Anti-ischaemic and antihypertensive 2-[pyrimidyloxy alhoxymethyl]-1,4-dihydropyridines

• US 4,618,609 A
• Filed: 06/05/1985
• Issued: 10/21/1986
• Est. Priority Date: 06/07/1984
• Status: Expired due to Term

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Alker, David, Cross, Peter E., Campbell, Simon F.
• Primary Examiner(s): Jiles, Henry R.
• Assistant Examiner(s): Bjorkman, Dale A.
• Application Number:
  US06/741,339
• Time in Patent Office: 503 Days
• Field of Search: 544/316, 544/317, 544/310, 544/321, 544/319, 544/122, 544/123, 514/252, 514/236
• US Class Current: 514/235.8
• 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: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 211/90 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings

Abstract

Dihydropyridine derivatives of the formula: ##STR1## and their pharmaceutically acceptable acid addition salts; wherein R is a substituted aryl group;

R¹ and R² are each independently C₁ -C₃ alkyl;

Y is --(CH₂)_n -- where n is 2, or --CH₂ CH(CH₃)--; and Het is a 6-membered aromatic heterocyclic group attached to the adjacent oxygen atom by a carbon atom.

The compounds have utility as anti-ischaemic and anti-hypertensive agents.

Claims

1. A dihydropyridine compound of the formula ##STR16## and a pharmaceutically acceptable acid addition salt thereof, wherein R is selected from the group consisting of 2-chlorophenyl and 2,3-dichlorophenyl;

R¹ and R² are each alkyl having from one to three carbon atoms;

Y is selected from the group consisting of --(CH₂)₂ -- and --CH₂ CH(CH₃)--; and

HET is selected from the group consisting of 2- and 4-pyrimidyl and substituted 2- and 4-pyrimidyl wherein said substituent is selected from the group consisting of carbamoyl, amino, alkoxy having from one to three carbon atoms, chloro, 2-aminoethylamino, 2-hydroxyethylamino, 2-pyridylmethylamino, 2,3-dihydroxypropylamino, 2-pyridylmethoxy, 1-methyl-2-imidazolylmethoxy and morpholino.

2. A compound of claim 1, wherein R¹ is methyl, R² is ethyl and Y is --(CH₂)₂ --.

3. The compound of claim 2, wherein HET is 2-pyrimidyl and R is 2-chlorophenyl.

4. The compound of claim 2, wherein HET is 4-pyrimidyl and R is 2-chlorophenyl.

5. The compound of claim 2, wherein HET is 2-pyrimidyl and R is 2,3-dichlorophenyl.

6. The compound of claim 2, wherein HET is 4-pyrimidyl and R is 2,3-dichlorophenyl.

7. A compound of claim 2, wherein HET is substituted 4-pyrimidyl wherein said substituent is selected from the group consisting of carbamoyl, amino, alkoxy having from one to three carbon atoms, chloro, 2-aminoethylamino, 2-hydroxyethylamino, 2-pyridylmethylamino, 2,3-dihydroxypropylamino, 2-pyridylmethoxy, 1-methyl-2-imidazolylmethoxy and morpholino.

8. A compound of claim 7, wherein R is 2,3-dichlorophenyl.

9. A compound of claim 7, wherein R is 2-chlorophenyl.

10. A pharmaceutical composition comprising an anti-hypertensive or anti-ischaemic effective amount of a compound according to claim 1, together with a pharmaceutically acceptable carrier or diluent.

11. A method for treating hypertension in a mammal which comprises administering to said mammal an effective antihypertensive amount of a compound according to claim 1.