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US 2003/0114395 A1Published application
Novel 11-O-substituted ketolide derivatives
AssigneeEnanta Pharmaceuticals, Inc.
InventorsLy Tam Phan, Deqiang Niu, Yat Sun Or
Life of this patent
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Abstract
There are described novel 11-O-substituted ketolide derivatives of clarithromycin analogs 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 a mammal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds.
Claims11
A compound represented by formula (I):
- 8
- In formula (I) above,
- 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:
- a. halogen;
- b. aryl;
- c. substituted aryl;
- d. heteroaryl;
- e. substituted heteroaryl;
- f. —O—R5, where R5 is selected from the group consisting of:
- i. hydrogen;
- ii. aryl;
- iii. substituted aryl;
- iv. heteroaryl;
- and
- v. substituted heteroaryl;
- g. —O—C1-C6-alkyl-R5, where R5 is as previously defined;
- h. —O—C1-C6-alkenyl-R5, where R5 is as previously defined
- i. —O—C2-C6-alkynyl-R5, where R5 is as previously defined;
- and
- j. —NR6R7, where R6 and R7 are each independently selected from hydrogen, C1-C6-alkyl, optionally substituted with one or more substituents selected from the group consisting of halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, C2-C6-alkenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic, C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of halogen, aryl, substituted aryl, heterocyclic and substituted heterocyclic or R6R7 taken with the nitrogen atom to which they are connected form a 3- to 7-membered ring which may optionally contain one or more hetero functions selected from the group consisting of —O—, —NH—, —N(C1-C6-alkyl)-, —N(aryl)-, —N(heteroaryl)-, —S—, —S(O)— and —S(O)2—;
- (3) —C(O)—R5, where R5 is as previously defined;
- (4) —C(O)—C1-C6-alkyl-R5, where R5 is as previously defined;
- (5) —C(O)—C2-C6-alkenyl-R5, where R5 is as previously defined;
- (6) —C(O)—C2-C6-alkynyl-R5, where R5 is as previously defined;
- (7) —C1-C6-alkyl-M—R5, where M=—OC(O)—, —OC(O)O—, —OC(O)NR6—, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7—, —NR6C(N)NR7—, S(O)n—, where n=0, 1 or 2, and where R5, R6, R7 are as previously defined;
- (8) —C2-C6-alkenyl-M—R5 where M=—OC(O)—, —OC(O)O—, —OC(O)NR6—, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7—, —NR6C(N)NR7—, S(O)n—, where n=0, 1 or 2, and where R5, R6, R7 are as previously defined;
- and
- (9) —C2-C6-alkynyl-M—R5 where M=—OC(O)—, —OC(O)O—, —OC(O)NR6—, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7—, —NR6C(N)NR7—, S(O)n—, where n=0, 1 or 2, and where R5, R6, R7 are as previously defined;
- 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:
- a. halogen;
- b. aryl;
- c. substituted aryl;
- d. heteroaryl;
- e. substituted heteroaryl;
- f. —O—C1-C6-alkyl-R5, where R5 is as previously defined;
- and
- g. —NR6R7, where R6 and R7 are as previously defined.
- (3) —C(=O)—R4, where R4 is H or R3 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;
- D and M are selected from the group consisting of:
- (1) one of D and M is hydrogen and the other is selected from the group consisting of:
- i. hydrogen;
- ii. hydroxy;
- iii. protected hydroxy;
- and
- iv. —NR6R7, where R6 and R7 are as previously defined;
- and
- (2) D and M taken together define Y, where Y is selected from the group consisting of:
- a. =O;
- b. =N—OH;
- c. =N—O—R8, where R8 is a C1-C6-alkyl group, optionally substituted with a group selected from an aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
- and
- d. =N—O—C(R9)(R10)—O—R11, where R9 and R10 are each independently selected from the group consisting of hydrogen or C1-C6-alkyl, and R11 is selected from the group consisting of:
- i. R8, as previously defined;
- ii. —C1-C6-alkyl, optionally substituted with C1-C6-alkoxy;
- and
- iii. —C1-C6-alkyl-O—C1-C6-alkyl-R5, where R5 is as previously defined;
- X is selected from the group consisting of:
- (1) hydrogen;
- (2) methyl;
- and
- (3) halogen;
- R13 is selected from:
- (1) hydrogen,
- (2) C1-C6-alkyl optionally substituted with halogen,
- (3) C2-C6-alkenyl,
- (4) C2-C6-alkynyl, or
- (5) —CH2-R″, where R″ is selected from hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl or phenyl, optionally substituted with halogen, or C1-C6-alkyl optionally substituted with R5, where R5 is as defined previously;
- (6) —C3-C8-cycloalkyl;
- and
- Rp is hydrogen or hydroxy protecting group.
73 more elements
Dependencies are inferred from the claim text.