HRP20020675A2 - Indazole compounds, pharmaceutical compositions and methods for mediating or inhibiting cell poliferation - Google Patents

Indazole compounds, pharmaceutical compositions and methods for mediating or inhibiting cell poliferation Download PDF

Info

Publication number: HRP20020675A2
Authority: HR; Croatia
Prior art keywords: image; substituted; heteroaryl; aryl; mmol
Prior art date: 2000-01-18

Application number

Other languages

English (en)

Croatian (hr)

Inventor

Siegfried Heinz Reich

Ted Michael Bleckman

Susan Elizabeth Kephart

William Henry Romines Iii

Michael Brennan Wallace

Original Assignee

Agouron Pharma

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-01-18

Filing date

2002-08-16

Publication date

2004-12-31

2002-08-16 Application filed by Agouron Pharma filed Critical Agouron Pharma

2004-12-31 Publication of HRP20020675A2 publication Critical patent/HRP20020675A2/hr

Links

238000000034 method Methods 0.000 title claims description 126
230000002401 inhibitory effect Effects 0.000 title claims description 11
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 199
229910052739 hydrogen Inorganic materials 0.000 claims description 173
229910052757 nitrogen Inorganic materials 0.000 claims description 160
229910052799 carbon Inorganic materials 0.000 claims description 159
125000000217 alkyl group Chemical group 0.000 claims description 76
150000003839 salts Chemical class 0.000 claims description 67
125000000623 heterocyclic group Chemical group 0.000 claims description 56
125000003118 aryl group Chemical group 0.000 claims description 54
125000001072 heteroaryl group Chemical group 0.000 claims description 54
239000000651 prodrug Substances 0.000 claims description 52
229940002612 prodrug Drugs 0.000 claims description 52
125000002837 carbocyclic group Chemical group 0.000 claims description 48
239000002207 metabolite Substances 0.000 claims description 48
-1 aryl heteroaryl Chemical group 0.000 claims description 44
239000003795 chemical substances by application Substances 0.000 claims description 41
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
201000010099 disease Diseases 0.000 claims description 32
102000001253 Protein Kinase Human genes 0.000 claims description 25
108060006633 protein kinase Proteins 0.000 claims description 25
230000000694 effects Effects 0.000 claims description 24
108091000080 Phosphotransferase Proteins 0.000 claims description 23
102000020233 phosphotransferase Human genes 0.000 claims description 23
230000004663 cell proliferation Effects 0.000 claims description 20
230000022983 regulation of cell cycle Effects 0.000 claims description 19
230000033115 angiogenesis Effects 0.000 claims description 17
239000000825 pharmaceutical preparation Substances 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
239000002904 solvent Substances 0.000 claims description 10
241000124008 Mammalia Species 0.000 claims description 9
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 9
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 9
101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims description 8
102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
239000003937 drug carrier Substances 0.000 claims description 7
230000005764 inhibitory process Effects 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
239000003981 vehicle Substances 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
230000001404 mediated effect Effects 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 2
125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
125000003441 thioacyl group Chemical group 0.000 claims description 2
125000005000 thioaryl group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
230000004614 tumor growth Effects 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 572
239000000543 intermediate Substances 0.000 description 368
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 279
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 250
238000005160 1H NMR spectroscopy Methods 0.000 description 218
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 170
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 144
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 139
229910001868 water Inorganic materials 0.000 description 138
239000000243 solution Substances 0.000 description 135
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239000007787 solid Substances 0.000 description 97
239000000203 mixture Substances 0.000 description 95
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 82
238000006243 chemical reaction Methods 0.000 description 80
238000010898 silica gel chromatography Methods 0.000 description 74
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 69
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
