Substituted 3-(4-phenyl-1-piperazinyl)alkylquinazolin-2,4-(1H,3H) diones, methods of preparation, compositions and method of use

• US 4,711,883 A
• Filed: 09/30/1985
• Issued: 12/08/1987
• Est. Priority Date: 09/30/1985
• Status: Expired due to Term

• Current Assignee: Ortho Pharmaceutical Corporation (Johnson & Johnson)
• Original Assignee: Ortho Pharmaceutical Corporation (Johnson & Johnson)
• Inventors: Falotico, Robert, Bandurco, Victor T., Schwender, Charles F., Tobia, Alfonso J.
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Turnipseed, James H.
• Application Number:
  US06/782,241
• Time in Patent Office: 799 Days
• Field of Search: 544/285, 514/253
• US Class Current: 514/252.17
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 239/96 Two oxygen atoms

Abstract

Novel substituted-3-(4-phenyl-1-piperazinyl)alkyl quinazolin-2,4-(1H,3H)diones are described. These compounds are useful as antihypertensive agents.

Claims

1. A compound of the formula ##STR13## wherein R₁ is hydroxy or alkoxy having 1-4 carbon atoms:

R₂ is hydroxy or alkoxy having 1-4 carbon atoms;

or when R₁ and R₂ are taken together they are lower alkylenedioxy;

n is an integer from 2 to 6;

R₄ and R₅ are the same or different and are hydrogen, hydroxy, alkyl having 1-6 carbon atoms, alkoxy having 1-4 carbon atoms, halo, or trifluoromethyl, or when R₄ and R₅ are taken together they are lower alkylenedioxy;

or the pharmaceutically acceptable salts thereof.

2. The compound of claim 1, wherein R₁, R₂ and R₄ are each lower alkoxy having 1-4 carbon atoms and R₅ is hydrogen.

3. The compound of claim 1, wherein R₁ and R₂ are each hydroxyl, and R₄ is 2-lower alkoxy having 1-4 carbon atoms.

10. A pharmaceutical composition useful as an antihypertensive in unit, topical, oral and intravenous dosage forms, comprising from about 0.05 mg/kg to about 100 mg/kg of a compound of claim 1 in admixture with a pharmaceutically acceptable carrier.

11. The composition of claim 10, comprising from about 0.1 mg/kg to about 20 mg/kg of the compound of claim 1, in admixture with the pharmaceutically acceptable carrier.

4. A compound selected from the group consisting of 3-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-5,6-dimethoxyquinazolin-2,4 (1H,3H)-dione or the pharmaceutically acceptable salts thereof.

5. A compound selected from the group consisting of 5,6-dihydroxy-3-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}quinazolin-2,4(1H,3H)-dione or the pharmaceutically acceptable salts thereof.

6. The compound 3-(2-hydroxyethyl)-5,6-dimethoxyquinazolin-2,4-(1H,3H)dione.

7. The compound 3-(2-chloroethyl)-5,6-dimethoxyquinazolin-2,4-(1H,3H)-dione.

8. An antihypertensive composition comprising an inert carrier and as an active ingredient an effective antihypertensive amount of a compound of the formula ##STR14## wherein R₁ is hydroxy or alkoxy having 1-4 carbon atoms:

R₂ is hydroxy or alkoxy having 1-4 carbon atoms;

or when R₁ or R₂ are taken together they are loweralkylenedioxy;

n is an integer from 2 to 6;

R₄ and R₅ are the same or different and are hydrogen. hydroxy, alkyl having 1-4 carbon atoms, alkoxy having 1-4 carbon atoms, halo, or trifluoromethyl, or when R₄ and R.sub. 5are taken together they are lower alkylenedioxy;

or the pharmaceutically acceptable salts thereof.

9. An antihypertensive composition according to claim 8 wherein said active ingredient is selected from the group consisting of 3-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-5,6-dimethoxyquinazolin-2,4(1H,3H)-dione and 5,6-dihydroxy-3-2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}quinazolin-2,4(1H,3H)-dione.

12. A method of treating hypertension, which comprises administering an effective antihypertensive amount in a pharmaceutically acceptable carrier of a compound of the formula ##STR15## wherein R₁ is hydroxy or alkoxy having 1-4 carbon atoms:

R₂ is hydroxy or alkoxy having 1-4 carbon atoms;

or when R₁ or R₂ are taken together they are loweralkylenedioxy;

n is an integer from 2 to 6;

R₄ and R₅ are the same or different and are hydrogen, hydroxy, alkyl having 1-4 carbon atoms, alkoxy having 1-4 carbon atoms, halo, or trifluoromethyl, or when R₄ and R₅ are taken together they are lower alkylenedioxy;

or the pharmaceutically acceptable salts thereof.