Aminopiperidine indanyl and benzocyclobutene compounds

• US 5,189,045 A
• Filed: 05/17/1991
• Issued: 02/23/1993
• Est. Priority Date: 05/18/1990
• Status: Expired due to Fees

• Current Assignee: Adir SA
• Original Assignee: Adir SA
• Inventors: Peglion, Jean-Louis, Colpaert, Francis
• Primary Examiner(s): Cintins, Marianne M.
• Assistant Examiner(s): SCALZO, CATHERINE KILBY
• Application Number:
  US07/702,591
• Time in Patent Office: 648 Days
• Field of Search: 546/205, 546/206, 514/319
• US Class Current: 514/337
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The invention relates to new compounds of formula I: ##STR1## in which: m represents zero, 1, 2, 3 or 4,

n and p represent zero, 1 or 2,

W represents an oxygen atom, an --NH-- radical, or a single bond,

R represents a benzocyclobuten-1-yl radical, or an indanyl radical, a 2,3-dihydrobenzofuran-2-yl

R₁ represents a hydrogen atom, an alkyl radical having from 1 to 6 carbon atoms, or an aryl radical, and

R₂ represents a hydrogen atom, an alkyl radical, an alkenyl radical, a cycloalkyl radical, a benzyl radical, a phenyl radical, an aralkyl radical, an alkoxyalkyl radical or a polyhalogenated alkyl radical, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid, and medicaments containing the same.

Claims

1. A compound selected from the hose of formula I ##STR202## in which:

m represents zero, 1, 2, 3 or 4,

n represents 1 and p represent zero, 1 or 2,

W represents oxygen, --NH--, or a single bond,

R represents;

benzocyclobuten-1-yl of formula B;

##STR203## or indanyl of formula C;

##STR204## in which;

R₇, R₈ and R₉, which may be the same or different, each represents hydrogen, halogen, (C₁ -C₆) -alkyl or -alkoxy, polyhalogenated (C₁ -C₆) alkyl, or hydroxy, or when R represents B, R₇ and R₈ or R₈ and R₉ together also may form methylenedioxy, ethylenedioxy, a furan ring, or a dihydrofuran ring when R represents (B), and have the same meanings less (C₁ -C₆)-alkoxy when R represents (C), and

R₁₀ represents hydrogen or (C₁ -C₆) alkyl;

R₁ represents hydrogen or (C₁ -C₆) alkyl, or carbocylic aryl, with the proviso, however, that when, simultaneously, R represents indanyl, p represents zero and W represents a single bond, R1 does not represent aryl;

R₂ represents hydrogen, (C₁ -C₆) alkyl, (C₂ -C₆) alkenyl, (C₄ -C₇) cycloalkyl, benzyl or phenyl (each optionally substituted by one or more halogen, hydroxy, (C₁ -C₆)-alkyl or -alkoxy, (C₇ -C₁₂) aralkyl, (C₂ -C₇) alkoxyalkyl or polyhalogenated (C₁ -C₆) alkyl, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

2. A compound of claim 1 which is:

N-(1-indan-2-ylpiperid-4-yl)-N-methylpropionamide, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

3. A compound of claim 1 which is:

propyl N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-methylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

4. A compound of claim 1 which is:

methyl N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-ethylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

5. A compound of claim 1 which is:

N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-ethylacetamide, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

6. A compound of claim 1 which is:

N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-methylbutyramide, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

7. A compound of claim 1 which is:

methyl N-[1-(benzocyclobuten-1-ylmethyl)piperid-4-yl]-N-methylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

8. A compound of claim 1 which is:

ethyl N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-ethylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

9. A compound of claim 1 which is:

phenyl N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-methylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

10. A compound of claim 1 which is:

benzyl N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-methylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

11. A compound of claim 1 which is:

vinyl N-[1-(benzocyclobuten-1-ylmethyl)-piperid-4-yl]-N-methylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

12. A compound of claim 1 which is:

isobutyl N-[1-(inden-2-yl)-piperid-4-yl]-N-methylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

13. A compound of claim 1 which is:

propyl N-[1-indan-2-yl)-piperid-4-yl]-N-methylcarbamate, the optical isomers thereof and the addition salts thereof with a pharmaceutically acceptable organic or mineral acid.

14. A method for treating a living animal body afflicted with a disease resulting from pain, stress, migraine, anxiety, depression and schizophrenia, comprising the step of administering an amount of a compound of claim 1 which is suitable for the alleviation of the said condition.

15. A pharmaceutical composition containing as active ingredient an effective amount of a compound of claim 1, alone or in combination with one or more physiologically tolerable inert carriers.