s, 3H), 2.35 (s, 6H). Example 51 1- (3, 4-Dimethylphenyl) -3 (Z) - [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 151) This compound was prepared as described in Scheme VIII. ?? NMR (500 MHz, DMSO-d6) 11.47 (br s, 1H), 10.68 (br s, 1H), 9.70 (br, 1H), 9.31 (br s, 1H), 7.50 (m, 1H), 7.36- 7.27 (m, 3H), 7.21 (s, 1H), 7.14 (m, 1H), 7.06-6.99 (m, 2H), 6.83 (m, 1H), 6.79 (m, 1H), 2.47 (s, 3H) , 2.30 (s, 3H), 2.29 (s, 3H). Example 52 3- (6-Chloro-3 (Z) - [(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl) benzoic acid (Compound 152) This compound was prepared as described in Scheme III. ¾ NR (500 MHz, D SO-de) 13.22 (s, 2H), 12.25 (s, 1H), 12.16 (s, 1H), 11.58 (s, 2H), 8.32-8.25 (m, 2H), 8.06- 7.94 (m, 5H), 7.81-7.55 (m, 9H), 7.33-7.24 (m, 2H), 7.20-7.04 (m, 2H), 6.83 (d, J = l .6, 1H), 6.79 (d , J = 1.6, 1H), 3.26 m, 2H), 2.86 (m, 2H), 1.23 (d, J = 6.3, 6H), 1.22 (d, J = 6.3, 6H), 1.20 (d, J = 6.8 , 6H), 1.19 (d, J = 6.8, 6H). Example 53 1- (3, 4-Dimethylphenyl) -3 (Z) - [1- (2,5-dihydroxybenzoylhydrazine) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 153) This compound was prepared as described in Scheme VIII. XH NR (500 MHz, DMS0-d6) 11.49 (s, 1H), 10.77 (s, 1H), 10.72 (s, 1H), 9.14 (s, 1H), 7.51 (m, 1H), 7.32 (d, J = 8.0, 1H), 7.23 (d, .7 = 3.0, 1H), 7.21 (d, J = 2.0, 1H), 7.14 (dd, J = 8.0, 2.0, 1H), 7.06-7.00 (m, 2H) , 6.89 (dd, J = 8.8, 3.0, 1H), 6.83 (d, J = 8.8, 1H), 6.79 (m, 1H), 2.48 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H). Example 54 1- (3, 4-Dimethylphenyl) -3 (Z) - [1- (3-nitro-4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 154) This compound was prepared as described in Scheme VIII. ?? NMR (500MHz, DMSO-d6) 11.30 (s, 1H), 9.84 (s, 1H), 8.36 (d, J = 2.3, 1H), 7.98 (dd, J "= 8.7, 2.3, 1H), 7.42 (ddd) , J = 7.7, 1.2, 0.5, 1H), 7.29 (d, J = 7.9, 1H), 7.16 (d, J = 8.7, 1H), 7.16 (d, .J "= 2.1, 1H), 7.10 (dd) , J = 7.9, 2.1, 1H), 6.96 (td, J = l .7, 1.2, 1H), 6.90 (td, J = l .7, 1.2, 1H), 6.76 (ddd, J = 7.7, 1.2, 0.5, 1H), 5.05 (br s, 1H), 2.60 (s, 3H), 2. 29 (s, 3H), 2.28 (s, 3H). Example 55 1- (3, 4-Dimethylphenyl) -3 (? - [1- (3-aminosulfonyl-4-chlorobenzoylhydrazino) ethylidene} -2-oxo-2,3-dihydroindole (Compound 155) This compound was prepared as describes in the Scheme VIII. ?? N R (500 MHz, SO-de) 11.48 (s, 1H), 11.29 (s, 1H), 8.52 (d, J = 2.2, 1H), 8.13 (dd, J "= 8.3, 2.2, 1H), 7.86 (d, J = 8.3, 1H), 7.79 (s, 2H), 7.52 (m, 1H), 7.32 (d, .7 = 8.0, 1H), 7.22 (d, J "= 2.2, 1H), 7.15 (dd, J = 8.0, 2.2, 1H), 7.07-7.01 (m, 2H), 6.79 (m, 1H), 2.50 (m, 3H) , 2.30 (s, 3H), 2.29 (s, 3H). 1- (3, 4-Dimethylphenyl) -3 (Z) - [1- (3-amino-4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 156) This compound was prepared as described in Scheme VIII. X H NMR (500 MHz, D SO-d 6) 7.54-7.42 (m, 3 H), 7.31 (m, 1 H), 7.17 (s, 1 H), 7.11 (m, 1 H), 7.08-7.00 (m, 2 H), 6.88 (br s, 1H), 6.78 (m, 1H), 4.61 (br s, 1H), 3.91 (s, 2H), 2.53 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H) . Example 57 1- (3, 4-Dimethylphenyl) -3 (Z) - [1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 157) This compound was prepared as described in Scheme VIII. ?? NMR (500 MHz, DMSO-d6) 11.91 (s, 1H), 11.44 (s, 1H), 10.83 (s, 1H), 7.83 (d, J "= 8.8, 1H), 7.51 (m, 1H), 7.32 (d, J = 8.0, 1H), 7.21 (d, J = 1.9, 1H), 7.14 (dd, J = 8.0, 1.9, 1H), 7.06-7.00 (m, 2H), 6.79 (m, 1H), 6.57 (dd, J "= 8.8, 2.4, 1H), 6.51 (d, J = 2.4, 1H), 3.80 (s, 3H), 2.48 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H).

Example 58 Acid 3-. { 3 (Z) - (1- (3,5-dimethylphenyl) -2 -oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl-benzoic acid (Compound 158) This compound was prepared as described in Scheme VIII. ?? NMR (500 MHz, DMS0-d6) 11.16 (d, J "= 13.0, 1H), 9.26 (s, 1H), 8.84 (d, J = 13.0, 1H), 8.12 (t, .7 = 1.7, 1H) , 7.94 (ddd, J = l .1, 1.7, 1.2, 1H), 7.81-7.72 (m, 3H), 7.60 (t, J = l .7, 1H), 7.13-7.05 (m, 6H), 7.01 (dd, J = 7.7, 1.5, 1H), 6.85 (m, 1H), 2.35 (s, 6H) Example 59 3 (Z) - (3- (3, 5-Dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2-oxo-2,3-dihydro-l-indolyl J-benzoic (Compound 159) This compound was prepared as described in Scheme III. XH NMR (500 MHz, DMSO-d ^) 11.20 (d, J = 13.1, 1H), 9.17 (br s, 1H), 8.95 (d, .7 = 13.1, 1H), 8.02 (s, 1H), 7.97 (d, J = 7.7, 1H), 7.76-7.66 (m, 4H), 7.14 (s, 2H), 7.07 (t, J = 1.7, 1H), 7.00 (s, 1H), 6.97 (d, -7 = 7.7, 1H), 6.90-6.86 (m, 2H), 2.32 (s, 6H). Example 60 Acid 3-. { 3 (Z) - (1- (3, 4-dimethylphenyl) -2 -oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl} Benzoic (Compound 160) This compound was prepared as described in Scheme VIII. H NMR (500 MHz, DMSO-de) 13.03 (s, 1H), 11.14 (d, J = 13.0, 1H), 9.25 (s, 1H), 8.83 (d, J "= 13.0, 1H), 8.11 (t , «7 = 1.7, 1H), 7.94 (ddd, J = 1.7, 1.7, 1.1, 1H), 7.80-7.75 (m, 2H), 7.73 (dd, .7 = 7.8, 1.5, 1H), 7.59 (t, J = 7.7, 1H), 7.32 (d, J "= 8.0, 1H), 7.25 (d, J = 2.1, 1H), 7.18 (dd,, 7 = 8.0, 2.1, 1H), 7.10 (t , .7 = 7.8, 1H), 7.07-7.03 (m, 2H), 7.00 (dd, J = 7.8, 1.5, 1H), 6.81 (m, 1H), 2.30 (s, 3H), 2.30 (s, 3H) ). Example 61 4- Acid. { l- (6-Fluoro-2-oxo-2,3-dihydro-3 (Z) - (2- (3,5-dimethylphenyl) aminocarbonylphenyl) aminomethylidene) indolyl} butanoic (Compound 161) This compound was prepared as described in Scheme III. XH NMR (500 MHz, DMSO-d6) 12.11 (s, 1H), 12.00 (d, J "= 12.8, 1H), 10.32 (s, 1H), 8.67 (d, J = 12.8, 1H), 7.84 (d , J = 8.2, 1H), 7.80 (dd, J = 7.9, 1.5, 1H), 7.63 (m, 1H), 7.60 (d, J = 9.3, 2.6, 1H), 7.35 (s, 2H), 7.23 ( m, 1H), 7.01 (dd, J = 8.5, 4.3, 1H), 6.91 (ddd, J = 9.5, 8.5, 2.6, 1H), 6.79 (s, 1H), 3.77 (t, J "= 7.3, 2H ), 2.29 (s, 6H), 2.26 (t, J "= 7.3, 2H), 1.80 (qn, J = 7.3, 3H). 4- Acid. { 1- (6-Chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3-dimethylphenyl) phenyl) aminomethylidene) indolyl Jbutanoic (Compound 162) This compound was prepared as described in Scheme III. XH MR (500 MHz, DMSO-d6) 11.25 (d, J "= 12.9, 1H), 10.68 (S, 1H), 8.65 (d, J = 12.9, 1H), 8.05 (s, 1H), 7.60 (d , J = 8.0, 1H), 7.57 (dd, J = 7.9, 1.3, 1H), 7.16 (d, J = 1.8, 1H), 7.11 (m, 2H), 7.02 (dd, J = 7.9, 7.7, 1H ), 7.02 (m, 1H), 7.00 (dd, J = 8.0, 1.8, 1H), 6.94 (dd, J = 1.7, 1.3, 1H), 3.94 (t, J = 7.2, 2H), 2.43 ( t, J = 7.2, 2H), 2.35 (m, 6H), 2.01 (qn, J = 7.2, 2H).

Acid 3-. { 1- (6-chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} benzoic (Compound 163) This compound was prepared as described in Scheme III. ¾ NMR (500 MHz, DMSO-de) 13.25 (s, 1H), 11.17 (d, J = 13.3, 1H), 9.15 (s, 1H), 8.94 (d, J = 13.3, 1H), 8.03- 7.99 ( m, 2H), 7.80 (m, 1H), 7.80 (d, .7 = 8.1, 1H), 7.72 (t, ^ = 7.8, 1H), 7.70 (d, J = 7.8, 1H), 7.16 (dd, J = 8.1, 1.9, 1H), 7.14 (s, 2H), 7.06 (t, .7 = 7.8, 1H), 7.00 (s, 1H), 6.97 (dd, J = 7.8, 1.2, 1H), 6.88 ( d, J = 1.9, 1H), 2.32 (s, 6H).

Example 64 4- Acid. { 1- (5-Fluoro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} butanoic (Compound 164) This compound was prepared as described in Scheme III. ¾ NMR (500 MHz, DMSO-d 11.30 (d, J = 12.8. 1H), 10.69 (s, 1H), 8.69 (d, J = 12.8, 1H), 8.06 (s, 1H), 7.58 (dd, J = 8.2, 1.4, 1H), 7.45 (dd, J = 9.3, 2.6, 1H), 7.11 (m, 2H), 7.07-7.01 (m, 3H), 6.94 (dd, .7 = 7.7, 1.5, 1H), 6.86 (ddd, J = 9.7, 8.2, 2.6, 1H), 3.92 (t, J = l .2, 2H), 2.41 (t, J = l .2, 2H), 2.35 (m, 6H), 2.00 (qn, J = l .2, 2H). Example 65 Acid 3-. { 3- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3 (Z) -indolidene) ethylamino) -2-hydroxyphenyl} benzoic acid (Compound 165) This compound was prepared as described in Scheme VIII. ¾ R (500 MHz, DMSO-de) 11.86 (s, 1H), 8.31 (t, J = 1.5, 1H), 8.06 (d, J = 7.8, 1H), 7.77 (d, J = 7.8, 1H), 7.53 (t, J = 7.8, 1H), 7.46 (d, J = 8.1 , 1H), 7.33 (dq, J = 8.1, 0. 9, 1H), 7.30 (dd, J = l .1, 1.3, 1H), 7.13 (dd, .J = 7.7, 1.3, 1H), 7.06 (s, 2H), 7.02 (t, J = 1.7, 1H), 6.99-6.97 (m, 2H), 2.42 (s, 3H), 2.37 (s, 6H). Example 66 Acid 3-. { 3- (1- (1- (3,4-dimethylphenyl) -6-trifluoromethyl-2-yl-2,3-dihydro-3 (Z) indolidene) ethylamino) -2-hydroxyphenyl} benzoic (Compound 166) This compound was prepared as described in Scheme VIII. X H NMR (500 MHz, DMSO-d 6) 11.91 (s, 1 H), 8.32 (br s, 1 H), 8.06 (d, J = l. 8, 1 H), 7.76 (d, J = 1.8, 1 H), 7.54. (t, 1H), 7.48 (d, J "= 8.1, 1H), 7.35-7.28 (m, 3H), 7.18 (s, 1H), 7.16-7.10 (m, 2H), 7.08 (s, 1H), 7.04 (t, J = 1.6, 1H), 2.49 (s, 3H), 2.33 (s, 3H), 2.32 (s, 3H) Example 67 Acid 3-. { 1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazone) indolyl J-benzoic (Compound 167) This compound was prepared as described in Scheme II. ?? NMR (500 MHz, DMS0-d6) 13.30 (s, 1H), 13.03 (s, 1H), 9.44 (s, 1H), 8.11 (dd, J = 2.1, 1.7, 1H), 8.08 (ddd, J "= 7.8, 1.7, 1.2, 1H), 7.99 (d, J = 8.0, 1H), 7.85 (ddd, J "= 7.8, 2.1, 1.2, 1H), 7.77 (t, J = 7.8, 1H), 7.56 (d , J = 2.5, 1H), 7.54 (dq, J "= 8.0, 0.8, 1H), 7.04 (m, 1H), 6.92 (d, .7 = 2.5, 1H), 2.97 (m, 1H), 1.81- 1.67 (m, 5H), 1.44-1.31 (m, 4H), 1.25 (m, 1H) Example 68 Acid 3-. { 1- (5-Fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3 (Z) cyclohexylphenyl) amino) ethylidene) indolyl Jbenzoic (Compound 168) This compound was prepared as described in Scheme III. ? NMR (500 MHz, DMSO-d6) 11.93 (s, 1H), 8.00-7.97 (m, 2H), 7.72-7.66 (m; 2H), 7.34 (dd, J = 10.1, 1.8, 1H), 7.23 (d , J = 2.5, 1H), 7.12 (d, J = 2.5, 1H), 6.91-6.84 (m, 2H), 2.95 (m, 1H), 2.49 (s, 3H), 1.82-1.67 (m, 5H) , 1.43-1.32 (m, 4H), 1.29-1.20 (m, 1H). Example 69 Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3 (Z) cyclohexylphenyl) aminomethylidene) indolyl} benzoic (Compound 169) This compound was prepared as described in Scheme III. ? NMR (500 MHz, DMS0-d6) 11.09 (d, J = 13.2, 1H), 9.38 (br s, 1H), 8.91 (d, J "= 112, 1H), 8.02 (t, J = 1.8, 1H) , 7.99 (ddd, J = 7.8, 1.8, 1.2, 1H), 7.77 (ddd, J = l.8, 1.8, 1.2, 1H), 7.70 (t, J = 7.8, 1H), 7.67 (m, 1H) , 7.66 (d, J = 2.3, 1H), 6.90 (d, J "= 2.3, 1H), 6.90-6.87 (m, 2H), 2.95 (m, 1H), 1.81-1.66 (m, 5H), 1.44 -1.22 (m, 5H). Example 70 Acid 4 -. { 2-Hydroxy-3 - (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) -indolylidene) methylaminophenyl} butanoic (Compound 170) This compound was prepared as described Scheme VIII. XH MR (500 MHz, DMSO-d6) 11.27 (d, J = 13.6, 1H), 9.01 (d, J = 13.6, 1H), 7.94 (d, J = 8.1, 1H), 7.60 (d, «7 = 7.6, 1H), 7.41 (d, J = 8.1, 1H), 7.12 (s, 1H), 7.10 (s, 2H), 6.94 (t, J "= 7.6, 1H), 6.93 (s, 1H), 6.88 (d, J = l .6, 1H), 2.65 (t, J = 7.4, 2H), 2.37 (s, 6H), 2.23 (t, .7 = 7.4, 2H), 1.77 (qn, J = 7.4, 2H) Example 71 4- Acid. { 2-Hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3 (Z) -indolylidene) methylaminophenyl} butanoic (Compound 171) This compound was prepared as described in Scheme VIII. ¾ NMR (300 MHz, DMSO-de) 8.72 (s, 1H), 7.76 (d, J = 7.6, 1H), 7.44 (m, 1H). 7.38-7.30 (m, 2H), 7.22 (d, J = 1.7, 1H), 7.15 (dd, J = 8.0, 1.7, 1H), 6.97-6.89 (m, 3H), 2.70 (t, J "= 7.2 , 2H), 2.36 (s, 6H), 2.33 (t, J = l2, 2H), 1.87 (qn, J = l2, 2H) Example 72 Acid 3-. { 3- (7- (6-Trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) indolylidene) methylamino) indolyl} propanic (Compound 172) This compound was prepared as described in Scheme VIII. X H NMR (500 MHz, DMSO-d 5) 12.10 (s, 1 H), 11.32 (m, 1 H), 10.94 (d, .7 = 12.8, 1 H), 8.92 (d, J = 12.8, 1 H), 7.95 (d , J = 7.8, 1H), 7.43 (d, J = 7.8, 1H), 7.40 (m, 1H), 7.30 (d, J = 7.8, 1H), 7.19 (d, J = 2.4, 1H), 7.14 ( m, 1H), 7.12 (m, 2H), 7.09 (t, J = 7.8, 1H), 6.94 (m, 1H), 2.94 (t, J = l .6, 2H), 2.61 (t, J = 7.6 , 2H), 2.37 (s, 6H).

Example 73 (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) -3 (Z) indolylidene) methylamino) indolyl} propanic (Compound 173) This compound was prepared as described in Scheme VIII. XH NMR (500 MHz, DMS0-d5) 12.09 (s, 1H), 11.33 (d, J = 2.2, 1H), 10.92 (d, .7 = 12.8, 1H), 8.91 (d, .7 = 12.8, 1H ), 7.94 (d, J = 8.0, 1H), 7.43 (d, J = 8.0, 1H), 7.40 (m, 1H), 7.37 (d,, 7 = 8.0, 1H), 7.30-7.28 (m, 214) ), 7.22 (dd, J "= 8.0, 2.0, 1H), 7.19 (d, J = 2.2, 1H), 7.09 (t, J = 8.0, 1H), 6.92 (d, J = 1.6, 1H), 2.94 (t, J = 7.7, 2H), 2.60 (t, J = 7.7, 2H), 2.32 (s, 3H), 2.31 (s, 3H) Example 74 4- Acid. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-1- (3, 5-dimethylphenyl) -3 (Z) -indolylidene) methylaminophenyl} butanoic (Compound 174) This compound was prepared as described in Scheme VIII. XH R (500 MHz, DMSO-d6) 12.07 (s, 1H), 11.08 (d, J = 13.0, 1H), 8.77 (d, J = 13.0, 1H), 7.74 (m, 1H), 7.54 (d, J = 7.8, 1H), 7.10-7.02 (m, 5H), 6.91 (m, 1H), 6.85-6.81 (m, 2H), 2.64 (m, 2H), 2.36 (s, 6H), 2.23 (m, 2H), 1.77 (m, 2H). Example 75 2-Chloro-3 (Z) acid. { 3-hydroxy-4- (2 -oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) indolylidene) methylaminophenyl} propenoic (Compound 175) This compound was prepared as described in Scheme VIII. X H NMR (500 MHz, DMSO-d 6) 13.48 (br s, 1 H), 11.06 (d,, 7 = 12.6, 1 H), 10.61 (s, 1 H), 8.84 (d, J "= 12.6, 1 H), 7. 85 (s, 1H), 7.78-7.73 (m, 3H), 7.41 (d, J = l., 1H), 7.10- 7.05 (m, 5H), 6.84 (m, 1H), 2.36 (s, 6H) . Example 76 2-Chloro-3 (Z) acid. { 3-Hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3, 4-dimethylphenyl) -3 (Z) -indolylidene) methylaminophenyl) rhopenoic (Compound 176) This compound was prepared as it is described in Scheme VIII. XH MR (500 MHz, DMSO-de) 13.53 (s, 1H), 11.22 (d, J = 13.2, 1H), 10.72 (s, 1H), 9.08 (d, J = 13.2, 1H), 7.95 (d, J = 7.8, 1H), 7.87 (s, 1H), 7.8 (d, J "= 8.5, 1H), 7.75 (d, J = 1.8, 1H), 7.44 (m, 1H), 7.43 (dd, J" = 8.5, 1.8, 1H), 7.36 (d, J = 8.0, 1H), 7.28 (d, J = 2.1, 1H), 7.21 (dd, J = 8.0, 2.1, 1H), 6.92 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H). 2-ethyl-3 (E) acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2, 3- dihydro-1- (3, 4-dimethylphenyl) -3 (Z) -indolylidene) methylaminophenyl} propenoic (Compound 177) This compound was prepared as described in Scheme VIII. ¾ NMR (500 MHz, acetone-d6) 11.42 (d, J = 12.9, 1H), 9.53 (s, 1H), 8.93 (d, .7 = 12.9, 1H), 7.87 (d, J = 8.1, 1H) , 7.73 (d, J = 8.1, 1H), 7.59 (s, 1H), 7.38 (m, 1H), 7.36 (d, J = 8.1, 1H), 7.32 (d, J = 2.1, 1H), 7.25 ( dd, J = 8.1, 2.1, 1H), 7.22 (d, J = 1.7, 1H), 7.11 (dd, J = 8.1, 1.7, 1H), 7.06 (m, 1H), 2.59 (q, J = 7.4, 2H), 2.36 (s, 6H), 1.19 (t, J = 7.4, 3H). Example 78 2-ethyl-3 (E) acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) -indolylidene) methylaminophenyl-Jpropenoic (Compound 178) This compound was prepared as describes in the Scheme VIII. H NMR (500 MHz, acetone-d6) 11.42 (d, .7 = 12.8, 1H), 9.54 (s, 1H), 8.94 (d, J "= 12.8, 1H), 7.87 (d, J = 8.0, 1H ), 7.74 (d, .7 = 8.5, 1H), 7.59 (s, 1H), 7.38 (dq, J "= 8.0, 0.9, 1H), 7.22 (d, J = 1.7, 1H), 7.16 (m, 2H), 7.13 (m, 1H), 7.11 (dd, J = 8.5, 1.7, 1H), 7.08 (s, 1H), 2.59 (q, J = 7.4, 2H), 2.40 (m, 6H), 1.19 (t, J "= 7.4, 3H) Example 79 2-ethyl-3 (E) acid. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3 (Z) indolylidene) methylaminophenyl} propenoic (Compound 179) This compound was prepared as described in Scheme VIII. ? NMR (500 MHz, acetone-dg) 11.24 (d, J "= 12.3, 1H), 9.40 (br s, 1H), 8.71 (d, J "= 12.3, 1H), 7.70 (m, 1H), 7.67 (d, J = 8.4, 1H), 7.59 (s, 1H), 7.21 ( d, J = l .8, 1H), 7.14 (m, 2H), 7.11-7.02 (m, 4H), 6.90 (m, 1H), 2.60 (q, J = l .4, 2H), 2.39 (s, 6H), 1.19 (t, J = 7.4, 3H). 4- Acid. { 2-Hydroxy-3- (4 (Z) - (2- (3, 4-dimethylphenyl) -3-OXO-3, 4- dihydro-5-methyl) irazolidene) methylaminophenyl Jbutanoic (Compound 180) This compound was prepared as described in Scheme VIII. ¾ R (500 MHz, methanol-d4) 8.46 (s, 1H), 7.58 (s, 1H), 7.49 (d, J = 8.3, 1H), 7.43 (m, 1H), 7.14 (d, J = 8.3, 1H), 7.01-6.88 (m, 2H), 6.92 (t, J = l .3, 1H), 2.70 (t, J = 7.3, 2H), 2.35 (t, J = 7.3, 2H), 2.31 (s) , 3H), 2.29 (s, 3H), 2.25 (s, 3H), 1.87 (qn, 7 = 7.3, 2H). Example 81 Acid (Z) -4-. { l- (2,5-DIOXO-3- (3- (3,5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl Jbutanoic (Compound 181) This compound was prepared as described in Scheme VIII. ?? NMR (300 MHz, CDC13) 10.08 (d, J "= 12.8, 1H), 7.30 (dt, 7 = 12.8, 0.8, 1H), 7.06 (s, 3H), 7.03 (dd, .7 = 7.8, 1.8, 1H), 6.95 (t, J = 7.8, 1H), 6.89 (dd, 7 = 7.8, 1.8, 1H), 3.64 (t, J "= 6.8, 2H), 3.35 (d, 7 = 0.8, 2H), 2.40 (t, .7 = 7.4, 2H), 2.37 (s, 6H), 1.97 (m, 2H). Example 82 Acid (E) -4-. { 1- (2, 5-DIOXO-3- (3- (3, 5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) irolidolidin} butanoic (Compound 182) This compound was prepared as described in Scheme VIII. XH NMR (500 MHz, CDC13) 7.91 (dt, .7 = 13.8, 1.5, 1H), 7.13 (dd, J = 7.8, 1.6, 1H), 7.06 (s, 1H), 7.04 (s, 2H), 6.99 (t, J = 7.8, 1H), 6.90 (dd, J = 7.8, 1.6, 1H), 6.81 (d, J = 13.8, lH), 3.64 (t, J = 6.7, 2H), 3.23 (d, J) = 1.5, 2H), 2.39 (t, J = 7.3, 2H), 2.38 (s, 6H), 1.96 (m, 2H). Example 83 Acid (Z) -3-. { 1- (2,5-DIOXO-3- (3- (3, 5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl} benzoic (Compound 183) This compound was prepared as described in Scheme VIII. ?? NMR (300 MHz, acetone-de) 10.28 (d, J "= 12.8, 1H), 8.15 (m, 1H), 8.04 (ddd, J = 7.9, 1.7, 1.2, 1H), 7.90 (s, 1H), 7.82 (dt, J "= 12.8, 1.1, 1H), 7.72 (ddd, J = 7.9, 2.1, 1.2, 1H), 7.63 (t, J = 7.9, 1H), 7.34 (dd, J = 7.8, 1.5, 1H), 7.08 (m, 2R), 7.00 (m, 1H), 6.98 (t, J = l.8, 1H), 6.86 (dd, J "= 7.8, 1.5, 1H), 3.54 (d, J = 11, 2H), 2.33 (s, 3H), 2.33 (s, 3H) Example 84 Acid (E) -3-. { l- (2, 5-Dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) pyrrolidinyl J-benzoic acid (Compound 184) This compound was prepared as described in Scheme VIII. XH NMR (300 MHz, acetone-d6) 8.12 (m, 1H), 8.04 (dt, J = 7.8, 1.5, 1H), 7.98 (d, J = 13.6, 1.8, 1H), 7.84 (d, J = 13.6 , 1H), 7.69 (ddd, J = l.8, 2.0, 1.5, 1H), 7.63 (t, J = l.8, 1H), 7.33 (dd, J = l.8, 1.6, 1H), 7.09 (m, 2H), 7.01 (t, J = 7.8, 1H), 7.01 (m, 1H), 6.92 (dd, J = 7.8.1.6, 1H), 3.57 (d, J = l.8, 2H), 2.34 (m, 6H). Example 85 4- Acid. { 3- (4-Oxo-2-thioxo-5- (3- (3, 5-dimethylphenyl) -2-hydroxyphenyl) hydrozono) thiazolidinyl} butanoic (Compound 185) This compound was prepared as described in Scheme I. X H NMR (500 MHz, methanol-d 4) 8.51 (s, 1 H), 7.13-7.09 (m, 2 H), 7.02-6.89 (m, 3 H) ), 4.21 (m, 2H), 2.36 (s, 3H), 2.35 (s, 3H), 2.33 (m, 2H), 2.03 (m, 2H). Example 86 Acid 3-. { 2 - (3 (Z) - (1- (3,5-Dimethylphenyl) -6-chloro-2-oxo-2, 3-dihydroindolidene) methylamino) phenylamino} benzoic (Compound 186) This compound was prepared as described in Scheme VIII. ?? NMR (500 MHz, DMSO-d &) 10.96 (d, J = 13.0, 1H), 8.90 (d, J "= 13.0, 1H), 7.94 (m, 1H), 7.82 (m, 1H), 7.75 (d , J = 8.2, 1H), 7.34-7.28 (m, 2H), 7.27-7.24 (m, 2H), 7.24 (t, J = 7.8, 1H), 7.13 (td, J = 7.6, 1.2, 1H), 7.10 (dd, .7 = 8.2, 2. 0, 1H), 7.07 (m, 1H), 6.97 (m, 2H), 6.93 (m, 1H), 6.68 (d, J = 2.0, 1H), 2.32 (s, 6H). Example 87 Acid 3-. { 2- (3- (1- (3, 5-Dimethylphenyl) -6-trifluoromethyl-2-yl-2,3-dihydroindolidene) methylamino) phenylaminobenzoic acid (Compound 187) This compound was prepared as described in Scheme VIII . 1 H NMR (500 MHz, DMSO-d 6) 11.13 (d, J = 13.2, 1 H), 9.07 (d, J = 13.2, 1 H), 7.99 (s, 1 H), 7.95 (d, J = 8.0, 1 H), 7.88 (m, 1H), 7.42 (dd, J = 8.0, 1.0, 1H), 7.34 (td, J = 7.5, 1.1, 1H), 7.32-7.26 (m, 3H), 7.25 (t, J = 7.6, 1H), 7.17 (td, J "= 7.5, 1.1, 1H), 7.10 (m, 1H), 7.00 (m, 2H), 6.95 (m, 1H), 6.86 (d, J = 1.0, 1H), 2.33 (s, 6H).

