Piperazine derivatives and their acid addition salts

• US 4,613,598 A
• Filed: 03/06/1985
• Issued: 09/23/1986
• Est. Priority Date: 03/13/1984
• Status: Expired due to Term

• Current Assignee: Mitsubishi Kasei Corp. (Mitsubishi Chemical Group Corp.)
• Original Assignee: Mitsubishi Chemical Industries Limited (Mitsubishi Chemical Group Corp.)
• Inventors: Fukami, Harukazu, Inoue, Shinya, Kikumoto, Ryoji, Nakao, Kenichiro, Nitta, Issei
• Primary Examiner(s): BOND, ROBERT
• Application Number:
  US06/708,641
• Time in Patent Office: 566 Days
• Field of Search: 260/239.3 B, 544/58.2, 544/105, 544/360, 544/392, 544/393, 544/394, 514/211, 514/225, 514/239, 514/255
• US Class Current: 514/211.06
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 265/36 condensed with one six-membered ring
• CPC Class Codes: C07D 267/14 condensed with one six-membered ring
• CPC Class Codes: C07D 279/16 condensed with one six-membered ring
• CPC Class Codes: C07D 295/092 with aromatic radicals attached to the chain
• CPC Class Codes: C07D 295/108 to an acyclic saturated chain
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

A piperazine derivative according to the present invention has the following general formula [I]: ##STR1## wherein R¹ is --OH, --OR³, --SR³, --SOR³ or --SO₂ R³ wherein R³ is alkyl group having 1 to 3 carbon atoms;

R² is --SO₂ NH₂, --SO₂ NHR⁴, --SO₂ NR⁴ R⁵, --COOH, --COOR⁴, --CONH₂, --CONHR⁴, --CONR⁴ R⁵, --NHCONH₂, --NHCSNH₂, --NHCONHR⁴, --NHCOR⁴ or --NHSO₂ R⁴ wherein R⁴ and R⁵ are independently alkyl group having 1 to 3 carbon atoms; or

R¹ and R² together with carbon atoms to which they are attached form ##STR2## Z is --CO-- or --CH(OH)--; Ar is pyridyl or substituted or unsubstituted phenyl; and

n is an integer of 3 to 5.

An acid addition salt of the piperazine derivative having the above formula [I] is included in the present invention. The piperazine derivative as well as its acid addition salt according to the present invention have the ability to reduce the blood pressure.

Claims

1. A piperazine compound of formula (I):

##STR63## wherein R¹ is --OH, --OR³, --SR³, --SOR³ or --SO₂ R³, wherein R³ is an alkyl group having 1 to 3 carbon atoms;

R² is --SO₂ NH₂, --SO₂ NHR⁴, --SO₂ NR⁴ R⁵, --COOH, --COOR⁴, --CONH₂, --CONHR⁴, --CONR⁴ R⁵, --NHCONH₂, --NHCSNH₂, --NHCONHR⁴, --NHCOR⁴ or --NHSO₂ R⁴, wherein R⁴ and R⁵ are independently alkyl groups having 1 to 3 carbon atoms;

or

R¹ and R² together with the carbon atoms to which they are attached form ##STR64## Z is --CO-- or --CH(OH)--;

Ar is pyridyl, phenyl, or halogen, C_1-3 alkyl or C_1-3 alkoxy substituted phenyl;

n is an integer of 3 to 5; and

therapeutically active acid addition salts thereof.

2. The compound according to claim 1, wherein R₂ is --SO₂ NH₂, --SO₂ NHR⁴ or --SO₂ NR⁴ R⁵ and the others are as defined in claim 1.

3. The compound according to claim 1, wherein R¹ is --OH or --OR³, R² is --COOH, --COOR⁴, --CONH₂, --CONHR⁴ or --CONR⁴ R⁵ and the others are as defined in claim 1.

4. The compound according to claim 1, wherein R² is --NHCONH₂, --NHCSNH₂, --NHCONHR⁴, --NHCOR⁴ or --NHSO₂ R⁴ and the others are as defined in claim 1.

5. The compound according to claim 1, wherein phenyl is substituted with methoxy.

6. The compound according to claim 1, wherein the acid addition salt is dihydrochloride.

7. A pharmaceutical composition which is effective in the treatment of hypertension, comprising:

at least one piperazine compound of the formula (I);

##STR65## wherein R¹ is --OH,--OR³, --SR³, --SOR³ or --SO₂ R³, wherein R³ is an alkyl group having 1 to 3 carbon atoms;

R² is --SO₂ NH₂, --SO₂ NHR⁴, --SO₂ NR⁴ R⁵, --COOH, --COOR⁴, --CONH₂, --CONHR⁴, --CONR⁴ R⁵, --NHCONH₂, --NHCSNH₂, --NHCONHR⁴, --NHCOR⁴ or --NHSO₂ R⁴, wherein R⁴ and R⁵ are indepedently alkyl groups having 1 to 3 carbon atoms;

or

R¹ and R² together with the carbon atoms to which they are attached form ##STR66## Z is --CO-- or --CH(OH)--;

Ar is pyridyl, phenyl, or halogen, C_1-3 alkyl or C_1-3 alkoxy substituted phenyl;

n is an integer of 3 to 5; and

therapeutically active acid addition salts thereof in combination with a pharmaceutically acceptable carrier.

8. The composition according to claim 7, wherein said composition is in a solid or liquid dosage unit form intended for oral administration.

9. The composition according to claim 14, wherein said composition is in a liquid dosage unit form intended for parenteral administration.