US 2004/0002464 A1Published application

11-C-substituted ketolides

AssigneeEnanta Pharmaceuticals, Inc.

InventorsLy Tam Phan, Jay Judson Farmer, Yat Sun Or

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Abstract

There are described 11-C-substituted derivatives of erythromycin and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described is a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds.

Claims10

Dependent claims

A compound represented by the formula

15
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein
A is selected from the group consisting of
(1) C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of:
i. halogen;
ii. aryl;
iii. substituted aryl;
iv. heterocyclic;
v. substituted heterocyclic;
vi. —O—R5, where R5 is selected from the group consisting of:
a. hydrogen;
b. aryl;
c. substituted aryl;
d. heterocyclic;
and
e. substituted heterocyclic;
vii. —O—C1-C6-alkyl-R5, where R5 is as previously defined;
viii. —O—C2-C6-alkenyl-R5, where R5 is as previously defined;
ix. —O—C2-C6-alkynyl-R5, where R5 is as previously defined;
and
x. —NR6R7, where R6 and R7 are each independently selected from the group consisting of:
a. hydrogen;
b. C1-C6-alkyl, optionally substituted with one or more substituents selected from the group consisting of:
(I) halogen;
(II) aryl;
(III) substituted aryl;
(IV) heterocyclic;
and
(V) substituted heterocyclic;
c. C2-C6-alkenyl, optionally substituted with one or more substituents selected from the group consisting of:
(I) halogen;
(II) aryl;
(III) substituted aryl;
(IV) heterocyclic;
and
(V) substituted heterocyclic;
d. C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of:
(I) halogen;
(II) aryl;
(III) substituted aryl;
(IV) heterocyclic;
and
(V) substituted heterocyclic, and
e. R6 R7 taken together with the nitrogen atom to which they are connected form a 3- to 7-membered ring which may optionally contain one or more functions selected from the group consisting of:
(I) —O—;
(II) —NH—;
(III) —N(C1-C6-alkyl)-;
(IV) —N(aryl)-;
(V) —N(heteroaryl)-;
(VI) —S—;
(VII) —S(O)—;
(VIII) —S(O)2—;
and
(IX) —C(O)—;
(2) —C(O)—R5, where R5 is as previously defined;
(3) —C(O)—C1-C6-alkyl-R5, where R5 is as previously defined;
(4) —C(O)—C2-C6-alkenyl-R5, where R5 is as previously defined;
(5) —C(O)—C2-C6-alkynyl-R5, where R5 is as previously defined;
(6) C1-C6-alkyl-M—R5, where M is —OC(O)—, —OC(O)O—, —OC(O)NR6—, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7—, —NR6C(N)NR7— or S(O)n—, where n=0, 1 or 2, and where R5, R6, R7 are as previously defined;
(7) —C2-C6-alkenyl-M—R5, where M and R5 are as previously defined;
and
(8) —C2-C6-alkynyl-M—R5, where M and R5 are as previously defined;
B, C, and D may be present singly or in combination and are each independently selected from the group consisting of:
(1) hydrogen;
(2) halogen;
(3) C1-C6-alkyl,
(4) aryl;
(5) substituted aryl;
(6) heterocyclic;
(7) substituted heterocyclic;
(8) O—R5 where R5 is as previously defined;
(9) B and C taken together are=O;
(10) B and C taken together are=N—O—R5, where R5 is as previously defined;
(11) B and C taken together are=N13 N—R6R7, where R6 and R7 are as previously defined;
(12) B and D taken together are —O—;
(13) B and D taken together are —S—;
(14) B and D taken together are —N(R6)—, where R6 is as previously defined;
and
(15) B and D taken together with the carbon atoms to which they are attached form a 4- to 8-membered ring which may optionally contain one or more functions selected from the group consisting of:
i. —O—;
ii. —NH—;
iii. —N(C1-C6-alkyl)-;
iv. —N(aryl)-;
V. —N(heteroaryl)-;
vi. —S—;
vii. —S(O)—;
viii. —S(O)2—;
and
ix. —C(O)—;
R1 is selected from the group consisting of:
(1) hydrogen;
(2) R3, where R3 is C1-C6-alkyl, C2-C6-alkenyl or C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of:
i. halogen;
ii. aryl;
iii. substituted-aryl;
iv. heteroaryl;
v. substituted-heteroaryl;
vi. —O—C1-C6-alkyl-R5, where R5 is as previously defined;
and
vii. —N—R6R7, where R6 and R7 are as previously defined;
(3) C(O)—R4, where R4 is hydrogen or R3, where R3 is as previously defined;
(4) —C(O)O—R3, where R3 is as previously defined;
and
(5) —C(O)N—R6R7, where R6 and R7 are as previously defined;
W is selected from the group consisting of:
(1) hydrogen;
(2) halogen;
(3) C1-C6-alkyl;
(4) C2-C6-alkenyl;
and
(5) C2-C6-alkynyl;
and
Rp1 is hydrogen or a hydroxy protecting group.

