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US 6,673,774 B2Granted
11-O-substituted macrolides and their descladinose derivatives
AssigneeEnanta Pharmaceuticals, Inc.
InventorsLy Tam Phan Phan, Deqiang Niu, Yat Sun Or
Life of this patent
Estimating the term…
Abstract
There are described 11-O-substituted macrolides and their descladinose derivatives 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.
Claims9
A compound represented by formula (I) or a pharmaceutical ester, salt or prodrug thereof:
- 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. heteroaryl;
- v. substituted heteroaryl;
- vi. —O—R5, where R5 is selected from the group consisting of:
- a. hydrogen;
- b. aryl;
- c. substituted aryl;
- d. heteroaryl;
- and
- e. substituted hereroaryl;
- and
- 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 independenly 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, hererocyclic 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—;
- (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=—OC(O)—, —OC(O)O—, —O C(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;
- (7) —C2-C6-alkenyl-M—R5, where M=—OC(O)—, —OC(O)O—, —O C(O)NR6—, —NR6C(O)—, —NR6C(O)O—, —NR6C(O)NR7-, —NR6C(N)NR7-, S(O)n—, where n=0, 1 or 2, and where R5R6, R7 are as previously defined;
- and
- (8) —C2-C6-alkynyl-M—R5, where M=—OC(O)—, —OC(O)O—, —O C(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) 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;
- (2) —C(═O)—R4, where R4 is H or R3, where R3 is as previously defined;
- (3) —C(═O)O—R3, where R3 is as previously defined;
- and
- (4) —C(═O)N—R6R7, where R6 and R7 are as previously defined;
- Rp1 is hydrogen or hydroxy protecting group;
- and
- Z is selected from the group consisting of:
- (1) hydrogen;
- (2) hydroxy protecting groups;
- and
- (3) —X—R3, where X=—C(O)—, —C(O)O—, —C(O)NH—, or absent, and R3 is as previously defined.
46 more elements
A compound represented by formula (II) or a pharmaceutical ester, salt or prodrug thereof:
- 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. heteroaryl;
- v. substituted heteroaryl;
- vi. —O—R5, where R5 is selected from the group consisting of:
- a. hydrogen;
- b. aryl;
- c. substituted aryl;
- d. heteroaryl;
- and
- e. substituted heteroaryl;
- 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 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-;
- (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=—OC(O)—, —OC(O)O—, —O C(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;
- (7) —C2-C6-alkenyl-M—R5, where M=—OC(O)—, —OC(O)O—, —O C(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 a previously defined;
- and
- (8) —C2-C6-alkynyl-M—R5, where M=—OC(O)—, —OC(O)O—, —O C(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;
- R2 is selected from the group consisting of:
- (1) hydroxy protecting group;
- (2) R5, where R5 is as previously defined;
- (3) —X—Y—R5, where R5 is as previously defined X=—C(O)—, —C(O)O—, —C(O)NH—, or absent, and Y=C1-C6-alkyl, or absent;
- 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:
- a. halogen;
- b. aryl;
- c. substituted aryl;
- d. heteroaryl;
- e. substituted heteroaryl;
- f. —O—R5, where R5 is as previously defined;
- g. —O—C1-C6-alkyl-R5, where R5 is as previously defined;
- h. —O—C2-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 as previously defined;
- and
- Rp1 is hydrogen or hydroxy protecting group.
58 more elements
Dependencies are inferred from the claim text.