239000003921 oil Substances 0.000 description 53
235000019198 oils Nutrition 0.000 description 53
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
230000015572 biosynthetic process Effects 0.000 description 43
238000000746 purification Methods 0.000 description 42
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235000019341 magnesium sulphate Nutrition 0.000 description 41
206010028980 Neoplasm Diseases 0.000 description 39
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FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 39
238000003786 synthesis reaction Methods 0.000 description 38
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 37
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 34
239000012044 organic layer Substances 0.000 description 34
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 33
229910052938 sodium sulfate Inorganic materials 0.000 description 33
235000011152 sodium sulphate Nutrition 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
239000012267 brine Substances 0.000 description 31
229920006395 saturated elastomer Polymers 0.000 description 31
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
238000010511 deprotection reaction Methods 0.000 description 29
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 28
239000000843 powder Substances 0.000 description 28
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
238000002360 preparation method Methods 0.000 description 26
238000003756 stirring Methods 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
239000006260 foam Substances 0.000 description 23
238000001816 cooling Methods 0.000 description 22
238000010992 reflux Methods 0.000 description 22
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
201000011510 cancer Diseases 0.000 description 21
239000000284 extract Substances 0.000 description 21
239000007832 Na2SO4 Substances 0.000 description 20
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 20
150000002148 esters Chemical class 0.000 description 20
108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 19
102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
238000006317 isomerization reaction Methods 0.000 description 19
108091007914 CDKs Proteins 0.000 description 18
239000003054 catalyst Substances 0.000 description 18
210000004027 cell Anatomy 0.000 description 18
229910052786 argon Inorganic materials 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
239000002244 precipitate Substances 0.000 description 16
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 15
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
235000011114 ammonium hydroxide Nutrition 0.000 description 15
239000000725 suspension Substances 0.000 description 15
230000022131 cell cycle Effects 0.000 description 14
239000000460 chlorine Substances 0.000 description 14
239000003112 inhibitor Substances 0.000 description 14
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235000017557 sodium bicarbonate Nutrition 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 13
229910052740 iodine Inorganic materials 0.000 description 13
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 13
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
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MRXKEDUXQQGSPV-ZRDIBKRKSA-N trimethyl-[2-[[5-(4-methylpyridin-3-yl)-3-[(e)-2-phenylethenyl]indazol-1-yl]methoxy]ethyl]silane Chemical compound CC1=CC=NC=C1C1=CC=C(N(COCC[Si](C)(C)C)N=C2\C=C\C=3C=CC=CC=3)C2=C1 MRXKEDUXQQGSPV-ZRDIBKRKSA-N 0.000 description 1
MGGDZIIHNHXJNA-UHFFFAOYSA-N trimethyl-[2-[[5-phenyl-3-(2-phenylethenyl)indazol-1-yl]methoxy]ethyl]silane Chemical compound C12=CC(C=3C=CC=CC=3)=CC=C2N(COCC[Si](C)(C)C)N=C1C=CC1=CC=CC=C1 MGGDZIIHNHXJNA-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
230000005747 tumor angiogenesis Effects 0.000 description 1
230000005748 tumor development Effects 0.000 description 1
230000005740 tumor formation Effects 0.000 description 1
230000005909 tumor killing Effects 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
238000007631 vascular surgery Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000012800 visualization Methods 0.000 description 1
VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
239000002699 waste material Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
230000029663 wound healing Effects 0.000 description 1
GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22D—CASTING OF METALS; CASTING OF OTHER SUBSTANCES BY THE SAME PROCESSES OR DEVICES
- B22D41/00—Casting melt-holding vessels, e.g. ladles, tundishes, cups or the like
- B22D41/50—Pouring-nozzles
- B22D41/56—Means for supporting, manipulating or changing a pouring-nozzle
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Mechanical Engineering (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