Acid 3-. { 2- (4- (2- (3, 5-Dimethylphenyl) -5-methyl-3 -oxo-3,4-dihydropyrazolidene) methylamino) phenylamino} benzoic (Compound 188) This compound was prepared as described in Scheme VIII. XH NMR (500 MHz, DMSO-d6) 11.50 (d, J "= 12.0, 1H), 8.66 (d, J "= 12.0, 1H), 8.08 (s, 1H), 7.86 (m, 1H), 7.67 (d, .7 = 2.0, 1H), 7.62 (dd, J = 8.3, 2.0, 1H), 7.38-7.33 (m, 2H), 7. 32-7.29 (m, 2H), 7.30 (t, J = l .7, 1H), 7.23 (td, J = l .6, 1.3, 1H), 7.10 (d, J = 8.3, 1H), 7.02 (m, 1H), 2.28 (s, 3H), 2.21 (s, 3H), 2.18 (s, 3H). Example 89 Acid (±) -3-methyl-5-. { 2-hydroxy-3- (3 (Z) - (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylamino) phenyl} pentanoic (Compound 189) This compound was prepared as described in Scheme VIII. XR NMR (500 MHz, DMSO-d6) 11.29 (d, J = 13.4, 1H), 9.01 (d, J "= 13.4, 1H), 7.94 (d, J" = 8.0, 1H), 7.58 (dd, J = 8.0, 1.5, 1H), 7.41 (dq, J = 8.0, 0.7, 1H), 7.13 (m, 1H), 7.10 (m, 2H), 6.95-6.91 (m, 2H), 6.89 (dd, J " = 7.7.1.5, 1H), 2.71- 2. 58 (m, 2H), 2.37 (s, 6H), 2.31 (dd, J = 15.0, 5.5, 1H), 2.04 (dd, J = 15.0.5.5, 1H), 1.87 (m, 1H), 1.56 (m, 1H), 1.42 (m, 1H), 0.95 (d, J = 6.6, 3H).

Acid (±) -3-. { l- (6-Chloro-2-oxo-2,3-dihydro-3- (3 (Z) - (1- (3,5-dimethylphenyl) -2-oxo-2,3-dihydro) indolyl) aminomethylidene) indolil } benzoic (Compound 190) This compound was prepared as described in Scheme III. ?? NMR (500 MHz, DMSO-de) 13.20 (s, 1H), 7.93 (ddd, J = 7.8, 1.6, 1.1, 1H), 7.73 (m, 1H), 7.58 (t, J = 7.8, 1H), 7.35 (m, 1H), 7.30 (dd, J = l.8, 1.8, 1H), 7.23 (td, J = 7.7, 1.2, 1H), 7.14-7.08 (m, 4H), 7.00 (s, 2H), 6.89 (t, J = 7.7, 1H), 6.67 (d, 1 = 7.8, 1H), 6.63 (d, J = 2.0, 1H), 6.31 (m, 1H), 2.33 (S, 6H). Example 91 Acid 3-. { 4- (3-Hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) iridinyl} benzoic acid ( Compound 191) This compound was prepared as described in Scheme IX, U NMR (300 MHz, DMSO-d6) 8.52 (s, 1H), 8.16 (m, 1H), 7.98 (m, 1H), 7.96 (m, 1H), 7.60-7.52 (m, 214), 7.59 (t, .7 = 7.8, 1H), 7.20-7.16 (m, 3H), 6.98 (s, 1H), 2.50 (s, 3H), 2.37 (s) , 6H) Example 92 Acid 3-. { 4- (3-Hydroxy-6-methyl-2- (3 (Z) - (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) pyridinyl J-benzoic acid ( Compound 192) This compound was prepared as described in Scheme VIII. ¾ NMR (500 MHz, DMSO-dff) 9.06 (s, 1H), 8.55 (s, 1H), 8.20 (m, 1H), 7.99 (d, J = l .8, 1H), 7.93 (d, J = 7.8, 1H), 7.61 (s, 1H), 7.56 (t, J = l .8, 1H), 7.48 (d, 1 7.8, 1H), 7.13 (m, 1H), 7.11 (m, 2H), 6.94 (m, 1H), 2.50 (s, 3H), 2.37 (S, 6H), Example 93 Acid 3-. { 4- (3-Hydroxy-2- (3 (Z) - (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) pyridinyl} benzoic acid (Compound 193) This compound was prepared as described in Scheme VIII. ¾ NMR (500 MHz, DMS0-d6) 9.13 (d, J = 12.9, 1H), 8.52 (s, 1H), 8.24 (m, 1H), 8.17 (m, 1H), 8.03-7.99 (m, 2H) , 7.84 (m, 1H), 7.65 (t, J = 7.7, 1H), 7.50 (dq, J = l .9, 0.6, 1H), 7.14 (m, 1H), 7.12 (m, 2H), 6.95 ( q, .7 = 0.8, 1H), 2.37 (s, 6H). Example 94 Acid 3-. { 4- (3-Hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) iridinyl} benzoic acid (Compound 194) This compound was prepared as described in Scheme IX. ¾ MR (500 MHz, D SO-de) 13.22 (s, 1H), 8.50 (s, 1H), 8.21 (m, 1H), 8.16 (d, .7 = 7.7, 1H), 8.04 (d, J = 7.8, 1H), 8.01 (d, J = 7.7, 1H), 7.80 (d, J = 5.4, 1H), 7.68 (t, J = l .1, 1H), 7.60 (dq, J = 7.8, 0.7, 1H), 7.19 (m, 1H), 7.17 (m, 2H), 6.98 (m, 1H), 2.37 (s, 3H), 2.37 (s, 3H). Example 95 Acid 3-. { 5- (4-Hydroxy-3- (3 (Z) - (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) pyridinyl} benzoic acid (Compound 195) This compound was prepared as described in Scheme VIII. ?? NMR (500 MHz, DMSO-de) 11.10 (d, J "= 13.8, 1H), 8.95 (d, J = 13.8, 1H), 8.39 (t,, 7 = 1.7, 1H), 8.35 (d, J = 1.3, 1H), 810 (d, J = 1.3, 1H), 7.98 ( ddd,, 7 = 7.7, 1.7, 1.2, 1H), 7.88 (ddd, J = 7.7, 1.7, 1.2, 1H), 7.86 (d, .7 = 7.9, 1H), 7. 53 (t, J = 7.7, 1 H), 7.43 (dq, J = 1.9, 0.9, 1H), 7.12 (m, 1H), 7. 10 (m, 2H), 6.94 (m, 1H), 2.37 (s, 6H). Example 96 Acid 3-. { 5- (4-Hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) pyridinyl} benzoic acid (Compound 196) compound was prepared as described in Scheme IX. X H NMR (300 MHz, DMSO-de) 12.91 (s, 1 H), 8.39 (t, J = 1.7, 1 H), 8.17 (d, J = 1.4, 1 H), 8.06 (d, J = 1.4, 1 H) ), 7.99 (m, 1H), 7.94-7.86 (m, 2H), 7.53 (m, 1H), 7.53 (t, J = 7.7, 1H), 7.18-7.15 (m, 3H), 6.97 (m, 1H) ), 2.37 (s, 6H). Example 97 Acid 3-. { 5- (4-Hydroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4-dimethylphenyl) pyrazolyl) hydrazono) pyridinyl} benzoic acid (Compound 197) This compound was prepared as described in Scheme IX. ¾ MR (500 MHz, DMSO-d6) 13.43 (s, 1H), 12.99 (s, 1H), 12.33 (s, 1H), 8.40 (t, < J = 1.6, 1H), 8.16 (s, 1H) , 8.10 (s, 1H), 7.99 (m, 1H), 7.91 (m, 1H), 7.71 (m, 1H), 7.63 (d, J = 8.1, 1.9, 1H), 7.55 (t, J = 7.7, 1H), 7.21 (d, J "= 8.1, 1H), 2.31 (s, 3H), 2.27 (s, 3H), 2.23 (s, 314) Example 98 4- Acid. { 2- (3-Oxo-3,4-dihydro-5-methyl-4- (3- (3, 4-dimethylphenyl) phenyl) hydrozono) pyrazolyl} butanoic (Compound 198) This compound was prepared as described in Scheme I. XH NMR (300 MHz, CDC13) 13.45 (s, 1H), 7.58 (s, 1H), 7.47-7.31 (m, 4H), 7.26 ( s, 1H), 7.22 (d, J = l .7, 1H), 3.84 (t, J = 6.8, 2H), 2.42 (t, J = 6.8, 2H), 2.34 (s, 3H), 2.07 (qn , J = 6.8, 2H), 2.31 (s, 3H), 2.27 (s, 3H). Example 99 Acid 3-. { 2-Amino-5-methyl-3- (3 (Z) - (6-trifluoromethyl-2-yl) -2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylamino) phenyl} benzoic (Compound 199) This compound was prepared as described in Scheme VIII. XH NMR (500 MHz, DMSO-d &) 10.91 (d, .7 = 13.1, 1H), 8.94 (d, J = 13.1, 1H), 7.98-7.93 (m, 3H), 7.65 (m, 1H), 7.62 (t, J "= 7.6, 1H), 7.43-7.40 (m, 2H), 7.12 (m, 1H), 7.09 (m, 2H), 6.93 (d, J" = 1.4, 1H), 6.81 (m , 1H), 4.38 (br s, 2H), 2.36 (s, 6H), 2.33 (s, 3H).

