Patent ID: 6596747
Filing Date: 2003-07-22
Classification: A61K,A61P,C07D

Abstract:
A compound of the formula, or a pharmaceutically-acceptable salt, hydrate or prodrug thereof, wherein:D is a monocyclic or bicyclic carbocyclic ring system optionally substituted by one to four (CR9R10)nE groups; R4 is selected from hydrogen, halogen, NO2, CF3, C0-C4 alkylCN, C1-C4alkoxy-, C0-C4 alkylhydroxy, C1-C4 alkyl-, C1-C4 alkylcarbonyl-, C0-C4 alkylOCOR6, C0-C4 alkylOC(&boxH;O)OR6, C0-C4 alkylOC(&boxH;O)NR6R7, C0-C4 alkylNR6R7, C0-C4alkylNR7C(&boxH;O)OR6, C0-C4 alkylNR6SO2NR6R7, C0-C4 alkylNR6SO2R7, C0-C4 alkylSR6, C0-C4 alkylS(O)R7, C0-C4 alkylSO2R7, SO3R7, C0-C4 alkylSO2NR6R7, C0-C4alkyl SO2NR7CO(CR9R10)qR6, C0-C4 alkylCO2R6, C0-C4 alkylC(&boxH;O)NR6R7, and C0-C4alkyl C(&boxH;O)NR6SO2(CR9R10)qR7; R is hydrogen or C1-C4alkyl; R1 and R2 are each independently selected from hydrogen, halogen, NO2, C1-C4alkyl, C3-C10 cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, haloalkyl, haloalkoxy, OR6, O(CR9R10)rCO2R6, O(CR9R10)m NR6R7, O(CR9R10)pCN, O(CR9R10)rC(&boxH;O)NR6R7, C1-C4alkylcarbonyl, CN, NR6R7, NR7(CR9R10)rCO2R6, NR7OR6, NR7(CR9R10)mOR6, NR7CH[(CR9R10)pOR6]2, NR7C[(CR9R10)pOR6]3, NR7(CR9R10)mOR6, NR7(CR9R10)mNR6R7, NR6(CR9R10)mSO2(CR9R10)qR7, SR7, S(O)R7, SO2R7, SO2NR6, SO3R7, CO2R6, and C(&boxH;O)NR6R7; or, alternatively, R1 and R2, when on adjacent carbon atoms, may be taken together to be methylenedioxy or ethylenedioxy; R6, R7 and R8 are each independently selected from hydrogen, C1-C6alkyl, C3-C10 cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6 alkylcarbonyl, C3-C7 cycloalkyl(C0-C5alkyl)carbonyl, C1-C6 alkoxycarbonyl, aryl(C0-C5 alkyl)carbonyl, aryl(C1-C5 alkoxy)carbonyl, heterocyclic(C0-C5 alkyl)carbonyl, heterocyclic(C1-C5 alkoxy)carbonyl, C1-C6alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, C0-C4alkylaryl, C0-C4alkylheterocyclic, wherein said cycloalkyl, aryl or heterocyclic groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4alkyl, hydroxy, C1-C4 alkoxy, F, Cl, Br, haloalkyl, NO2 and CN; ; provided, however, that when directly attached to a sulfonyl group as in S(O)R7, SO2R7, SO2NR6, or SO3R7, then R7 is not hydrogen; or, alternatively, R6 and R7, or R6 and R8, or R7 and R8, when both substituents are on the same nitrogen atom [as in (â€”NR6R7) or (â€”NR7R8)], can be taken together with the nitrogen atom to which they are attached to form a heterocycle selected from 1-aziridinyl, 1-azetidinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, 1-piperazinyl, 1-imidazolyl, 3-azabicyclo[3,2,2]nonan-3-yl, and 1-tetrazolyl, said heterocycle being optionally substituted with 0-3 groups selected from oxo, C0-C4alkylOH, C0-C4alkylOC1-C4alkyl, C0-C4alkylC(&boxH;O)NH2, C0-C4alkylCO2C0-C4alkyl, C1-C6 alkyl, C1-C4 alkoxy, C3-C7 cycloalkyl, â€”C0-C6 alkylcarbonyl, C3-C7 cycloalkylcarbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkoxycarbonyl, â€”NHCOalkyl, aryl, heteroaryl, arylalkoxycarbonyl, heteroarylalkoxycarbonyl, C1-C6 alkylsulfonyl, arylsulfonyl and