Patent IL-132808-A (IL)
Title: C-4"-substituted erythromycin and azithromycin derivatives, their preparation and pharmaceutical compositions containing them
IPC: A61P31/04
Filed: 1998-05-25
Abstract: An antibacterial and antiprotozoa compound of the formula 2269 י" ד באלול התשס" ד - August 31, 2004 or a pharmaceutically acceptable salt thereof, wherein: X is -CH(NR9R10)-, -C(O)-, -C(=NOR9)-, -CH2NR9-, or -N(C1-C6 alkyl) CH2- 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; R1 is H, hydroxy or methoxy; R2 is hydroxy; R3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, cyano, -CH2S(O)nR8 wherein n is an integer ranging from 0 to 2, -CH2OR8, -CH2N(OR9)R8, -CH2NR8R15, -(CH2)m(C6-C10 aryl), or -(CH2)m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the foregoing R3 groups are optionally substituted by 1 to 3 R16 groups; or R2 and R3 are taken together to form an oxazoline ring as shown below R4 is H, -C(O)R9, -C(O)OR9, -C(O)NR9R10 or a hydroxy protecting group; R5 is -SR8, -(CH2)mC(O)R8 wherein n is 0 or 1, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, -(CH2)m(C6-C10 aryl), or -(CH2)m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the foregoing R5 groups are optionally substituted by 1 to 3 R16 groups; each R6 and R7 is independently H, hydroxy, C1-C6 alkoxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -(CH2)m(C6-C10 aryl), or -(CH2)m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4; each R8 is independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, -(CH2)q CR11R12(CH2)rNR13R14 wherein q and r are each independently an integer ranging from 0 to 3 except q and r are not both 0, -(CH2)m(C6-C10 aryl), or -(CH2)m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the foregoing R8 groups, except H, are 2270 י" ד באלול התשס" ד - August 31, 2004 optionally substituted by 1 to 3 R16 groups; or where R8 appears as part of the group -CH2NR8R15, R15 and R8 may be taken together to form a 4-10 membered saturated monocyclic or polycyclic saturated ring or a 5-10 membered heteroaryl ring, wherein said saturated and heteroaryl rings optionally include 1 or 2 heteroatoms selected from O, S and -N(R8)-, in addition to the nitrogen to which R15 and R8 are attached, said saturated ring optionally includes 1 or 2 carbon-carbon double or triple bonds, and said saturated and heteroaryl rings are optionally substituted by 1 to 3 R16 groups; each R9 and R10 is independently H or C1-C6 alkyl; each R11, R12, R13 and R14 is independently selected from H, C1-C10 alkyl, -(CH2)m (C6-C10 aryl), and -(CH2)m (5-10 membered heteroaryl), wherein m is an integer ranging from 0 to 4, and wherein the foregoing R11, R12, R13 and R14 groups, except H, are optionally substituted by 1 to 3 R16 groups; or R11 and R13 are taken together to form -(CH2)p- wherein p is an integer ranging from 0 to 3 such that a 4-7 membered saturated ring is formed that optionally includes 1 or 2 carbon-carbon double or triple bonds; or R13 and R14 are taken together to form a 4-10 membered monocyclic or polycyclic saturated ring or a 5-10 memberfed heteroaryl ring, wherein said saturated and heteroaryl rings optionally include 1 or 2 heteroatoms selected from O, S and -N(R8)-, in addition to the nitrogen to which R13 and R14 are attached, said saturated ring optionally includes 1 or 2 carbon-carbon double or triple bonds, and said saturated and heteroaryl rings are optionally substituted 1 to 3 R16 groups; R15 is H, C1-C10 alkyl, C2-C10 alkenyl, or C2-C10 alkynyl, wherein the foregoing R15 groups are optionally substituted by 1 to 3 substituents independently selected from halo and -OR9; each R16 is independently selected from halo, cyano, nitro, trifluoromethyl, azido, -C(O)R17, -C(O)OR17, -OC(O)OR17, -NR6C(O)R7, -C(O)NR6R7, -NR6R7, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, -(CH2)m (C6-C10 aryl), and -(CH2)m (5-10 membered heteroaryl) wherein m is an integer rangin