CA2692013A1 - Modulators of ccr9 receptor and methods of use thereof - Google Patents
Modulators of ccr9 receptor and methods of use thereof Download PDFInfo
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- CA2692013A1 CA2692013A1 CA002692013A CA2692013A CA2692013A1 CA 2692013 A1 CA2692013 A1 CA 2692013A1 CA 002692013 A CA002692013 A CA 002692013A CA 2692013 A CA2692013 A CA 2692013A CA 2692013 A1 CA2692013 A1 CA 2692013A1
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
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Abstract
Provided are compounds that are modulators of CCR9 receptor activity, compositions containing the compounds and methods of use of the compounds and compositions. In certain embodiments, provided are methods for treating or ameliorating diseases associated with modulation of CCR9 receptor activity.
Claims (35)
1. A compound of Formula I:
or pharmaceutically acceptable derivatives thereof, wherein each R1 is selected as follows:
i) each R1 is independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, halo, pseudohalo, OR8, C(O)R9 and S(O)p R9; or ii) two R1 groups together with the carbon atoms on which they are substituted form a cycloalkyl, aryl, heteroaryl or heterocyclyl ring;
R2 is selected from H, alkyl, alkenyl, alkynyl, aryl and cycloalkyl;
R3, R4, R5, R6 and R7 are each independently selected as follows:
a) R3, R4, R5, R6 and R7 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, cycloalkyl, heterocyclyl, heteroaryl, halo, pseudohalo, OR8, C(O)R9 and S(O)p R9, or b) at least two of R3, R4, R5, R6 and R7, which substitute adjacent carbons on the ring, together with the carbon atoms on which they are substituted form a fused cycloalkyl, heterocyclyl, heteroaryl or aryl ring. The R3, R4, R5, R6 and R7 groups not forming this ring are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, halo, pseudohalo, OR8, C(O)R9 and S(O)p R9;
R8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylcarbonyl, cycloalkylcarbonyl or arylcarbonyl;
R9 is hydrogen, hydroxy, alkyl, haloalkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, cycloalkyl, aralkyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, alkylaryloxy, heterocyclyloxy, cycloalkyloxy, aralkoxy or ~C(O)R8;
n is 0-2; and p is 0-2;
with a proviso that:
i) when R1 is optionally substituted phenyl, pyridinyl or thienyl, then R3-R7 each are other than methyl or chloro;
ii) when R1 and R2 are each hydrogen, then R5 is other than H or chloro, and iii) when R2 is benzyl, then R5 is other than methoxy, where R1-R9 are optionally substituted with 1, 2, 3 or 4 substituents, each independently selected from Q1, where Q1 is halo, pseudohalo, hydroxy, oxo, thioxo, nitrile, nitro, formyl, mercapto, hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, haloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, heteroarylalkylidene, cycloalkylalkylidene, cycloalkylidene, heterocyclylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, heterocyclylcarbonyl, aralkylcarbonyl, heteroarylalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, aralkylaminocarbonyl, diaralkylaminocarbonyl, cycloalkylaminocarbonyl, dicycloalkylaminocarbonyl, cycloalkylalkylaminocarbonyl, dicycloalkylalkylaminocarbonyl, heteroarylaminocarbonyl, diheteroarylaminocarbonyl, heteroarylalkylaminocarbonyl, diheteroarylalkylaminocarbonyl, heterocyclylaminocarbonyl, diheterocyclylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, cycloalkylalkoxy, haloalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, ureido, N-alkylureido, N-arylureido, N'-alkylureido, N',N'-dialkylureido, N'-alkyl-N'-arylureido, N',N'-diarylureido, N'-arylureido, N,N'-dialkylureido, N-alkyl-N'-arylureido, N-aryl-N'-alkylureido, N,N'-diarylureido, N,N',N'-trialkylureido, N,N'-dialkyl-N'-arylureido, N-alkyl-N',N'-diarylureido, N-aryl-N',N'-dialkylureido, N,N'-diaryl-N'-alkylureido, N,N',N'-triarylureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, -N+R51R52R53, P(R50)2, P(=O)(R50)2, OP(=O)(R50)2, -NR60C(=O)R63, dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q1 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylene, alkylenoxy, alkylenthioxy, alkylenedioxy, thioalkylenoxy or alkylenedithioxy; or two Q1 groups, which substitute the same atom, together form alkylene; and each Q1 is independently unsubstituted or substituted with one, two or three substituents, each independently selected from Q2;
