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Synthesis of Ranolazine Derivatives Containing the (1 S ,4 S )‐2,5‐Diazabicyclo[2.2.1]Heptane Moiety and Their Evaluation as Vasodilating Agents
Author(s) -
LópezOrtiz Manuel,
Monsalvo Ivan,
Demare Patricia,
Paredes Cristina,
Mascher Dieter,
Hernández Carlos,
Hernández Marcos,
Regla Ignacio
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12285
Subject(s) - moiety , ranolazine , chemistry , heptane , stereochemistry , combinatorial chemistry , pharmacology , organic chemistry , medicine
Two diazabicyclic analogues of ranolazine, ( S , S , S )‐5 and ( S , S , R )‐5 , and their epimeric mixture were synthesized. Furthermore, their vasomotor effects on rat aorta rings precontracted with phenylephrine were analyzed. These compounds showed vasodilating effects significantly greater than ranolazine. The vasodilating activities of these analogues have two components, one that depends on the endothelium, due to the release of NO , and another one due to a direct effect on the vascular smooth muscle. The compounds [( S , S , S )( S , S , R )]‐5 and ( S , S , R )‐5 induce, in a manner similar to ranolazine, the release of a prostanoid from the cyclooxygenase pathway, whose vasoconstrictor effect is masked by the predominant vasodilation induced by these compounds.