HRP20020675 2000-01-18 2002-08-16 Indazole compounds, pharmaceutical compositions and methods for mediating or inhibiting cell poliferation HRP20020675A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US17648400P	2000-01-18	2000-01-18
PCT/US2001/001477 WO2001053268A2 (en)	2000-01-18	2001-01-18	Indazole compounds, pharmaceutical compositions, and their use for mediating or inhibiting cell proliferation

Publications (1)

Publication Number	Publication Date
HRP20020675A2 true HRP20020675A2 (en)	2004-12-31

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HRP20020675 HRP20020675A2 (en)	2000-01-18	2002-08-16	Indazole compounds, pharmaceutical compositions and methods for mediating or inhibiting cell poliferation

Country Status (39)

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US (4)	US6555539B2 (ru)
EP (1)	EP1250326A2 (ru)
JP (1)	JP2003520273A (ru)
KR (1)	KR20020073505A (ru)
CN (1)	CN1394205A (ru)
AP (1)	AP1609A (ru)
AR (1)	AR032438A1 (ru)
AU (1)	AU785013B2 (ru)
BG (1)	BG107011A (ru)
BR (1)	BR0107783A (ru)
CA (1)	CA2388885A1 (ru)
CO (1)	CO5280070A1 (ru)
CR (1)	CR6630A (ru)
DO (1)	DOP2001000120A (ru)
DZ (1)	DZ3301A1 (ru)
EA (1)	EA200200768A1 (ru)
EE (1)	EE200200398A (ru)
GE (1)	GEP20043363B (ru)
GT (1)	GT200100009A (ru)
HN (1)	HN2001000007A (ru)
HR (1)	HRP20020675A2 (ru)
HU (1)	HUP0203965A3 (ru)
IL (1)	IL150730A0 (ru)
IS (1)	IS6474A (ru)
MA (1)	MA27589A1 (ru)
MX (1)	MXPA02007058A (ru)
MY (1)	MY136604A (ru)
NO (1)	NO20022117L (ru)
NZ (1)	NZ518531A (ru)
OA (1)	OA12160A (ru)
PA (1)	PA8509901A1 (ru)
PE (1)	PE20011334A1 (ru)
PL (1)	PL357590A1 (ru)
SK (1)	SK10052002A3 (ru)
SV (1)	SV2002000293A (ru)
UA (1)	UA75880C2 (ru)
WO (1)	WO2001053268A2 (ru)
YU (1)	YU54202A (ru)
ZA (1)	ZA200203040B (ru)

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2000
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2001
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- 2001-01-18 CN CN01803552A patent/CN1394205A/zh active Pending
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2002
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Also Published As

Publication number	Publication date
US6919461B2 (en)	2005-07-19
WO2001053268B1 (en)	2002-01-24
PE20011334A1 (es)	2002-01-14
SV2002000293A (es)	2002-12-02
DZ3301A1 (fr)	2001-07-26
NO20022117D0 (no)	2002-05-03
MY136604A (en)	2008-10-31
AR032438A1 (es)	2003-11-12
SK10052002A3 (sk)	2003-03-04
CR6630A (es)	2004-01-29
US7232912B2 (en)	2007-06-19
GT200100009A (es)	2002-03-14
US20060111322A1 (en)	2006-05-25
BR0107783A (pt)	2002-11-19
KR20020073505A (ko)	2002-09-26
US6555539B2 (en)	2003-04-29
HUP0203965A3 (en)	2003-07-28
EP1250326A2 (en)	2002-10-23
CA2388885A1 (en)	2001-07-26
DOP2001000120A (es)	2002-04-15
UA75880C2 (en)	2006-06-15
CO5280070A1 (es)	2003-05-30
US20050239855A1 (en)	2005-10-27
AP1609A (en)	2006-05-08
JP2003520273A (ja)	2003-07-02
US20020161022A1 (en)	2002-10-31
HUP0203965A2 (en)	2003-05-28
WO2001053268A3 (en)	2001-12-27
NO20022117L (no)	2002-09-16
PL357590A1 (en)	2004-07-26
US20030139463A1 (en)	2003-07-24
HN2001000007A (es)	2001-06-13
ZA200203040B (en)	2003-08-11
MA27589A1 (fr)	2005-11-01
MXPA02007058A (es)	2003-01-28
NZ518531A (en)	2004-09-24
AP2002002564A0 (en)	2002-06-30
CN1394205A (zh)	2003-01-29
BG107011A (bg)	2003-04-30
IL150730A0 (en)	2003-02-12
AU2953901A (en)	2001-07-31
IS6474A (is)	2002-07-16
YU54202A (sh)	2006-01-16
EE200200398A (et)	2003-10-15
GEP20043363B (en)	2004-05-10
OA12160A (en)	2006-05-08
WO2001053268A2 (en)	2001-07-26
AU785013B2 (en)	2006-08-24
PA8509901A1 (es)	2002-08-26
EA200200768A1 (ru)	2003-02-27

Legal Events

Date	Code	Title	Description
2004-12-31	A1OB	Publication of a patent application
2005-06-30	ARAI	Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application
2007-01-12	PNAN	Change of the applicant name, address/residence	Owner name: AGOURON PHARMACEUTICALS, INC., US
2008-12-11	OBST	Application withdrawn

Publication	Publication Date	Title
US6555539B2 (en)	2003-04-29	Indazole compounds, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation
EP1614683B1 (en)	2007-11-21	Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
US6884890B2 (en)	2005-04-26	Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use
EP2468729A1 (en)	2012-06-27	Novel indazole derivative
CN105073742A (zh)	2015-11-18	Flap调节剂