each Q2 is independently halo, pseudohalo, hydroxy, oxo, thioxo, nitrile, nitro, formyl, mercapto, hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, ureido, N-alkylureido, N-arylureido, N'-alkylureido, N',N'-dialkylureido, N'-alkyl-N'-arylureido, N',N'-diarylureido, N'-arylureido, N,N'-dialkylureido, N-alkyl-N'-arylureido, N-aryl-N'-alkylureido, N,N'-diarylureido, N,N',N'-trialkylureido, N,N'-dialkyl-N'-arylureido, N-alkyl-N',N'-diarylureido, N-aryl-N',N'-dialkylureido, N,N'-diaryl-N'-alkylureido, N,N',N'-triarylureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, -N+R51R52R53, P(R50)2, P(=O)(R50)2, OP(=O)(R50)2, -NR60C(=O)R63, dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q2 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylene, alkylenoxy, alkylenthioxy, alkylenedioxy, thioalkylenoxy or alkylenedithioxy ; or two Q2 groups, which substitute the same atom, together form alkylene;
R50 is hydroxy, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or -NR70R71, where R70 and R71 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclyl, or R70 and R71 together form alkylene, azaalkylene, oxaalkylene or thiaalkylene;
R51, R52 and R53 are each independently hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl;
R60 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl; and R63 is alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or -NR70R71.
or pharmaceutically acceptable derivatives thereof, wherein each R1 is selected as follows:
i) each R1 is independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, halo, pseudohalo, OR8, C(O)R9 and S(O)p R9; or ii) two R1 groups together with the carbon atoms on which they are substituted form a cycloalkyl, aryl, heteroaryl or heterocyclyl ring;
R2 is selected from H, alkyl, alkenyl, alkynyl, aryl and cycloalkyl;
R3, R4, R5, R6 and R7 are each independently selected as follows:
a) R3, R4, R5, R6 and R7 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, cycloalkyl, heterocyclyl, heteroaryl, halo, pseudohalo, OR8, C(O)R9 and S(O)p R9, or b) at least two of R3, R4, R5, R6 and R7, which substitute adjacent carbons on the ring, together with the carbon atoms on which they are substituted form a fused cycloalkyl, heterocyclyl, heteroaryl or aryl ring. The R3, R4, R5, R6 and R7 groups not forming this ring are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, halo, pseudohalo, OR8, C(O)R9 and S(O)p R9;
R8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, alkylcarbonyl, cycloalkylcarbonyl or arylcarbonyl;
R9 is hydrogen, hydroxy, alkyl, haloalkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, cycloalkyl, aralkyl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, alkylaryloxy, heterocyclyloxy, cycloalkyloxy, aralkoxy or ~C(O)R8;
n is 0-2; and p is 0-2;
with a proviso that:
i) when R1 is optionally substituted phenyl, pyridinyl or thienyl, then R3-R7 each are other than methyl or chloro;