heteroarylsulfonyl; B is a 5-membered heterocycle containing one N and additional 0-3 heteroatoms selected from N, O, and S, and wherein B is optionally substituted by one to four R11 groups; R9 hydrogen or C1-C4alkyl; R10 is selected from hydrogen or C1-C4 alkyl, C1-C4 alkylhydroxy, C1-C4alkylaryl or C1-C4alkylheteroaryl, wherein said aryl or heteroaryl group may be substituted with 0-3 groups independently selected from hydrogen, halogen, NO2, C1-C4alkyl, C3-C10 cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, haloalkyl, haloalkoxy, OH, C1-C4alkoxy, C1-C4alkylcarbonyl, CN, NR6R7, SR6, S(O)R7, SO2R7, SO3R7, SO2NR6, CO2R6, and C(&boxH;O)NR6R7; R11 is selected from hydrogen, halogen, NO2, C1-C4alkyl, C3-C10 cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, haloalkyl, haloalkoxy, C1-C4alkoxy-, OR6, O(CR9R10)rCO2R6, O(CR9R10)m NR6R7, O(CR9R10)pCN, O(CR9R10)rC(&boxH;O)NR6R7, C1-C4alkylcarbonyl-, CN, NR6R7, NR7(CR9R10)rCO2R6, NR7OR6, NR7(CR9R10)mOR6, NR7CH[(CR9R10)pOR6]2, NR7C[(CR9R10)pOR6]3, NR7C(&boxH;O)R6, NR7(CR9R10)mOR6, NR7(CR9R10)mNR6R7, NR6(CR9R10)mSO2(CR9R10)qR7, SR7, S(O)R7, SO2R7, SO2NR6, SO3R7, CO2R6, and C(&boxH;O)NR6R7; E is selected from hydrogen, halogen, NO2, C1-C4alkyl, C3-C10 cycloalkyl, C2-C6alkenyl, C2-C6 alkynyl, haloalkyl, haloalkoxy, OR6, CN, CHO, CO2R6, C(&boxH;O)NR6R7, OCOR6, OC(&boxH;O)OR6, OC(&boxH;O)NR6R7, OCH2CO2R6, C(&boxH;O)R6, NR6R7, NR7C(&boxH;O)R6, NR7C(&boxH;O)OR6, NR7C(&boxH;O)C(&boxH;O)OR6, NR7C(&boxH;O)C(&boxH;O)NR6R7, NR7C(&boxH;O)C(&boxH;O)(C1-C6alkyl), NR7C(&boxH;NCN)OR6, NR7C(&boxH;O)NR6R7, NR7C(&boxH;NCN)NR6R7, NR7C(&boxH;NR6)NR7R8, NR6SO2NR6R7, NR6SO2R7, SR6, S(&boxH;O)R7, SO2R7, SO3R7, SO2NR6R7, NHOR6, NR6NR7NR8, N(COR6)OH, N(CO2R6)OH, CO2R6, C(&boxH;O)NR7(CR9R10)rR6, CO(CR9R10)pO(CHR9)qCO2R6, CO(CR9CR10)rOR6, CO(CR9R10)pO(CR9R10)qR6, CO(CR9CR10)rNR6R7, OC(O)O(CR9R10)mNR6R7, O(CO)N(CR9R10)rR6, O(CR9R10)m NR6R7, NR7C(O)(CR9R10)rR6, NR7C(O)(CR9R10)rOR6, NR7C(&boxH;NC)(CR9R10)rR6, NR7CO(CR9R10)r NR6R7, NR7(CR9R10)mOR6, NR7(CR9R10)rCO2R6, NR7(CR9R10)mNR6R7, NR6(CR9R10)nSO2(CR9R10)qR7, C(&boxH;O)NR6(CR9R10)nSO2(CR9R10)qR7, SO2NR7(CR9R10)nCO(CR9R10)qR6, SO2NR6(CR9R10)mOR6, C3-C10 cycloalkylmethyl, aryl, heterocyclic and alkylaryl, wherein said aryl groups may be substituted with 0-2 substituents independently selected from R12; R12 at each occurrence is independently selected from hydrogen, halogen, NO2, C1-C4alkyl, C3-C10 cycloalkyl, C2-C6alkenyl, C2-C6alkynyl, haloalkyl, haloalkoxy, oxo, OR6, O(CR9R10)rCO2R6, O(CR9R10)mNR6R7, O(CR9R10)pCN, O(CR9R10)rC(&boxH;O)NR6R7, C1-C4alkylcarbonyl-, CN, NR6R7, NR7(CR9R10)rCO2R6, NR7OR6, NR7(CR9R10)mOR6, NR7CH[(CR9R10)pOR6]2, NR7C[(CR9R10)pOR6]3, NR7C(&boxH;O)R6, NR7(CR9R10)mOR6, NR7(CR9R10)mNR6R7, NR6(CR9R10)mSO2(CR9R10)qR7, SR7, S(O)R7, SO2R7, SO2NR6, SO3R7, CO2R6, and C(&boxH;O)NR6R7; n is an integer having a value from 0-4; m is an integer having a value from 2-6; p is an integer having a value from 1-3; q is an integer having a value from 0-3; and r is an integer having a value from 0-6.