2-substituted adenosine 5'-carboxamides as antihypertensive agen

Details 2-substituted adenosine 5'-carboxamides as antihypertensive agen 2-substituted adenosine 5'-carboxamides as antihypertensive agen

1989-08-04

1990-11-06

Rollins, John W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

514 45, 536 23, 536 24, 536 26, A61K 3170, C07H 19167

Patent

active

049686976

ABSTRACT:
The compounds of the formula I ##STR1## wherein R represents hydrogen or lower alkyl; R.sub.1 represents C.sub.3 -C.sub.6 -cycloalkyl optionally substituted by lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl-lower alkyl optionally substituted by lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, aryl, aryl-lower alkyl, aryl-C.sub.3 -C.sub.6 -cycloalkyl, 9-fluorenyl, diaryl-lower alkyl, 9-fluorenyl-lower alkyl, cycloalkenyl-lower alkyl, bicycloalkenyl-lower alkyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl or adamantyl-lower alkyl; or R.sub.1 represents a bicyclic benzo-fused 5- or 6-membered saturated carbocyclic radical or a benzo-fused 5- or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur which is directly attached to the fused benzene ring, any said bicyclic radical being unsubstituted or substituted on the benzo portion by lower alkyl, lower alkoxy, hydroxy, halogen or trifluoromethyl, or by a substituent -W-Z in which W represents a direct bond, lower alkylene, lower alkenylene, thio-lower alkylene or oxy-lower alkylene and Z represents cyano, carboxy or carboxy derivatized in the form of a pharmaceutically acceptable ester or amide, or R.sub.1 represents any said bicyclic radical substituted-lower alkyl; or R.sub.1 represents aryl-hydroxy-lower alkyl; R.sub.2 represents hydrogen, lower alkyl or aryl-lower alkyl; R.sub.3 represents hydrogen or hydroxy; R.sub.4 represents hydrogen, lower alkyl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl or hydroxy-lower alkyl; aryl represents an optionally substituted carbocyclic aromatic radical, being preferably 1- or 2-naphthyl, phenyl, or naphthyl or phenyl substituted by one to three of lower alkyl, lower alkoxy, hydroxy, halogen or trifluoromethyl, or naphthyl or phenyl substituted by a substitutent -W-Z in which W represents a direct bond, lower alkylene, lower alkenylene, thio-lower alkylene or oxy-lower alkylene and Z represents cyano, carboxy or carboxy derivatized in the form of a pharmaceutically acceptable ester or amide; or aryl represents a heterocyclic aromatic radical, being preferably pyridyl or thienyl, each optionally substituted as described above for phenyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in the form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; their preparation; and their use as adenosine-2 receptor agonists are disclosed.

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