ii) when R1 and R2 are each hydrogen, then R5 is other than H or chloro, and iii) when R2 is benzyl, then R5 is other than methoxy, where R1-R9 are optionally substituted with 1, 2, 3 or 4 substituents, each independently selected from Q1, where Q1 is halo, pseudohalo, hydroxy, oxo, thioxo, nitrile, nitro, formyl, mercapto, hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, haloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, heteroarylalkylidene, cycloalkylalkylidene, cycloalkylidene, heterocyclylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkylcarbonyl, haloalkylcarbonyl, heterocyclylcarbonyl, aralkylcarbonyl, heteroarylalkylcarbonyl, cycloalkylalkylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, aralkylaminocarbonyl, diaralkylaminocarbonyl, cycloalkylaminocarbonyl, dicycloalkylaminocarbonyl, cycloalkylalkylaminocarbonyl, dicycloalkylalkylaminocarbonyl, heteroarylaminocarbonyl, diheteroarylaminocarbonyl, heteroarylalkylaminocarbonyl, diheteroarylalkylaminocarbonyl, heterocyclylaminocarbonyl, diheterocyclylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, cycloalkylalkoxy, haloalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, ureido, N-alkylureido, N-arylureido, N'-alkylureido, N',N'-dialkylureido, N'-alkyl-N'-arylureido, N',N'-diarylureido, N'-arylureido, N,N'-dialkylureido, N-alkyl-N'-arylureido, N-aryl-N'-alkylureido, N,N'-diarylureido, N,N',N'-trialkylureido, N,N'-dialkyl-N'-arylureido, N-alkyl-N',N'-diarylureido, N-aryl-N',N'-dialkylureido, N,N'-diaryl-N'-alkylureido, N,N',N'-triarylureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, -N+R51R52R53, P(R50)2, P(=O)(R50)2, OP(=O)(R50)2, -NR60C(=O)R63, dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q1 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylene, alkylenoxy, alkylenthioxy, alkylenedioxy, thioalkylenoxy or alkylenedithioxy; or two Q1 groups, which substitute the same atom, together form alkylene; and each Q1 is independently unsubstituted or substituted with one, two or three substituents, each independently selected from Q2;
each Q2 is independently halo, pseudohalo, hydroxy, oxo, thioxo, nitrile, nitro, formyl, mercapto, hydroxycarbonyl, hydroxycarbonylalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, ureido, N-alkylureido, N-arylureido, N'-alkylureido, N',N'-dialkylureido, N'-alkyl-N'-arylureido, N',N'-diarylureido, N'-arylureido, N,N'-dialkylureido, N-alkyl-N'-arylureido, N-aryl-N'-alkylureido, N,N'-diarylureido, N,N',N'-trialkylureido, N,N'-dialkyl-N'-arylureido, N-alkyl-N',N'-diarylureido, N-aryl-N',N'-dialkylureido, N,N'-diaryl-N'-alkylureido, N,N',N'-triarylureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, -N+R51R52R53, P(R50)2, P(=O)(R50)2, OP(=O)(R50)2, -NR60C(=O)R63, dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, hydroxycarbonylalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q2 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylene, alkylenoxy, alkylenthioxy, alkylenedioxy, thioalkylenoxy or alkylenedithioxy ; or two Q2 groups, which substitute the same atom, together form alkylene;
R50 is hydroxy, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or -NR70R71, where R70 and R71 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclyl, or R70 and R71 together form alkylene, azaalkylene, oxaalkylene or thiaalkylene;
R51, R52 and R53 are each independently hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl;
R60 is hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl; and R63 is alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or -NR70R71.
2. The compound of claim 1, wherein R1 is H or alkyl.
3. The compound of claims 1 or 2, wherein R1 is H.
4. The compound of any of claims 1 or 2, wherein two R1 groups together with the carbon atoms on which they are substituted form an optionally substituted aryl or heteroaryl ring, wherein the substituents for the ring formed are selected from alkyl and halo.
5. The compound of any of claims 1-4, wherein R2 is H or alkyl.
6. The compound of any of claims 1-5, wherein R3 and R7 are each independently selected from hydrogen, hydroxy, alkyl, halo, aryl, dialkylaminoaryl, heteroaryl, haloaryl, heterocyclyl, cycloalkyl, alkoxy, cyano, aralkyl, alkylcarbonyl, aryloxy, cycloalkylalkenyl, cycloalkylalkyl, alkoxyalkenyl, alkoxyalkyl and hydroxycarbonylalkenyl.
