Cis, endo-2-azabicyclo-[3.3.0]-octane-3-carboxylic acids, a process for their preparation, agents containing these compounds and their use

• US 5,061,722 A
• Filed: 01/12/1989
• Issued: 10/29/1991
• Est. Priority Date: 11/05/1981
• Status: Expired due to Term

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Inventors: Becker, Reinhard, Scholkens, Bernward, Teetz, Volker, Urbach, Hansjorg, Geiger, Rolf
• Primary Examiner(s): Ceperley, Mary E.
• Application Number:
  US07/296,513
• Time in Patent Office: 1,020 Days
• Field of Search: 548/452, 514/412
• US Class Current: 514/412
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 209/52 condensed with a ring other than six-membered
• CPC Class Codes: C07K 5/0222 with the first amino acid being heterocyclic, e.g. Pro, Trp

Abstract

Compounds of the formula I ##STR1## in which the carboxyl group on carbon atom 3 is orientated in the endo-position relative to the bicyclic ring system of cis-configuration, and in which R¹ denotes hydrogen, allyl, vinyl or a side-chain of a naturally occurring α-aminoacid, which may be protected, R² denotes hydrogen, alkyl, alkenyl or aralkyl, Y denotes hydrogen or hydroxyl and 2 denotes hydrogen, or Y and Z together denote oxygen, and X denotes alkyl, alkenyl or cycloalkyl, or aryl which is optionally mono-, di- or tri-substituted by alkyl, alkoxy, hydroxyl, halogen, nitro, amino, alkylamino, dialkylamino or methylenedioxy, or denotes indol-3-yl, a process for their preparation, agents containing these compounds and their use.

Claims

1. A compound of the formula ##STR11## or a physiologically acceptable salt thereof, wherein R² is hydrogen, methyl, ethyl, or benzyl, and wherein hydrogen atoms on the ring carbon atoms in the 1- and 5-positions are in the cis-configuration relative to one another, the carboxyl group on the ring carbon atom in the 3-position is in the endo position relative to the bicyclic ring system, and the chirality centers in the chain and on the ring carbon atom in the 3-position all have the S-configuration, said compound or salt being substantially free of other isomers.

2. A compound or salt as in claim 1 which is N-(1-S-carboethoxy-3-phenyl-propyl)-S-alanyl-cis,endo-2-azabicyclo-[3.3.0]-octane-3-S-carboxylic acid or a salt thereof.

3. A compound or salt as in claim 1 which is N-(1-S-carboxy-3-phenyl-propyl)-S-alanyl-cis,endo-2-azabicyclo-[3.3.0]-octane-3-S-carboxylic acid or a salt thereof.

4. A hypotensive composition for reducing blood pressure comprising a hypotensively effective amount of a compound or salt as in claim 1 and a pharmaceutically acceptable excipient therefor.

5. A method for reducing blood pressure in a patient which comprises administering to said patient a hypotensively effective amount of a compound or salt as in claim 1.