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US 6,387,885 B1Granted
3′,3′-N-bis-desmethyl-3′-N-cycloalkyl erythromycin derivatives as LHRH antagonists
AssigneeAbbott Laboratories
InventorsChristopher R. Dalton, Milan Bruncko, Michele A. Kaminski, Lisa M. Frey, Daryl R. Sauer, Fortuna Haviv
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Abstract
Disclosed are 3′,3′-N-bis-desmethyl-3′-N-cycloalkyl-6-O-methyl-11-deoxy-11,12-cyclic carbamate erythromycin A derivatives which are antagonists of lutenizing hormone-releasing hormone (LHRH). Also disclosed are pharmaceutical compositions comprising the compounds, to methods of using the compounds and to the process of making the same.
Claims13
A compound having the formula:
- or a pharmaceutically acceptable salt or ester thereof, wherein
- A is selected from the group consisting of:
- (a) —C,
- (b) —N, and
- (c) —O;
- X and Y are independently at each occurrence selected from the group consisting of:
- (a) hydrogen,
- (b) halide,
- (c) alkoxy,
- (d) alkyl,
- (e) aryl, and
- (f) substituted aryl;
- R and R1 are independently at each occurrence selected from the group consisting of:
- (a) alkyl,
- (b) cycloalkyl,
- (c) heterocylic,
- (d) substituted heterocyclic,
- (e) alkylcycloalkyl,
- (f) substituted alkylcycloalkyl,
- (g) alkylaryl,
- (f) alkylheterocyclic,
- (g) alkenyl, and
- (h) alkynyl,
- m is 1, 2 or 3
- R2 and R3 are independently at each occurrence
- (a) hydrogen,
- (b) methyl, or
- R2 and R3 together form a cycloalkyl moiety, when A is C;
- and
- n=1, 2 or 3.
27 more elements
A process of preparing a compound of formula:
- or a pharmaceutically acceptable salt or ester thereof, wherein
- A is selected from the group consisting of:
- (a) —C,
- (b) —N, and
- (c) —O;
- X and Y are independently at each occurrence selected from the group consisting of:
- (a) hydrogen,
- (b) halide,
- (c) alkoxy,
- (d) alkyl,
- (e) aryl, and
- (f) substituted aryl;
- R and R1 are independently at each occurrence selected from the group consisting of:
- (a) alkyl,
- (b) cycloalkyl,
- (c) heterocylic,
- (d) substituted heterocyclic,
- (e) alkylcycloalkyl,
- (f) substituted alkylcycloalkyl,
- (g) alkylaryl,
- (f) alkylheterocyclic,
- (g) alkenyl, and
- (h) alkynyl,
- m is 1, 2 or 3
- R2 and R3 are independently at each occurrence
- (a) hydrogen,
- (b) methyl, or
- R2 and R3 together form a cycloalkyl moiety, when A is C;
- and
- n=1, 2 or 3;
- comprising the steps of:
- (a) reacting a compound of formula:
- with sodium hexamethyldisilazide and carbonyldiimidazole to afford a compound of the formula:
- (b) reacting the compound obtained in step (a) with an amino compound of the formula:
- and deprotection to afford a compound of the formula:
- (c) stepwise bisdesmethylating the 3′-amino by treating the compound obtained in step (b) twice with iodine in presence of a base to afford a compound of the formula:
- (d) alkylating the 3′,3′-N-bisdesmethylated compound obtained in step (c) with an alkylating agent.
34 more elements
Dependencies are inferred from the claim text.