Patent ID: 6492396
Filing Date: 2002-12-10
Classification: A61P,C07C,C07D

Abstract:
A compound of formula (I-A): wherein:Ar1 and Ar2 are each independently selected from C6-C10 aryl or heteroaryl; wherein each of Ar1 or Ar2 may be independently optionally substituted with 1-3 substituents independently selected from: a) H, C6-C10 aryl, heteroaryl, F, Cl, Br, I, â€”CN, â€”CF3, â€”NO2, â€”OH, â€”OR7, â€”O(CH2)pNR9R10, â€”OC(&boxH;O)R7, â€”OC(&boxH;O)NR9R10, â€”O(CH2)pOR8, â€”CH2OR8, â€”NR9R10, â€”NR8S(&boxH;O)2R7, â€”NR8C(&boxH;O)R7, or â€”NR8C(&boxH;S)R7; b) â€”CH2OR11; c) â€”NR8C(&boxH;O)NR9R10, â€”NR8C(&boxH;S)NR9R10, â€”CO2R12, â€”C(&boxH;O)R13, â€”C(&boxH;O)NR9R10, â€”C(&boxH;S)NR9R10, â€”CH&boxH;NOR12, â€”CH&boxH;NR7, â€”(CH2)pNR9R10, â€”(CH2)pNHR11, â€”CH&boxH;NNR12R12A, â€”C(&boxH;NR8)NR8AR8B â€”NR8C(&boxH;NH)R8A, â€”NR8C(&boxH;NH)NR8AR8B,d) â€”S(O)yR7, â€”(CH2)pS(O)yR7, â€”CH2S(O)yR7; and f) C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, where: 3) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 4) each alkyl, alkenyl or alkynyl group is independently substituted with 1 to 3 groups independently selected from C6-C10 aryl, heteroaryl, F, Cl, Br, I, CF3, â€”CN, â€”NO2, â€”OH, â€”OR7, â€”CH2OR8, â€”NR9R10, â€”Oâ€”(CH2)pâ€”OH, â€”Sâ€”(CH2)pâ€”OH, â€”X1(CH2)pOR7, X1(CH2)pNR9R10, â€”X1(CH2)pC(&boxH;O)NR9R10, â€”X1(CH2)pC(&boxH;S)NR9R10, â€”X1(CH2)pOC(&boxH;O)NR9R10, â€”X1(CH2)pCO2R8, â€”X1(CH2)pS(O)yR7, â€”XS (CH2)pNR8C(&boxH;O)NR9R10, â€”C(&boxH;O)R13, â€”CO2R12, â€”OC(&boxH;O)R7, â€”C(&boxH;O)NR9R10, â€”OC(&boxH;O)NR12R12A, O-tetrahydropyranyl, â€”C(&boxH;S)NR9R10, â€”CH&boxH;NNR12R12A, â€”CH&boxH;NOR12, â€”CH&boxH;NR7, â€”CH&boxH;NNHCHCN&boxH;NH)NH2, â€”NR8CO2R7, â€”NR8C(&boxH;O)NR9R10, â€”NR8C(&boxH;S)NR9R10, â€”NHC(&boxH;NH)NH2, â€”NR8C(&boxH;O)R7, â€”NR8C(&boxH;S)R7, â€”NR8S(&boxH;O)2R7, â€”S(O)yR7, â€”S(&boxH;O)2NR12R12A, â€”P(&boxH;O)(OR8)2, â€”OR11, and a C5-C7 monosaccharide where each hydroxyl group of the monosaccharide is independently either unsubstituted or is replaced by H, C1-C4 alkyl, C1-C4 alkoxy, or â€”Oâ€”C(&boxH;O)R7; X1 is â€”Oâ€”, â€”Sâ€”, â€”N(R8)â€”; Y is selected from C1-C4 alkylene, â€”C(R1)(R2)â€”, C6-C10 arylene, heteroarylene, C3-C8 cycloalkylene, heterocyclylene, â€”Oâ€”, â€”N(R8)â€”, â€”S(O)y, â€”CR9A&boxH;CR8Bâ€”, â€”CH&boxH;CHâ€”CH(R8)â€”, â€”CH(R8)â€”CH&boxH;CHâ€”, or â€”Câ‰¡Câ€”; with the proviso that when Y is â€”Oâ€”, â€”N(R8)â€”, or â€”S(O)y, m and n cannot be 0; R3 and R4 are the same or different and are each selected from H, C1-C6 alkyl, â€”OH, and â€”CH(R6)â€”CONR8AR8B, provided that R3 and R4 are not both OH; or R3 and R4, together with the nitrogen to which they are attached, form a 3-7 member heterocyclyl ring; R6 is H, C1-C4 alkyl or the side chain of an &agr;-amino acid; R7 is C1-C6 alkyl, C6-C10 aryl, or heteroaryl; R8, R8A and R8B are each independently H, C1-C4 alkyl, or C6-C10 aryl; R9 and R10 are independently selected from H, C1-C4 alkyl, and C6-C10 aryl; or R9and R10 together with the nitrogen to which they are attached, form a 3-7 member heterocyclyl ring; R11 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R12 and R12A are each independently selected from H, C1-C6 alkyl, cycloalkyl, C6-C10 aryl, and heteroaryl; or R12 and R12A, together with the nitrogen to which they are attached, form a 5-7 member heterocyclyl ring; R13 is H, C1-C6 alkyl, cycloalkyl, C6-C10 aryl, heteroaryl, â€”C(&boxH;O)R7, â€”C(&boxH;O)NR9R10, or â€”C(&boxH;S)NR9R10; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; p is from 1, 2, 3, or 4; q is 0, 1, or 2; t is 2, 3, or 4; y is 0, 1 or 2; with the proviso that when Ar1 is phenyl and Ar2 is phenyl or pyridyl, then Y cannot be C1-C4 alkylene; with the further proviso that when Ar1 and Ar2 are phenyl, q=1, m and n=0, Y is and R3 is H, then R4 is not C1-C6 alkyl;and the stereoisomeric forms, mixtures of stereoisomeric forms, or pharmaceutically acceptable salt and ester forms thereof.