Carboxamide compounds

• US 4,822,780 A
• Filed: 07/08/1987
• Issued: 04/18/1989
• Est. Priority Date: 07/08/1987
• Status: Expired due to Term

• Current Assignee: Otsuka Pharmaceutical Factory Incorporated (Otsuka Holdings Company Limited)
• Original Assignee: Otsuka Pharmaceutical Factory Incorporated (Otsuka Holdings Company Limited)
• Inventors: Tsuda, Yoshiaki, Tsuda, Yoshihiko
• Primary Examiner(s): Sneed, H. M. S.
• Assistant Examiner(s): Pak, Chung K.
• Application Number:
  US07/071,010
• Time in Patent Office: 650 Days
• Field of Search: 558/190, 558/191, 558/192, 514/119
• US Class Current: 514/119
• CPC Class Codes: C07F 9/4056 Esters of arylalkanephosphonic acids C07F9/4025 takes precedence
• CPC Class Codes: C07F 9/572 Five-membered rings
• CPC Class Codes: C07F 9/59 Hydrogenated pyridine rings
• CPC Class Codes: C07F 9/6506 having the nitrogen atoms in positions 1 and 3
• CPC Class Codes: C07F 9/650952 having the nitrogen atoms in the positions 1 and 4
• CPC Class Codes: C07F 9/6533 Six-membered rings

Abstract

A carboxamide compound of the formula: ##STR1## wherein R¹, R², R³, R⁴ and X are as defined and pharmaceutically acceptable salts thereof, and composition containing the compound are disclosed.

The compound is useful as a calcium antagonistic agent and an antiinflammatory agent.

Claims

1. A carboxamide compound of the formula:

##STR141## wherein R¹ and R² represent, respectively, a hydrogen atom, an alkyl group, a cycloalkyl group, a diphenyl lower alkyl group, or a group of the formula;

##STR142## in which R⁵, R⁶ and R⁷ represent, respectively, a hydrogen atom, a halogen atom, a nitro group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkyl group, a halogen-substituted lower alkyl group, a cyano group, a carboxy group or a hydroxy group;

A represents a lower alkylene group;

l represents 0 or 1;

or R¹ and R² together with the nitrogen atom to which they are attached form a heterocyclic group or a heterocyclic group containing additional hetero atoms(s) selected from the group consisting of a nitrogen atom and an oxygen atom, or R¹ and R² form said heterocyclic group substituted with a lower alkyl group, a phenyl lower alkyl group, a phenyl group or a phenyl group substituted with a lower alkyl group, a lower alkoxy group, a halogen atom, or a halogen-substituted lower alkyl group as a substituent group;

R³ represents a hydrogen atom, an alkyl group, or a phenyl lower alkyl group;

R⁴ represents a lower alkyl group or a phenyl group; and

X represents an oxygen atom or a sulfur atom.

2. A carboxamide compound as claimed in claim 1, wherein each of said R¹ and R² represents a hydrogen atom, a C₁ -C₈ alkyl group, or a group of the formula:

##STR143## wherein R⁵, R⁶, and R⁷ represent, respectively, a hydrogen atom, a halogen atom, a nitro group, a C₁ -C₆ alkoxy group, a C₁ -C₆ alkoxycarbonyl group, a C₁ -C₆ alkyl group, a C₁ -C₆ alkyl group having 1 to 3 halogen atoms or a cyano group;

A represents a C₁ -C₆ alkylene group; and

l represents 0 or 1;

R³ represents a hydrogen atom and R⁴ represents a C₁ -C₆ alkyl group.

3. A carboxamide compound as claimed in claim 2, selected from the group consisting of:

3-diethoxyphosphinylmethyl-N-(4-methoxycarbonylphenyl)-N-phenylbenzamide,

4-diethoxyphosphinylmethyl-N-benzyl-N-phenylbenzamide,

4-diethoxyphosphinylmethyl-N-(2-hydroxyphenyl)benzamide,

4-diethoxyphosphinylmethyl-N-n-octyl-N-phenylbenzamide,

4-diethoxyphosphinylmethyl-N-benzyl-N-(4-methylphenyl)-benzamide,

4-diethoxyphosphinylmethyl-N-benzyl-N-(4-methoxyphenyl)-benzamide,

4-diethoxyphosphinylmethyl-N-benzyl-N-(3-trifluoromethylphenyl)benzamide,

4-diethoxyphosphinylmethyl-N-benzyl-N-(4-nitrophenyl)-benzamide,

4-diethoxyphosphinylmethyl-N-benzyl-N-(4-cyanophenyl)-benzamide,

4-diethoxyphosphinylmethyl-N-benzyl-N-(3,4-dichlorophenyl)benzamide,

4-diethoxyphosphinylmethyl-N-(4-nitrobenzyl)-N-phenylbenzamide, and

4-diethoxyphosphinylmethyl-N-(4-bromophenyl)benzamide.

4. A pharmaceutical composition containing a pharmaceutically effective amount, as a calcium antagonistic agent, of the compound as claimed in claim 1 and a pharmaceutically acceptable carrier or diluent.

5. A method of therapeutic treatment of man or animal in need of calcium antagonistic action comprising administering a therapeutically effective amount of the compound as claimed in claim 1.

6. A carboxamide compound as claimed in claim 1, wherein said heterocyclic group formed by R¹ and R² is selected from the group consisting of a pyrrolidinyl group, a piperidono group, a piperazinyl group and a morpholino group.