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US 2004/0006027 A1Published application
11-C-substituted derivatives of clarithromycin
AssigneeEnanta Pharmaceuticals, Inc.
InventorsLy Tam Phan, Jay Judson Farmer, Yat Sun Or
Life of this patent
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Abstract
There are described 11-C-substituted derivatives of clarithromycin 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.
Claims17
A compound represented by the formula
- 14
- or a pharmaceutically acceptable ester, salt or prodrug thereof, wherein
- A is selected from the group consisting of
- (1) 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. 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;
- and
- 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;
- or
- e. R6 R7 taken 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)—;
- and
- (VIII) —S(O)2—
- (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—, —C(O)NR6, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7—, —NR6C(NH)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 independently selected from the group consisting of:
- (1) hydrogen;
- (2) halogen;
- (3) C1-C6-alkyl;
- (4) aryl;
- (5) substituted aryl;
- (6) heteroaryl;
- (7) substituted heteroaryl;
- (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=N—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;
- R2 is selected from the group consisting of:
- (1) a hydroxy protecting group;
- (2) R5, where R5 is as previously defined;
- (3) —X—Y—R5, where X is —C(O), —C(O)O—, —C(O)NR6—, or absent, and Y is C1-C6-alkyl or absent, where R5 and R6 are as previously defined;
- and
- (4) 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—R5 where R5, is as previously defined;
- 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. —N—R6R7, where R6 and R7 are as previously defined;
- Rp1 is hydrogen or a hydroxy protecting group;
- and
- Z is selected from the group consisting of:
- (1) hydrogen;
- (2) a hydroxy protecting group;
- and
- (3) —X—R3, where X and R3 are as previously defined.
127 more elements
Dependencies are inferred from the claim text.