Carbamylpiperazine compounds

• US 4,435,397 A
• Filed: 03/26/1981
• Issued: 03/06/1984
• Est. Priority Date: 04/08/1980
• Status: Expired due to Fees

• Current Assignee: Nippon Shinyaku Company Limited
• Original Assignee: Nippon Shinyaku Company Limited
• Inventors: Enomoto, Hiroshi, Tanaka, Haruo, Aoyagi, Yoshiaki, Matsumura, Shingo
• Primary Examiner(s): Daus, Donald G.
• Assistant Examiner(s): Gibson, S. A.
• Application Number:
  US06/247,881
• Time in Patent Office: 1,076 Days
• Field of Search: 544/390, 544/391, 424/250
• US Class Current: 514/249
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: C07C 255/00 Carboxylic acid nitriles cyanogen or compounds thereof C01C3/00
• CPC Class Codes: C07C 59/64 containing six-membered aromatic rings
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 215/227 only one oxygen atom which is attached in position 2
• CPC Class Codes: C07D 235/28 Sulfur atoms
• CPC Class Codes: C07D 295/215 Radicals derived from nitrogen analogues of carbonic acid
• CPC Class Codes: C07D 311/16 substituted in position 7
• CPC Class Codes: C07D 311/18 substituted otherwise than in position 3 or 7
• CPC Class Codes: C07D 335/06 Benzothiopyrans; Hydrogenated benzothiopyrans

Abstract

4-(3-Aryloxy-2-hydroxypropyl)piperazines bearing a carbamyl group in the 1-position are β-adrenergic blockers. A typical example is 1-carbamyl-4-{3-[2-allyl-3-(2-carbethoxyaminoethyl)phenoxy]-2-hydroxypropyl}piperazine.

Claims

1. A compound of the formula:

##STR34## or a pharmaceutically acceptable salt thereof, wherein R is ##STR35## in which R¹ is alkyl of up to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms or alkanoyl of up to 6 carbon atoms

R² is hydrogen or alkyl of up to 6 carbon atoms, and

Z is --CH₂ CH₂ NHCO₂ R³, --NHSO₂ R³ or ##STR36## in which R³ is alkyl of up to 4 carbon atoms and each of R⁴ and R⁵ independently of the other is alkyl of up to 4 carbon atoms, or

(b) a bicyclic group of the formula;

##STR37## in which Z is a chain of 3 or 4 atoms, said chain being selected from the group consisting of --(CH₂)₂ (CH₂)_n --;

--CH═

CH--(CH₂)_n --;

##STR38## n has a value of 1 or 2 and R² is as herein defined.

2. A compound according to claim 1 wherein R is ##STR39## in which R¹ is alkyl of up to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms or alkanoyl of up to 6 carbon atoms

R² is hydrogen or alkyl of up to 6 carbon atoms, and

Z is --CH₂ CH₂ NHCO₂ R³, --NHSO₂ R³ or ##STR40## in which R³ is alkyl of up to 4 carbon atoms and each of R⁴ and R⁵ independently of the other is alkyl of up to 4 carbon atoms.

3. A compound according to claim 1 wherein R is ##STR41## in which n has a value of 1 or 2.

4. A compound according to claim 1 wherein R is ##STR42## in which n has a value of 1 or 2.

5. A compound according to claim 1 wherein R is ##STR43##

6. A compound according to claim 1 wherein R is ##STR44## in which n has a value of 1 or 2.

7. The method of effecting β

-adrenergic blocking activity in humans and other animals which comprises administering thereto an effective amount of a compound according to claim 1.

8. A pharmaceutical composition comprising an amount of a compound according to claim 1 sufficient to effect a β

-adrenergic blocking response in combination with a pharmaceutically acceptable carrier.