Patent ID: 6670358
Filing Date: 2003-12-30
Classification: A61P,C07C,C07D

Abstract:
A compound of the formula (II-A): whereinX is a bond, â€”CH2CH2â€”, â€”Oâ€”, â€”S(O)yâ€”, â€”N(R8)â€”, â€”CHN(R8)â€”, â€”CH&boxH;CHâ€”, â€”CH2â€”CH&boxH;CHâ€”, C(&boxH;O), â€”C(R8)&boxH;Nâ€”, â€”N&boxH;C(R8)â€”, â€”C(&boxH;O)â€”N(R8)â€”, or â€”NR8â€”C(&boxH;O)â€”; Rings A and B, together with the carbon atoms to which they are attached, are each independently selected from: (a) a 6-membered aromatic carbocyclic ring in which from 1 to 3 carbon atoms may be replaced by hetero atoms selected from oxygen, nitrogen and sulfur; and b) a 5-membered aromatic carbocyclic ring in which either: i) one carbon atom is replaced with an oxygen, nitrogen, or sulfur atom; ii) two carbon atoms are replaced with a sulfur and a nitrogen atom, an oxygen and a nitrogen atom, or two nitrogen atoms; or iii) three carbon atoms are replaced with three nitrogen atoms, one oxygen and two nitrogen atoms, or one sulfur and two nitrogen atoms; wherein Ring A and Ring B may each be independently substituted with 1-3 substituents 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)NR8AR8Bâ€”NR8C(&boxH;NH)R8A, â€”NR8C(&boxH;NH)NR8AR8B, d) â€”S(O)yR7, â€”(CH2)pS(O)yR7, â€”CH2S(O)yR7; and e) C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, where: 1) each alkyl, alkenyl, or alkynyl group is unsubstituted; or 2) 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€”X1(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;N7, â€”CH&boxH;NNHCH(N&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; R3 and R4 are the same or different and are each selected from H, C1-C6 alkyl, â€”OH, 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 heterocyclic 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 R9 and R10 together with the nitrogen to which they are attached, form a 3-7 member heterocyclic 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 heterocyclic 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; X1 is â€”Oâ€”, â€”Sâ€”, â€”N(R8)â€”; Y is selected from C1-C4 alkylene, C6-C10 arylene, heteroarylene, C3-C8 cycloalkylene, heterocyclylene, â€”Oâ€”, â€”N(R8)â€”, â€”S(O)y, â€”CR8A&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; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; p is from 1 to 4; q is 0, 1, 2; t is 2, 3, or 4; y is 0, 1 or 2; provided that when rings A and B are phenyl, X is â€”CH2CH2â€”, q is 0, m and n are 0, and Y is C1-C4 alkylene, then R3 and R4 are the same or different and are each selected from H, â€”OH, 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 heterocyclic ring; and the stereoisomeric forms, mixtures of stereoisomeric forms, or pharmaceutically acceptable salt and ester forms thereof.