Acid 3-. { 1- (5-Fluoro-2-oxo-2,3-dihydro-3 (Z) - (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 200) This compound was prepared as described in Scheme III. ¾ NMR (500 MHz, DMSO-d6) 13.23 (s, 1H), 10.85 (d, J = 12.8, 1H), 8.96 (d, J = 12.8, 1H), 8.06 (m, 1H), 7.99 (m, 1H), 7.82-7.78 (m, 2H), 7.74-7.69 (m, 2H), 7.56 (s, 1H), 7.5 1-7.39 (m, 4H), 7.26 (d, J = 7.8, 1H), 6.94 -6.86 (m, 2H), 2.32 (s, 3H), 2.28 (s, 3H). Example 101 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4 (Z) - (3- (3,4-dlH-ethylphenyl) phenyl) aminomethylidene) irazolyl} butanoic (Compound 201) This compound was prepared as described in Scheme VIII. X H N R (300 Hz, methanol-d 4) 8.52 (s, 1 H), 7.63 (s, 1 H), 7.49-7.43 (m, 2 H), 7.41-7.30 (m, 2 H), 7.23-7.09 (m, 2H), 3.80 (t, J = 6.8, 2H), 2.34 (s, 3H), 2.30 (s, 3H), 2.28 (m, 2H), 2.26 (s, 3H), 2.01 (qn, J = 6.8, 2H). Example 102 Acid (3- (5-Fluoro-2-hydroxy-3- (3 (Z) - (6-trifluoromethyl-2-yl) -2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylamino ) -1-pyrazolyl) acetic acid (Compound 202) This compound was prepared as described in Scheme VIII.XH NMR (500 MHz, DMS0-d5) 13.26 (s, 1H), 11.35 (s, 1H), 11.26 (d, J = 13.0, 1H), 9.06 (d, J "= 13.0, 1H), 7.97 (d, J = 2.4, 1H), 7.93 (d, J = 7.9, 1H), 7.71 (dd, J = 10.3, 2.8, 1H), 7.46 (dq, J = 7.9, 0.9, 1H), 7.42 (dd, J "= 9.5, 2.8, 1H), 7. 36 (d, J = 8.0, 1H), 7.29 (d, J = 2.1, 1H), 7.22 (dd, J = 8.0, 2.1, 1H), 7.03 (d, J = 2.4, 1H), 6.94 (m, 1H), 5.15 (s, 2H), 2. 32 (s, 3H), 2.31 (s, 3H). Example 103 Acid (3- (5-Fluoro-2-hydroxy-3- (3 (Z) - (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) -1-pyrazolyl) acetic (Compound 203) This compound was prepared as described in Scheme VIII. U NMR (500 MHz, DMSO-d6) 13.26 (s, 1H), 11.30 (s, 1H), 11.13 (d, .7 = 12.7, 1H), 8.83 (d, .7 = 12.7, 1H), 7.96 (d, J = 2.4, 1H), 7.75 (m, 1H), 7.66 ( dd, J = 10.4, 2.8, 1H), 7.35 (dd, J = 9.6, 2.8, 1H), 7.11-7.07 (m, 5H), 7.01 (d, J = 2.4, 1H), 6. 87 (m, 1H), 5.14 (s, 2H), 2.36 (s, 6H). Example 104 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 204) This compound was prepared as described in the Scheme VIII. ¾ NMR (300 MHz, methanol-d4) 8.47 (s, 1H), 7.42 (m, 1H), 7.28-7.14 (m, 5H), 6.94-6.85 (m, 2H), 3.81 (t, • 7 = 6.7 , 2H), 3.02-2.84 (m, 4H), 2.32 (t, J = 7.6, 2H), 2.26 (s, 3H), 2.00 (m, 2H). Example 105 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 205) This compound was prepared as described in Scheme VII. ¾ NMR (300 MHz, methanol-d4) 7.54 (m, 1H), 7.28- 7. 12 (m, 5H), 6.92-6.84 (m, 2H), 3.79 (t, .7 = 6.8, 2H), 3.00-2.84 (m, 4H), 2.34 (t, J = 7.4, 2H), 2.26 ( s, 3H), 2.01 (m, 2H). Example 106 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 206) This compound was prepared as described in Scheme VII. 1 H NMR (300 MHz, methanol-d 4) 7.53 (m, 1 H), 7.11-7.03 (m, 4 H), 6.91-6.86 (m, 2 H), 3.79 (t, J = 6.6, 2 H), 2.93 (m, 2H), 2.85 (m, 2H), 2.34 (t, J = 7.3, 2H), 2.28 (s, 3H), 2.26 (s, 3H), 2.01 (m, 2H). Example 107 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanico (Compound 207) This compound was prepared as described in Scheme VII. X H NMR (300 MHz, methanol-d 4) 7.53 (m, 1 H), 7.12 (m, 1 H), 7.04-6.87 (m, 5 H), 3 79 (t, J = 6.6, 2 H), 2.98-2.82 (m , 4H), 2.34 (t, J = l .3, 2H), 2.29 (s, 3H), 2.26 (s, 3H), 2.01 (m, 2H). Example 108 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 208) This compound was prepared as described in Scheme VII. ¾ NMR (300 MHz, methanol-d4) 7.54 (m, 1H), 7.16-7.04 (m, 4H), 6.93-6.84 (m, 2H), 3.80 (t, J = 6.7, 2H), 2.90 (m, 4H), 2.34 (t, J = 7.3, 2H), 2.28 (s, 3H), 2.26 (s, 3H), 2.01 (m, 2H). Example 109 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (1-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 209) This compound was prepared as described in Scheme VII. ¾ NMR (300 MHz, methanol-d4) 8.17 (d, .7 = 7.9, 1H), 7.86 (d, J = 7.9, 1H), 7.71 (d, 7 = 7.9, 1H), 7.57-7.43 (m, 3H), 7.36 (m, 1H), 7.31 (m, 1H), 6.91-6.86 (m, 2H), 3.80 (t, 7 = 6.6, 2H), 3.37 (dd, J "= 9.2, 6.5, 2H) , 3.09 (dd, 7 = 9.2, 6.5, 2H), 2.35 (t, .7 = 7.3, 2H), 2.27 (s, 3H), 2.02 (m, 2H) Example 110 Acid 3-. { 1- (5-Nitro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 210) This compound was prepared as described in Scheme III. H NMR (500 MHz, DMSO-d 13.28 (s, 1H), 11.26 (d, J = 13.4, 1H), 9.29 (d, J = 13.4, 1H), 9.26 (s, 1H), 8.82 (d, J = 2.4, 1H), 8.06-8.03 (m, 2H), 8.02 (dd, J = 8.8, 2.4, 1H), 7.82 (ddd, J = 8.1, 2.1, 1.3, 1H), 7.79 (m, 1H), 7.75 (t, J = 8.1, 1H), 7.14 (m, 2H), 7.09 (t, J = 7.7, 1H), 7.06 (d, J = 8.8, 1H), 7.01 (dd, J = 7.7, 1.5, 1H), 7.01 (m, 1H), 2.33 (s, 6H) Example 111 Acid 3-. { 1- (5-Nitro-2-oxo-2,3-dihydro-3 (Z) - (5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic acid (Compound 211) This compound was prepared as described in Scheme III. ?? NMR (300 MHz, acetone-d6) 11.43 (d, J = 13.3, 1H), 9.15 (d, J = 13.3, 1H), 8.67 (d, J = 2.3, 1H), 8.24 (t, .7 = 1.7, 1H), 8.15 (m, 1H), 8.08 (dd, J = 8.8, 2.3, 1H), 7.88 (m, 1H), 7.78 (t, .7 = 7.8, 1H), 7.66 (dd, J = 10.0, 2.9, 1H), 7.14 (m, 2H), 7.14 (d, J = 8.8, 1H), 7.04 (m, 1H), 6.78 (dd, J = 9.2, 2. 9, 1H), 2.34 (s, 6H). Example 112 2-hydroxy-3- acid. { 3 (Z) - (2 -oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminobenzoic acid (Compound 212) [03101] This compound was prepared as described in Scheme VIII. ¾ NMR (500 MHz, DMSO-dff) 11.02 (d, .7 = 12.8, 1H), 8.84 (d, .7 = 12.8, 1H), 7.96 (dd, J = 8.1, 1.5, 1H), 7.74 (m , 1H), 7.52 (dd, J = 8.1, 1.5, 1H), 7.10-7.06 (m, 5H), 7.04 (t, J = 8.1, 1H), 6.85 (m, 1H), 2.36 (s, 3H) , 2.36 (s, 3H). Example 113 2-hydroxy-3- acid. { 3 (Z) - (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) benzoic acid (Compound 213) This compound was prepared as described in Scheme VIII. H NMR (500 MHz, DMS0-d5) 11.18 (d, J = 12.9, 1H), 9.07 (d, J = 12.9, 1H), 8.00 (dd, J = 8.0, 1.4, 1H), 7.93 (d, J = 7.8, 1H), 7.57 (dd, .7 = 8.0, 1.4, 1H), 7.44 (dq, J = 7.8, 0.9, 1H), 7.36 (d, J = 8.1, 1H), 7.28 (d,. 7 = 2.1, 1H), 7.21 (dd, J = 8.1, 2.1, 1H), 7.06 (t, J = 8.0, 1H), 6.92 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H) ). Example 114 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3-methyl-1 (Z) butenyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 214) This compound was prepared as described in Scheme VIII. XU R (300 MHz, methanol-d4) 8.49 (s, 1H), 7.49 (d, J = 7.6, 1H), 7.02-6.90 (m, 2H), 6.30 (d, J = ll.l, 1H), 5.65 (dd, J = ll.l, 10.3, 1H), 3.80 (t, J = 6.7, 2H), 2.66 (m, 1H), 2.31 (t, J = 7.5, 2H), 2.27 (s, 3H) , 2.00 (m, 2H), 1.01 (d, J = 6.7, 6H). Example 115 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3-heptanylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 215) This compound was prepared as described in Scheme VII. XH NMR (300 MHz, methanol-d4) 7.53 (dd, J = 7.6, 1.5, 1H), 6.97 (dd, J = 7.6, 1.5, 1H), 6.91 (t, J = 7.6, 1H), 3.79 (t , J "= 6.7, 2H), 2.65 (t, .7 = 7.7, 2H), 2.34 (t, J = 7.3, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 1.60 (ra, 2H), 1.42-1.27 (m, 8H), 0.90 (t, J = 6.8, 3H) Example 116 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3 (Z) - (2- (4-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl} butanico (Compound 216) This compound was prepared as described in Scheme VII. ¾ NMR (300 MHz, methanol-d ^) 7.60 (d, J "= 7.9, 1H), 7.50-7.41 (m, 4H), 7.21-7.08 (m, 3H), 7.01 (t, .7 = 7.9, 1H), 3.79 (t, J = 6.6, 2H), 2.34 (s, 3H), 2.34 (t, d = 7.3, 2H), 2. 27 (s, 3H), 2.01 (m, 2H). Example 117 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3 (Z) - (2- (3-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 217) This compound was prepared as described in Scheme VII. XH NMR (300 Hz, methanol-d4) 7.59 (d, J = 1.8, 1H), 7.09-6.95 (m, 4H), 6.88 (d, J = 1.8, 1H), 6.79 (t, J) = l .8, 1H), 6.73 (d, J = 12.2, 1H), 6.59 (d, J- = 12.2, 1H), 3.79 (t, J = 6.7, 2H), 2.34 (t, J = 7.3, 2H), 2.27 (s, 3H), 2.20 (s, 3H), 2.01 (m, 2H). Example 118 4- Acid. { l- (2-0x0-2, 3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl Jbutanoic (Compound 218) This compound was prepared as described in Scheme VII. 1?? NMR (500 MHz, DMS0-de) 13.04 (s, 1H), 9.13 (br s, 1H), 7.61 (dd, J = 7.7, 0.7, 1H), 7.51 (dd, J = 7.7, 1.6, 1H), 7.33 (td, J = 7.7, 1.2, 1H), 7.23 (m, 1H), 7.20 (d, J = 7.7, 1H), 7.16-7.07 (m, 4H), 6.91 (t, J 7.7, 1H), 6.83 (dd, J = 7.7, 1.5, 1H), 3.84 (t, J = 7.1.2H), 2.89-2.79 (m, 4H), 2.32 (t, J = 7.1, 2H), 2.29 (s) , 3H), 1.88 (qn, J = 7.1, 2H). Example 119 Acid 2-. { 1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) hydrazone) indolyl} acetic (Compound 219) This compound was prepared as described in Scheme II. 1 H NMR (500 MHz, methanol-d 4) 7.66 (dd, J = 1.7, 1.6, 1H), 7.65 (m, 1H), 7.27 (td, J = 7.7, 1.1, 1H), 7.14-7.10 (m , 3H), 7.01 (m, 1H), 6.99 (t, J = 7.7, 1H), 6.95 (d, J = l .1, 1H), 6.89 (dd, J = l .1, 1.6, 1H), 4.55 (s, 2H), 2.36 (s, 6H). Example 120 Acid 2-. { l- (2-0x0-2, 3-dihydro-3- (2-hydroxy-3- (2- (2- methyl) phenyl) ethylphenyl) hydrazone) indolyl} acetic (Compound 220) This compound was prepared as described in Scheme VII. ?? NR (500 MHz, SO-de) 12.95 (s, 1H), 9.16 (s, 1H), 7.62 (dd, J = 7.6, LO, 1H), 7.53 (dd, J = l .1, 1.6, 1H ), 7.30 (td, J = 7.6, 1.2, 1H), 7.23 (m, 1H), 7.16-7.07 (m, 5H), 6.91 (t, .7 = 7.7, 1H), 6.84 (dd, J = l .7, 1.6, 1H), 4.59 (s, 2H), 2.89-2.79 (m, 4H), 2.29 (s, 3H). Example 121 4- Acid. { 4- (2- (3 (Z) - (6-Trifluoromethyl-2-oxo-2,3-dihydro-1- (3, 4-dimethylphenyl) indolylidene) methylamino) thiazolyl} benzoic acid (Compound 221) This compound was prepared as described in Scheme VIII.XH NMR (500 MHz, DMSO-d6) 12.99 (s, 2H), 11.83 (d, J "= 12.2, 1H), 11.39 (d, J = 12.2, 1H) 8.95 (d, J = 12.2, 1H), 8.56 (d, J = 12.2, 1H), 8.32 (d, .7 = 7.8, 1H), 8.16 (d, J = 8.5, 2H), 8.08 (d, J " = 8.5, 2H), 8.08 (m, 1H), 8.03 (d, J = 8.5, 2H), 8.02 (d, J = 8.5, 2H), 7.93 (s, 1H), 7.91 (s, 1H), 7.51 (d, J = 7.8, 1 H), 7.44 (dq, J = 7.8, 0.9, 1H), 7.37 (d, J = 7.9, 1H), 7.36 (d, J = 7.9, 1H), 7.30 (d, J = 2.1, 1H), 7.24 (d, J = 2.1, 1H), 7.23 (dd, J = 7.9, 2.1, 1H), 7.18 (dd, J = 1.9, 2.1, 1H), 6. 91 (m, 1H), 6.85 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 2.31 (s, 3H), 2.30 (s, 3H). Example 122 Acid 3-. { 1- (5-Nitro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-5-methyl-3- (1-adamantano) phenyl) aminomethylidene) indolyl} benzoic (Compound 222) This compound was prepared as described in Scheme III. ?? NMR (500 MHz, DMSO-d6) 13.28 (s, 1H), 11.22 (d, .7 = 13.7, 1H), 9.19 (d, J = 13.7, 1H), 8.81 (d, J "= 2.4, 1H) , 8.40 (s, 1H), 8.09-8.04 (m, 2H), 8.01 (dd, J = 8.8, 2.4, 1H), 7.83-7.73 (m, 2H), 7.50 (d, J = 1.5, 1H), 7.07 (d, J "= 8.8, 1H), 6.79 (d, J = 1.5, 1H), 2.33 (s, 3H), 2.09-2.06 (m, 6H), 2.05-2.02 (m, 3H), 1.75- 1.72 (m, 6H). Example 123 Acid 3-. { 1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (4-hydroxy-5- (3,4-dimethylphenyl) iridinyl) hydrazono) indolyl} Benzoic (Compound 223) This compound was prepared as described in Scheme I. E NMR (500 MHz, methanol-d4) 8.25 (s, 1H), 8.11 (dt, "7 = 7.7, 1.6, 1H), 8.07 (t," 7 = 1.6, 1H), 7.90 (d, "7 = 7.8, 1H), 7.82 (m, 1H), 7.66 (t," 7 = 7.7, 1H), 7.62 (m, 1H), 7.48 (m, 1H), 7.42 (m, 1H), 7.34 ( m, 1H), 7.17 (d, "7 = 7.8. 1H), 7.08 (brs, 1H), 2.30 (s, 3H), 2.28 (s, 3H). Example 124 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 224) This compound was prepared as described in Scheme VIII. XE NMR (300 MHz, methanol-d 8.47 (s, 1H), 7.43 (m, 1H), 7.15-7.03 (m, 4H), 6.93-6.86 (m, 2H), 3.81 (t, "7 = 6.8, 2H), 2.90 (m, 4H), 2.32 (t, "7 = 7.4, 2H), 2.27 (s, 3H), 2.26 (s, 3H), 2.00 (m, 2H) Example 125 4- (2- (5-Ethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluoro) phenyl) -ethylphenyl) aminomethylidene) irazolyl acid} butanoic (Compound 225) This compound was prepared as described in Scheme VIII.H NMR (300 MHz, methanol-d4) 8.47 (s, 1H), 7.43 (m, 1H), 7.23-7.14 (m, 2H ), 7.07-6.97 (m, 2H), 6.90-6.85 (m, 2H), 3.81 (t, .7 = 6.8, 2H), 2.96 (m, 4H), 2.32 (t, J = 7.3, 2H), 2.26 (s, 3H), 2.00 (m, 2H) Example 126 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (1-naphthyl) ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic acid (Compound 226) This compound was prepared as described in Scheme VIII. 2 H NMR (500 MHz, DMSO) 8.48 (s, 1 H), 8.17 (d, J = 8.6 Hz, 1 H), 7.85 (d, J 7.4 Hz, 1 H), 7.71 (d, J = 1.4 Hz, 1H), 7.55-7.28 (m, 5H), 6.91-6.88 (m, 2H), 3.82 (t, J = 6.7 Hz, 2H), 3.37 (dd, J = 9.3, 6.4 Hz, 2H), 3.10 (dd) , J = 9.3, 6.4 Hz, 2H), 2.33 (t, J = 7.5 Hz, 2H), 2.27 (s, 3H), 2.01 (m, 2H). 4- Acid. { 2- (5-ethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 227) This compound was prepared as described in Scheme VIII. ¾ NMR (300MHz, CD3OD) 8.47 (br s, 1H), 7.42 (m, 1H), 6.94-6.88 (m, 2H), 6.82-6.79 (m, 3H), 3.80 (t, J = 6.7 Hz, 2H ), 2.92 (m, 2H), 2.79 (m, 2H), 2.32 (t, .7 = 7.5 Hz, 2H), 2.26 (s, 3H), 2.24 (s, 6H), 2.00 (m, 2H). Example 128 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2-methoxyphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 228) This compound was prepared as described in Scheme VIII. ? NMR (300MHz, CD3OD) 8.47 (s, 1H), 7.41 (m, 1H), 7.24-7.04 (m, 3H), 6.94-6.78 (m, 4H), 3.82 (s, 3H), 3.81 (m, 2H) ), 2.89 (s, 4H), 2.36-2.24 (m, 5H), 2.01 (m, 2H). Example 129 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- ((2-fluoro-3-methylphenyl) ethyl) phenyl) aminomethylidene) pyrazolyl butanoic (Compound 229 ) This compound was prepared as described in Scheme VIII. ¾ NMR (300MHz, CD30D) 7.47-7.30 (m, 1H), 7.07-6.85 (m, 6H), 3.82 (m, 2H), 2.98-2.88 (m, 4H), 2.30-2.20 (m, 8H), 2.00 (m, 2H). Example 130 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl } butanoic (Compound 230) This compound was prepared as described in Scheme VIII. XH MR (300MHz, CD3OD) 8.45 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.56-7.32 (m, 4H), 7.16 (m, 1H), 6.91 (s, 2H), 3.81 (t, J = 6.5 Hz, 2H), 3.12-2.93 (m, 4H), 2.29 (t, .7 = 7.4 Hz, 2H), 2.25 (m, 3H), 2.00 (m, 2H). Example 131 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 231) This compound was prepared as described in Scheme VIII. XH NMR (300MHz, CD3OD) 7.59-7.56 (m, 3H), 7.51 (d, J = 7.8 Hz, 2H), 7.46-7.37 (m, 4H), 7.33-7.26 (m, 4H), 6. 95-6.91 (m, 2H), 3.81 (t, J = 6.5 Hz, 2H), 3.04-2.92 (m, 4H), 2. 32 (t, J "= 7.7 Hz, 2H), 2.27 (s, 3H), 2.02 (m, 2H) Example 132 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-cyanophenyl) -ethyl) phenyl) aminotnetylidene) pyrazolyl Jbutanoic (Compound 232) This compound was prepared as described in Scheme VIII. XH NR (300MHz, CD3OD) 8.45 (s, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.48-7.32 (m, 3H), 6.92-6.8 1 (m, 2H), 3.80 (t, J = 6.7 Hz, 2H), 3.13 (m, 2H), 3.05 (m, 2H), 2.30 (m, 2H), 2.26 (s, 3H), 2.01 (m , 2H). Example 133 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 233) This compound was prepared as described in Scheme VIII. XH NMR (300MHz, CD3OD) 8.47 (s, 1H), 7.43 (m, 1H), 7.35 (m, 1H), 7.24-7.14 (m, 3H), 6.93-6.85 (m, 2H), 3.81 (t J = 6.7 Hz, 2H), 3.08-2.94 (m, 4H), 2.32 (t,, 7 = 7.5 Hz, 2H), 2. 26 (s, 3H), 2.00 (m, 2H). Example 134 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) aminomethylidene) irazolyl} butanoic (Compound 234) This compound was prepared as described in Scheme VIII. XH NMR (300MHz, CD30D) 8.48 (s, 1H), 7.45 (m, 1H), 6.98-6.87 (m, 5H), 3.81 (t, J = 6.9 Hz, 2H), 2.93 (m, 2H), 2.83 (m, 2H), 2.32 (t, J = 7.1 Hz, 2H), 2.29 (s, 6H), 2.27 (s, 3H), 2.00 (m, 2H) Example 135 Acid 3-. { 2- (5-Trifluoromethyl-3-oxo-3, 4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 235) This compound was prepared as described in Scheme VIII. XH NMR (300MHz, DMSO) 8.81 (s, 1H), 8.66 (dd, • 7 = 2.2, 1.5Hz, 1H), 8.24 (ddd, J = 8.2, 2.2, 1.1 Hz, 1H), 7.84 (ddd, J = 7.7, 1.5, 1.1 Hz, 1H), 7.78 (dd, J = Q .0, 1.6Hz, 1H), 7.70 (m, 1H), 7.66-759 (m, 3H), 7.44 (m, 1H), 7.03 (dd, J = 7.7, 1.6 Hz, 1H), 6.97 ( dd, J = 8.0, 7.7 Hz, 1H), 3.05-2.93 (m, 4H). Example 136 Acid 3 -. { 2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 236) This compound was prepared as described in Scheme VIII. XH NR (300MHz, DMSO) 9.84 (s, 1H), 8.79 (s, 1H), 8.65 (dd, J = 2.2, 1.6 Hz, 1H), 8.23 (ddd, J = 8.2, 2.2, 1.1 Hz, 1H) , 7.84 (ddd, J = 1.8, 1.6, 1.1 Hz, 1H), 7.75 (m, 1H), 7.62 (dd, J = 8.2, 7.8 Hz, 1H), 7.33 (m, 1H), 7.25 (m , 1H), 7.18-7.09 (m, 2H), 7.01 (dd, .7 = 7.8, 1.5 Hz, 1H), 6.93 (t, .7 = 7.8 Hz, 1H), 3.00-2.85 (m, 4H). Example 137 Acid 3-. { 2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 237) This compound was prepared as described in Scheme VIII. ¾ NR (300MHz, DMSO) 9.80 (s, 1H), 8.80 (m, 1H), 8.65 (dd, J = 2.2, 1.5 Hz, 1H), 8.23 (ddd, J = 8.2, 2.2, 1.1 Hz, 1H) , 7.84 (ddd,, 7 = 7.8, 1.5, 1.1 Hz, 1H), 7.77 (m, 1H), 7.63 (dd, J = 8.2, 7.8 Hz, 1H), 7.22 (m, 1H), 7.17-7.05 ( m, 4H), 6.96 (t, J = 7.8 Hz, 1H), 2.90 (m, 2H), 2.82 (m, 2H), 2.29 (s, 3H). Example 138 Acid 3-. { 2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,5-dimethyl-phenyl) ethyl) phenyl) aminoniethylidene) pyrazoyl} Benzoic (Compound 238) This compound was prepared as described in Scheme VIII. XH NMR (300MHz, CD3OD) 8.65 (dd, J = 2.2, 1.6 Hz, 1H), 8.60 (s, 1H), 8.23 (ddd, J "= 8.1, 2.2, 1.0 Hz, 1H), 7.92 (ddd,. 7 = 7.8, 1.6, 1.0 Hz, 1H), 7.56 (dd, J = 8.1, 7.8 Hz, 1H), 7.47 (m, 1H), 7.00-6.86 (m, 5H), 2.93 (m, 2H), 2.85 (m, 2H), 2.25 (s, 3H), 2.24 (s, 3H) Example 139 Acid 3-. { 2- (5-Trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} Benzoic (Compound 239) This compound was prepared as described in Scheme VIII. ¾ NMR (300MHz, CD3OD) 8.66 (dd, J = 2.1, 1.6 Hz, 1H), 8.60 (s, 1H), 8.25 (ddd, J = 8.1, 2.1, 1.0 Hz, 1H), 7.92 (ddd, J = 7.7, 1.6, 1.0 Hz, 1H), 7.57 (dd, J "= 8.1, 7.7 Hz, 1H), 7.48 (m, 1H), 6.99-6.94 (m, 5H), 2.95 (m, 2H), 2.85 ( m, 2H), 2.31 (s, 6H) Example 140 Acid 3-. { 2- (5-Phenyl-3-oxo-3f 4-dihydro- (Z) - (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) irazolyl} benzoic (Compound 240) This compound was prepared as described in Scheme VIII. XH NMR (300MHz, DMSO) 8.79 (dd, J = 2.1, 1.6 Hz, 1H), 8.69 (br s, 1H), 8.36 (ddd, J "= 8.2, 2.1, 1.1 Hz, 1H), 7.94-7.89 ( m, 2H), 7.78 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.67-7.51 (m, 5H), 7.08-7.00 (m, 3H), 6.96-6.88 (m, 2H), 2.87 ( m, 2H), 2.77 (m, 2H), 2.25 (s, 6H) Example 141 Acid 3-. { 2- (5-tert-Butyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2 - (2,5-dimethylphenyl) ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 241) This compound was prepared as described in Scheme VIII. ? NMR (300MHz, CD3OD) 8.65 (dd, J = 2.1, 1.7 Hz, 1H), 8.58 (s, 1H), 8.25 (m, 1H), 7.83 (m, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.36 (m, 1H), 6.99-6.84 (m, 5H) ), 2.95-2.80 (m, 4H), 2.24 (s, 3H), 2.23 (s, 3H), 1.47 (s, 9H). Example 142 TO Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2-methylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoi (Compound 242) This compound was prepared as described in Scheme VIII. XH NMR (500MHz, DMSO) 11.86 (d, J = 13.6 Hz, 1H), 9.50 (br s, 1H), 8.71 (d, J 13.6 Hz, 1H), 8.66 (dd, J = 2.1, 1.6 Hz, 1H), 8.26 (ddd, J = 8.1, 2.1, 1.1 Hz, 1H ), 7.71 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.64 (dd, J = 8.0, 1.5 Hz, 1H), 7. 53 (dd, J = 8.1, 7.7 Hz, 1H), 7.22 (m, 1H), 7.16-7.07 (m, 3H), 6. 98 (dd, J = 7.6, 1.5 Hz, 1H), 6.94 (m, 1H), 2.88 (m, 2H), 2.82 (m, 2H), 2.32 (s, 3H), 2.29 (s, 3H). Example 143 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluoro-phenyl) -ethyl) -phenyl) -hydrazono)-Irazolyl-Jbutanico (Compound 243) This compound was prepared as described in Scheme VII. ¾ R (300MHz, CD3OD) 7.53 (m, 1H), 7.23-7.15 (m, 2H), 7.07-6.97 (m, 2H), 6.91-6.83 (m, 2H), 3.79 (t, J = 6.6 Hz, 2H), 2.95 (s, 4H), 2.34 (t, J = 1. 3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H). Example 144 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 244) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD30D) 7.54 (ra, 1H), 6.93-6.88 (m, 2H), 6.83-6.79 (m, 3H), 3.79 (t, J = 6.6 Hz, 2H), 2.92 (m, 2H) , 2.80 (m, 2H), 2.34 (t, J = 1. 4 Hz, 2H), 2.26 (s, 3H), 2.25 (s, 6H), 2.01 (m, 2H). Example 145 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic compound (Compound 245) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.6 1-7.49 (m, 5H), 7.41 (t, J = 7.4 Hz, 2H), 7.33-7.26 (m, 3H), 6.96-6.87 (m, 2H), 3.80 (t , .7 = 6.7 Hz, 2H), 3.02-2.94 (m, 4H), 2.33 (t, J = 7.4 Hz, 2H), 2. 26 (s, 3H), 2.01 (m, 2H). 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 246) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.51 (m, 1H), 7.19-7.04 (m, 2H), 6.93-6.78 (m, 4H), 3.82 (s, 3H), 3.79 (t, J = 6.8 Hz, 2H), 2.88 (s, 4?), 2.34 (t, J = 1. 5 Hz, 2H), 2.25 (s, 3H), (m, 2H). Example 147 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4 - (2-hydroxy-3 - (2- (2-fluoro-3-methylphenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanico (Compound 247) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.52 (m, 1H), 7.22-6.83 (m, 5H), 3.79 (t, J = 6.7 Hz, 2H), 2.92 (s, 4H), 2.34 (t, J = 7.5 Hz , 2H), 2.26-2.22 (m, 6H), 2.01 (qn, J = 7.0 Hz, 2H).

Example 148 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro- - (2-hydroxy-3- (2- (2-trifluoromethyl-phenyl) -ethyl) -phenyl) -hydrazono) -pyrazolyl} butanoic (Compound 248) This compound was prepared as described in Scheme VII. XH NR (300MHz, CD3OD) 7.65 (d, J = 1.6 Hz, 1H), 7. 58-7.47 (m, 2H), 7.44-7.32 (m, 2H), 6.96-6.86 (m, 2H), 3.79 (t, J = 6.6 Hz, 2H), 3.07 (m, 2H), 2.97 (m, 2H), 2.35 (t, J = l .5 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H). Example 149 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyanophenyl) ethyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 249) This compound was prepared as described in Scheme VII. 1H NMR (300MHz, DMSO) 9.60 (s, 1H), 7.78 (d, J = 7.5 Hz, 1H), 7.64 (t, J 7.5 Hz, 1H), 7.53-7.47 (m, 2H), 7. 41 (t, J = 7.5 Hz, 1H), 6.95-6.84 (m, 2H), 3.69 (t, J = 6.6 Hz, 2H), 3.05 (m, 2H), 2.99 (m, 2H), 2.26 (t, J = 7.0 Hz, 2H), 2.20 (s, 3H), 1.86 (m, 2H). Example 150 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (2-chlorophenyl) ethyl) -phenyl) hydrazono) irazolyl Jbutanoic (Compound 250) This compound is prepared as described in the Scheme VII. XH NR (300MHz, CD3OD) 7.53 (m, 1H), 7.35 (m, 1H), 7.24-7.14 (m, 3H), 6.92-6.83 (m, 2H), 3.79 (t, .7 = 6.7 Hz, 2H ), 3.08-2.92 (m, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H). Example 151 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 251) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.54 (d, J = 1.6 Hz, 1H), 6.97-6.85 (m, 5H), 3.79 (t, J 6.7 Hz, 2H), 2.93 (m, 2H), 2.82 ( m, 2H), 2.34 (t, J = 1. 4 Hz, 2H), 2.30 (s, 6H), 2.26 (s, 3H), 2.01 (m, 2H). Example 152 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) irazolyl Jbutanico (Compound 252) [0351] This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.54 (m, 1H), 7.19-7.06 (m, 4H), 6.93-6.86 (m, 2H), 3.79 (t, J = 6.7 Hz, 2H), 2.92 (s, 4H), 2.66 (q, J "= 7.5 Hz, 2H), 2.34 (t, J = 1. 3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 1.19 (t, J = 1.5 Hz, 3H) Example 153 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 253) This compound was prepared as described in Scheme VII. XH NMR (300MHz, DMSO) 13.60 (s, 1H), 12.07 1H), 9.43 (s, 1H), 7.50-7.43 (m, 3H), 7.27 (m, 1H), 6.91 1H), 6.83 (m, 1H), 3.69 (t, J = 6.7 Hz, 2H), 3.15 (m, 2H), 2.89 (m, 2H), 2.25 (t, J = 7.6 Hz, 2H), 2.20 ( s, 3H), 1.85 (m, 2H).