110 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound represented by the formula

15
or a pharmaceutically acceptable salt, ester or prodrug thereof, wherein
A is selected from the group consisting of
(1) C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of:
i. halogen;
ii. aryl;
iii. substituted aryl;
iv. heterocyclic;
v. substituted heterocyclic;
vi. —O—R5, where R5 is selected from the group consisting of:
a. hydrogen;
b. aryl;
c. substituted aryl;
d. heterocyclic;
and
e. substituted heterocyclic;
vii. —O—C1-C6-alkyl-R5, where R5 is as previously defined;
viii. —O—C2-C6-alkenyl-R5, where R5 is as previously defined;
ix. —O—C2-C6-alkynyl-R5, where R5 is as previously defined;
and
x. —NR6R7, where R6 and R7 are each independently selected from the group consisting of:
a. hydrogen;
b. C1-C6-alkyl, optionally substituted with one or more substituents selected from the group consisting of:
(I) halogen;
(II) aryl;
(III) substituted aryl;
(IV) heterocyclic;
and
(V) substituted heterocyclic;
c. C2-C6-alkenyl, optionally substituted with one or more substituents selected from the group consisting of:
(I) halogen;
(II) aryl;
(III) substituted aryl;
(IV) heterocyclic;
and
(V) substituted heterocyclic;
d. C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of:
(I) halogen;
(II) aryl;
(III) substituted aryl;
(IV) heterocyclic;
and
(V) substituted heterocyclic, and
e. R6 R7 taken together with the nitrogen atom to which they are connected form a 3- to 7-membered ring which may optionally contain one or more functions selected from the group consisting of:
(I) —O—;
(II) —NH—;
(III) —N(C1-C6-alkyl)-;
(IV) —N(aryl)-;
(V) —N(heteroaryl)-;
(VI) —S—;
(VII) —S(O)—;
(VIII) —S(O)2—;
and
(IX) —C(O)—;
(2) —C(O)—R5, where R5 is as previously defined;
(3) —C(O)—C1-C6-alkyl-R5, where R5 is as previously defined;
(4) —C(O)—C2-C6-alkenyl-R5, where R5 is as previously defined;
(5) —C(O)—C2-C6-alkynyl-R5, where R5 is as previously defined;
(6) C1-C6-alkyl-M—R5, where M is —OC(O)—, —OC(O)O—, —OC(O)NR6—, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7—, —NR6C(N)NR7— or S(O)n—, where n=0, 1 or 2, and where R5, R6, R7 are as previously defined;
(7) —C2-C6-alkenyl-M—R5, where M and R5 are as previously defined;
and
(8) —C2-C6-alkynyl-M—R5, where M and R5 are as previously defined;
B, C, and D may be present singly or in combination and are each independently selected from the group consisting of:
(1) hydrogen;
(2) halogen;
(3) C1-C6-alkyl,
(4) aryl;
(5) substituted aryl;
(6) heterocyclic;
(7) substituted heterocyclic;
(8) O—R5 where R5 is as previously defined;
(9) B and C taken together are=O;
(10) B and C taken together are=N—O—R5, where R5 is as previously defined;
(11) B and C taken together are=N13 N—R6R7, where R6 and R7 are as previously defined;
(12) B and D taken together are —O—;
(13) B and D taken together are —S—;
(14) B and D taken together are —N(R6)—, where R6 is as previously defined;
and
(15) B and D taken together with the carbon atoms to which they are attached form a 4- to 8-membered ring which may optionally contain one or more functions selected from the group consisting of:
i. —O—;
ii. —NH—;
iii. —N(C1-C6-alkyl)-;
iv. —N(aryl)-;
V. —N(heteroaryl)-;
vi. —S—;
vii. —S(O)—;
viii. —S(O)2—;
and
ix. —C(O)—;
R1 is selected from the group consisting of:
(1) hydrogen;
(2) R3, where R3 is C1-C6-alkyl, C2-C6-alkenyl or C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of:
i. halogen;
ii. aryl;
iii. substituted-aryl;
iv. heteroaryl;
v. substituted-heteroaryl;
vi. —O—C1-C6-alkyl-R5, where R5 is as previously defined;
and
vii. —N—R6R7, where R6 and R7 are as previously defined;
(3) C(O)—R4, where R4 is hydrogen or R3, where R3 is as previously defined;
(4) —C(O)O—R3, where R3 is as previously defined;
and
(5) —C(O)N—R6R7, where R6 and R7 are as previously defined;
W is selected from the group consisting of:
(1) hydrogen;
(2) halogen;
(3) C1-C6-alkyl;
(4) C2-C6-alkenyl;
and
(5) C2-C6-alkynyl;
and
Rp1 is hydrogen or a hydroxy protecting group.

110 more elements