Patent ID: 6777543
Filing Date: 2004-08-17
Classification: A61P,C07H

Abstract:
A compound of formula 1 or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:A is H or halogen; X is selected from â€”C(O)â€”, â€”CH(NR8R9)â€”, â€”CHR8NR9â€”, â€”NR9CHR8â€”, â€”C(&boxH;NR8)â€” and â€”C(&boxH;Nâ€”OR8)â€”, wherein the first dash of each of the foregoing X groups is attached to the C-10 carbon of the compound of formula 1 and the last dash of each group is attached to the C-8 carbon of the compound of formula 1; Y is selected from CH2, C(O), CHF, CF2, C&boxH;C(RaRb), CHSR7, CHR7, C&boxH;S, â€”C(&boxH;NR8)â€”, â€”C(&boxH;Nâ€”OR8), CH(OR8), CH(OC(O)R8), CH(OC(O)Ar), CH(OC(O)NR8R9), CH(O(CRaRb)nAr), CH(OC(O)(CRaRb)nAr), CH(OC(O)(CRaRb)nNR8(CRaRb)nAr), CH(OC(O)NR8NR8R9), CH(OC(O)NR8(CRaRb)nNR8(CRaRb)nAr), CH(OC(O)NR8NR8(CRaRb)nNR8(CRaRb)nAr), â€”CH(NR8R9)â€”, CH(NR8C(O)R8), CH(NR8C(O)NR8R9), CH(NR8C(O)OR8), CH(S(CRaRb)nAr), â€”CH(NH(CRaRb)nNR8(CRaRb)nAr) and CH(NH(CRaRb)nAr), wherein n is an integer ranging from 0 to 10; or Y has the following structure: each of Ra and Rb is independently selected from H, halo and a C1-C6 alkyl; Ra and Rb together with the carbon to which they are attached can form a 3- to 10-membered cyclic or heterocydic diradical, wherein one or two carbons of said diradical are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; (CRaRb)n is alkylene, wherein n is an integer ranging from 0 to 10, uninterrupted or interrupted by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C6)alkyl- and â€”C(O)â€” and optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R1 and R2 taken with the intervening atoms form an additional ring having one of the following structures: wherein Z is CH2 or C(&boxH;O); B1 is selected from NH, NMe and CH2; and R6 is (CH2)nAr1, wherein n is an integer ranging from 0 to 10 and Ar1 is selected from quinolin-4-yl, 4-phenyl-imidazol-1-yl, imidazo(4,5-b)pyridin-3-yl and 4-pyridin-3-yl-imidazol-1-yl;R3is OR10; R3 and X can be taken together; when taken together, R3 and X taken with the intervening atoms form an additional ring having one of the following structures: R3 and Y can be taken together; when taken together, R3 and Y taken with the intervening atoms form an additional ring having one of the following structures: R4 is selected from H, a C(O)(C1-C18)alkyl, C(O)Ar, a OC(O)(C1-C18)alkyl and OC(O)Ar, wherein the alkyl moieties of the foregoing R4 groups are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R5 is selected from H, halo, a C1-C10 alkyl, a C3-C10 alkenyl, a C3-C10 alkynyl, â€”C(RaRb)â€”C(Ra)&boxH;C(Rb)â€”Ar, (CRaRb)nAr, OR8, O(CO)R8, OC(O)NR8R9, NR8R9, NR8C(O)R8 NR8C(O)NR8R9, O(CRaRb)nAr, S(CRaRb)nAr and NR8(CRaRb)nAr, wherein n is an integer ranging from 0 to 10, wherein one or two carbons of said alkyl, alkenyl and alkynyl are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R5 Y can be taken together; when taken together, R5 and Y taken with the intervening atoms form the following structure: each of R7, R8 and R9 is independently selected from H and a C1-C12 alkyl, wherein one or two carbons of said alkyl are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6) alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R8and R9 together with the nitrogen to which they are attached can form a 3- to 10-membered ring, in which one or two carbons are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6) alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R10 is selected from a C1-C10 alkyl, a C3-C10 alkenyl, a C3-C10 alkynyl, â€”C(RaRb)â€” C(Ra)&boxH;C(Rb)â€”Ar and (CRaRb)nAr, wherein n is an integer ranging from 1 to 10, wherein one or two carbons of said alkyl, alkenyl and alkynyl are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents, provided that R10 not unsubstituted methyl; R11 