Example 154 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 254) This compound was prepared as described in Scheme VII. ?? MR (300MHz, CD3OD) 7.54 (m, 1H), 7.00 (m, 2H), 6.92-6.85 (m, 3H), 3.79 (t, .7 = 6.7 Hz, 2H), 2.93 (m, 4H), 2.34 (t, J = 1. 4 Hz, 2H), 2.26 (s, 3H), 2.24 (s, 2.22 (s, 3H), 2.01 (m, 2H) Example 155 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-6-trifluoromethylphenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 255) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.56 (m, 1H), 7.52 (m, 1H), 7.47-7.31 (m, 2H), 6.96-6.87 (m, 2H), 3.80 (t, J = 6.7 Hz, 2H) , 3.11 (m, 2H), 2.95 (m, 2H), 2.34 (t, J = 1. 4 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H). Example 156 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 256) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD30D) 7.55 (dd, J = 7.9, 1.5 Hz, 1H), 7.24-720 (m, 2H), 7.16-7.12 (m, 2H), 7.06 (dd, J = 7.9, 1.5 Hz, 1H), 6.92 (t, J = 1.9 Hz, 1H), 401 (m, 1H), 3.80 (t, J "= 6.7 Hz, 2H), 3.35 (dd, J" = 15.3, 8.2 Hz, 2H ), 3.02 (dd, J = 15.3, 7.6 Hz, 2H), 2.34 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H). Example 157 4- Acid. { 2- . { 5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) irazolyl Jbutanóico (Compound 257) This compound was prepared as described in Scheme VII. ? NMR (500MHz, DMSO) 12.11 (br s, 1H), 9.53 (br s, 1H), 7.59 (m, 1H), 7.52-7.45 (m, 3H), 7.36 (m, 1H), 7. 28 (m, 1H), 7.19 (m, 1H), 7.10 (m, 1H), 3.89 (s, 2H), 3.70 (t, .7 = 6.7 Hz, 2H), 2.26 (t, J = 1 .2 Hz, 2H), 2.21 (s, 3H), 1.87 (m, 2H). Example 158 Acid (±) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanyl-ethyl-phenyl) -phenyl) -hydrazono) -pyrazolyl-J-tatanoic (Compound 258) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.58 (dd,, 7 = 7.7, 1.1 Hz, 1H), 7.19 (m, 1H), 7.13-7.06 (m, 3H), 6.98-6.91 (m, 2H), 3.79 (t, J "= 6.7 Hz, 2H), 3.51 (m, 1H), 3.19 ( dd, J "= 13.8, 6.1 Hz, 1H), 2.93 (m, 1H), 2.78 (m, 1H), 2.72 (dd, J = 13.8, 9.4 Hz, 1H), 2.34 (t, J = 7.3 Hz, 2H), 2.27 (s, 3H), 2.10 (m, 1H), 2.01 (m, 2H), 1.78 (m, 1H). Example 159 Acid (±) -3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) hydrazono) irazolyl} benzoic (Compound 259) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD30D) 8.58 (dd, J = 1.9, 1.5 Hz, 1H), 8.49 (s, 1H), 8.12 (m, 1H), 7.83 (ddd, J = 1.8, 1.5, 1.0 Hz, 1H), 7.62 (dd, J = 1.6, 1.7 Hz, 1H), 7.48 (t, J = 1.8 Hz, 1H), 7.19 (m, 1H), 7.15-7.07 (m, 3H), 7.00 -6.93 (m, 2H), 3.53 (m, 1H), 3.21 (dd, J "= 14.0, 5.8 Hz, 1H), 2.94 (m, 1H), 2.80 (m, 1H), 2.74 (dd, J = 14.0, 9.4 Hz, 1H), 2.38 (s, 3H), 2.12 (m, 1H), 1.80 (m, 1H) Example 160 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl} benzoic (Compound 260) This compound was prepared as described in Scheme VII. aH R (500MHz, DMSO) 13.78 (s, 1H), 9.64 1H), 8.56 (t, J = 1.6 Hz, 1H), 8.20 (m, 1H), 7.79 (m, 1H), 7 (t, J = 7.9 Hz, 1H), 7.56 (m, 1H), 7.22 (m, 1H), 7.16-7.08 314), 7.02 (d, .7 = 7.5 Hz, 1H), 6.97 (t, J = 7.5 1-Iz, 1H), 3 (m, 2H), 2.90 (m, 2H), 2.83 (m, 2H), 2.35 (s, 3H), 2.29 3H), 1.76 (m, 2H). Example 161 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyi) ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 261) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 13.75 (br s, 1H), 13.15 (br s, 1H), 9.66 (br s, 1H), 8.55 (dd, J = 2.2, 1.6 Hz, 1H), 8.20 (ddd, J = 8.2, 2.2, 1.0 Hz, 1H), 7.79 (ddd, J = l.8, 1.6, 1.0 Hz, 1H), 7.60 (dd, J "= 8.2, 7.8 Hz, 1H), 7.55 (dd, J = 1.4, 2.2 Hz, 1H), 7.16-7.10 (m, 2H), 7.01 (t, J = 1. 4 Hz, 1H), 6.99-6.93 (m, 2H), 2.94 (m, 2H), 2.88 (m, 2H), 2.34 (s, 3H), 2.23 (d, J = 1.7 Hz, 3H) Example 162 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 262) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 13.75 (s, 1H), 9.68 (s, 1H), 8.55 (t,, 7 = 1.7 Hz, 1H), 8.20 (m, 1H), 7.78 (m, 1H), 7.59 (t, J "= 7.9 Hz, 1H), 7.55 (m, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 7. 17-7.11 (m, 2H), 6.97-6.92 (m, 2H), 2.95 (m, 2H), 2.90 (m, 2H), 2.34 (s, 3H). Example 163 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} Benzoic (Compound 263) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 13.79 (s, 1H), 9.55 (s, 1H), 8.56 (t, .7 = 1.7 Hz, 1H), 8.20 (ddd, "7 = 7.9, 1.7, 1.1 Hz, 1H), 7.79 (ddd, J = 7.9, 1.7, LI Hz, 1H), 7.60 (t, J = 7.9 Hz, 1H), 7.57 (dd, J = 7.8, 1.6 Hz, 1H), 7.05-6.98 (m, SH), 2.83 (m, 2H), 2.78 (m, 2H), 2.35 ( s, 3H), 2.32 (s, 6H). Example 164 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 264) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 9.59 (br s, 1H), 8.55 (s, 1H), 8.20 (d, J = 7.6 Hz, 1H), 7.78 (d, .7 = 7.6 Hz, 1H), 7.64-7.54 (m, 2H), 7.48-7.43 (m, 2H), 7.28 (dd, J = 8.4, 7.5 Hz, 1H), 7.00-6.86 (m, 2H), 3.17 (m, 2H), 2.93 (m, 2H) ), 2.35 (s, 3H). Example 165 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (2- methyl-6-trifluoromethylphenyl) ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 265) This compound was prepared as described in Scheme VII. ¾ MR (500MHz, DMSO) 9.58 (br s, 1H), 8.55 (s, 1H), 8.21 (d,, 7 = 7.6 Hz, 1H), 7.79 (m, 1H), 7.64-7.50 (m, SH) , 7.02-6.8 8 (m, 2H), 3.04 (m, 2H), 2.92 (m, 2H), 2.35 (s, 3H). Example 166 -Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 266) This compound was prepared as described in Scheme VII. ¾ NMR (500MHz, DMSO) 13.78 (br s, 1H), 9.67 (br s, 1H), 8.56 (s, 1H), 8.20 (d, J = 1.9 Hz, 1H), 7.78 (m, 1H) , 7.60 (t, J = 7.9 Hz, 1H), 7.56 (d, < J = 7.7 Hz, 1H), 7.28-7.12 (m, 5H), 6.98 (t, J = 1.6 Hz, 1H), 4.03 (m, 1H), 3.29 (dd, J = 15.6, 7.9 Hz, 2H), 2.98 (dd, J = 15.6, 8.1 Hz, 2H), 2.35 (s, 3H). Example 167 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 267) This compound was prepared as described in Scheme VII. 2H R (500MHz, DMSO) 8.57 (s, 1H), 8.21 (d, .7 = 8.0 Hz, 1H), 7.79 (m, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.53-7.50 (m, 2H), 7.47 (m, 1H), 7.41 (m, 1H), 7.29 (t, J = 7.4 Hz, 1H), 7.20 (t, J = 7.4 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 3.91 (s, 2H), 2.36 (s, 3H). Example 168 Acid (E) -4 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2 - (2,4-difluorophenyl) -ethenyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 268) This compound was prepared as described in Scheme VIII. XH NMR (500MHz, CD3OD) 8.48 (br s, 1H), 7.78 (m, 1H), 7.57-7.43 (m, 3H), 7.25 (d, J "= 15.8 Hz, 1H), 7.03- 6.95 (m, 3H), 3.81 (t, J = 6.5 Hz, 2H), 2.27 (t, J = 1.7 Hz, 2H), 2. 26 (s, 3H), 2.00 (m, 2H). Example 169 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3,4-methylphenyl) -2-pyridyl) hydrazone) irazolyl) benzoic acid (Compound 269) compound was prepared as described in Scheme VII. 1H MR (500MHz, CD3OD) 8.62 (m, 1H), 8.21 (ra, 1H), 8.03 (m, 1H), 7.93-7.87 (m, 2H), 7.61 (m, 1H), 7.58-7.53 (m, 2H), 7.37 (m, 1H), 2.42 (s, 3H), 2.38 (s, 3H), 2.37 (s, 3H). Example 170 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl Jbutanoic (Compound 270) compound was prepared as described in Scheme VII. ? NMR (500MHz, CD30D) 7.66 (s, 1H), 7.55 (s, 1H), 7.49 (d, J = 7.1 Hz, 1H), 7.33 (d, .7 = 7.1 Hz, 1H), 3.79 (t, J) = 6.6 Hz, 2H), 2.62 (s, 3H), 2.37 (s, 3H), 2.35 (s, 3H), 2.35 (m, 2H), 2.28 (s, 3H), 2.01 (m, 2H). Example 171 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 271) This compound was prepared as described in Scheme VII. XH NMR (500MHz, CD3OD) 8.62 (s, 1H), 8.23-8.12 (m, 2H), 7.97 (m, 1H), 7.89 (m, 1 H), 7.60-7.51 (ra, 3H), 7.41 (m , 1H), 2.42 (s, 3H), 2.39 (s, 3H), 2.39 (s, 3H). Example 172 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 272) This compound was prepared as described in Scheme VII. ¾ NMR (500MHz, CD30D) 8.52 (t, J = 1.6 Hz, 1H), 8.17 (d, J = 6.3 Hz, 1H), 8.14 (m, 1H), 7.87 (d, J = 6.3 Hz, 1H ), 7. 81 (d, J "= 7.8 Hz, 1H), 7.49 (t, J = 1.8 Hz, 1H), 7.37 (s, 2H), 7.31 (s, 1H), 2.44 (s, 6H), 2.38 ( s, 3H) Example 173 Acid 3-. { 1- (6-Trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy 3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazone) indolyl} Benzoic (Compound 273) This compound was prepared as described in Scheme VII. H NMR (500MHz, DMSO) 13.20 (s, 1H), 9.34 (s, 1H), 8.11 (dd, J "= 2.0, 1.6 Hz, 1H), 8.08 (ddd, J = l.8, 1.6, 1.2 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.86 ( ddd, J = l .8, 2.0, 1.2 Hz, 1H), 7.77 (t, J "= 7.8 Hz, 1H), 7.62 (dd, J = 7.8, 1.7 Hz, 1H), 7.55 (dq, J = 8.0, 0.6 Hz, 1H), 7.22 (m, 1H), 7.15-7.07 (m, 3H), 7.06 (m, 1H), 6.95 (t, J = l.8 Hz, 1H), .91 (dd, J "= 7.8, 1.7 Hz, 1H), 2.88 (m, 2H), 2.82 (m, 2H), 2.28 (s, 3H) Example 174 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl Jbutanoic (Compound This compound was prepared as described in Scheme VII. ¾ NMR (500MHz, DMSO) 7.49 (d, J = 7.7 Hz, 1H), 730-7.26 (m, 2H), 7.23-7.16 (m, 3H), 6.92 (t, .J = l .7 Hz, 1H ), 6.86 (dd,, 7 = 17.7, 1.4 Hz, 1H), 4.02 (s, 2H), 3.69 (t, J = 6.7 Hz, 2H), 2.24 (t, J = 7.2 Hz, 2H), 2.19 ( s, 3H), 1.85 (m, 2H). Example 175 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 275) This compound was prepared as described in the Scheme VII. H NMR (500MHz, DMSO) 9.43 (s, 1H), 7.47 (d, J "= 7.4 Hz, 1H), 7.16 (t, J = 7.4 Hz, 1H), 7.03-6.90 (m, 5H), 3.69 (t, J" = 6.8 Hz, 2H), 2.67 (t, J = l .7 Hz, 2H), 2.58 (m, 2H), 2. 27 (s, 3H), 2.25 (t, J = 7.3 Hz, 2H), 2.19 (s, 3H), 1.85 (m, 4H). Example 176 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-phenylpropyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 276) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 9.44 (s, 1H), 7.47 (d, J = 7.4 Hz, 1H), 7.28 (t, J = 7.4 Hz, 2H), 7.21 (m, 2H), 7.17 (tt, J = 7.4, 1.4 Hz, 1H), 6.96 (dd, J = 1.4, 1.6 Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 3.69 (t, J = 6.8 Hz, 2H), 2.68 (t, J = 7.7 Hz, 2H), 2.62 (m, 2H), 2.25 (t, J = 1. 2 Hz, 2H), 2.19 (s, 3H), 1.86 (t, J = 7.4 Hz, 4H) . Example 177 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 277) This compound is prepared as described in the Scheme VII. ?? NMR (500MHz, DMSO) 13.59 (s, 1H), 12.09 (s, 1H), 9.45 (s, 1H), 1.48 (dd,, 7 = 7.8, 1.2 Hz, 1H), 7.15-7.04 (m, 4H) , 6.98 (dd, J = l .8, 1.2 Hz, 1H), 6.93 (t, J = 7.8 Hz, 1H), 3.69 (t, J = 6.7 Hz, 2H), 2.72 (t, J = l .1 Hz, 2H), 2.60 (t, J = 8.1 Hz, 2H), 2.25 (t, J = 7.3 Hz, 2H), 2.23 (s, 3H), 2.19 (s, 3H), 1.86 (m, 2H), 1.78 (m, 2H). Example 178 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (2,4-difluorophenyl)} - ethyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 278) This compound was prepared as described in Scheme VII. XH NMR (300MHz, DMSO) 7.48 (m, 1H), 7.34 (td J = 8.5, 6.9 Hz, 1H), 7.16 (ddd, J = 10.2, 9.5 2.4 Hz, 1H), 7.0 (tdd, J "= 8.5 , 2.4, 0.8 Hz, 1H), 6.94-6.84 (m, 2H), 3.69 (t J = 6.7 Hz, 2H), 2.95-2.80 (m, 4H), 2.25 (t, J = 7.2 Hz, 2H) 2.19 (s, 3H), 1.86 (m, 2H) Example 179 Acid (?) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydrazono) irazolyl} butanoic (Compound 279) This compound was prepared as described in Scheme VII. XH NMR (500MHz, CD3OD) 8.56 (br s, 1H), 8.19 (br s, 1H), 7.77 (m, 1H), 7.55 (dd, J = 7.8, 1.5 Hz, 1H), 7.38-7.28 (m, 2H), 6.98 (dd, J "= 7.8, 1.5 Hz, 1H), 6.89 (t, J = 1.8 Hz, 1H), 3.80 (t, J = 6.7 Hz, 2H), 3.17 (m, 2H) , 3.08 (m, 2H), 2.35 (m, 2H), 2.26 (s, 3H), 2.01 (m, 2H). 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2,6-dimethylphenyl) - (Z) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic acid (Compound 280) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.48 (d, J = 1.0 Hz, 1H), 7.09-6.95 (m, 3H), 6.88 (d, J = 12.1 Hz, 1H), 6.70 (d, .7 = 12.1 Hz, 1H), 6.55 (t, J = 7.8 Hz, 1H), 6.44 (d, J = 1.8 Hz, 1H), 3.79 (t, J = 6.7 Hz, 2H), 2.34 (t, J = 7.5 Hz, 2H), 2.24 (s, 3H), 2.13 (s, 6H), 2.01 (m, 2H). Example 181 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 281) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 7.71 (d, J = 1. 4 Hz, 1H), 7.69-7.62 (m, 3H), 7.48 (s, 1H), 7.34 (t, < J = 7.4 Hz, 1H) , 7.27 (t, J "= 7.4 Hz, 1H), 7.17 (m, 1H), 3.71 (t, J" = 6.6 Hz, 2H), 2.26 (t, J = 7.1 Hz, 2H), 2.22 (s, 3H), 1.87 (m, 2H). Example 182 Acid (Z) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- bromoethenyl) phenyl) -hydrazono) pyrazolyl jbutanoic (Compound 282) This compound was prepared as described in Scheme VII. ¾ NR (300MHz, CD3OD) 7.71-7.59 (m, 2H), 7.48 (d, J = 7.9 Hz, 1H), 7.41 (d, .7 = 13.8 Hz, 1H), 7.25-7.19 (m, 2H), 7.09-6.95 (m, 3H), 6.71 (d, J = 7.9 Hz, 1H), 3.79 (t, J = 6.6 Hz, 4H), 2.34 (t, J = 7.3 Hz, 4H), 2.26 (s, 6H) ), 2.01 (m, 4H). Example 183 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) hydrazono) pyrazolyl jbutanoic (Compound 283) This compound was prepared as described in Scheme VII. ¾ NMR (300MHz, CD30D) 7.60 (dd, J = 7.3, 1.6 Hz, 1H), 7.00-6.90 (m, 2H), 6.30 (d, J = 11.3 Hz, 1H), 5.65 (dd, J = 11.3, 10.4 Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.68 (m, 1H), 2. 34 (t, J "= 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 1.01 (d, J = 6.6 Hz, 6H). Example 184 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2-cyclopropyletenyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 284) This compound was prepared as described in Scheme VII. ¾ NR (300MHz, CD3OD) 7.59 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H), 6.95 (t, J = 7.8 Hz, 1H), 6.33 (d, J = 11.0 Hz, 1H), 5.21 (t, J "= 11.0Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.33 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 1.71 (m, 1H), 0.81 (m, 2H), 0.48 (m, 2H) Example 185 4- Acid. { 2- (5-ethyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 285) This compound was prepared as described in Scheme VII. ? NMR (300MHz, CD3OD) 7.51 (d, J = 1.6 Hz, 1H), 6. 96 (d, .7 = 7.6 Hz, 1H), 6.91 (t, J = 1.6 Hz, 1H), 3.78 (t, J = 6.6 Hz, 2H), 2.66 (t, J = 1.9 Hz, 2H), 2.32 (t, J "= 7.4 Hz, 2H), 2.25 (s, 3H), 2.01 (m, 2H), 1.62 (m, 1H), 1.49 (m, 2H), 0.97 (d, J = 6.6 Hz, 6H) Example 186 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fl 3- (3,5-dimethylphenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 286) This compound was prepared as described in the Scheme I. XH NMR (300MHz, CD3OD) 7.38 (dd, J = 9.4, 3.1 Hz, 1H), 7.13 (s, 2H), 7.04 (s, 1H), 6.78 (dd, J "= 9.2, 3.1 Hz, 1H), 3.78 (t, J = 6.7 Hz, 2H), 2.36 (s, 6H), 2.33 (t, J = 1. 3 Hz, 2H), 2.27 (s, 3H), 2.00 (m, 2H). Example 187 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (3,4- dimethylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 287) This compound was prepared as described in Scheme I. 1 H NMR (300MHz, CD3OD) 7.66 (m, 1H), 7.28 (s, 1H), 7.23-7.20 ( m, 2H), 7.08-6.99 (m, 2H), 3.78 (t, J = 6.7 Hz, 2H), 2.33 (m, 2H), 2.32 (s, 3H), 2.31 (s, 3H), 2.27 (s) , 3H), 2.00 (m, 2H). Example 188 Acid 4 { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) irazolyl Jbutanoic (Compound 288) This compound was prepared as described in Scheme VII. XH NMR (300MHz, CD3OD) 7.47 (d, J = 2.0 Hz, 1H), 6.96 (d, J "= 2.0 Hz, 1H), 3.78 (t, J = 6.8 Hz, 2H), 2.93 (m, 1H) , 2.34 (t, .7 = 7.1 Hz, 2H), 2.26 (s, 3H), 2.00 (m, 2H), 1.91-1.72 (m, 5H), 1.58-1.27 (m, 5H) Example 189 Acid 4 -. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (3,5-dimethylphenyl) phenyl) hydrazono) irazolyl} butanoic (Compound 289) This compound was prepared as described in Scheme I. XH NMR (500MHz, Acetone-d6) 10.58 (br s, 1H), 8.28 (br s, 1H), 7.70 (dd, J = 7.6, 1.9 Hz, 1H), 7.11 (m, 2H), 7.08 (t, J = 7.6 Hz, 1H), 7.04 (dd, .7 = 7.6, 1.9 Hz, 1H), 7.03 (m, 1H), 3.78 (t , J = 7.0 Hz, 2H), 2.38 (t, J "= 7.4 Hz, 2H), 2.34 (m, 6H), 2.23 (s, 3H), 2.00 (m, 2H) Example 190 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 290) This compound was prepared as described in Scheme I. XH NMR (500MHz, DMSO) 13.75 (s, 1H), 9.56 (s, 1H), 8.56 (t, .J = 1.8 HZ, 1H), 8.19 (ddd, J = 8.0, 1.8, 1.0 Hz, 1H), 7.78 (ddd, J = 8.0, 1.8, 1.0 Hz, 1H), 7.68 ( dd, J = 5.5, 4.1 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.17 (m, 2H), 7.11 (d, J = 4.1 Hz, 1H), 7.11 (d, J "= 5.5 Hz, 1H), 7.03 (s, 1H), 2.36 (s, 3H), 2.34 (s, 6H) Example 191 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 291) This compound was prepared as described in Scheme VII. ?? NMR (300MHz, DMSO) 8.53 (m, 1H), 8.19 (d, J = 7.7 Hz, 1H), 7.79 (d, J = 1.7 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H) , 7.48 (d, J = 2.2 Hz, 1H), 7.04 (d, J = 2.2 Hz, 1H), 2.97 (m, 1H), 2.35 (s, 3H), 1.84-1.67 (m, 6H), 1.46- 1.20 (m, 4H). Example 192 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (3,4-dimethylphenyl) phenyl) -hydrazono) irazolyl} benzoic (Compound 292) This compound was prepared as described in Scheme I. XH NMR (300MHz, CD3OD) 8.60 (s, 1H), 8.17 (d, J = 7.8 Hz, 1H), 7.84 (d, J = l .8 Hz, 1H), 7.71 (m, 1H), 7.50 (t, "7 = 7.8 Hz, 1H), 7.30 (m, 1H), 7.25-7.22 (m, 2H), 7.10-7.02 (m, 2H ), 2.39 (s, 3H), 2.33 (s, 3H), 2.32 (s, 3H). Example 193 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 293) This compound was prepared as described in Scheme VII. XH NMR (300MHz, DMSO) 13.75 (s, 1H), 9.61 (s, 1H), 8.55 (t, "7 = 1.6 Hz, 1H), 8.20 (dd, .7 = 7.9, 1.2 Hz, 1H), 7.78 (d, «J = 7.9 Hz, 1H), 7.59 (t,« 7 = 7.9 Hz, 1H), 7.55 (dd, «7 = 7.9, 1.2 Hz, 1H), 7.16-7.03 (m, 5H), 6.97 (t, "J = 7.9 Hz, 1H), 2.75 (t," J = 7.8 Hz, 2H), 2.62 (t, "7 = 7.8 Hz, 2H), 2.34 (s, 3H), 2.23 (s, 3H) ), 1.80 (m, 2H). Example 194 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) irazolyl} benzoic (Compound 294) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 8.57 (t, J = 1.7 Hz, 1H), 8.20 (m, 1H), 7.80 (m, 1H), 7.75 (m, 1H), 7.73 (m, 1H), 7.70 (dd, J = 1.9, 1.3 Hz, 1H), 7.65 (d, J = 1.9 Hz, 1H), 7.61 (t, J = 1.9 Hz, 1H), 7.49 (m, 1H), 7.36 (td, J = 1.5, 1.2 Hz, 1H), 7.29 (td, J = 7.5, 0.8 Hz, 1H), 7.24 (t, J = 1.9 Hz, 1H), 2.36 (s, 3H). Example 195 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-fluorophenyl) propyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 295) This compound was prepared as described in Scheme VII. XH NMR (300MHz, DMSO) 13.74 (s, 1H), 9.61 (s, 1H), 8.55 (t, J = 1.6 Hz, 1H), 8.20 (m, 1H), 7.78 (m, 1H), 7.59 (t, J "= 7.9 Hz, 1H), 7.54 (m, 1H), 7.31 (m, 1H), 7.24 (m, 1H), 7. 16-7.11 (m, 2H), 7.02 (m, 1H), 6.97 (t, J = 1.7 Hz, 1H), 2.72 (t, J = 7.7 Hz, 2H), 2.67 (t, J = 7.7 Hz, 2H), 2.34 (s, 3H), 1.85 (m, 2H). Example 196 Acid 3-. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyrazolylbenzoic acid (Compound 296) This compound was prepared as described in the Scheme VIII. XH NR (500MHz, DMSO) 11.77 (m, 1H), 9.37 (s, 1H), 8.73 (m, 1H), 8.64 (m, 1H), 8.25 (ddd, J "= 8.1, 2.2, 1.0 Hz, 1H ), 7.76 (m, 1H), 7.70 (ddd,, 7 = 7.7, 1.6, 1.0 Hz, 1H), 7.52 (dd, J = 8.1, 7.7 Hz, 1H), 7.34 (m, 1H), 7.26 (dd) , J = 7.8, 1.7 Hz, 1H), 7.23 (d, J = 1.8 Hz, 1H), 7.10-7.05 (m, 2H), 2.33 (s, 3H), 2.29 (s, 3H), 2.27 ( s, 3H) Example 197 Acid 3-. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) irazolyl J-benzoic acid (Compound 297) This compound is prepared as described in Scheme VIII. XH NMR (500MHz, DMSO) 11.78 (s, 1H), 8.74 (br s, 1H), 8.65 (m, 1H), 8.24 (m, 1H), 7.76 (m, 1H), 7.70 (m, 1H), 7.52 (t, .7 = 7.9 Hz, 1H), 7.16 (s, 2H), 7.10-7.05 (m, 2H), 7.01 (s, 1H), 2.33 (s, 9H). Example 198 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 298) This compound was prepared as described in Scheme VIII. H NMR (500MHz, DMSO) 8.53 (s, 1H), 7.64 (m, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.25 (dd, J "= 7.7, 1.6 Hz, 1H), 7. 21 (d, J = 1.7 Hz, 1H), 7.02-6.97 (m, 2H), 3.64 (t, J "= 6.7 Hz, 2H), 2.27 (s, 3H), 2.26 (s, 3H), 2.19 (t, J = 1. 4 Hz, 2H), 2.18 (s, 3H), 1.82 (m, 2H) Example 199 Acid 3-. { 1- (2-Oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) hydrazone) indolyl} propionic (Compound 299) This compound was prepared as described in Scheme II. XH NMR (500MHz, CD30D) 7.63 (dd, J = 7.7, 1.6 Hz, 1H), 7.61 (m, 1H), 7.27 (td, J = 7.7, 1.2 Hz, 1H), 7.12-7.08 (m, 4H) , 7.00 (m, 1H), 6.98 (t, J = 1.7 Hz, 1H), 6.88 (dd, J = 7.7, 1.6 Hz, 1H), 4.10 (t, J = 1.2 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 2.36 (s, 6H). Example 200 Acid 3-. { l- (2-OXO-2, 3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazone) -indolyl} benzoic (Compound 300) This compound was prepared as described in Scheme VII. XH NR (500MHz, DMSO) 13.01 (s, 1H), 9.37 (br s, 1H), 8.07 (dd, J = 2.0, 1.7 Hz, 1H), 8.05 (ddd, J = 7.8, 1.7, 1.2 Hz, 1H ), 7.82 (ddd, J = l .8, 2.0, 1.2 Hz, 1H), 7.74 (t, J "= 7.8 Hz, 1H), 7.72 (dd, J" = 7.5, 1.0 Hz, 1H), 7.57 ( dd, J = 8.1, 1.5 Hz, 1H), 7.29 (td, J = l.5, 1.0 Hz, 1H), 7.28 (t, J = l .1 Hz, 2H), 7.23 (m, 2H), 7.20 (td, .7 = 7.5, 1.0 Hz, 1H), 7.18 (tt, J = 7.1, 1.5 Hz, 1H), 6.94-6.90 (m, 2H), 6.75 (dd, J = 7.7, 1.5 Hz, 1H) , 4.02 (s, 2H). Example 201 Acid 3-. { 1- (2-Oxo-2, 3-dihydro-3- (2-hydroxy-3 - (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl Jpropionic (Compound 301) This compound was prepared as described in Scheme VII. U NMR (500MHz, CD3OD) 7.61 (d, J = 1.6 Hz, 1H), 7.49 (dd, J = 8.0, 1.4Hz, 1H), 7.29 (td, J = 1.6, 0.9 Hz, 1H) , 7.17-7.03 (m, 6H), 6.86 (dd, J = 8.0, 7.5 Hz, 1H), 6.73 (dd, J = 1.5, 1.4 Hz, 1H), 4.13 (t, J = l .3 Hz, 2H ), 2.90 (s, 4H), 2.71 (t, J = 7.3 Hz, 2H), 2.30 (s, 3H). Example 202 Acid 3-. { l- (6-Chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (3- (3-methylphenyl) rovyl) phenyl) aminomethylidene) indolyl J-benzoic (Compound 302) This compound was prepared as described in Scheme VIII. ? NR (500MHz, DMSO) 11.13 (d, J "= 13.4 Hz, 1H), 9.17 (br s, 1H), 8.89 (d, J = 13.4 Hz, 1H), 8.03-8.00 (m, 2H), 7.79 ( ra, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.55 (dd, J = 7.9, 1.5 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H), 7.14 (dd, J = 8.1, 2.0 Hz, 1H), 7.02-6.96 (m, 3H), 6.93 (t, J = 7.9 Hz, 1H), 6.88 (dd, J = 7.9, 1.5 Hz , 1H), 6.86 (d, J "= 2.0 Hz, 1H), 2.67 (t, J = 7.7 Hz, 2H), 2.58 (m, 2H), 2.27 (s, 3H), 1.83 (m, 2H). Example 203 Acid (±) -3-. { l- (6-Chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (1,2-dihydro-l-methyl-2-indolylphenyl) aminomethylidene) indolyl) benzoic (Compound 303) This compound was prepared as described in Scheme VIII. XH NR (500MHz, DMSO) 11.14 (d, J "= 13.2 Hz, 1H), 9.78 (br s, 1H), 8.94 (d, J" = 13.2 Hz, 1H), 8.03-7.99 (m, 2H), 7.79 (m, 1H), 7.79 (d, J "= 8J Hz, 1H), 7.72 (t, J = 7.7 Hz, 1H), 7.67 (dd, J = 8.1, 1.2 Hz, 1H), 7.16 (dd, J = 8.1, 2.0 Hz, 1H), 7.14-7.08 (m, 3H), 7.03 (t, J = 1.8 Hz, 1H), 6.87 (d, J = 2.0 Hz, 1H), 6.76-6.70 (m , 2H), 4.65 (dd, J = 11.2, 8.7 Hz, 1H), 3.41 (dd, J- = 15.6, 8.7 Hz, 1H), 2.72 (dd, J = 15.6, 11.2 Hz, 1H), 2.62 (s) , 3H) Example 204 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl} butanoic (Compound 304) This compound was prepared as described in Scheme VII. ¾ NMR (500MHz, DMSO) 13.57 (brs, 1H), 12.12 (brs, 1H), 10.50 (s, 1H), 10.27 (br s, 1H), 7.63 (m, 1H), 7.54 (m, 1H), 7.45 (m, 1H), 7.37-7.32 (m, 2H), 7.24 (m, 1H), 7.02 (m, 1H), 3.70 (t, .7 = 6.7 Hz, 2H), 2.44 (s, 3H), 2.26 (t, .7 = 7.3 Hz, 2H), 2.21 (s, 3H), 1.87 (m, 2H).

