Octahydroindole-2-carboxylic acids

• US 5,162,362 A
• Filed: 12/27/1983
• Issued: 11/10/1992
• Est. Priority Date: 08/30/1980
• Status: Expired due to Term

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Hoechst Aktiengesellschaft (Sanofi )
• Inventors: Henning, Rainer, Scholkens, Bernward, Teetz, Volker, Urbach, Hansjorg, Geiger, Rolf
• Primary Examiner(s): Vaughn, V.
• Assistant Examiner(s): Turnipseed, James H.
• Application Number:
  US06/565,887
• Time in Patent Office: 3,241 Days
• Field of Search: 548/452, 548/455, 548/467, 548/204, 548/181, 548/336, 548/374, 548/454, 548/492, 424/274, 514/414, 514/419
• US Class Current: 514/414
• 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: C07D 217/26 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07K 5/0222 with the first amino acid being heterocyclic, e.g. Pro, Trp

Abstract

What are disclosed are aminoacid compounds of the formula ##STR1## wherein n is 0 or 1, and salts thereof, said compounds and salts having hypotensive properties; methods for making the compounds; pharmaceutical compositions containing the compounds or salts; and use of the compounds and salts for treating hypertension.

Claims

1. A compound of the formula

or a physiologically tolerated salt thereof, wherein R₁ is

(a) (C₁ -C₆)-alkyl or

(b) (C₁ -C₆)-alkyl substituted by(C₅ -C₇)-cycloalkyl

amino,

(C₁ -C₆)-alkoxycarbonylamino,(C₁ -C₆)-alkanoylamino, or(C₁ -C₆)-alkoxyphenyl;

R₂ is

(a) (C₁ -C₆)-alkyl,

(b) (C₁ -C₆)-alkyl substituted by

1) (C₅ -C₇)-cycloalkyl,

2) phenoxy,

3) phenoxy substituted by

3.1 halogen,

3.2 methyl, or

3.3 methoxy,

4) amino,

5) (C₁ -C₆)-alkylureido,

6) cyclohexylureido,

7) phenylureido,

8)

(C₁ -C₆)-alkylmercapto,

(C₁ -C₆)-alkylsulfinyl, or

(C₁ -C₆)-alkylsulfonyl,

9) phenylmercapto, phenylsulfinyl, or phenylsulfonyl,

10) benzylmercapto, benzylsulfinyl, or benzylsulfonyl,

11) a heterocycle selected from the group consisting of indole, imidazole, pyrrole, pyrazole, thiophene, thiazole, or

12) such a heterocycle substituted by

12.1 halogen,

12.2 methyl, or

12.3 amino; and

wherein R₃ is hydrogen, (C₁ -C₆)-alkyl, or benzyl.

2. A compound as in claim 1 which is N-(1-S-carboethoxy-2-phenoxy-ethyl)-S-alanyl-octahydroindole-2-S-carboxylic acid.

3. A compound as in claim 1 which is N-[1-S-carboethoxy-3-(3-indolyl)-propyl]-S-alanyl-octahydroindole-2-S-carboxylic acid.

4. A compound as in claim 1 which is N-[1-S-carboethoxy-3-(3-indolyl)-ethyl]-S-alanyl-octahydroindole-2-S-carboxylic acid.

5. A compound as in claim 1 which is N-[1-S-carboethoxy-3-(2-thienyl)-propyl]-S-alanyl-octahydroindole-2-S-carboxylic acid.

6. A compound as in claim 1 which is N-(1-S-carboethoxy-2-phenylthioethyl)-S-alanyl-octahydroindole-2-S-carboxylic acid.

7. A pharmaceutical preparation for the treatment of hypertension, said preparation comprising a hypotensively effective amount of a compound or salt as in claim 1 and a pharmaceutically acceptable carrier therefor.

8. A method for treating hypertension in a patient suffering therefrom, which method comprises orally, intravenously, or subcutaneously administering to said patient a hypotensively effective amount of a compound as in claim 1.