Benzimidazole derivatives

• US 4,886,803 A
• Filed: 07/15/1987
• Issued: 12/12/1989
• Est. Priority Date: 07/25/1986
• Status: Expired due to Term

• Current Assignee: Nisshin Seifun Group Incorporated
• Original Assignee: Nisshin Flour Milling Incorporated (Nisshin Seifun Group Incorporated)
• Inventors: Yamada, Hiroaki, Yanai, Makoto, Suzuki, Yoshikuni, Sugai, Toshiji, Sueda, Noriyoshi
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Turnipseed, James H.
• Application Number:
  US07/073,738
• Time in Patent Office: 881 Days
• Field of Search: 544/295, 544/238, 544/310, 544/317, 544/319, 544/321, 544/328, 544/331, 544/357, 544/363, 544/364, 544/365, 544/370, 544/405, 546/141-143, 546/153, 546/155, 546/157, 546/162, 546/271, 548/159, 548/255, 548/265, 548/268, 548/303, 514/252, 514/253, 514/269, 514/272, 514/274-275, 514/309-310, 514/312-313, 514/338, 514/359, 514/367, 514/395
• US Class Current: 514/252.02
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• 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
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Compounds are described of formula (I) ##STR1## wherein R¹ is a hydrogen atom, an alkyl group, an alkoxy group, a dialkylamino group or a halogen atom; n is 1 to 4; R² is a hydrogen atom, an alkyl group, an unsubstituted or substituted aminoalkyl group, an acyl group, an unsubstituted or substituted aralkyl group, a carboxyalkyl group, an alkoxycarbonyalkyl group or ##STR2## wherein X is an unsubstituted or substituted-phenyl, -benzyl, -benzoyl or -furoyl group; A is -NR³ - where R³ is hydrogen or alkyl, an alkylene or an alkylidene; and B is a heterocyclic group selected from triazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzothiazolyl, quinolyl and isoquinolyl, said heterocyclic group being optionally substituted by one or more alkyl, alkoxy, nitro or phenyl group, and the physiologically acceptable acid addition salts thereof. The compound of formula (I) are or cardiotonic activity and thus may be useful for the treatment of circulatory diseases.

Claims

1. A compound of Formula I ##STR42## wherein R¹ is a hydrogen atom, a (C₁ -C₃) alkyl group, a (C₁ -C₃) alkoxy group or a halogen atom;

n is 1 to 4;

R² is a hydrogen atom, a (C₁ -C₄) alkyl group, an amino (C₂ -C₃) alkyl group, a mono- or di- (C₁ -C₃) alkyl-amino (C₂ -C₃) alkyl group, acetyl, propionyl, butyryl, stearoyl, benzyl, phenethyl, a carboxy (C₁ -C₃) alkyl group, a (C₁ -C₃) alkoxy carbonyl (C₁ -C₃) alkyl group or (C₂ -C₄) ##STR43## wherein X is a (C₁ -C₃) alkoxy phenyl group benzyl, a (C₁ -C₃) alkoxybenzoyl or furoyl group;

A is --NR³ -- where R³ is hydrogen or (C₁ -C₃) alkyl, a (C₁ -C₄) alkylene or a (C₂ -C₄) alkyldiene; and

B is a heterocylic group selected from triazolyl, pyridyl, pyridazinyl pyrimidinyl, pyrazinyl, benzimidozolyl, benzothiazolyl, quinolyl and isoquinolyl, said heterocyclic group being optionally substituted by one or more (C₁ -C₃) alkyl, (C₁ -C₃) alkoxy, nitro or phenyl groups, or the physiologically acceptable acid addition salts thereof.

2. A compound of claim 1 wherein R¹ is hydrogen, (C₁ -C₃) alkyl or (C₁ -C₃) alkoxy and n is 1 or 2.

3. A compound of claim 1 wherein R² is hydrogen, (C₁ -C₄) alkyl di-(C₁ -C₃) alkylamino (C₂ -C₃) alkyl, acetyl, benzyl, phenethyl, carboxy (C₁ -C₃) alkyl, (C₁ -C₃) alkoxylcarbonyl (C₁ -C₃) alkyl or (4-substituted -1- piperazinyl) (C₂ -C₄) alkyl.

4. A compound of claim 1 wherein R² is methyl, ethyl, propyl, butyl, acetyl, propionyl, butyryl, stearoyl, aminoethyl, aminopropyl, monomethylaminoethyl, dimethylaminoethyl, carboxymethyl, 3-carboxypropyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, benzyl, phenethyl, (4-(dimethoxybenzoyl)-1-piperazinyl)ethyl, (4-furoyl-1-piperazinyl)ethyl, (4-benzyl-1-piperazinyl)ethyl, (4-(methoxyphenyl)-1-piperazinyl)ethyl or (4-(ethoxyphenyl)-1-piperazinyl)ethyl.

5. A compound of claim 1 wherein A is --NH--, --N(CH₃)--, --N(C₂ H₅)--, methylene, ethylene, propylene, butylene, ethylidene, propylidene or butylidene.

6. A compound of claim 1 wherein B is 5-(1,2,3-triazolyl), 3-(1,2,4-triazolyl), 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 2-benzimidazolyl, 2-benzothiazolyl, 3-benzoisothiazolyl, 2-quinolyl or 1-isoquinolyl.

7. A compound of claim 1 wherein B is (C₁ -C₃) alkyl-substituted pyridyl, (C₁ -C₃) alkyl-substituted pyrimidinyl, phenyl-substituted pyridyl, nitro-substituted pyridyl or (C₁ -C₃) alkoxy-substituted benzothiazolyl.

8. A pharmaceutical composition which comprises as an active ingredient an effective amount of a compound of claim 1 or the physiologically acceptable acid addition salt thereof, optionally in admixture with additives for pharmaceutical preparations.

9. A pharmaceutical composition of claim 8 wherein the active ingredient is the compound of claim 2 or the acid addition salt thereof.

10. A pharmaceutical composition of claim 8 wherein the active ingredient is the compound of claim 3 or the acid addition salt thereof.

11. A pharmaceutical composition of claim 8 wherein the active ingredient is the compound of claim 4 or the acid addition salt thereof.

12. A pharmaceutical composition of claim 8 wherein the active ingredient is the compound of claim 5 or the acid addition salt thereof.

13. A pharmaceutical composition of claim 8 wherein the active ingredient is the compound of claim 6 or the acid addition salt thereof.

14. A pharmaceutical composition of claim 8 wherein the active ingredient is the compound of claim 7 or the acid addition salt thereof.