Example 205 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenyl-carbonylamino) phenyl) hydrazono) pyrazolyl} butanoic (Compound 305) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 10.30 (br s, 1H), 7.65 (d, J = 7.3 Hz, 1H), 7.48-7.40 (m, 3H), 7.36-7.32 (m, 2H), 3.69 (t, J = 6.7 Hz, 2H), 2.43 (s, 3H), 2.26 (t, J = 1. 3 Hz, 2H), 2.21 (s, 3H), 1.86 (m, 2H). Example 206 Acid 3-. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-1- (2- (2-fluorophenyl) ethyl) indolylidene) -hydrazinophenyl-J-benzoic acid (Compound 306) This compound was prepared as described in Scheme IX. ? NR (500MHz, DMSO) 13.03 (s, 1H), 12.97 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 1.7. , 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.67 (dd, .7 = 8.1, 1.6 Hz, 1H), 7.62 (m, 1H), 7.60 (t , J = l .7 Hz, 1H), 7.34-7.23 (m, 3H), 7.15-7.07 (m, 5H), 6.98 (dd, J = 1.7, 1.6 Hz, 1H), 4.04 (dd, J = l .2, 6.8 Hz, 2H), 3.02 (t, J = 7.2 Hz, 2H). Example 207 Acid 3-. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-1- (2- (2-chlorophenyl) ethyl) indolylidene) -hydrazinophenyl} Benzoic (Compound 307) This compound was prepared as described in Scheme IX. XH NMR (500MHz, DMSO) 13.03 (s, 1H), 12.97 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.68 (dd, J = 7.8, 1.6 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.41 (m, 1H), 7.34 (m, 1H), 7.29 (td, J- = 7.7, 1.2 Hz, 1H), 7.27-7.22 (m, 2H), 7.13-7.06 (m , 3H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 4.05 (t, J = 1. 3 Hz, 2H), 3.10 (t, J = 7.3 Hz, 2H).

Example 208 Acid 3-. { 3-Hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridi1} benzoic acid (Compound 308) This compound was prepared as described in Scheme IX. ¾ R (500MHz, DMSO) 8.53 (t, J = 1.6 Hz, 1H), 820-8.15 (m, 2H), 8.04 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.71-7.64 ( m, 3H), 7.61 (dd, J "= 8.4, 2.3 Hz, 1H), 7.22 (d, < J = 8.4 Hz, 1H), 2.34 (s, 3H), 2.27 (s, 3H), 2.23 ( s, 3H) Example 209 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 309) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 13.75 (s, 1H), 9.66 (s, 1H), 8.10 (d, J = 8.8 Hz, 2H), 8.04 (d, J = 8.8 Hz, 2H), 7.56 (d, J) = 7.6 Hz, 1H), 7.22 (dd, J = 7.3, 1.6 Hz, 1H), 7.16-7.08 (m, 3H), 7.02 (d, J = 7.6 Hz, 1H), 6.97 (t, J = 7.6 Hz , 1H), 2.93-2.87 (m, 2H), 2.86-2.80 (m, 2H), 2.35 (s, 3H), 2.29 (s, 3H). Example 210 Acid 3-. { 3-hydroxy-2- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolylidene-hydrazino) -4-pyridyl} Benzoic (Compound 310) This compound was prepared as described in Scheme IX. ? NMR (500MHz, DMSO) 13.02 (brs, 1H), 9.68 (brs, 1H), 8.52 (brs, 1H), 8.25 (brs, 1H), 8.16 (brs, 1H), 7.96 (d, J "= 7.1 Hz, 1H), 7.76 (d, J" = 71 Hz, 1H), 7.61 (t, J = l .1 Hz, 1H), 7.60 (m, 1H), 7.35 (td, J = l .6, 1.2 Hz, 1H), 7.21 (td, J = 1.S, 0.7 Hz, 1H), 7.16-7.13 (m, 3H), 6.89 (d, J = 7.6 Hz, 1H), 2.37 (s, 6H). Example 211 Acid 3-. { 1- (2-Oxo-2, 3-dihydro-3- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazone) indolyl} benzoic (Compound 3H) This compound was prepared as described in Scheme VII. ¾ NMR (500MHz, DMSO) 12.93 (s, 1H), 8.07 (t, J = 1.7 Hz, 1H), 8.04 (m, 1H), 7.81-7.74 (m, 2H), 7.74-7.60 (m, 3H) , 7.42 (s, 1H), 7.35 (t, .7 = 7.6 Hz, 1H), 7.23 (t, J = 1.6 Hz, 1H), 7.20 (d, J = 7.9 Hz, 1H), 6.92 (d , J = 7.6 Hz, 1H), 2.47 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H).

Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4 (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 312) This compound was prepared as described in Scheme VII. 1H NMR (500MHz, DMSO) 8.50 (dd, J = 2.1, 1.6 Hz 1H), 8.15 (ddd, J "= 8.1, 2.1, 1.0 Hz, 1H), 7.82 (ddd, .7 = 7.7, 1.6, 1.0 Hz, 1H), 7.71 (s, 1H), 7.62-7.54 (m, 2H), 7.62 (dd, J = 8.1, 7.7 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 2.63 (s, 3H), 2.38 (s, 3H), 2.32 (s, 6H). Example 213 Acid 3-. { 3-Hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino) -2-pyridyl} Benzoic (Compound 313) This compound was prepared as described in Scheme IX. XH NMR (500MHz, DMSO) 13.25 (s, 1H), 8.42 (t, J = 1.5 Hz, 1H), 8.32 (d, J 6.1 Hz, 1H), 8.10 (dd, J = 7.8, 1.5 Hz, 1H) , 8.10 (m, 1H), 8.03 (d, J = 7.9 Hz, lH), 7.93 (d, J = 6.1 Hz, 1H), .72 (t, J = 7.8 Hz, 1H), 7.61 (dq, J = l .9, 0.8 Hz, 1H), 7.19 (m, 1H), 7.17 (m, 2H), 6.99m, 1H), 2.37 (s, 6H). Example 214 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,5-dimethylphenyl) 4-pyridyl) hydrazono) pyrazolyl Jbutanoic (Compound 314) This compound was prepared as it is described in Scheme VII. XH NMR (500MHz, CD30D) 7.89 (m, 1H), 7.80 (m, 1H), 7.45 (s, 2H), 7.19 (s, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.41 (s) , 6H), 2.36 (t, J "= 7.3 Hz, 2H), 2.28 (s, 3H), 201 (m, 2H) Example 215 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl Jbutanoic (Compound 315) This compound was prepared as described in Scheme VI. XH NMR (500MFIz, DMSO) 12.13 (s, 1H), 11.25 (s, 1H), 8.04 (d, J = 1.8 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.74 (m, 2H) ), 7.70 (dd, J = 8.4, 1.8 Hz, 1H), 7.51 (t, J = 1.6 Hz, 2H), 7.40 (tt, .7 = 7.6, 1.0 Hz, 1H), 3.85 (t, J) = 6.7 Hz, 2H), 2.3 1-2.23 (m, 5H), 1.92 (m, 2H). Example 216 Acid 3-. { 3-Hydroxy-2- (5-methyl-3 -oxo-2,3-dihydro-2 - (3,4-dimethylphenyl) -4-pyrazolidene) hydrazino-5-benzothienyl} benzoic acid (Compound 316) This compound was prepared as described in Scheme VI. ¾ NMR (500MHz, DMSO) 8.29 (t, J = 1.6 Hz, 1H), 8.18 (d, J = 1.7 Hz, 1H), 8.01 (ddd, J "= 7.8, 1.6, 0.9 Hz, 1H), 7.97 (ddd, J = 7.8, 1.6, 0.9 Hz, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.73 (dd, J "= 8.3, 1.7 Hz, 1H), 7.69 (d, .7 = 1.7 Hz, 1H), 7.64 (t, J "= 7.8 Hz, 1H), 7.62 (dd, J" = 8.3, 1.7 Hz, 1H), 7.22 (d, J "= 8.3 Hz, 1H), 2.31 (s) , 3H), 2.28 (s, 3H), 2.24 (s, 3H) Example 217 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 317) This compound; was prepared as described in Scheme I.? NMR (500MHz, DMSO) 12.13 (s, 1H), 7.99 (dd, J = 7.6, 1.2 Hz, 1H), 7.75 (d, J = 7.6, 1.2 Hz, 1H), 7.71 (t, J "= 7.6 Hz , 1H), 7.58-7.55 (m, 2H), 7.50 (m, 1H), 7.15 (m, 1H), 3.86 (s, 3H), 3.69 (t, J = l .0 Hz, 2H), 3.63 ( s, 3H), 2.26 (t, J = 7.0 Hz, 2H), 2.18 (s, 3H), 1.86 (qn, J = l .0 Hz, 2H) Example 218 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3,5-diisopropylphenyl) -carbonylhydrazinomethylidene) pyrazolyl} butanoic (Compound 318) This compound was prepared as described in Scheme VIII. XH NMR (500MHz, CD3OD) 7.77 (br s, 1H), 7.30- 7.23 (m, 2H), 3.84 (t, J = S .7 Hz, 2H), 2.96-2.82 (m, 2H), 2.34 (t , J "= 7.5 HZ, 2H), 2.20 (s, 3H), 2.03 (m, 2H), 1.28 (d, J = l .0 Hz, 6H), 1.23 (d, J = 6.1 Hz, 6H). Example 219 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -aminomethylidene) irazolyl Jbutanoic (Compound 319) This compound is prepared as described in Scheme VIII. U NMR (500MHz, CD30D) 8.52 (br s, 1H), 7.55 (m, 1H), 7.11-7.09 (m, 2H), 7.06-7.01 (m, 3H), 3.79 (t, J = 6.8 Hz, 2H), 2.36 (s, 6H), 2.29 (t, J = 7.5 Hz, 2H), 2.27 (s, 3H), 1.99 (m, 2H).

Acid (±) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-l-methyl-2-oxo-3 -indolyl) methyl) phenyl) hydrazone ) Jizo tantal pyrazolyl (Compound 320) This compound was prepared as described in Scheme VII. XE NMR (300MHz, CD30D) 7.64 (dd, J "= 8.0, 1.3 Hz, 1H), 7.32 (td, J = 1.7, 0.9 Hz, 1H), 7.01-6.91 (m, 2H), 6.84 (dd, "7 = 8.0, 7.6 Hz, 1H), 6.78 (m, 1H), 6.62 (dd, .7 = 7.6, 1.3 Hz, 1H), 3.79 (t, 7 = 6.7 Hz, 2H), 3.51 ( d, 7"= 14.4 Hz, 1H), 3.20 (s, 3H), 2.81 (d, 7" = 14.4 Hz, 1H), 2.33 (t, 7 = 7.5 Hz, 3H), 2.27 (s, 3H), 2.01 (m, 2H). Example 221 Acid 3-. { l- (2-OXO-2,3-dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl Jpropionic (Compound 321) This compound is prepared as described in the Scheme VII. ?? NMR (500MHz, DMSO) 13.10 (s, 1H), 9.24 (s, 1H), 8.08 (t, J = 1.8 Hz, 1H), 8.04 (m, 1H), 7.82 (m, 1H), 7.74 (t, 7"= 7.7 Hz, 1H), 7.61 (dd, J = 1.9, 1.6 Hz, 1H), 7.55 (dd, 7 = 8.2, 2.6 Hz, 1H), 7.22 (m, 1H), 7.16-7.07 (m, 4H), 6.96-6.92 (m, 2H), 6.88 (dd, 7"= 7.6, 1.6 Hz, 1H), 2.87 (m, 2H), 2.81 (m, 2H), 2.28 (s, 3H). Example 222 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono) irazolyl} benzoic (Compound 322) This compound was prepared as described in Scheme VII. XH NMR (500MHz, DMSO) 13.77 (s, 1H), 9.62 (s, 1H), 8.56 (m, 1H), 8.21 (m, 1H), 7.78 (d, J = 1. 8 Hz, 1H), 7.63. -7.53 (m, 2H), 7.08-6.88 (m, 5H), 2.87 (m, 2H), 2.77 (m, 2H), 2.35 (s, 3H), 2.25 s, 3H), 2.24 (s, 3H) . Example 223 Acid (±) -3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2,3-dihydro-l-methyl-2-??? -3-indolyl) methyl) phenyl ) hydrazono) pyrazolyl Jbenzoic (Compound 323) This compound was prepared as described in Scheme VII. ? NMR (300MHz, CD3OD) 8.59 (dd, .J "= 2.1, 1.6 Hz, 1H), 8.19 (ddd, J = 8.2, 2.1, 1.0 Hz, 1H), 7.82 (ddd, J = l .7, 1.6, 1.0 Hz, 1H), 7.60 (dd, J "= 8.1, 1.4 Hz, 1H), 7.49 (dd, J" = 8.2, 7.7 Hz, 1H), 7.32 (td, J "= 7.6, 1.2 Hz, 1H) , 7.00-6.93 (m, 2H), 6.83-6.79 (m, 2H), 6.60 (dd, J = 7.6, 1.4 Hz, 1H), 3.51 (d, J = 14.4 Hz, 1H), 3.20 (s, 3H) ), 2.80 (d, J = 14.4 Hz, 1H), 2.34 (s, 3H).

Acid 3-. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-1-methyl-2-oxo-3-indolylidene) methyl) phenyl) hydrazone ) pyrazolyl} Benzoic (Compound 324) This compound was prepared as described in Scheme VII. XH MR (500MHz, DMSO) 13.65 (br s, 1H), 13.16 (br s, 1H), 10.54 (s, 1H), 8.53 (dd, J = 2.1, 1.6 Hz, 1H), 8.20 (ddd, J = 8.2, 2.1, 1.0 Hz, 1H), 7.84-7.76 (m, 3H), 7.59 (dd, J = 8.2, 7.9 Hz, 1H), 7.46 (m, 1H), 7.40 (d, J = 1.6 Hz) , 1H), 7.34 (td, J = 1.S, 1.0 Hz, 1H), 7.16 (m, 1H), 7.07 (d, J = l.6 Hz, 1H), 6.93 (td, J = 7.6, 1.0 Hz, 1H), 3.24 (s, 3H), 2.37 (s, 3H).