7. The compound of any of claims 1-6, wherein R3 and R7 are each independently selected from hydrogen, methyl, phenyl, 4-dimethylaminophenyl, 2-chloropyridin-4-yl, piperidin-1-yl, pyrimidin-5-yl, hydroxy, 3-chlorophenyl, 3-fluorophenyl, morpholin-4-yl, bromo, chloro, fluoro, cyclopentyl, 4-chlorophenyl, 2-styryl, methoxy, hydroxy, cyano, phenethyl, acetoxy, ethyl, phenoxy, cyclopropylvinyl, 3-methoxyprop-1-enyl, propyl, 2-cyclopropylethyl, pentyl, 3-methoxypropyl, furan-3-yl, vinyl and 2-carboxyvinyl.
8. The compound of any of claims 1-7, wherein one of R3 and R7 is selected from hydrogen, halo and alkyl and the other is selected from hydrogen, hydroxy, alkyl, halo, aryl, dialkylaminoaryl, heteroaryl, haloaryl, heterocyclyl, cycloalkyl, alkoxy, cyano, arylalkyl, alkylcarbonyl, aryloxy, cycloalkylalkenyl, cycloalkylalkyl, alkoxyalkenyl, alkoxyalkyl and hydroxycarbonylalkenyl.
9. The compound of any of claims 1-6, wherein one of R3 and R7 is selected from hydrogen, chloro and methyl and the other is selected from methyl, phenyl, 4-dimethylaminophenyl, 2-chloropyridin-4-yl, piperidin-1-yl, pyrimidin-5-yl, hydroxy, 3-chlorophenyl, 3-fluorophenyl, morpholin-4-yl, bromo, chloro, fluoro, cyclopentyl, 4-chlorophenyl, 2-styryl, methoxy, hydroxy, cyano, phenethyl, acetoxy, ethyl, phenoxy, cyclopropylvinyl, 3-methoxyprop-1-enyl, propyl, 2-cyclopropylethyl, pentyl, 3-methoxypropyl, furan-3-yl, vinyl and 2-carboxyvinyl..
10. The compound of any of claims 1-9, wherein R5 is selected from hydrogen, alkyl, halo, haloalkyl, heterocyclyl, cycloalkyl, heteroaryl and haloalkoxy.
11. The compound of any of claims 1-9, wherein R5 is selected from hydrogen, fluoro, tert-butyl, tert-pentyl, trifluoromethyl, 4-morpholinyl, sec-butyl, isopropyl, butyl, 1-pyrrolidinyl, cyclohexyl, pyrazol-1-yl, cyclopentyl and trifluoromethoxy.
12. The compound of any of claims 1-9, wherein R4 and R5 together with the carbon atoms on which they are substituted form a fused 5 or 6 membered cycloalkyl ring, optionally substituted with 1-4 methyl groups.
13. The compound of any of claims 1-9, wherein R4 and R5 together with the carbon atoms on which they are substituted form a fused 6 membered aryl ring.
14. The compound of any of claims 1-13, wherein R4 and R6 are each independently selected from hydrogen, aryl, alkylaryl, alkoxyaryl and alkyl.
15. The compound of any of claims 1-13, wherein R4 and R6 are each independently selected from hydrogen, methyl, phenyl, 2-methylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, 2-isopropylphenyl, 2- propoxyphenyl and 2-ethylphenyl.
16. The compound of any of claims 1-13 wherein one of R4 and R6 is hydrogen and the other is selected from hydrogen, aryl, alkylaryl, alkoxyaryl and alkyl.
17. The compound of any of claims 1-13, wherein one of R4 and R6 is hydrogen and the other is selected from hydrogen, methyl, phenyl, 2-methylphenyl, 2,6-dimethylphenyl, 3,5-dimethylphenyl, 2-isopropylphenyl, 2- propoxyphenyl and 2-ethylphenyl.
