As an extension of previous investigations (Tetrahedron 1999, 55, 5433-5440; J. Heterocycl. Chem. 2000, 37, 875-878), a series of 21 [1,4]thiazino[3,4-c][1,2,4]oxadiazolones, which has already been synthesized (except for compounds 5a, 5b, 6), was evaluated as calcium entry blockers by functional studies, namely, in isolated guinea-pig left and right atria and K+-depolarized aortic strips. With the aim of investigating the effect of a condensed benzene ring on the molecular structure and the influence of substituents on the 8-phenyl ring of 4a, ab initio computations (RHF/3-21*G) were performed on compounds 3, 4a-d, 4f, and 4k. The results obtained show that many of the compounds studied are potent and selective negative inotropic agents; in particular, compounds 4e and 4f are about 3- and 2-fold more potent than diltiazem, respectively.
Budriesi R., Cosimelli B., Ioan P., Lanza C.Z., Spinelli D., Chiarini A. (2002). Cardiovascular characterization of [1,4]thiazino[3,4-c][1,2,4]oxadiazol-1-one derivatives: Selective myocardial calcium channel modulators. JOURNAL OF MEDICINAL CHEMISTRY, 45(16), 3475-3481 [10.1021/jm020815d].
Cardiovascular characterization of [1,4]thiazino[3,4-c][1,2,4]oxadiazol-1-one derivatives: Selective myocardial calcium channel modulators
Budriesi R.
;Chiarini A.
2002
Abstract
As an extension of previous investigations (Tetrahedron 1999, 55, 5433-5440; J. Heterocycl. Chem. 2000, 37, 875-878), a series of 21 [1,4]thiazino[3,4-c][1,2,4]oxadiazolones, which has already been synthesized (except for compounds 5a, 5b, 6), was evaluated as calcium entry blockers by functional studies, namely, in isolated guinea-pig left and right atria and K+-depolarized aortic strips. With the aim of investigating the effect of a condensed benzene ring on the molecular structure and the influence of substituents on the 8-phenyl ring of 4a, ab initio computations (RHF/3-21*G) were performed on compounds 3, 4a-d, 4f, and 4k. The results obtained show that many of the compounds studied are potent and selective negative inotropic agents; in particular, compounds 4e and 4f are about 3- and 2-fold more potent than diltiazem, respectively.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.