Patent ID: 6436923
Filing Date: 2002-08-20
Classification: A61P,C07D

Abstract:
A compound having the structure: or a stereoisomer or a pharmaceutically acceptable salt thereof;wherein a is 0, 1 or 2; D is â€”(CH2)râ€” or â€”(CH2)nC(&boxH;O)(CH2)mâ€”; E and F are independently H or R; R1 represents one or two substituents independently selected from â€”Xâ€”Y; R2 is C1-8alkyl, C6-12alkyl, C7-12aralkyl, â€”C(&boxH;O)R5, pyridinyl, pyrimidinyl, furanyl, thienyl, triazenyl, imidazolyl, thiazolyl, pyrazolyl, pyridazinyl, pyrazinyl, furanyl, thiophenyl, imidiazolyl, pyranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, oxazinyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, diazinyl, indolyl, benzo[b]furanyl, benzo[b]thiophenyl, isoindolyl, benzo[c]furanyl, benzo[c]thiophenyl, benzodiazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, quinolinyl, isoquinolinyl, quinolizinyl, indolizinyl, cinnolinyl, quinoxalinyl, phthalizinyl, tetrahydropyranyl or tetrahydrofuranyl, wherein each of the above groups are optionally substituted with one to three substituents independently selected from â€”Xâ€”Y or R4; and R3 is hydrogen, â€”R6, â€”(CH2)sC(&boxH;O)R6, â€”(CH2)sC(&boxH;O)OR6, â€”(CH2)sC(&boxH;O)NR6R7, â€”(CH2)sC(&boxH;O)R6(CH2)nC(&boxH;O)R7R8, â€”(CH2)sNR6C(&boxH;O)R7, â€”(CH2)sNR6C(&boxH;O)NR7R8, â€”(CH2)sNR6R7, â€”(CH2)sOR6, â€”(CH2)sSO2R6, â€”(CH2)2SO2NR6R7; and wherein R4 is at each occurrence independently halogen, hydroxy, carboxy, C1-6alkyl, C1-4alkoxy, C1-4haloalkyl, C1-4acyloxy, C1-4thio, C1-4alkylsulfinyl, C1-4alkylsulfonyl, (hydroxy)C1-4alkyl, C6-12aryl, C7-12aralkyl, â€”C(&boxH;O)OH, â€”C(&boxH;O)OR, â€”C(&boxH;O)R, â€”C(&boxH;O)NHR, â€”C(&boxH;O)NRR, â€”C(&boxH;O)NHOR, â€”SO2NHR, â€”NHSO2R, â€”CN, â€”NO2, â€”NH2, C1-4alkylamino, C1-4dialkylamino, â€”NHC(&boxH;O)R, pyridinyl, pyrimidinyl, furanyl, thienyl, triazenyl, imidazolyl, thiazolyl, pyrazolyl, pyridazinyl, pyrazinyl, furanyl, thiophenyl, imidiazolyl, pyranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, oxazinyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, diazinyl, indolyl, benzo[b]furanyl, benzo[b]thiophenyl, isoindolyl, benzo[c]furanyl, benzo[c]thiophenyl, benzodiazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, quinolinyl, isoquinolinyl, quinolizinyl, indolizinyl, cinnolinyl, quinoxalinyl, phthalizinyl, tetrahydropyranyl or tetrahydrofuranyl, or â€”NHC(&boxH;O)(pyridinyl, pyrimidinyl, furanyl, thienyl, triazenyl, imidazolyl, thiazolyl, pyrazolyl, pyridazinyl, pyrazinyl, furanyl, thiophenyl, imidiazolyl, pyranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, oxazinyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, diazinyl, tetrahydropyranyl or tetrahydrofuranyl); and R5, R6, R7, and R8 are at each occurrence independently hydrogen, C1-8alkyl, C6-12aryl, C7-12aralkyl, pyridinyl, pyrimidinyl, furanyl, thienyl, triazenyl, imidazolyl, thiazolyl, pyrazolyl, pyridazinyl, pyrazinyl, furanyl, thiophenyl, imidiazolyl, pyranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, oxazinyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, diazinyl, wherein each of the above groups are optionally substituted with one to three substituents independently selected from R4; X is at each occurrence independently a direct bond; â€”(CH2)nZ(CH2)mâ€”; â€”O(CH2)nZ(CH2)mâ€”; â€”S(CH2)nZ(CH2)mâ€”; â€”NRc(CH2)nZ(CH2)mâ€”; â€”O(CH2)nCRaRbâ€”; â€”NRc(CH2)nCRaRbâ€”; â€”OCHRcCHRdâ€”; or â€”SCHRcCHRdâ€”; Y is at each occurrence independently â€”NReRf; â€ƒoptionally fused on adjacent carbon atoms with one or two phenyl or cycloalkyl rings, and with each carbon optionally and independently substituted with carbonyl or with one or two substituents independently selected from R4, with any two R4 substituents on a single carbon atom optionally being taken together to form a five- or six-membered oxygen-, nitrogen-, or sulfur-containing ring,; and with each nitrogen atom optionally and independently substituted with R4, wherein W is â€”NReâ€”, â€”Oâ€”, â€”Sâ€” or CReRfâ€”; or where â€”Xâ€”Y is Z is CH2, CH&boxH;CH, Câ‰¡C, O, NRc, S(O)q, C(&boxH;O), C(OH)Rc, C(&boxH;O)NRc, NRcC(&boxH;O) or G is O, S, or NRe; n and in are at each occurrence independently 0, 1, 2 or 3; p is at each occurrence independently 1, 2 or 3; q is at each occurrence independently 0, 1, or 2; r is at each occurrence independently 1, 2, 3, 4 or 5; s is at each occurrence independently 0, 1, 2, 3 or 4; R is at each occurrence independently C1-6alkyl; Ra and Rb are at each occurrence independently C1-8alkyl or taken together form a C3-8cyclic alkyl; Rc and Rd are at each occurrence independently hydrogen or C1-4alkyl; and Re and Rf are at each occurrence independently hydrogen, C6-12aryl, C1-4alkyl, C7-12aralkyl, pyridinyl, pyrimidinyl, furanyl, thienyl, triazenyl, imidazolyl, thiazolyl, pyrazolyl, pyridazinyl, pyrazinyl, furanyl, thiophenyl, imidiazolyl, pyranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, oxazinyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, diazinyl, indolyl, benzo[b]furanyl, benzo[b]thiophenyl, isoindolyl, benzo[c]furanyl, benzo[c]thiophenyl, benzodiazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, quinolinyl, isoquinolinyl, quinolizinyl, indolizinyl, cinnolinyl, quinoxalinyl, phthalizinyl, tetrahydropyranyl or tetrahydrofuranyl; and wherein each Re and Rf are optionally substituted with up to three substituents independently selected from R4.