18. The compound of any of claims 1-17, wherein R8 is hydrogen, alkyl, haloalkyl, aryl or alkylcarbonyl.
19. The compound of any of claims 1-18, wherein R8 is hydrogen, methyl, acetyl or phenyl.
20. The compound of any of claims 1-19, wherein R9 is hydrogen, hydroxy, alkoxy or alkyl.
21. The compound of any of claims 1-20, wherein the compound has formula II:
or a pharmaceutically acceptable derivative thereof, where R1 is hydrogen or alkyl.
or a pharmaceutically acceptable derivative thereof, where R1 is hydrogen or alkyl.
22. The compound of claim 1, wherein the compound has formula III:
or a pharmaceutically acceptable derivative thereof, wherein n is 0 or 1 and R5 is alkyl, heterocyclyl, cycloalkyl or halo.
or a pharmaceutically acceptable derivative thereof, wherein n is 0 or 1 and R5 is alkyl, heterocyclyl, cycloalkyl or halo.
23. The compound of claim 22, wherein R5 is tert-butyl.
24. The compound of claim 1, wherein the compound has formula IV:
or pharmaceutically acceptable derivative thereof, wherein R2 is hydrogen or alkyl;
R5 is alkyl, cycloalkyl, haloalkyl, haloalkoxy or halo; and R7 is alkyl, halo, alkoxy, cyano, aralkyl, aryloxy, cycloalkyl, cycloalkylalkenyl, alkoxyalkenyl, cylcoalkylalkyl, alkoxyalkyl, aryl, heteroaryl, hydroxycarbonylalkenyl or alkenyl.
or pharmaceutically acceptable derivative thereof, wherein R2 is hydrogen or alkyl;
R5 is alkyl, cycloalkyl, haloalkyl, haloalkoxy or halo; and R7 is alkyl, halo, alkoxy, cyano, aralkyl, aryloxy, cycloalkyl, cycloalkylalkenyl, alkoxyalkenyl, cylcoalkylalkyl, alkoxyalkyl, aryl, heteroaryl, hydroxycarbonylalkenyl or alkenyl.
25. The compound of claim 24, wherein R5 is tert-butyl, n-butyl, trifluoromethyl, trifluoromethoxy or cyclopentyl.
26. The compound of claim 24, wherein the compound has formula V:
or a pharmaceutically acceptable derivative thereof.
or a pharmaceutically acceptable derivative thereof.
27. The compound of claim 1, wherein the compound has formula VI:
or a pharmaceutically acceptable derivative thereof, wherein each Q1 is independently selected from alkyl and alkoxy and n2 is 0, 1 or 2.
or a pharmaceutically acceptable derivative thereof, wherein each Q1 is independently selected from alkyl and alkoxy and n2 is 0, 1 or 2.
28. The compound of claim 27, wherein each Q1 is independently selected from methyl, ethyl, isopropyl and propoxy.
29. The compound of claim 1, wherein the compound has formula XA:
or a pharmaceutically acceptable derivative thereof, wherein each Q1 is independently selected from alkyl and alkoxy; and n2 is 0, 1 or 2.
or a pharmaceutically acceptable derivative thereof, wherein each Q1 is independently selected from alkyl and alkoxy; and n2 is 0, 1 or 2.
30. The compound of claim 1, wherein the compound has formula XIA:
or a pharmaceutically acceptable derivative thereof, wherin Q1 is selected from alkyl and alkoxy and n2 is 0, 1 or 2.
or a pharmaceutically acceptable derivative thereof, wherin Q1 is selected from alkyl and alkoxy and n2 is 0, 1 or 2.
31. A compound selected from:
or a pharmaceutically acceptable derivative thereof.
or a pharmaceutically acceptable derivative thereof.
32. A pharmaceutical composition comprising a compound of any of claims 1-31 or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable carrier.
33. A method for modulating CCR9 receptor activity comprising contacting the CCR9 receptor with the compound of any of claims 1-31 or a pharmaceutically acceptable derivative thereof.