Acid 3-. { 2- (5-methyl-3-oxo--2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 325) This compound was prepared as described in Scheme VII. ?? NMR (500MHz, DMSO) 13.77 (s, 1H), 13.15 (s, 1H), 9.66 (s, 1H), 8.55 (dd, J = 2.1, 1.6 Hz, 1H), 8.20 (ddd, J = 8.2, 2.1 , 1.0 Hz. 1H), 7.79 (ddd, .7 = 7.8, 1.6, 1.1 Hz, 1H), 7.60 (dd, J "= 8.2, 7.8 Hz, 1H), 7.57 (dd, .7 = 7.9, 1.6 Hz , 1H), 7.17 (dd, 2. 8 Hz, 1H), 7.02 (dd, J = 7.6, 1.6 Hz, 1H), 6.97 (m, 1H), 6.92 (ddd, J = 8.6, 8.2, 2.8 Hz, 1H), 2.90 (m, 2H), 2.83 (m, 2H), 2.35 (s, 3H), 2.25 (s, 3H). Example 226 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro- (E) - (2-hydroxy-3- (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 326) This compound was prepared as described in Scheme VII. 1H NMR (300MHz, DMSO) 7.85 (m, 1H), 7.62-7.45 (m, 3H), 7.36-7.14 (m, 3H), 7.01 (m, 1H), 3.69 (t, J = 6.5 Hz, 2H), 2.25 (t, J = 7.2 Hz, 2H), 2.20 (s, 3H), 1.86 (m, 2H). Example 227 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-phenyl-phenyl) -hydrazono) -pyrazolyl} Benzoic (Compound 327) This compound was prepared as described in Scheme VII. XH R (300MHz, CD3OD) 8.61 (dd, J = 2.1, 1.5 Hz, 1H), 8.20 (ddd, J = 8.1, 2.1, 1.0 Hz, 1H), 7.84 (ddd, J = 7.7, 1.5, 1.0 Hz, 1H), 7.54 (m, 1H), 7.52 (dd, J = 8.1, 7.7 Hz, 1H), 6.97 (m, 1H), 6.88 (t, "7 = 7.8 Hz, 1H), 2.36 (s, 3H) , 2.28 (s, 3H). Example 228 4- Acid. { 2- (5-. Methyl-3-oxo-2, 3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-l-methyl-2-oxo-3-indolylidene) methyl) phenyl) hydrazone) pyrazolyl} butanoic (Compound 328) This compound was prepared as described in Scheme VII. NMR (500MHz, DMSO) 13.54 (s, 1H), 10.41 (br S, 1H), 8.42 (br, 1H), 7.76 (s, 1H), 7.74 (m, 1H), 7.43-7.37 (m, 2H), 7.33 (t, J = l.8 Hz, 1H), 7.12 (t, J = l.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.92 (t, J = 7.8 Hz, 1H), 3.69 (t, J = 6.6 Hz, 2H), 3.23 (s, 3H), 2.26 (t, J = 7.1 Hz, 2H), 2.21 (s, 3H), 1.87 (m, 2H). Example 229 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 329) This compound was prepared as described in Scheme VII. ?? R (300MHz, CD30D) 7.53 (m, 1H), 7.09 (dd, J = 8.4, 6.1 Hz, 1H), 6.93-6.84 (m, 3H), 6.78 (td, .7 = 8.4, 2.8 Hz, 1H) , 3.79 (t, J = 6.7 Hz, 2H), 2.96-2.82 (m, 4H), 2.35 (t, J = 7.4 Hz, 2H), 2.25 (s, 3H), 2.23 (s, 3H), 2.01 ( m, 2H). Example 230 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (2,6-difluorophenyl) -ethyl) phenyl) hydrazono) irazolyl} butanoic (Compound 330) This compound was prepared as described in Scheme VII. ? NMR (300MHz, CD3OD) 7.53 (m, 1H), 7.21 (m, 1H), 6.91-6.76 (m, 4H), 3.79 (t, J = 6.6 Hz, 2H), 3.03-2.92 (m, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H). Example 231 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2 - (2,6-dimethylphenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanico (Compound 331) This compound can be prepared as described in Scheme VII. Example 232 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3. {E) (2-methylphenyl) -ethenyl) phenyl) hydrazone) irazolyl} butanoic (Compound 332) This compound can be prepared as described in Scheme VII. Example 233 4- Acid. { 2- . { 5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (JE?) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 333) This compound was prepared as described in Scheme VII. ¾ NMR (300MHz, CD3OD) 7.63 (d, J "= 8.0 Hz, 1H), 7.49-7.29 (m, 4H), 7.18 (dd, J" = 8.3, 6.2 Hz, 1H), 7.03 (m, 1H) , 6.89 (td, J = 8.3, 2.3 Hz, 1H), 3.79 (t, J = 6.6 Hz, 2H), 2.40 (s, 3H), 2.34 (t, J = 7.4 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H). Example 234 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 334) This compound can be prepared as described in Scheme VII. Example 235 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3. {E) - (2 - (3-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 335) This compound can be prepared as described in Scheme VII. Example 236 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2 - (4-fluorophenyl) | ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 336) This compound can be prepared as described in Scheme VII. Example 237 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanico (Compound 337) This compound can be prepared as described in Scheme VII. Example 238 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2-phenylethenyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 338) This compound can be prepared as described in Scheme VII. Example 239 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenylethynyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 339) This compound can be prepared as described in Scheme VII. Example 240 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 340) This compound can be prepared as described in Scheme VII. Example 241 4- Acid. { 2- (5-ethyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -etinyl) phenyl) hydrazono) irazolyl Jbutanóico (Compound 341) Este The compound can be prepared as described in Scheme VII. Example 242 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) ethynyl) -phenyl) hydrazono) pyrazolyl jbutanoic (Compound 342) This compound can prepare as described in Scheme VII. Example 243 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -etinyl) phenyl) hydrazono) irazolyl} butanoic (Compound 342) This compound can be prepared as described in Scheme VII. Example 244 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-phenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 344) This compound can be prepared as described in Scheme VII. Example 245 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-tnenyl-1-indenyl-2-) phenyl) -hydrazono) irazolyl Jbutanoic (Compound 345) This The compound can be prepared as described in Scheme VII. Example 246 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,3-dimethyl-2-indenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 346) This compound can prepare as described in Scheme VII. Example 247 Acid 4 -. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) hydrazone) irazolyl} butanoic (Compound 347) This compound can be prepared as described in Scheme VII. Example 248 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-dimethyl-2-indenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 348) This compound can be prepared as described in Scheme VII. Example 249 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono) irazolyl Jbutanico (Compound 349) This compound can prepare as described in Scheme VII. Example 250 Acid 3-. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolylidene) methylaminophenyl} benzoic (Compound 350) This compound was prepared as described in Scheme VIII. XH NMR (500MHz, DMSO) 13.05 (s, 1H), 11.29 (d, J = 13.4 Hz, 1H), 9.39 (s, 1H), 8.95 (d, J "= 13.4 Hz, 1H), 8.13 (m, 1H), 7.95 (dd, J = 1.8, 1.0 Hz, 1H), 7.83 (d, J "= 8.1 Hz, 1H), 7.80 (m, 1H), 7.75 (d, J = 8.1 Hz, 1H) 7.61 (t, J = 1.8 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.20 (m, 1H), 7.16-7.07 (m, 5H), 7. 05 (d, J = 7.8 Hz, 1H), 4.06 (t, J = 7.4 Hz, 2H), 2.93 (t, J = 1. 4 Hz, 2H), 2.32 (s, 3H). Example 251 Acid 3 -. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) indolylidene) methylaminophenyl} benzoic (Compound 351) This compound can be prepared as described in Scheme VIII. Example 252 Acid (±) 4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2,3,4-tetrahydro) -naphthyl) phenyl) hydrazono) irazolyl} butanoic (Compound 352) This compound was prepared as described in Scheme VII. ?? NMR (500MHz, CD3OD) 7.57 (dd, .J = 8.0, 1.6 Hz, 1H), 7.11-7.04 (m, 5H), 7.00 (t, .7 = 8.0 Hz, 1H), 3.79 (t, J = 6.7 Hz, 2H), 3.39 (m, 1H), 3.05-2.80 (m, 4H), 2.34 (t, J = 7.3 Hz, 2H), 2.26 (s, 3H), 2.01 (m, 2H), 2.10-1.91 (m, 2H). Example 253 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 353) The compound can be prepared as described in Scheme VII. Example 254 4- Acid. { 2- (5-ethyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (1-indanylidene) -methylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 354) This compound can be prepared as is described in Scheme VII Example 255 TO L-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-trifluoromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 355) This compound can be prepared as described in Scheme VII. Example 256 Acid 4 -. { 2 - (5-methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (6-fluoro-2-trifluoro-methylphenyl) ethenyl) phenyl) hydrazone) pyrazolyl Jbutanoic (Compound 356) This compound can be prepared as described in Scheme VII. Example 257 4- Acid. { 2- (5-ethyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) (6-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 357) This compound can be prepared as described in Scheme VII. Example 258 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 358) This compound can be prepared as described in Scheme VII. Example 259 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (£) - (2- (3-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) irazolyl} butanoic (Compound 359) This compound can be prepared as described in Scheme VII. Example 260 4- Acid. { 2- (5-ethyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 360) This compound can be prepared as described in Scheme VII. Example 261 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2 - (2,5-difluorophenyl) -ethenyl) phenyl) hydrazono) irazolyl} butanoic (Compound 361) This compound can be prepared as described in Scheme VII. Example 262 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) (4-fluoro-2-trifluoromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 362) This compound can be prepared as described in Scheme VII. Example 263 Ác o 4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -etinyl) phenyl) hydrazono) irazolyl Jbutanoic (Compound 363) This The compound can be prepared as described in Scheme VII. Example 264 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) (1,2,3,4-tetrahydro) -naphthylidene) methylphenyl) hydrazono) pyrazolyl} butanoic (Compound 364) This compound can be prepared as described in Scheme VII. Example 265 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-5-methylphenyl) ethenyl) phenyl) hydrazono) irazolyl} butanoic (Compound 365) This compound can be prepared as described in Scheme VII. Example 266 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3,5-dimethyl-4-isoxazolyl) ethenyl) phenyl) hydrazone) pyrazolyl } butanoic (Compound 366) This compound can be prepared as described in Scheme VII. Example 267 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 5-dimethyl-4-isoxazolyl) ethyl) phenyl) hydrazono) irazolyl} butanoic (Compound 367) This compound can be prepared as described in Soheme VII. Example 268 Acid 3-. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E) - (2-methylphenyl) ethenyl) -3 (Z) indolylidene) methylaminophenyl} benzoic (Compound 368) This compound can be prepared as described in Scheme VIII. Example 269 Acid 3-. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E) - (2,4-difluorophenyl) ethenyl) -3 (Z) indolylidene) methylaminophenyl} benzoic (Compound 369) This compound can be prepared as described in Scheme VIII.

Acid 3-. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-1- (2-indenyl) -3 (Z) indolylidene) methylaminophenyl} benzoic (Compound 370) This compound can be prepared as described in Scheme VIII. Example 271 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) irazolyl} benzoic acid (Compound 371) This compound was prepared as described in Scheme VII. ¾ NMR (500MHz, DMSO) 13.72 (s, 1H), 13.13 (br s, 1H), 10.23 (s, 1H), 8.54 (dd, J = 2.1, 1.6 Hz, 1H), 8.21 (ddd, J = 8.0 , 2.1, 1.0 Hz, 1H), 7.79 (ddd, J "= 7.8, 1.6, 1.0 Hz, 1H), 7.65 (dd, J = 7.9, 1.3 Hz, 1H), 7.60 (dd, J = 8.0, 7.8 Hz , 1H), 7.60 (dd, J = 7.9, 1.3 Hz, 1H), 7.55 (dd, .J = 10.6, 2.8 Hz, 1H), 7.50 (d, .7 = 15.9 Hz, 1H), 7.35 (dd, .7 = 15.9, 1.5 Hz, 1H), 7.26 (dd, J "= 8.4, 6.2 Hz, 1H), 7.07 (t, J = 1.9 Hz, 1H), 7.04 (td, J = 8.4, 2.8 Hz , 1H), 2.39 (s, 3H), 2.35 (s, 3H). Example 272 Acid (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3-) methylphenyl) hydrazone) -pyrazolyl} butanoic (Compound 372) This compound was prepared as described in Scheme VII. XH MR (500MHz, DMSO) 13.57 (br s, 1H), 12 (br s, 1H), 9.45 (br s, 1H), 7.46 (d, J = l.8 Hz, 1H), 6.95 1H), 6.89 (t, J "= 7.8 Hz, 1H), 3.69 (t, J = 6.8 Hz, 2H), 2.25 J = 7.2 Hz, 2H), 2.24 (s, 3H), 2.19 (s, 3H), 1.86 (m, 2H). Example 273 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 373) This compound can be prepared as described in Scheme VII. Example 274 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 374) This compound can be prepared as described in Scheme VII. Example 275 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 375) This compound can be prepared as described in Scheme VII. Example 276 Acid 3. { 2- (5-ethyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2 - (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 376) This compound can be prepared as described in Scheme VII.

Example 277 Acid -. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (B) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 377) This compound can be prepared as described in Scheme VII. Example 278 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-6-methyl-phenyl) -ethenyl) -phenyl) -hydrazono) -pyrazolyl} benzoic (Compound 378) This compound can be prepared as described in Scheme VII. Example 279 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (2,3-difluorophenyl) -ethenyl) phenyl) hydrazono) irazolyl} benzoic (Compound 379) This compound can be prepared as described in Scheme VII. Example 280 4- Acid. { 2- (5-Methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2 - (2,3-difluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 380 This compound can be prepared as described in Scheme VII. Example 281 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-4-methylphenyl) ethenyl) phenyl) hydrazono) irazolyl} butanoic (Compound 381) This compound can be prepared as described in Scheme VII. Example 282 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2 - (2-chlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 382) This compound can be prepared as described in Scheme VII. Example 283 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-dichlorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 383 This compound can be prepared as described in Scheme VII. Example 284 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-chlorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 384) This The compound can be prepared as described in Scheme VII.

Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2, 5-difluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 385) This compound can be prepared as described in Scheme VII.

Acid 4 -. { 2 - (5-methyl-3 -oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2 - (2-chloro-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 386) This compound can be prepared as described in Scheme VII. Example 287 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 387) This compound can be prepared as described in Scheme VII. Example 288 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,4-dichlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 388) This compound can be prepared as described in Scheme VII. Example 289 Acid 3-. { 2- (5-ethyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (2-chloromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 389) This compound can be prepared as described in Scheme VII. Example 290 Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) (2,4-dichloromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 390) This compound can be prepared as described in Scheme VII. Example 291 3- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro) -naphthyl) phenyl) hydrazono) pyrazolyl acid} benzoic (Compound 353) This compound can be prepared as described in Scheme VII. Example 292 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 392) This compound can be prepared as described in Scheme VII. Example 293 4- Acid. { 2- (5-ethyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-8-methyl) -naphthyl) phenyl) hydrazono) irazolyl} butanoic (Compound 393) This compound can be prepared as described in Scheme VII. Example 294 4- Acid. { 2- (5-ethyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-7-methyl) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 394) This compound can be prepared as described in Scheme VII. Example 295 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 - (2- (3,4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 395) This compound can be prepared as described in Scheme VII. Example 296 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3,4-dihydro-6-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 396) This compound can be prepared as described in Scheme VII. Example 297 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-5-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 397) This compound can be prepared as described in Scheme VII. Example 298 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-8-chloro) -naphthyl) phenyl) hydrazono) irazolyl Jbutanóico ( Compound 398) This compound can be prepared as described in Scheme VII.

Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 399) This compound can be prepared as described in Scheme VII.

Claims (40)