is H or OCH3; R12 and R13 together with the carbon to which they are attached can form â€”C(O)â€”, â€”C(&boxH;NR8)â€” or â€”C(&boxH;Nâ€”OR8); R12 and R13 together with the carbon to which they are attached can form a 3- to 10-membered ring, wherein one or two carbons of said ring are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R12 is selected from H, a C1-C10 alkyl, a C3-C10 alkenyl, a C3-C10 alkynyl, â€”C(RaRb)â€” C(Ra)&boxH;C(Rb)â€”Ar and (CRaRb)nAr, wherein n is an integer ranging from 0 to 10, wherein one or two carbons of said alkyl, alkenyl and alkynyl are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R13 is selected from H, a C1-C10 alkyl, a C3-C10 alkenyl, a C3-C10 alkynyl, OR8, OC(O)R8, OC(O)(CRaRb)nAr, OC(O)(CRaRb)nNR8(CRaRb)nAr, OC(O)NR8R9, OC(O)NR8NR8R9, OC(O)NR8(CRaRb)nNR8(CRaRb)nAr, OC(O)NR8NR8(CRaRb)nNR8(CRaRb)nAr, NR8R9, NR8(CO)R8, NR8C(O)NR8R9, NR8C(O)OR8, O(CRaRb)nAr, O(CRaRb)nNR8(CRaRb)nAr, S(CRaRb)nAr, NH(CRaRb)nNR8(CRaRb)nAr and NH(CRaRb)nAr, wherein n is an integer ranging from 0 to 10; each of R14 and R15 is independently selected from H, a C1-C12 alkyl, an aryl-substituted C1-C12 alkyl and a beteroaryl-substituted C1-C12 alkyl, wherein one or two carbons of said alkyl are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6) alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R4 and R15 together with the carbon to which they are attached can form a 3- to 10-membered ring, in which one or two carbons are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and are optionally substituted by 1 to 3 substituents independently selected from the group S substituents; R17 is a C1-C20 alkcyl, wherein one or two carbons of said alkyl is/are optionally replaced by a diradical independently selected from â€”Oâ€”, â€”Sâ€”, â€”S(O)â€”, â€”S(O)2â€”, a â€”N(C1-C6)alkyl- and â€”C(O)â€” and one or two carbons of said alkyl is/are optionally substituted by 1 to 3 substituents independently selected from the group S substituents, provided that R17 is not unsubstituted ethyl; R18 is selected from the group consisting of an aryl, a substituted aryl, a heteroaryl, a substituted heteroaryl and a heterocycloalkyl; each of R19 and R20 independently selected from the group consisting of a C1-C12 alkenyl, a C1-C12 alkynyl, an aryl, a C3-C8 cycloalkyl, a heterocycloallcyl and a heteroaryl, wherein said alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl and heteroaryl are substituted or unsubstituted; R19 and R20 together with the carbon to which they are attached can form a 3- to 10-membered heterocycloalkyl ring that may be substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, a C1-C3 alkcoxy, a C1-C3 alkoxy-C1-C3 alkoxy, oxo, a C1-C3 alkyl, a halo-C1-C3 alkyl and a C1-C3 alkoxy-C1-C3 alkyl; each Ar is independently a 4- to 10-membered heterocyclic or a C6-C10 aryl, wherein said heterocyclic and aryl groups are optionally substituted by one or more substituents independently selected from the group S substituents; and the group S substituents are selected from the group consisting of: nitro, halogens, hydroxy, N3, CN, CHO, C1-C10 alkoxy, C1-C3 alkoxy-C1-C3 alkoxy, oxo, C1-C10 alkanoyl, C1-C10 alkyl, C1-C12 alkyl substituted with an aromatic heterocyclic, C1-C6 alkyl substituted with Oâ€”SO2, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, substituted C3-C10 cycloalkyl, 4 to 10 membered heterocyclic, substituted heterocyclic, aryl, substituted aryl, trialkylsilyl, â€”C(O)R8, â€”C(O)R18, â€”C(O)OR8, â€”C(O)NR8R9, â€”NR8R9, â€”NR19R20, â€”NHC(O)R8, â€”NHC(O)NR8R9, &boxH;Nâ€”Oâ€”R8, &boxH;Nâ€”NR8R9, &boxH;Nâ€”NR19R20, &boxH;Nâ€”R8, &boxH;Nâ€”R18, &boxH;Nâ€”NHC(O)R8, &boxH;Nâ€”NHC(O)NR8R9, â€”Câ‰¡N, â€”S(O)n, wherein n is 0, 1 or 2, â€”S(O)nR8, wherein n is 0, 1 or 2, â€”Oâ€” S(O)nR8, wherein n is 0, 1 or 2, and â€”SO2NR8R9.