34. A method for treating, preventing or ameliorating a disease associated with CCR9 receptor modulation comprising administering the compound of any of claims 1-31 or a pharmaceutically acceptable derivative thereof.
35. The method of claim 34, wherein the disease is Crohn's disease, ulcerative colitis, celiac disease, primary sclerosing cholangitis, HIV, prostate cancer, leukemia, small intestinal cancer or melanoma.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96264007P | 2007-07-30 | 2007-07-30 | |
| US60/962,640 | 2007-07-30 | ||
| PCT/US2008/009142 WO2009017719A2 (en) | 2007-07-30 | 2008-07-28 | Modulators of ccr9 receptor and methods of use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2692013A1 true CA2692013A1 (en) | 2009-02-05 |
| CA2692013C CA2692013C (en) | 2012-08-28 |
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| CA2692013A Expired - Fee Related CA2692013C (en) | 2007-07-30 | 2008-07-28 | Modulators of ccr9 receptor and methods of use thereof |
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| EP (1) | EP2220065A2 (en) |
| KR (1) | KR20100033418A (en) |
| AU (1) | AU2008282903B2 (en) |
| CA (1) | CA2692013C (en) |
| MX (1) | MX2010001187A (en) |
| SG (1) | SG183667A1 (en) |
| WO (1) | WO2009017719A2 (en) |
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| MY157017A (en) | 2009-01-12 | 2016-04-15 | Pfizer Ltd | Sulfonamide derivatives |
| EP2560636A4 (en) * | 2010-04-23 | 2013-11-27 | Kineta Inc | Anti-viral compounds |
| US9145407B2 (en) | 2010-07-09 | 2015-09-29 | Pfizer Limited | Sulfonamide compounds |
| MX339201B (en) * | 2010-10-12 | 2016-05-13 | Zafgen Inc | Sulphonamide compounds and methods of making and using same. |
| TW201512171A (en) | 2013-04-19 | 2015-04-01 | Pfizer Ltd | Chemical compounds |
| WO2023074408A1 (en) * | 2021-10-28 | 2023-05-04 | 四国化成工業株式会社 | Thiophene compound, method for synthesizing same, and composition containing said thiophene compound |
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| BR9714350A (en) * | 1996-10-16 | 2000-04-11 | American Cyanamid Co | Preparation and use of hydroxamic heteroaryl orthosulfonamide acids with matrix and theta metalloproteinase inhibitors |
| JP3972163B2 (en) * | 1999-06-18 | 2007-09-05 | 株式会社大塚製薬工場 | Phosphonic acid diester derivatives |
| CA2767153A1 (en) * | 2003-02-20 | 2004-09-02 | Encysive Pharmaceuticals Inc. | Phenylenediamine urotensin-ii receptor antagonists and ccr-9 antagonists |
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2008
- 2008-07-28 AU AU2008282903A patent/AU2008282903B2/en not_active Ceased
- 2008-07-28 SG SG2012056255A patent/SG183667A1/en unknown
- 2008-07-28 WO PCT/US2008/009142 patent/WO2009017719A2/en active Application Filing
- 2008-07-28 CA CA2692013A patent/CA2692013C/en not_active Expired - Fee Related
- 2008-07-28 MX MX2010001187A patent/MX2010001187A/en not_active Application Discontinuation
- 2008-07-28 EP EP08794832A patent/EP2220065A2/en not_active Withdrawn
- 2008-07-28 KR KR1020107001995A patent/KR20100033418A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009017719A2 (en) | 2009-02-05 |
| AU2008282903A1 (en) | 2009-02-05 |
| WO2009017719A8 (en) | 2010-02-11 |
| EP2220065A2 (en) | 2010-08-25 |
| KR20100033418A (en) | 2010-03-29 |
| SG183667A1 (en) | 2012-09-27 |
| AU2008282903B2 (en) | 2011-06-30 |
| CA2692013C (en) | 2012-08-28 |
| WO2009017719A3 (en) | 2009-04-23 |
| MX2010001187A (en) | 2010-03-04 |
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