1. CLAIMS 1. A compound of Formula I, II, III, IV, V or SAW : or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, a Ci-C3 alkyl optionally substituted, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted C1-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, C6-C6 haloalkyl, Ci-C6 heteroalkyl and Cx-C6 haloheteroalkyl; R6 is selected from an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl and an optionally substituted C1-C10 heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is selected from (CH2) mR18 , C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Cx-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Cx-C6 heteroalkyl, (CH2) mR18, and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR R, SR, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen CX-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and haloheteroalkyl R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and Ci-C4 haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and C1-C6 heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Cx-C6 alkyl, an optionally substituted Cx-C3 haloalkyl, an optionally substituted Cx-C6 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C3 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a non-aromatic heterocycle or carbocycle, wherein when R18 contains a non-aromatic heterocycle or carbocycle, the linking position can be found either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, C1-C3 alkyl, Ci-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; W is selected from 0, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C3 alkyl, an optionally substituted Ci-C6 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Ci0 aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted heterocycle or non-aromatic carbocycle, and a 1-5 atoms selected from an optionally substituted Ci-Ce alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is 0, 1, 2, or 3; and n is 0 or 1; each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, 0-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanate, thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, = 0, = S, amino, and protected derivatives of amino groups; whenever, if Y is found oriented in the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) D is not naphthyl if X is N and W is NH, (ii) D is not phenyl if X is CH, W is NH, Z is phenyl and R10 or R11 is - (CH2) 0-6OH, (iii) RII- is not pyrazolyl or optionally substituted-5-hydroxypyrazolyl; and (iv) U is not NH; further provided that, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and is NH in the compounds of Formulas III or IV, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisoster.
2. 2. A compound of Formula I, II or III: pharmaceutically acceptable prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-Ce alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl, an optionally substituted C1-C10 heteroalkyl, (CH2) mR18, C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere; each R8 and each R9 is independently selected from hydrogen, OR16, NR1SR17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, (CH2) mR18 and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R 10 is selected from hydrogen, halogen, oxo, OR 16, NR 16 R 17, SR 16, an optionally substituted C 1 -C 6 alkyl, an optionally substituted Ci-C 6 haloalkyl and an optionally substituted Ci-C 6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR1R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-Ce heteroalkyl, and haloheteroalkyl R14 is selected from hydrogen, Ci-C3 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and heterohaloalkyl d- C6; R15 is selected from hydrogen, S02R19, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and C1-C6 heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C3 haloalkyl, an optionally substituted C6-C6 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R1S and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from O, NR4, CR3R4, CO, and null; W is selected from O, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-C10 aryl, and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted heterocycle or non-aromatic carbocycle, and a 1-5 atoms selected from a optionally substituted Ci-C6 alkyl, an optionally substituted C6-C6 heteroalkyl and an optionally substituted Cx-C6 haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is 0, 1, 2, or 3; and n is 0 or 1; each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, 0-carboxy, isocyanate, thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, = 0, = S, amino, and protected derivatives of amino groups; "^ N ÍL provided, if Y is R-oriented in the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) D is not naphthyl if X is N and W is NH, (ii) D is phenyl if X is CH, W is NH, Z is phenyl and R10 or R11 is - (CH2) 0-6OH, (iii) R - D - 10 is not pyrazolyl or 5- I optionally substituted hydroxypyrazolyl; and (iv) U is not NH; further provided that, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and W is NH in the compounds of Formula III, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisoster.
3. 3. The compound of claim 2, wherein: R1 is selected from halogen, OR14, N02, CN, NR14R15, Ci-C4 alkyl, haloCi-C4 alkyl, an optionally substituted Ci-C4 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisoster selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (0) NR14R15, and wherein A, B, and C are each independently selected from 0, S, and NR20; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, Ci-C4 alkyl, Ci-C haloalkyl, Ci-C4 heteroalkyl and Ci-C4 heterohaloalkyl; R3 and R4 are independently selected from hydrogen, Cx-d alkyl, Ci-C4 haloalkyl and an optionally substituted Ci-C4 heteroalkyl; R5 is selected from hydrogen, OR14, C1-C4 alkyl, Ci-C4 haloalkyl, C1-C4 heteroalkyl and Ci-C4 haloheteroalkyl; R6 is selected from C1-C10 alkyl, Ci-C10 haloalkyl, an optionally substituted C1-C10 heteroalkyl, (CH2) mR18, C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR1R15, SO3R14, S02NR14R15 and a carboxylic acid bioisostere selected from tetrazole, HS02R19, OC (S) NR14R15, SC (0) NR1R15, and wherein A, B, and C are each independently selected from O, S, and N; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, C1-C4 alkyl, C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, (CH2) mR18 and none; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R 10 is selected from hydrogen, halogen, oxo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl and optionally substituted C 1 -C 4 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen, Ci- C4, haloalkyl C -C1r heteroalkyl C1-C4, and haloheteroalkyl Ci-C4; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, and Ci-C4 haloheteroalkyl; R 14 is selected from hydrogen, C 1 -C 6 alkyl, C 1 -C 5 haloalkyl, C 1 -C 4 heteroalkyl, and C 1 -C 6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci-C4 alkyl, C1-C4 haloalkyl, and Ci-C4 heteroalkyl; R 16 and R 17 are each independently selected from hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, an optionally substituted C 1 -C 4 heteroalkyl, and (CH 2) mR 18; or one of R16 and R17 is C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C4-C7 ring; R19 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and aryl; G is selected from O, S and NR14; J is selected from 0, S, NR14 and CR14R15; K is O or S; And it is selected from: 4. A compound of Formula IV, V or VI: or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, a optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR1R15 and a bioisoster of carboxylic acid; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 haloalkyl, an optionally substituted C-C10 heteroalkyl, (CH2) mR18, C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisoster; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Cx-C6 heteroalkyl, (CH2) mR18, and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and haloheteroalkyl Cys; R is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and C, L-C4 haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and heterohaloalkyl Ci-Ce; R15 is selected from hydrogen, S02R19, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-Cs heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, Ci-C3 alkyl, C1-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; W is selected from 0, NR4, CR3R4, CO, and null; X is N or CR5; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Cio aryl and an optionally substituted Cx-C8 heteroaryl, each optionally fused with an optionally substituted heteroaryl or non-aromatic carbocycle, and a 1-5 atoms selected from a optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is 0, 1, 2, or 3; and n is 0 or 1; each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, 0-carboxy, isocyanate, thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, = 0, = S, amino, and protected derivatives of amino groups; provided, if X is N and W is NH, then D is not phenyl; and provided that if X is N and is NH in the compounds of Formulas VI, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfarate functionality or a carboxylic acid bioisostere. 5. The compound of claim 4, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, Ci-C6 alkyl, Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere selected from tetrazole , NHS02R19, OC (S) NR1R15, SC (O) NR1R15, and wherein A, B, and C are each independently selected from 0, S, and N; and R7 is selected from C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (O) NR1R15, and wherein A, B, and C are each independently selected from 0, S, and N. 6. A compound of Formula I, II, III, IV, V or or a pharmaceutically acceptable salt, ester, amide or prodrug thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-Ce haloalkyl, a optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02 R14R15 and a carboxylic acid bioisostere; each R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Ci-Ce alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-Ce heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted C1-C10 alkyl, an optionally substituted Ci-C10 haloalkyl and an optionally substituted C1-C10 heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is selected from (CH2) mR18 , C (0) NHR18, C = CR18, CR3 = CR4R18 and CR3 = R18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted C6-C6 heteroalkyl, (CH2) raR18, and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted C1-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and haloheteroalkyl Ci-C6; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, C1-C4 alkyl, C1-C4 haloalkyl, Ci-C heteroalkyl, and Ci-C haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and C6-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Cx-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle, wherein R18 contains a heterocycle or non-aromatic carbocycle, the binding position can be either in the heterocycle or non-aromatic carbocycle or in the aromatic ring system; R19 is selected from hydrogen, C3-C3 alkyl, C1-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is sted from 0, NR4, CR3R4, CO, and null; it is sted from 0, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups sted from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-Ce heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is sted from: null, a 2-5 atom spacer selected from an optionally substituted C6-Cio aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted heteroaryl or non-aromatic carbocycle, and a 1-5 atom spacer selected from a optionally substituted Ci-C6 alkyl, an optionally substituted C6-C6 heteroalkyl and an optionally substituted C6-C6haloalkyl, each optionally fused to an aryl C < -Cio optionally substituted; m is 0, 1, 2, or 3; and n is 0 or 1; provided that, if X is N, W is NH, and Y is not found -N = CR12- oriented to form a dihydropyrazole, and Z or R6 are not an optionally substituted non-aromatic ring fused to an optionally substituted aromatic ring; or if X is N, W is NH, R6 is alkoxy, an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted heteroaryl, and is -N = CR12-oriented to form a dihydropyrazole, and Z is not a non-ring. optionally substituted aromatic fused with an optionally substituted aromatic ring, then D is not a phenyl; provided, if X is N, W is NH and Y is -N = CR12- oriented to form a dihydropyrazole, then D does not it is a naphthyl; whenever, if U is NH; or if D and one of R10 and R11 form a 5-hydroxypyrazole, X is N and W is NH; or if E and one of R10 and R11 form a 5-hydroxypyrazole and X is N, and is NH: or if E is phenyl, one of R10 or R11 is - (CH2) 0-GOH, X is C, W is NH , R6 is optionally substituted aryl or an optionally substituted heteroaryl, and Z is zero, an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted heteroaryl; or if E is phenyl, one of R10 or R11 is - (CH2) 0-6OH, X is N, W is NH, Z is zero, an optionally substituted alkyl, optionally substituted aryl or an optionally substituted heteroaryl, and R6 is alkyl Ci-C6, Ci-C6 alkoxy, - (CH2) o-eOR20, an optionally substituted aryl, an optionally substituted heteroaryl, NR21R22 or a heterocyclic methylene substituent represented by Formula VII; or if D is phenyl, one of R10 or R11 is - (CH2) 0 -sOH, X is C, W is NH, Z is aromatic, and R6 is alkoxy, an optionally substituted alkyl, an optionally substituted aryl or a heteroaryl optionally replaced; then Y is not found -N = CR12- oriented to form a dihydropyrazole; R20 is selected from hydrogen, a substituted alkyl, a substituted aryl, and a substituted heteroaryl; R21 and R22 are each independently selected from hydrogen, alkyl and aryl; or R21 and R22 taken together with the nitrogen to which they are attached represent a 5 or 6 membered saturated ring containing up to another heteroatom selected from oxygen and nitrogen; (VII) wherein A, B, C and V are each independently selected from O, S and NR20. 7. A compound of Formula I, II, III, IV, V or SAW : wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, a optionally substituted Ci-C6haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02-14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere; R2 is selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted Ci-Ci0 alkyl, an optionally substituted Ci-C10 haloalkyl or an optionally substituted Ci-Cio heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is (CH2) mR18 or C (0) NHR18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere; R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, (CH2) mR18, and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-s haloheteroalkyl; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and Ci-C4 haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci- C6 alkyl / Ci-C3 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Cx-C6 alkyl, an optionally substituted haloalkyl -Ce, a heteroalkyl Ci-C6 optionally substituted and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle. R19 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; it is selected from O, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Ci0 aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused with an optionally substituted heterocycle or non-aromatic carbocycle, and a 1-5 atoms selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is 0, 1 or 2; and n is 0 or 1; each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, 0-thiocarbamyl, N-thiocarbamyl, C-amido, N- amido, S-sulfonamido, N-sulfonamido, C-carboxy, 0-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, = 0, = S, amino, and protected derivatives of amino groups; whenever, if Y is found oriented in the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) D is not naphthyl if X is N and W is NH, (ii) D is not phenyl if X is CH, W is NH, Z is phenyl and R10 or R11 is - (CH2) or -6OH, (ii) r 1 D- -10 is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl; and (iv) U is not NH; further provided that, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and W is NH in the compounds of Formulas III or IV, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisoster. 8. A compound of Formula I, II or III: wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-Cs heteroalkyl, C02R14, CONR14R15, S03R14, S02NR1R15 and a carboxylic acid bioisostere; R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Cx-Cg heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C5 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C3 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an Ci-Ci0 alkyl optionally substituted, an optionally substituted C1-C10 haloalkyl and an optionally substituted C1-C10 heteroalkyl, (CH2) mR18 and C (0) NHR18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere; R8 and R9 are each independently selected from hydrogen, OR16, NR16R17, an optionally substituted C6-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, (CH2) mR18, and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl and haloheteroalkyl R14 is selected from hydrogen, Ci-C6 alkyl, Cx-C6 haloalkyl, Ci-C6 heteroalkyl, and heterohaloalkyl Ci- R is selected from hydrogen, S02R, Ci-C6 alkyl, Ci-C6 haloalkyl / Ci-C6 heteroalkyl, and Ci-C6 heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and (22) p 18 18; or one of R16 and R17 is an optionally substituted C2-C3 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; R19 is selected from hydrogen, Ci-C3 alkyl, Ci-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms, and optionally fused with a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fusing with a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; W is selected from 0, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Cio aryl and an optionally substituted Cx-Ce heteroaryl, each optionally fused to an optionally substituted heteroaryl or non-aromatic carbocycle, and a 1-5 atoms selected from an optionally substituted Ci-Cg alkyl, an optionally substituted C-C6 heteroalkyl and an optionally substituted Cx-Cg haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is O, l or 2, - and provided, if Y is "" "" R12 oriented on the compounds of Formulas I or II to form a dihydropyrazolylene, then: (i) D is not naphthyl if X is N and is NH, (ii) D is not phenyl if X is CH, W is NH, Z is phenyl and R10 or R11 is - (CH2) or -6OH, (iii) Ri-t-RIO is not pyrazolyl or optionally substituted 5-hydroxypyrazolyl; and (iv) U is not NH; further provided that, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and W is NH in the compounds of Formula III, then R6, R10, and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisoster. 9. The compound of claim 2, wherein: R1 is selected from a halogen, OR14, N02, CN, NR14R15, Ci-C4 alkyl, Ci-C4 haloalkyl, an optionally substituted Ci-C4 heteroalkyl, C02R14, CONR14R15, S03R14 , S02NR14R15 and carboxylic acid bioisosteres selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (0) NR14R15, and where A, B, and C are each selected independently of O, S and NR20; R2 is independently selected from hydrogen, halogen, OR14, NR14R15, C1-C4 alkyl, Ci-C4 haloalkyl / C1-C4 heteroalkyl and Ci-C4 heterohaloalkyl; R3 and R4 are independently selected from hydrogen, C1-C4 alkyl, C1-C4 haloalkyl and an optionally substituted C1-C4 heteroalkyl; R5 is selected from hydrogen, OR14, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl and Ci-C4 haloheteroalkyl; R6 is selected from C1-C10 alkyl, Ci-C10 haloalkyl, an optionally substituted C1-C10 heteroalkyl, (CH2) mR18 and C (0) NHR18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR14R15 and a carboxylic acid bioisostere selected from tetrazole, NHS02R19, OC (S) NR14R15, SC (O) NR14R15, and A, wherein A, B, and C are each independently selected from O, S, and N; each R8 and each R9 is independently selected from hydrogen, OR16, NR16R17, CX-C4 alkyl, Cx-C ^ haloalkyl, an optionally substituted C1-C4 heteroalkyl, (CH2) mR18 and nothing; or R8 and R9 taken together form an olefin optionally substituted; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, C1-C4 alkyl, haloalkyl Cx-d and an optionally substituted C1-C heteroalkyl; R12 is selected from hydrogen, halogen Ci-C4 alkyl, haloalkyl C1-C4, heteroalkyl Ci-C4, and haloheteroalkyl Ci-C4; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and Ci-C haloheteroalkyl; R14 is selected from hydrogen, Ci-C4 alkyl, Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and Ci-C4 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci- C4 alkyl / Ci-C4 haloalkyl, and Ci-C heteroalkyl; R16 and R17 are each independently selected from hydrogen, Ci-C alkyl, Ci-C4 haloalkyl, an optionally substituted Ci-C4 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C-C7 ring; R 19 is selected from hydrogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, and aryl; G is selected from 0, S and NR14; is selected from 0, S, NR and CR R K is O or S; L is H or null; and Y is selected from: 10. A compound of Formula IV, V or VI: or a pharmaceutically acceptable prodrug salt, ester, amide thereof, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, a heteroalkyl Ci-C6 optionally substituted, C02R14, CONR14R15, S03R14, S02NR1 R15 and a bioisoster of carboxylic acid; R2 is selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted xC6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, C6-C6 haloalkyl, Ci-C6 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted CÍ-CIO alkyl, an optionally substituted C 1 -C 10 haloalkyl and an optionally substituted Ci-Ci 0 heteroalkyl, (CH 2) MR 18 / C (0) NHR 18; R7 is selected from C02R14, CONR14R15, S03R14, S02 R14R15 and a carboxylic acid bioisostere; R8 and R9 are each independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, (CH2) MR18, and nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-Ce ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-Cg heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-Cg haloheteroalkyl; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, Ci-C4 alkyl / Ci-C4 haloalkyl, Ci-C4 heteroalkyl, and Ci-C haloheteroalkyl; R14 is selected from hydrogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-Cs heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and heterohaloalkyl R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, and (CH2) mR18; or one of R16 and R17 is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; R19 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from O, NR4, CR3R4, CO, and null; W is selected from 0, NR4, CR3R4, CO, and null; X is N or CR5; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Ci0 aryl and an optionally substituted Ci-C8 heteroaryl, each optionally fused to an optionally substituted non-aromatic heterocycle or carbocycle, and a spacer of 1-5 atoms selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused to an optionally substituted C6-Cio aryl; m is 0, 1 or 2; and n is 0 or 1; provided, if X is N and W is NH, then D is not phenyl; and further provided that, if X is N and W is NH in the compounds of Formulas VI, then R6, R10 and R11 do not contain a carboxylic, amido, ester or sulfurate functionality or a carboxylic acid bioisostere. 11. The compound of claim 4, wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted C6-C6 haloalkyl, an optionally substituted Ci-C6 heteroalkyl, C02R14, CONR14R15, S03R14, S02NR1R15 and carboxylic acid bioisostere selected from tetrazole, NHS02R19, SC ( ) NR14R15 and wherein A, B, and C are each independently selected from 0, S, and N; and R7 is selected from C02R14, C0NR14R15, S03R14, S02NR R and a carboxylic acid bioisostere selected from tetrazole, NHS02R19, OC (S) NR1R15, SC (O) R1R15, and wherein A, B, and C are each independently selected from O, S, and N. 12. A compound of Formula I, II, III, IV, V or SAW : wherein: R1 is selected from hydrogen, halogen, OR14, N02, CN, NR14R15, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, a heteroalkyl Ci-C6 optionally substituted, C02R, C0NR14R, S03R, S02NR14R15 and a carboxylic acid bioisostere; R2 is independently selected from hydrogen, halogen, OR14, NR14R15, an optionally substituted C6-C6 alkyl, an optionally substituted Ci-Ce haloalkyl and an optionally substituted Ci-C6 heteroalkyl.; R3 and R4 are independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Ci-C6 heteroalkyl; R5 is selected from hydrogen, halogen, OR14, Ci-C6 alkyl, Ci-C3 haloalkyl, Ci-C6 heteroalkyl and Ci-C6 haloheteroalkyl; R6 is selected from an optionally substituted Ci-Ci0 alkyl, an optionally substituted Ci-Ci0 haloalkyl and an optionally substituted CÍ-CIO heteroalkyl, each optionally fused with a substituted aryl or a substituted heteroaryl, or R6 is selected from (CH2) mR18 , C (O) HR18; R7 is selected from C02R14, CONR14R15, S03R14, S02NR1 R15 and a carboxylic acid bioisostere; R8 and R9 are each independently selected from hydrogen, OR16, NR16R17, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, an optionally substituted Ci-Ce heteroalkyl, (CH2) mR18, Y nothing; or R8 and R9 taken together form an optionally substituted olefin; or R8 and R9 are linked to form an optionally substituted C3-C8 ring; R10 is selected from hydrogen, halogen, oxo, OR16, NR16R17, SR16, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl and an optionally substituted Gi-C6 heteroalkyl; R11 is selected from hydrogen, halogen, OR14, NR14R15 and SR14; or R11 and R4 are linked to form an optionally substituted heterocycle; R12 is selected from hydrogen, halogen CX-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-C6 haloheteroalkyl; R13 is selected from hydrogen, halogen, CN, N02, C02R14, S (0) mR14, C3-C4 alkyl, C1-C4 haloalkyl, C1-C4 heteroalkyl, and Ci-C4 haloheteroalkyl; R14 is selected from hydrogen, C! -C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Cx-C6 heterohaloalkyl; R15 is selected from hydrogen, S02R19, Ci- C6 alkyl, Ci-C6 haloalkyl, Ci-C6 heteroalkyl, and Ci-Cg heterohaloalkyl; R16 and R17 are each independently selected from hydrogen, an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-C6 haloalkyl, a heteroalkyl Ci-C6 optionally substituted and (CH2) mR; or one of R and R is an optionally substituted C2-C6 alkyl and the other of R16 and R17 is null; or R16 and R17 are linked to form an optionally substituted C3-C8 ring; R18 is selected from an optionally substituted monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; R19 is selected from hydrogen, C1-C3 alkyl, Ci-C3 haloalkyl, and an optionally substituted aryl; D is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused to a heterocycle or non-aromatic carbocycle; E is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; L is NH or is zero; Q is a monocyclic or bicyclic aromatic ring system optionally containing one or more heteroatoms and optionally fused with a heterocycle or non-aromatic carbocycle; U is selected from 0, NR4, CR3R4, CO, and null; W is selected from 0, NR4, CR3R4, CO, and null; X is N or CR5; Y is a 1-4 atom spacer comprising one or more groups selected from an optionally substituted Ci-C6 alkyl, an optionally substituted Ci-Ce heteroalkyl, an optionally substituted phenyl and an optionally substituted heteroaryl; Z is selected from: null, a 2-5 atom spacer selected from an optionally substituted C6-Ci0 aryl and an optionally substituted Cx-Ce heteroaryl, each optionally fused to an optionally substituted heteroaryl or non-aromatic carbocycle, and a 1-5 atoms selected from an optionally substituted Cx-C6 alkyl, an optionally substituted Ci-C6 heteroalkyl and an optionally substituted Ci-C6 haloalkyl, each optionally fused with an optionally substituted C6-Cio aryl; m is 0, 1 or 2; and n is 0 or 1; provided that, if X is N, it is NH, and Y is not found -N = CR12- oriented to form a dihydropyrazole, and Z or R6 are not an optionally substituted non-aromatic ring fused with an optionally substituted aromatic ring; or if X is N, W is NH, R6 is alkoxy, an alkyl optionally substituted, an optionally substituted aryl or an optionally substituted heteroaryl, and -N = CR12-oriented to form a dihydropyrazole, and Z is not an optionally substituted non-aromatic ring fused with an optionally substituted aromatic ring, then D is not a phenyl; provided, if X is N, W is NH and Y is -N = CR12- oriented to form a dihydropyrazole, then D is not a naphthyl; whenever, if U is NH; or if D and one of R10 and R11 form a 5-hydroxypyrazole, X is N and W is NH; or if E and one of R10 and R11 form a 5-hydroxypyrazole and X is N, and W is NH; or if E is phenyl, one of R10 or R11 is - (CH2) 0-6OH, X is C, W is NH, R6 is optionally substituted aryl or an optionally substituted heteroaryl, and Z is zero, an optionally substituted alkyl, a optionally substituted aryl or an optionally substituted heteroaryl; or if E is phenyl, one of R10 or R11 is - (CH2) 0-6OH, X is N, W is NH, Z is zero, an optionally substituted alkyl, aryl optionally substituted an optionally substituted heteroaryl, and R6 is Ci alkyl. -C6, Ci-C6 alkoxy, - (CH2) o-eOR20, an optionally substituted aryl, an optionally substituted heteroaryl, NR21R22 or a heterocyclic methylene substituent rsented by Formula VII; or if D is phenyl, one of R10 or R11 is - (CH2) 0-6OH, X is C, W is NH, Z is aromatic, and R6 is alkoxy, an optionally substituted alkyl, an optionally substituted aryl or an optionally substituted heteroaryl; then Y is not found -N = CR12- oriented to form a dihydropyrazole; R20 is selected from hydrogen, a substituted alkyl, a substituted aryl, and a substituted heteroaryl; R21 and R22 are each independently selected from hydrogen, alkyl and aryl; or R21 and R22 taken together with the nitrogen to which they are attached represent a 5 or 6 membered saturated ring containing up to another heteroatom selected from oxygen and nitrogen; wherein A, B, C and V are each independently selected from 0, S and NR20. 13. The compound of claim 3, wherein the compound is of Formula I. The compound of claim 3, wherein the compound is of Formula II. 15. The compound of claim 3, wherein the compound is of Formula III. 16. The compound of claim 5, wherein the compound is of Formula IV. 17. The compound of claim 5, wherein the compound is of Formula V. 18. The compound of claim 5, wherein the compound is of Formula VI. 19. The compound of claim I, selected from: 3 '- acid. { [1- (3, 5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-yldenomethyl] amino} -2 '-hydroxybiphenyl-3-carboxylic acid (Compound 101); Acid 2, -dihydroxybenzoic N '-. { 1- [1- (3, 5-dimethylphenyl) -2- ??? -6-trifluoromethyl-1,2-dihydroindol-3-ethylhene] ethyl} hydrazide (Compound 102); Acid 3-. { 3- [(5-chloro-2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 103); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 104); 3 'acid. { [1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -4-fluoro-2'-hydroxybiphenyl-3-carboxylic acid (Compound 105); 2- (3 '- { [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -2'-hydroxybiphenyl-3 acid -yl) -2-methylpropionic (Compound 106); 3 'acid. { [1- (3,4-dimethylphenyl) -2-OXO-6- trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -2 '-hydroxybiphenyl-3-carboxylic acid (Compound 107); 4- Acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 108); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 109); Methyl ester of 3- acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-yl-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 110); Methyl ester of 3 - acid. { 3 - [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 111); Acid 3-. { 3- [(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 112); Acid 3-. { 3- [1- (3 ', 5'-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-l-ylidenamino] -2 -oxo-2,3-dihydrobenzooxazol-7-yl} benzoic (Compound 113); Acid 3-. { 3- [(2-hydroxy-3, 3 ', 4' -trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 114); 3-Hydroxybenzoic acid N '-. { l- [1- (3, 5-dimethylphenyl) -2 -oxo-6-trifluoromethyl-1,2-dihydroindol -3- ilidene] ethyl} hydrazide (Compound 115); 1- (3, 5-dimethylphenyl) -3-. { 1- [2- (4-hydroxyphenyl) -2-oxo-ethylamino] ethylidene} -6-trifluoromethyl-1,3-dhydroindol-2 -one (Compound 116). Acid 3.. { 3- [(5-fluoro-2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 117); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic (Compound 118); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-yl) hydrazono] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 119); Acid 3-. { 3- [(2-hydroxy-3 ', 4'-dimethylbiphenyl-3-ylamino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl} benzoic (Compound 120); 4- Acid. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} butyric (Compound 121); 2-Chloro-3- (4. {[1- (3,5-dimethylphenyl) -2 -oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidenemethyl] amino} -3-hydroxyphenyl acid acrylic) (Compound 122); 4-Hydroxybenzoic acid N '-. { l- (3,5-Dimethylphenyl) -2- ??? -6-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 123); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-yl) hydrazono] -5-nitro-2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 124); Acid 3-. { 3- [(2-hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylidene] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 125); Acid 3-. { 3- [(2-hydroxy-5, 3 ', 5' -trimethylbiphenyl-3-yl) hydrazono] -2-oxo-2,3-dihydroindol-1-yl} benzoic (Compound 126); 4-aminobenzoic acid N '-. { l- [1- (3,5-Dimethylphenyl) -2-phenyl-trifluoromethyl-1,2-dihydroindol-3-ylidene] ethyl} hydrazide (Compound 127); 3- (7- {? '- [1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindol-3-ylidene] hydrazino}. -1H-indole 3-yl) propionic (Compound 128); 4- Acid. { 3- ['- (4-methylbenzoyl) hydrazinomethylidene] -2-OXO-2,3-dihydroindol-1-yl} benzoic (Compound 129); Acid 3-. { 2-Oxo-6-trifluoromethyl -3 - [4- (3-trifluoromethyl-phenyl) -lH-pyrrol-2-ylmethylidene] -2,3-dihydroindol-1-yl} benzoic (Compound 130); 3- (7- { N '- [l- (3,4-dimethylphenyl) -3-methyl-5-oxo-1,5-dihydropyrazol-4-ylidene] hydrazino-lH-indol-3-yl acid ) propionic (Compound 131); 3- (3 { [4- (3, 4-Dimethylphenyl) thiazol-2-ylamino] methylidene} -2-oxo-6-trifluoromethyl-2,3-dihydroindole-1- il) benzoic (Compound 132); 3- (3 { [4- (4-Methoxyphenyl) thiazol-2-ylamino] methylene} -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-iD-benzoic acid (Compound 133); 3- {3 - [(2-Hydroxy-3 ', 5'-dimethylbiphenyl-3-ylamino) methylene] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 134); 3- {3 - [(4- (4-methylphenyl) -2-thiazolylamino) methylene] -2-oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl}. benzoic (Compound 135); 3 -. {3 - [(3,4-Dimethylbenzoylhydrazino) methylidene] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 136); 3 - { 3 - [(4-Chlorobenzoylhydrazino) methylidene] -2-phenyl-2,3-trifluoromethyl-2,3-dihydroindol-1-yl} benzoic acid (Compound 137); {.3 - [(4-methoxybenzoylhydrazino) methylidene] -2 -oxo-6-trifluoromethyl-2,3-dihydroindol-1-yl.