Benzimidazolone derivatives

• US 5,576,318 A
• Filed: 03/23/1994
• Issued: 11/19/1996
• Est. Priority Date: 07/30/1991
• Status: Expired due to Term

• Current Assignee: Sprout Pharmaceuticals, Inc. (Sprout2, Inc.)
• Original Assignee: Boehringer Ingelheim Italia SPA (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Borsini, Franco, Bietti, Giuseppe, Giraldo, Ettore, Bignotti, Maura, Turconi, Marco
• Primary Examiner(s): TSANG, CECILIA J
• Application Number:
  US08/216,742
• Time in Patent Office: 972 Days
• Field of Search: 544/370, 544/366, 544/295, 514/253, 514/252, 548/304.4, 548/304.7, 548/306.4
• US Class Current: 514/252.19
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 235/26 Oxygen atoms
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links

Abstract

Pharmacologically active benzimidazolone derivatives as 5-HT_1A and 5-HT₂ receptors, useful in the treatment of CNS disorders, of formula: ##STR1## wherein the substituents are defined herein.

Claims

1. A compound of formula I ##STR18## wherein R₁ and R₂ may each independently be a hydrogen atom, halogen, C_1-3 alkyl or C_1-3 alkoxy,

R3 is hydrogen, C_1-3 alkyl or C_2-6 alkenyl

A is --CO-- or --CONH-- or it is absent;

B is a straight chain C_2-6 alkyl;

m and n are both the integer 2;

R₄ is phenyl, naphtyl, benzodioxanyl, or pyrimidinyl, each being optionally substituted by one substituent selected from halogen, trifluoromethyl, C_1-3 alkoxy,

or a physiologically acceptable acid addition salt thereof.

2. Compounds of formula (I) according to claim 1 characterized in that A is absent, B is a straight, saturated C_2-4 alkyl, m and n are the integer 2, R₄ is a substituted phenyl ring wherein the substituents are selected from methoxy, chloro or trifluoromethyl, and acid addition salts thereof.

4. Salts according to claim 1, characterized in that the physiologically acceptable acids are hydrochloric, maleic or fumaric acid.

5. Pharmaceutical compositions for the use in the treatment of patients suffering from depression, bipolar disorder, anxiety, sleep and sexual disorder, psychosis, schizophrenia, personality disorders, mental organic disorders, mental disorders in childhood, aggressiveness and age associated memory impairment, comprising as active ingredient a pharmaceutically effective amount of a compound of formula (I), as defined in claim 1 or physiologically acceptable acid additional salts thereof, in association with pharmaceutically acceptable carriers, diluents or excipients.

6. Pharmaceutical compositions for the use in the treatment of patients suffering from hypertension and thrombosis, comprising as active ingredient a therapeutically effective amount of a compound as defined in claim 1, or physiologically acceptable acid addition salts thereof, in association with pharmaceutically acceptable carriers, diluents or excipients.

3. Compound of formula (I) selected from

1-[2-(4-(3-trifluoromethyl-phenyl)piperazin-1-yl)ethyl]-2,3 -dihydro-1H-benzimidazol-2-one

1-[4-(4-(3-chloro-phenyl)piperazin-1-yl) butyl]-2,3-dihydro-1H-benzimidazol-2-one

1-[4-(4-(3-trifluoromethyl-phenyl)piperazin-1-yl)butyl]-2,3-dihydro-1H-benzimidazol-2-one

1-[4-(4-(3-trifluoromethyl-phenyl)piperazin-1-yl)butyl]-3-methyl-2,3-dihydro-1H-benzimidazol-2-one

1-[4-(4-(3-trifluoromethylphenyl)piperazin-1-yl)butyl]-3-isopropil-2,3-dihydro-1H-benzimidazol-2-one

1-[3-(4-(3-trifluoromethyl-phenyl)piperazin-1-yl)propyl]-2,3-dihydro-1H-benzimidazol-2-one

6-methoxy-1-[4-(4-(3-trifluoromethyl-phenyl)piperazin-1-yl)butyl]-2,3-dihydro-1H-benzimidazol-2-one

1-[4-(4-(1-naphtyl)piperazin-1-yl)butyl]-2,3-dihydro-1H-benzimidazol-2-one.