Patent ID: 6562792
Filing Date: 2003-05-13
Classification: A61P,C07H

Abstract:
A compound of the formula or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:X is H, F, OH, or NH2; Y is O or CH2; Z1 is R3 and Z2 is OR13; or Z1 is H and Z2 is R3, â€”NR3R4, â€”NR3C(O)R4, or F; or Z1 and Z2 are taken together to form &boxH;O or &boxH;NOR3; W1 is R3 and W2 is OR13; or W1 is H and W2 is R3, â€”NR3R4, â€”NR3C(O)R4, or F; or W1 and W2 are taken together to form &boxH;O or &boxH;NOR3; V is a group having the following structure â€ƒor V is R3OC(O)â€”, R3R4NC(O)â€” or R3O(R4)NC(O)â€”, in which groups R3 and R4 optionally can be taken together to form a 4 to 10 membered heterocyclic group which may be optionally substituted by 1 to 3 R6 groups; or V is a group having the following structure: â€ƒor V is a group of the structure â€ƒwhere both E and Z isomers are included; or V is a carbon-linked 4 to 10 membered heterocyclic group, which may be optionally substituted by 1 to 3 R6 groups; R1 is H and R2 is â€”NR3R4, â€”NR4C(O)R3, â€”OC(O)NR3R4 or â€”OR3; or R1 and R2 are taken together to form O, &boxH;Nâ€”OR3, or &boxH;C(R5) X1â€”X2â€”R8, wherein: X1 is â€”CR9R10â€”, and X2 is selected from the group consisting of â€”CR9R10â€”, â€”S(O)nâ€” wherein n is an integer from 0 to 2, â€”NR9â€”, and O; where X2 is â€”NR9â€”, then R8 and R9 may be taken together to form a 5 to 12 membered heterocyclic group, which is optionally substituted by 1 to 3 R6 groups; or X1 and X2 independently or together represent a bond with the proviso that if X1 is a bond than X2 is either a bond or â€”CR9R10â€”; each R3 is independently selected from the group consisting of H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, â€”(CR9R10)t(C3-C10 cycloalkyl), â€”(CR9R10)t(C6-C10 aryl), and â€”(CR9R10)t(4 to 10 membered heterocyclic), wherein each t is independently an integer from 0 to 5, said alkyl, alkenyl and alkynyl groups optionally contain 1 or 2 hetero moieties selected from the group consisting of O, â€”S(O)jâ€” wherein j is an integer from 0 to 2, and â€”N(R9)â€” with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other, and the proviso that an O atom, a S atom or a N atom are not attached directly to a triple bond or non-aromatic double bond; said cycloalkyl, aryl and heterocyclic R3 groups are optionally fused to a benzene ring, a C5-C8 cycloalkyl group, or a 4 to 10 membered heterocyclic group; the â€”(CR9R10)tâ€” moieties of the foregoing R3 groups optionally include a carbon-carbon double or triple bond where t is an integer between 2 and 5; and the foregoing R3 groups , except H but including any optional fused rings referred to above, are optionally substituted by 1 to 5 R6 groups, and with the proviso that R3 must be attached through a carbon atom unless R3is H; each R4 is independently H or C1-C10 alkyl; R5 is H or C1-C6 alkyl, wherein the foregoing R5 alkyl group is optionally substituted by 1 or 2 R6 groups; each R6 is independently selected from the group consisting of C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, oxo, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, â€”OR7, C(O)R7, â€”C(O)OR7, â€”NR9C(O)OR11, â€”OC(O)R7, â€”NR9SO2R11, â€”SO2NR7R9, â€”NR9C(O)R7, â€”C(O)NR7R9, â€”NR7R9, S(O)j(CR9R10)m(C6-C10 aryl), â€”S(O)j(C1-C6 alkyl), wherein j is an integer from 0 to 2, â€”(CR9R10)m(C6-C10 aryl), â€”O(CR9R10)m (C6-C10 aryl), â€”NR9(CR9R10)m(C6-C10 aryl), and â€”(CR9R10)m(4 to 10 membered heterocyclic), wherein each m is independently an integer from 0 to 4; said alkyl, alkenyl and alkynyl groups optionally contain 1 or 2 hetero moieties selected from the group consisting of O, â€”S(O)jâ€” wherein j is an integer from 0 to 2, and â€”N(R7)â€” with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other, and the proviso that an O atom, a S atom or a N atom are not attached directly to a triple bond or a non-aromatic double bond; said cycloalkyl, aryl and heterocyclic R6 groups are optionally fused to a C6-C10 aryl group, a C5-C8 cycloalkyl group, or a 4 to 10 membered heterocyclic group; and said alkyl, cycloalkyl, aryl and heterocyclic R6 groups are optionally substituted by 1 to 5 substituents independently selected from the group consisting