Claims
- 1. A compound represented by the formula and the pharmaceutically acceptable salts, esters and prodrugs thereof, whereinL is selected from the group consisting of: (1) —CH(OH)CH3; (2) C1-C6 alkyl, optionally substituted with one or more substituents selected from the group consisting of aryl, substituted aryl, heteroaryl and substituted heteroaryl; (3) C2-C6 alkenyl, optionally substituted with one or more substituents selected from the group consisting of aryl, substituted aryl, heteroaryl and substituted heteroaryl; and (4) C2-C6 alkynyl, optionally substituted with one or more substituents selected from the group consisting of aryl, substituted aryl, heteroaryl and substituted heteroaryl; R1 is selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, each optionally substituted with one or more substituents selected from the group consisting of: (1) halogen; (2) aryl; (3) substituted aryl; (4) heteroaryl; (5) substituted heteroaryl; (6) —O—R5, where R5 is selected from the group consisting of: a. hydrogen; b. aryl; c. substituted aryl; d. heteroaryl; and e. substituted heteroaryl; (7) —O—C1-C6-alkyl-R5; (8) —O—C2-C6-alkenyl-R5; (9) —O—C2-C6-alkynyl-R5; and (10) —NR6R7, where R6 and R7 are each independently selected from the group consisting of: 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; and 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 together 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—; R2 is selected from the group consisting of: (1) hydrogen; (2) C1-C6-alkyl, optionally substituted with one or more substituents selected from the group consisting of: a. halogen; b. aryl; c. substituted aryl; d. heterocyclic; e. substituted heterocyclic; f. —O—R3, where R3 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-R3; h. —O—C2-C6-alkenyl-R3; i. —O—C2-C6-alkynyl-R3; and j. —NR6R7; (3) C2-C6-alkenyl, optionally substituted with one or more substituents selected from the group consisting of: a. halogen; b. aryl; c. substituted aryl; d. heterocyclic; e. substituted heterocyclic; f. —O—R3; g. —O—C1-C6-alkyl-R3; h. —O—C2-C6-alkenyl-R3; i. —O—C2-C6-alkynyl-R3; and j. —NR6R7; and (4) C2-C6-alkynyl, optionally substituted with one or more substituents selected from the group consisting of: a. halogen; b. aryl; c. substituted aryl; d. heterocyclic; e. substituted heterocyclic; f. —O—R3; g. —O—C1-C6-alkyl-R3; h. —O—C2-C6-alkenyl-R3; i. —O—C2-C6-alkynyl-R3; and j. —NR6R7; X is selected from the group consisting of: (a) S(O)n, where n is 0, 1, or 2; (b) O; and (c) NR5; and Rp is hydrogen or a hydroxy protecting group.
- 2. A compound according to claim 1 wherein L is CH2CH3, X is —S—, R1 is CH3 and R2 and Rp are as defined in claim 1.
- 3. A compound according to claim 1 which is selected from the group consisting of:Compound of formula (I): L=CH2CH3, X=S, R1=CH3, R2=2-[6-(dimethylamino-methyleneamino)purin-9-yl]-ethyl and Rp=H; Compound of formula (I): L=CH2CH3, X=S, R1=CH3, R2=2-(6-amino-purin-yl)-ethyl and Rp=H; Compound of formula (I): L=CH2CH3, X=S, R1=CH3, R2=3-(3-pyridinyl)-1H-pyrazole-ethyl and Rp=H; Compound of formula (I): L=CH2CH3, X=S, R1=CH3, R2=[3-(3-pyridinyl)-1H-1,2,4-triazole-1-yl]-ethyl and Rp=H; Compound of formula (I): L=CH2CH3, X=S, R1=CH3, R2=[4-(3-pyridinyl)-1H-imidazole]-1-ethyl and Rp=H; and Compound of formula (I): L=CH2CH3, X=O, R1=CH3, R2=CH2CH2-phenyl and Rp=H.
- 4. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, or a pharmaceutically-acceptable salt, ester or prodrug thereof, in combination with a pharmaceutically acceptable carrier.
- 5. A method for controlling a bacterial infection in an animal comprising administering to an animal a therapeutically-effective amount of a pharmaceutical composition according to claim 4.
- 6. A process for preparing a compound represented by the formula wherein L, X, R1, R2, and Rp are as defined in claim 1, the method comprising(a) acylating a compound represented by the formula wherein L and R1 are as defined in claim 1 and Rp is a hydroxy protecting group, by reaction with a carboxylic acid, optionally in the presence of a catalyst, optionally in the presence of a dehydration reagent and optionally in the presence of a base in an aprotic organic solvent to provide a product represented by the formula wherein L, R1, and Rp are as defined in claim 1, and where Y is halogen;(b) reacting a compound from step a with an anion of R2—X—M where R2 and X are as defined in claim 1, Rp is a hydroxy protecting group and M is sodium, potassium, or lithium, or R2—X—H in the presence of a base in the presence of an aprotic solvent at a temperature from −20° C. to 50° C. for 1-48 hours to provide compound represented by the formula wherein L, R1, R2, Rp and X are as defined in claim 1; and(c) reacting a compound from step b with a base in organic solvent to effect cyclization to provide a compound of formula (I).
REFERENCE TO RELATED APLICATIONS
Reference is made to prior copending, commonly assigned application Ser. No. 10/223,144, filed Aug. 19, 2002.
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