} Benzoic acid (Compound 138); 3 -. {3 - [(3 , -dimethylbenzoylhydrazino) methylidene] -2-oxo-6-chloro-2,3-dihydroindole-1 -yl.} benzoic (Compound 139); 1- (3, 4-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 140); 1- (3,4-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2-oxo-2,3-dihydroindole (Compound 141); 1- (3,4-dimethylphenyl) -3 - [(2,4-dihydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 142); 1- (3,5-dimethylphenyl) -3- [1- (2,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 143); 1- (3, 5-dimethylphenyl) -3- [1- (4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 144); 1- (3, 5-dimethylphenyl) -3 - [(2,4-dihydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 145); 1- (3, 5-dimethylphenyl) -3- [(4-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 146); 3- (3- [1- (3,4-Dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-6-chloro-2,3-dihydroindol-1-yl) benzoic acid (Compound 147); 1- (3,4-dimethylphenyl) -3 - [(4-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 148); 1- (3, -dimethylphenyl) -3- [(3,5-diisopropyl-2-hydroxybenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindole (Compound 149); 1- (3,5-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 150); 2- (3,4-dimethylphenyl) -3- [1- (3,4-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 151); 3- (6-Chloro-3- [(2-hydroxy-3,5-diisopropylbenzoylhydrazino) methylidene] -2 -oxo-2,3-dihydroindol-1-yl) benzoic acid (Compound 152); 1- (3,4-Dimethylphenyl) -3- [1- (2,5-dihydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 153), 1- (3,4-dimethylphenyl) - 3- [1- (3-nitro-4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 154); 1- (3,4-dimethylphenyl) -3- [1- (3-aminosulfonyl-4-chlorobenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 155); 1- (3,4-dimethylphenyl) -3- [l-3-amino-4-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 156); 1- (3,4-Dimethylphenyl) -3- [1- (4-methoxy-2-hydroxybenzoylhydrazino) ethylidene] -2 -oxo-2,3-dihydroindole (Compound 157); Acid 3-. { 3- (1- (3,5-dimethylphenyl) -2-oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl} benzoic (Compound 158); Acid 3-. { 3- (3, 5-dimethylphenyl) -2-hydroxyphenyl) aminomethylidene) -2-oxo-2,3-dihydro-l-indolyl} benzoic (Compound 159); Acid 3-. { 3- (1- (3,4-Dimethylphenyl) -2-oxo-2,3-dihydro-3-indolidene) methylamino-2-hydroxyphenyl} benzoic (Compound 160); 4- Acid. { 1- (6-Fluoro-2-oxo-2,3-dihydro-3- (2- (3,5-dimethylphenyl) -aminocarbonylphenyl) aminomethylidene) indolyl} butanoic (Compound 161); 4- Acid. { l- (6-Chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) -aminomethylidene) indolyl} butanoic (Compound 162); Acid 3 -. { 1- (6-chloro-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} benzoic (Compound 163); 4- Acid. { l. (5-Fluoro-2-oxo-2,3-dihydro-3- (2-hydroxo-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) indolyl} butanoic (Compound 164); Acid 3-. { 3- (1- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydro-3-indolidene) ethylamino) -2-hydroxyphenyl-benzoic acid (Compound 165); Acid 3-. { 3- (1- (3, 4-dimethylphenyl) -6-trifluoromethyl- 2-OXO-2, 3-dihydro-3-indolidene) ethylamino) -2-hydroxyphenyl} benzoic (Compound 166); Acid 3-. { 1- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) hydrazone) indolyl} benzoic (Compound 167); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (1- (5-chloro-2-hydroxy-3-cyclohexylphenyl) amino) ethylidene) indolyl} benzoic (Compound 168); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (5-chloro-2-hydroxy-3-cyclohexylphenyl) aminomethylidene) indolyl} benzoic (Compound 169); 4- Acid. { 2-Hydroxy-3- (6-trifluoromethyl-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminophenyl} butanoic (Compound 170); 4- Acid. { 2-hydroxy-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylaminophenyl} butanoic (Compound 171); Acid 3-. { 3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolidene) methylamino) indolyl} propanic (Compound 172); Acid 3-. { 3- (7- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3, 4-dimethylphenyl) ^ 3 -indolidene) methylamino) indolyl} propanic (Compound 173); 4- Acid. { 2-Hydroxy-3- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminophenyl} butanoic (Compound 174); 2-chloro-3- acid. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propionic (Compound 175); 2-chloro-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl} propionic (Compound 176); 2-ethyl-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolylidene) methylaminophenyl} propionic (Compound 177); 2-ethyl-3- acid. { 3-hydroxy-4- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic (Compound 178); 2-ethyl-3- acid. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolylidene) methylaminophenyl} propenoic (Compound 179); 4- Acid. { 2-hydroxy-3- (4- (2- (3,4-dimethylphenyl) -3-oxo-3,4-dihydro-5-methyl) pyrazolidene) methylaminophenyl} butanoic (Compound 180); Acid (Z) -4-. { l- (2,5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl Jbutanoic (Compound 181); Acid (E) -4-. { 1- (2, 5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl Jbutanoic (Compound 182); Acid (Z) -3-. { l- (2, 5-dioxo-3- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) irolidolidylbenzoic acid (Compound 183); Acid (E) -3-. { l- (2, 5-dioxo-3- (3, 5-dimethylphenyl) -2-hydroxypheni) aminomethylidene) pyrrolidinyl J-benzoic acid (Compound 184); 4- Acid. { 3- (4-γ-2-thioxo-5- (3- (3, 5-dimethylphenyl) -2-hydroxypheni) hydrozono) thiazolidinyl} butanoic (Compound 185); Acid 3-. { 2- (3- (1- (3,5-dimethylphenyl) -6-chloro-2-oxo-2,3-dihydroindolidene) methylamino) phenylamino} benzoic (Compound 186); Acid 3-. { 2- (3- (1- (3,5-Dimethylphenyl) -6-trifluoromethyl-2-oxo-2,3-dihydroindolidene) methylamino) phenylaminobenzoic acid (Compound 187); Acid 3-. { 2- (4- (2- (3, 5-dimethylphenyl) -5-methyl-3-oxo-3,4-dihydropyrazolidene) methylamino) phenylamino} benzoic (Compound 188); Acid (+) - 3-methyl-5-. { 2-hydroxy-3- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) phenyl Jpentanoic (Compound 189); Acid (+) - 3 - (1- (6-chloro-2-oxo-2,3-dihydro-3- (3- (1- (3,5-dimethylphenyl) -2-oxo-2,3-dihydro) ) indolyl) aminomethylidene) indolyl Jbenzoic (Compound 190); Acid 3-. { 4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) iridinyl} benzoic acid ( Compound 191); 3- {4- (3-hydroxy-6-methyl-2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl)) indolidene) methylamino) pyridinyl J-benzoic acid (Compound 192); 3- ({4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-yl) -2,3-dihydro-l- (3 , 5-dimethylphenyl) indolidene) methylamino) pyridinyl} benzoic acid (Compound 193); 3- {4- (3-hydroxy-2- (3- (6-trifluoromethyl-2-oxo-2, 3- dihydro-1- (3, 5-dimethylphenyl) indolyl) hydrazono) pyridinyl} benzoic acid (Compound 194); 3- ({5- (4-hydroxo-3- (3- (6-trifluoromethyl) -2- oxo-2, 3-dihydro-1- (3, 5-dimethylphenyl) indolidene) methylamino) pyridinyl J-benzoic acid (Compound 195); 3- ({5- (4-hydroxo-3- (3- (6-trifluoromethyl)} -2 -oxo-2, 3-dihydro-1- (3,5-dimethylphenyl) indolyl) hydrazono) pyridinyl} benzoic acid (Compound 196); 3- ({5- (4-h) acid idroxy-3- (4- (3-oxo-3,4-dihydro-5-methyl-2- (3,4-dimethylphenyl) pyrazolyl) hydrazono) pyridinyl} benzoic (Compound 197); 4- Acid. { 2- (3-yl) -3,4-dihydro-5-methyl-4- (3- (3,4-dimethylphenyl) phenyl) hydrozono) pyrazolyl Jbutanoic (Compound 198); Acid 3-. { 2-amino-5-methyl-3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) phenyl} benzoic (Compound 199); Acid 3-. { l- (5-Fluoro-2-oxo-2,3-dihydro-3- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) indolyl J-benzoic acid (Compound 200); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (3- (3,4-dimethylphenyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic acid (Compound 201); Acid (3- (5-fluoro-2-hydroxy-3- (3- (6-trifluoromethyl) -2 -oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylamino) -1-pyrazolyl) acetic acid (Compound 202); Acid (3- (5-fluoro-2-hydroxy-3- (3- (2-OXO-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino) -1-pyrazolyl) acetic acid (Compound 203 ); 4- ({2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenyl) -ethyl) -phenyl) -aminomethylidene) -pyrazolyl-Jbutanic acid (Compound 204); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy 3- (2-phenyl) ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 205); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 206); 4- Acid. { 2- (5-methyl-2-oxo-2,3-dihydro-4 - (2-hydroxo) 3- (2- (3-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 207); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl) phenyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 208); 4- Acid. { 2- (5-Methyl-2-oxo-2,3-dihydro-4- (2-hydroxo-3- (2- (l-naphthyl) ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 209); Acid 3-. { 1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxo-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 210); Acid 3-. { l- (5-Nitro-2-oxo-2,3-dihydro3- (5-fluoro-2-hydroxy-3- (3,5-dimethylphenyl) phenyl) aminomethylidene) indolyl} benzoic (Compound 211); 2-hydroxy-3- acid. { 3 - (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylaminobenzoic acid (Compound 212); 2-Hydroxy acid -3-. { 3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) indolidene) methylamino} benzoic (Compound 213); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) aminomethylidene) pyrazolyl} butanoic (compound 214); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3-heptanylphenyl) hydrazono) pyrazolyl} butanoic (Compound 215); 4- Acid. { 2- (5-methyl-3-oxo-3, -dihydro-4- (2-hydroxy-3- (2,4-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 216); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (3-methyl) phenyl) ethenylphenyl) hydrazono) pyrazolyl Jbutanoic (Compound 217); 4- Acid. { l- (2-OXO-2, 3-dihydro-3- (2-hydroxy-3- (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl Jbutanoic (Compound 218); Acid 2-. { 1 - (2 - ??? - 2, 3-dihydro-3- (2-hydroxy-3 - (3, 5-dimethylphenyl) phenyl) hydrazone) indolyl} acetic (Compound 219); Acid 2-. { l. (2-OXO-2, 3-dihydro-3- (2-hydroxy-3 - (2- (2-methyl) phenyl) ethylphenyl) hydrazono) indolyl} acetic (Compound 220); 4- Acid. { 4- (2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3, 4-dimethylphenyl) indolidene) methylamino) thiazolyl} benzoic acid (Compound 221); {4- (2- (3- (6-trifluoromethyl-2-oxo-2,3-dihydro-1- (3,4-dimethylphenyl) indolidene) methylamino) thiazolyl} benzoic acid (Compound 221); -. {1- (5-Nitro-2-oxo-2,3-dihydro-3- (2-hydroxy-5-methyl-3- (1-adamantane) phenyl) aminomethylidene) indolyl} benzoic acid (Compound 222): 3- ({l- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (4-hydroxo-5- (3,4-dimethylphenyl) pyridinyl) hydrazono) indolyl}. benzoic acid (Compound 223); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxo-3- (2- (2-methyl) phenyl) -ethylphenyl) aminomethylidene) pyrazolyl} butanoic (Compound 224); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2- (2-fluoro) phenyl) -ethylphenyl) aminomethylidene) pyrazolyl} butanoic (Compound 225); and a pharmaceutically acceptable salt, ester or prodrug of any of these compounds. 21. The compound of claim 1, selected from: 4- Acid. { 2- (5-Methyl-3-oxo-3, -dihydro-4 (Z) - (2-hydroxy-3- (2- (1-naphthyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 226); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (3, 5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compounds 227); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 228); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluoro-3-methyl-phenyl) ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanóico (Compound 229); 4- Acid. { 2- (5-methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxo-3- (2- (2-fluoro-3-methyl-phenyl) ethyl) phenyl) aminomethylidene) irazolyl Jbutanico (Compound 230); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 231); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-cyano-phenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 232); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-chlorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 233); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 2. 3. 4); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-trifluoromethylphenyl) ethyl) phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 235): Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 236); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 237 ); Acid 3-. { 2- (5-trifluoromethyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2, (2,5-dimethyl-phenyl) aminomethylidene) pyrazolyl J-benzoic acid (Compound 238); Acid 3-. { 2- (5-trifluoromethyl-3 -oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethyl-phenyl) ethyl) phenyl) aminomethylidene) irazolyl} benzoic (Compound 239); Acid 3-. { 2- (5-phenyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 240); Acid 3-. { 2- (5-tert-Butyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 241); Acid 3-. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 242); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 243); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 244); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (4-phenylphenyl) -ethyl) phenyl) hydrazono) irazolyl} butanoic (Compound 245); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methoxyphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 246); 4- Acid. { 2- (5-methyl-2-oxo-2,3-dihydro-4- (2-hydroxy) 3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydrazone) irazolyl} butanoic (Compound 247); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 248); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-cyano-phenyl) -ethyl) -phenyl) -hydrazono) -pyrazolyl-J-tatanoic acid (Compound 249); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-chlorophenyl) ethyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 250); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 251); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-ethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 252); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono) irazolyl} butanoic (Compound 253); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazone) prazolyl Jbutanoic (Compound 254); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-6-trifluoromethylphenyl) ethyl) phenyl) hydrazone) pyrazolyl} butanoic (Compound 255); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 256); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 257); Acid (+) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 258); Acid (+) -3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1-indanylmethyl) phenyl) -hydrazono) pyrazolyl J-benzoic acid (Compound 259); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) -phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 260); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluoro-3-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 261); Acid 3-. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 262); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 263); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxo-3- (2,6-dichlorophenyl) -ethyl) phenyl) hydrazono) irazolyl J-benzoic acid (Compound 264); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methyl-6-trifluoromethylphenyl) ethyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 265); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanyl) phenyl) -hydrazono) pyrazolyl J-benzoic (Compound 266); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indenyl) phenyl) -hydrazono) pyrazolyl J-benzoic (Compound 267); Acid (E) -4 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl) phenyl) aminomethylidene) pyrazolyl Jbutanoic (Compound 268); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl J-benzoic acid (Compound 269); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} butanoic (Compound 270); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3,4-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl J-benzoic acid (Compound 271); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (3-hydroxy) 2- (3,5-dimethylphenyl) -4-pyridyl) hydrazone) irazolyl} benzoic (Compound 272); Acid 3 -. { 1- (6-trifluoromethyl-2-oxo-2,3-dihydro-3- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazone) indolyl} benzoic acid (Compound 273); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-benzylphenyl) hydrazono) -pyrazolyl} butanoic (Compound 274); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 275); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3-phenylpropyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 276); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 277); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 278); Acid (E) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-pyridyl) ethyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 279); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2- (2,6-dimethylphenyl) - (Z) -ethenyl) phenyl) hydrazone) pyrazolyl} butanoic (Compound 280); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 281); Acid (Z) -4-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-bromoethenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 282); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3-methyl-1-butenyl) phenyl) -hydrazono) pyrazolyl} butanoic (Compound 283); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (2-cyclopropyletenyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 284); Acid 3-. { 2- (5-methyl-3-oxo-2; 3-dihydro-4- (2-hydroxy-3- (3-methylbutyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 285); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-fluoro-3- (3,5-dimethylphenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 286); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 287); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 288); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3- (3,5-dimethylphenyl) phenyl) -hydrazono) irazolyl} butanoic (Compound 289); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -hydrazono) irazolyl} benzoic (Compound 290); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (5-chloro-2-hydroxy-3-cyclohexylphenyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 291); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3,4-dimethylphenyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 292); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3- (2-methylphenyl) propyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 293); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-benzofuranyl) phenyl) -hydrazono) pyrazolyl} benzoic (Compound 294); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-fluorophenyl) propyl) -phenyl) hydrazono) pyrazolyl Jbutanoic acid (Compound 295); Acid 3-. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3, 4-dimethylphenyl) -phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 296); Acid 3-. { 2. (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) aminomethylidene) pyrazolyl} benzoic (Compound 297); 4- Acid. { 2- (5-Methyl-3-oxo-3,4-dihydro-4 (Z) - (2-hydroxy-3- (3,4-dimethylphenyl) -phenyl) aminomethylidene) pyrazolyl} butanoic (Compound 298); Acid 3-. { l- (2-Oxo-2f 3-dihydro-3- (2-hydroxy-3- (3,5-dimethylphenyl) -phenyl) hydrazone) indolyl Jpropionic (Compound 299); Acid 3-. { 1- (2-OXO-2,3-dihydro-3- (2-hydroxy-3-benzylphenyl) hydrazone) -indolyl} benzoic (Compound 300); Acid 3-. { 1 - (2 - ?? - 2, 3-dihydro-3- (2-hydroxy-3 - (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolyl Jpropionic (Compound 301); Acid 3-. { 1- (6-chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (3- (3-methylphenyl) propyl) -phenyl) aminomethylidene) indolyl J-benzoic (Compound 302); Acid (+) -3-. { l- (6-chloro-2-oxo-2,3-dihydro-3 (Z) - (2-hydroxy-3- (1,2-dihydro-l-methyl-2-indolylphenyl) aminomethylidene) indolyl Jbenzoic (Compound 303); 4- {2- (5-Methyl-3-oxo-3,4-dihydro-4- (2-hydroxy-3- (2-methylphenylcarbonyl-amino) phenyl) hydrazono) pyrazolyl}. butanoic (Compound 304); 4- ({2- (5-methyl-3-oxo-3, -dihydro-4- (5-chloro-2-hydroxy-3- (2-methylphenylcarbonylamino) phenyl)} hydrazono) pyrazolyl Jbutanoic (Compound 305); 3-, {2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2- (2- fluorophenyl) ethyl) indolidene) -hydrazinophenyl} benzoic (Compound 306); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2- (2-chlorophenyl) ethyl) indolylidene) -hydrazinophenyl} benzoic (Compound 307); Acid 3 -. { 3-hydroxy-2 - (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) -pyrazolylidene) hydrazino-4-pyridyl} benzoic (Compound 308); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 309); Acid 3-. { 3-hydroxy-2- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -3-indolylidene-hydrazino) -4-pyridyl} benzoic (Compound 310); Acid 3-. { l- (2-OXO-2, 3-dihydro-3- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazino) indolyl J-benzoic acid (Compound 311); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-6-methyl-4- (3,4-dimethylphenyl) -2-pyridyl) hydrazono) pyrazolyl} benzoic (Compound 312); Acid 3-. { 3-hydroxy-4- (2-oxo-2,3-dihydro-1- (3,5-dimethylphenyl) -6-trifluoromethyl-3-indolylidenehydrazino) -2-pyridyl} benzoic (Compound 313); 4- Acid. { 2-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-2- (3, 5-dimethylphenyl) -4-pyridyl) hydrazono) pyrazolyl Jbutanóico (Compound 314); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3-hydroxy-5-phenyl-2-benzothienyl) -hydrazono) pyrazolyl Jbutanoic acid (Compound 315); Acid 3-. { 3-hydroxy-2- (5-methyl-3-oxo-2,3-dihydro-2- (3,4-dimethylphenyl) - - pyrazolidene) hydrazino - 5 - benzothienyl} benzoic (Compound 316); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (3- (2,3-dimethoxycarbonylphenyl) phenyl) -hydrazono) pyrazolyl Jbutanoic (Compound 317); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3,5-diisopropylphenyl) -carbonylhydrazinomethylidene) pyrazolyl Jbutanoic acid (Compound 318); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 (Z) - (2-hydroxy-3- (3,5-dimethylphenyl) phenyl) -aminomethylidene) pyrazolyl} butanoic (Compound 319); Acid (+) -4-. { 2- (5-methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2,3-dihydro-l-methyl-2-oxo-3-indolyl) methyl) phenyl) hydrazone Jubuntuic pyrazolyl (Compound 320); Acid 3-. { 1- (2-OXO-2,3-dihydro-5-fluoro-3- (2-hydroxy-3- (2- (2-methylphenyl) ethyl) phenyl) -hydrazono) indolylj propionic (Compound 321); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,5-dimethylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 322); Acid (+) -3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2,3-dihydro-l-methyl-2-oxo-3-indolyl) methyl) phenyl) hydrazone Pyrazolyl Jbenzoic (Compound 323); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1, 2-dihydro-l-methyl-2-oxo-3-indolylidene) methyl) phenyl) hydrazone ) J benzoic pyrazolyl (Compound 324); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 325); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4 (E) - (2-hydroxy-3- (2- (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 326); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyl} benzoic (Compound 327); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (1,2-dihydro-l-methyl-2-oxo-3-indolylidene) methyl) phenyl) hydrazone ) pyrazolyl} butanoic (Compound 328); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (5-fluoro-2-methylphenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 329), - 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3- (2 - (2,6-difluorophenyl) -ethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 330); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-dimethylphenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 331); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-methylphenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 332); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 333); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (Z) - (2- (5-fluoro-2-methyl) phenyl) ethenyl) phenyl) hydrazone) pyrazolyl } butanoic (Compound 334); 4- Acid. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2 - (3-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 335); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 336); 4- Acid. { 2- (5-Methyl-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 337); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2-phenylethenyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 338); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-phenylethynyl) -phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 339); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-methylphenyl) ethynyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 340); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,6-dimethylphenyl) -etinyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 341); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-fluorophenyl) ethynyl) -phenyl) hydrazono) pyrazolyl} butanoic (Compound 342); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2-trifluoromethylphenyl) -etinyl) phenyl) hydrazono) pyrazolyl jbutanoic (Compound 343); 4- Acid. { 2- (5-methyl-3 -oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-phenyl) ethenyl) phenyl) hydrazono) pyrazolyl jbutanoic (Compound 344 ); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (l-methyl-l-indenyl-2-phenyl) -hydrazono) pyrazolyl-jbutanoic acid (Compound 345); 4- ({2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (3, 3-dimethyl-2-indenyl) phenyl) hydrazono) pyrazolyl-jbutanoic (Compound 346); 4- {2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-5-methoxy-3- (2-indenyl) -phenyl) -hydrazono) -pyrazolyl acid jbutanoic (Compound 347); 4- ({2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy)) 3- (4,7-dimethyl) -2-indenyl) phenyl) hydrazono) irazolyl Jbutanoic (Compound 348); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (4,7-difluoro-2-indenyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 349); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2- (2-methylphenyl) -ethyl) -3 (Z) -indolylidene) methylaminophenyl} benzoic (Compound 350); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-6-trifluoromethyl-1- (2-indenyl) -3 (Z) -indolylidene) methylaminophenyl-benzene (Compound 351); Acid (+) -4-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2 - (1,2,3,4-tetrahydro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 352); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro) -naphthyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 353); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (1-indanylidene) -methylphenyl) hydrazono) pyrazolyl} butanoic (Compound 354); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-trifluoromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl Jbutanoic ( Compound 355); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (6-fluoro-2-trifluoro-methylphenyl) ethenyl) phenyl) hydrazone) irazolil} butanoic (Compound 356); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (6-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 357); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 358); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 359); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 360); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,5-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 361); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (4-fluoro-2-trifluoro-methylphenyl) ethenyl) phenyl) hydrazone) pyrazolyl } butanoic (Compound 362); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (2,4-difluorophenyl) -etinyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 363); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (1,2,3,4-tetrahydro) -naphthylidene) methylphenyl) hydrazono) pyrazolyl} butanoic (Compound 364); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-5-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyljbutanoic (Compound 365); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (3,5-dimethyl-4-isoxazolyl) ethenyl) phenyl) hydrazono) pyrazolyljbutanoic acid (Compound 366); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 5-dimethyl-4-isoxazolyl) ethyl) phenyl) hydrazono) pyrazolyljbutanoic (Compound 367 ); Acid 3 -. { 2-hydroxy-3 - (2-oxo-2,3-dihydro-1- (2 (E) - (2-methylphenyl) ethenyl) -3 (Z) -indolylidene) methylaminophenyl-benzene (Compound 368); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2 (E) - (2,4-difluorophenyl) ethenyl) -3 (Z) -indolylidene) methylaminophenyl} benzoic (Compound 369); Acid 3-. { 2-hydroxy-3- (2-oxo-2,3-dihydro-1- (2-indenyl) -3 (Z) -indolylidene) methyl-aminophenyl-benzene (Compound 370); Acid 3-. { 2-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (5-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 371); 4- Acid. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3-methylphenyl) hydrazono) -pyrazolyljbutanoic acid (Compound 372); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylidenemethyl) phenyl) hydrazono) pyrazolyl Jbutanoic (Compound 373); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2-indanylmethyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 374); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,4-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 375); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2,6-difluorophenyl) -ethenyl) phenyl) hydrazono) irazolyl} benzoic (Compound 376); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (4-fluoro-2-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 377); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-6-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 378); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,3-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic acid (Compound 379); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,3-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 380); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-fluoro-4-methylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 381); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 382); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,6-dichlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 383); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3 (E) - (2- (3-chlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 384); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2, 5-difluorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 385); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chloro-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 386); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-trifluoromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 387); 4- Acid. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2,4-dichlorophenyl) -ethenyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 388); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 (E) - (2- (2-chloromethyl-4-fluorophenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 389); Acid 3-. { 2- (5-methyl-3-oxo-2,3-dihydro-4- (2-hydroxy) 3 (E) - (2- (2,4-dichloromethylphenyl) ethenyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 390); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro) -naphthyl) phenyl) hydrazono) pyrazolyl J-benzoic acid (Compound 353); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2- (3,4-dihydro-8-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 392); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-8-methyl) -naphthyl) phenyl) hydrazono) irazolyl} butanoic (Compound 393); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3 - (2 - (3,4-dihydro-7-methyl) -naphthyl) phenyl) hydrazono) irazolyl} butanoic (Compound 394); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2 - (3, 4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 395); Acid 4 -. { 2 - (5-Methyl-3-oxo-2,3-dihydro-4 - (2-hydroxy-3- (2- (3, 4-dihydro-6-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 396); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-5-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 397); 4- Acid. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-8-chloro) -naphthyl) phenyl) hydrazono) pyrazolyl} butanoic (Compound 398); Acid 3-. { 2- (5-Methyl-3-oxo-2,3-dihydro-4- (2-hydroxy-3- (2- (3, 4-dihydro-7-fluoro) -naphthyl) phenyl) hydrazono) pyrazolyl} benzoic (Compound 399); and a pharmaceutically acceptable salt, ester, or prodrug of any of those compounds. 21. A compound of any of the preceding claims which is a selective TPO modulator. 22. The compound of claim 21 which is a TPO mimetic. 23. The compound of claim 21 which is a selective TPO receptor agonist. 24. The compound of claim 21 which is a selective TPO receptor partial agonist. 25. The compound of claim 21 which is a selective TPO receptor antagonist. 26. The compound of any of the preceding claims which is a selective TPO receptor binding compound. 27. The compound of claim 26, wherein the compound is a tissue-specific modulator. 28. A method for modulating a TPO activity in a cell comprising contacting a cell with a compound of any of the preceding claims. 29. A method for identifying a compound that modulates a TPO activity, comprising contacting a cell expressing a TPO receptor with a compound of any of claims 1-27; and monitor an effect of the compound on the cell. 30. A method for treating a patient, comprising administering to the patient a compound of any of claims 1-27. 31. The method of claim 30, wherein the patient undergoes a form of thrombocytopenia. 32. The method of claim 31, wherein the thrombocytopenia results from radiation or chemotherapy. 33. The method of claim 30, further comprising harvesting the patient's cells. 34. The method of claim 30, wherein the treatment is prophylactic. 35. The method of claim 30, wherein the patient suffers from a condition that affects the nervous system. 36. The method of claim 35, wherein the patient suffers from a disease selected from amyotrophic lateral sclerosis, multiple sclerosis, and multiple dystrophy. 37. The method of claim 35, wherein the patient suffers from a lesion in the nervous system. 38. The method of claim 35, wherein the patient suffers from a spinal cord injury. 39. A pharmaceutical composition comprising a physiologically acceptable carrier, diluent or excipient; and a compound of any of claims 1-27. 40. The pharmaceutical composition of claim 39 for use in treating a condition selected from thrombocytopenia and a condition affecting the nervous system.