Cardioselective aryloxy- and arylthio- hydroxypropylene-piperazinyl acetanilides which affect calcium entry

• US 4,567,264 A
• Filed: 05/18/1983
• Issued: 01/28/1986
• Est. Priority Date: 05/18/1983
• Status: Expired due to Term

• Current Assignee: Syntec Incorporated (Atos SE)
• Original Assignee: Syntec Incorporated (Atos SE)
• Inventors: Kluge, Arthur F., Clark, Robin D., Whiting, Roger, Strosberg, Arthur M., Pascal, Jean-Claude G.
• Primary Examiner(s): Daus, Donald G.
• Assistant Examiner(s): Shen, Cecilia
• Application Number:
  US06/495,904
• Time in Patent Office: 986 Days
• Field of Search: 544/377, 544/400, 424/250, 514/255
• US Class Current: 544/400
• 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: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 295/088 to an acyclic saturated chain
• CPC Class Codes: C07D 295/15 to an acyclic saturated chain
• CPC Class Codes: C07D 303/22 with monohydroxy compounds
• CPC Class Codes: C07D 317/66 Nitrogen atoms not forming part of a nitro radical

Abstract

Novel compounds of the general formula ##STR1## and the pharmaceutically acceptable esters and acid addition salts thereof, wherein:

R¹, R², R³, R⁴ and R⁵ are each independently hydrogen, lower alkyl, lower alkoxy, cyano, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, N-optionally substituted alkylamido, except that when R¹ is methyl, R⁴ is not methyl; or

R² and R³ together form --OCH₂ O--;

R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each independently hydrogen, lower acyl, aminocarbonylmethyl, cyano, lower alkyl, lower alkoxy, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, di-lower alkyl amino; or

R⁶ and R⁷ together form --CH═CH--CH═CH--;

R⁷ and R⁸ together form --OCH₂ O--;

R¹¹ and R¹² are each independently hydrogen or lower alkyl; and

W is oxygen or sulfur.

These cardioselective compounds have calcium entry blockade properties and therefore are useful in therapy in the treatment of cardiovascular diseases, including arrhythmias, variant and exercise induced angina and myocardial infarction.

Claims

1. A compund of the formula:

##STR14## and the pharameutically acceptable esters and acid addition salts thereof, wherein;

R1 and R5 are each methyl

R² and R³ and R⁴ are each hydrogen and R⁶ to R¹² are each hydrogen, i.e., 1-[3-phenoxy-2-hydroxypropyl]-4-[2,6-dimethylphenyl)-aminocarbonylmethyl]-piperazine, and the pharaceutically acceptable esters and acid addition salts thereof.

2. A compound of the formula:

##STR15## and the pharmaceutically acceptable esters and acid addition salts thereof, wherein;

R¹ and R⁵ are each methyl

R², R³, and R⁴ are each hydrogen, R⁶ is methoxy and R⁷ to R¹² are each hydrogen, i.e., 1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6,-dimethylphenyl)-aminocarbonylmethyl]-piperazine, and the pharaceutically acceptable esters and acid addition salts thereof.

3. A compound of the formula:

##STR16## and the pharmaceutically acceptable esters and acid addition salts thereof, wherein;

R¹ and R⁵ are each methyl;

R², R³, and R⁴ are each hydrogen, R⁶ is cyano and R⁷ to R¹² are each hydrogen, i.e., 1-[3-(2-cyanohenoxy)-2-hydroxypropyl]-4-[2,6-dimethylphenyl)aminocarbonylmethyl]piperazine.