of oxo, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, â€”NR9SO2R11, â€”SO2NR7R9, â€”C(O)R7, â€”C(O)OR7, â€”OC(O)R7, â€”NR9C(O)OR11, â€”NR9C(O)R7, â€”C(O)NR7R9, â€”NR7R9, â€”OR7, C1-C10 alkyl, â€”(CR9R1)m(C6-C10 aryl), and â€”(CR9R10)m(4 to 10 membered heterocyclic), wherein each m is independently an integer ranging from 0 to 4; each R7 is independently selected from the group consisting of H, C1-C10 alkyl, C3-C10 cycloalkyl, â€”(CR9R10)m(C6-C10 aryl), and â€”(CR9R10)m(4 to 10 membered heterocyclic), wherein each m is independently an integer from 0 to 4; said alkyl group optionally includes 1 or 2 hetero moieties selected from the group consisting of O, â€”S(O)jâ€” wherein j is an integer ranging from 0 to 2, and â€”N(R9)â€” with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other; said cycloalkyl, aryl and heterocyclic R7 groups are optionally fused to a C6-C10 aryl group, a C5-C8 cycloalkyl group, or a 4 to 10 membered heterocyclic group; and the foregoing R7 substituents, except H, are optionally substituted by 1 to 5 substituents independently selected from the group consisting of oxo, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, â€”C(O)R9, â€”C(O)OR9, â€”OC(O)R9, â€”NR9C(O)R10, â€”C(O)NR9R10, â€”NR R10, hydroxy, C1-C6 alkyl, and C1-C6 alkoxy, and with the proviso that R7 must be attached through a carbon atom unless R7 is H; each R8 is independently selected from the group consisting of R3, â€”C(O)R3, or â€”C(O)NR9R3, wherein R3 is as defined above; each R9 and R10 is independently H or C1-C6 alkyl; and, R11 is selected from the [substituents provided in the definition of R7 except H] group consisting of C1-C10 alkyl, C3-C10 cycloalkyl, â€”(CR9R10)m(C6-C10 aryl), and â€”(CR9R10)m(4 to 10 membered heterocyclic), wherein each m is independently an integer from 0 to 4; said alkyl group optionally includes 1 or 2 hetero moieties selected from the group consisting of O, â€”S(O)jâ€” wherein j is an integer ranging from 0 to 2, and â€”N(R9)â€” with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other; said cycloalkyl, aryl and heterocyclic R7 groups are optionally fused to a C6-C10 aryl group, a C5-C8 cycloalkyl group, or a 4 to 10 membered heterocyclic group; and the foregoing R11 substituents are optionally substituted by 1 to 5 substituents independently selected from the group consisting of oxo, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, â€”C(O)R9, â€”C(O)OR9, â€”OC(O)R9, â€”NR9C(O)R10, â€”C(O)NR9R10, â€”NR9R10, hydroxy, C1-C6 alkyl, and C1-C6 alkoxy, and with the proviso that R11 must be attached through a carbon atom; R12 is selected from the [substituents provided in the definition of R3,] group consisting of H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, â€”(CR9R10)t(C3-C10 cycloalkyl), â€”(CR9R10)t(C6-C10 aryl), and â€”(CR9R10)t(4 to 10 membered heterocyclic), wherein each t is independently an integer from 0 to 5, said alkyl, alkenyl and alkynyl groups optionally contain 1 or 2 hetero moieties selected from the group consisting of O, â€”S(O)jâ€” wherein j is an integer from 0 to 2, and â€”N(R9)â€” with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other, and with the proviso that an O atom, a S atom or a N atom are not attached directly to a triple bond or non-aromatic double bond; said cycloalkyl, aryl and heterocyclic R3 groups are optionally fused to a benzene ring, a C5-C8 cycloalkyl group, or a 4 to 10 membered heterocyclic group; the â€”(CR9R10)tâ€” moieties of the foregoing R12 groups optionally include a carbon-carbon double or triple bond where t is an integer between 2 and 5; and the foregoing R12 groups, except H but including any optional fused rings referred to above, are optionally substituted by 1 to 5 R6 groups, and with the proviso that R12 must be attached through a carbon atom unless R12 is H, and wherein R12 cannot be methyl if (a) X is OH, Y is O, W1 is H, W2 is &agr;-OH, Z1 is H, Z is &bgr;-OH; or (b) if X is OH, Y is O, W1 is H, W2 is &agr;-OH, Z1 and Z2 are both H; and with the proviso that R12 must be attached through a carbon atom unless R12 is H; R13 is defined as described for R3; and, R14 is H or C1-C10 alkyl, except that R14 cannot be H when R13 is H.