Watanabe, Toshihiro; Kakefuda, Akio; Kinoyama, Isao; Takizawa, Kenji; Hirano, Seiko; Shibata, Hiroshi; Yanagisawa, Isao published the artcile< Synthesis of novel succinamide derivatives having a 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton as potent and selective M2 muscarinic receptor antagonists. II>, Computed Properties of 197638-83-8, the main research area is pyridobenzodiazepinone preparation muscarinic receptor antagonist; succinamide pyridobenzodiazepinone preparation muscarinic receptor antagonist; structure activity pyridobenzodiazepinone muscarinic receptor antagonist; antibradycardiac pyridobenzodiazepinone piperazinylbenzylmethylamino preparation; cardiotonic pyridobenzodiazepinone piperazinylbenzylmethylamino preparation.
Title compounds I (R = H, OMe, Cl, Me, Et, i-Pr, MeS, HO, n-PrO, Me2N, pyrrolidino, morpholino, 4-alkyl-1-piperazinyl; R1 = Me, Et)(26 compounds) were prepared and evaluated for binding affinity to muscarinic receptors in vitro and for antagonism of bradycardia and salivation in vivo in comparison with AF-DX 116 (II). Structure-activity relationships studies in vitro indicated that the 4-(4-alkyl-1-piperazinyl)benzylamino moiety plays a crucial role in enhancing the affinity for M2 muscarinic receptors. I containing a 4-(4-isopropyl-1-piperazinyl)benzylmethylamino moiety, exhibited the highest affinity for M2 muscarinic receptors, being 200 times as potent as II, and I (R = C-4 4-ethyl-1-piperazinyl, R1 = Et)(III) containing a 4-(4-ethyl-1-piperazinyl)benzylethylamino moiety, showed the highest selectivity for M2 over M3 muscarinic receptors. III and I (R = C-4 4-isopropyl-1-piperazinyl, R1 = Me) also antagonized the oxotremorine-induced bradycardia in rats after i.v. or oral administration. Oral evaluation in conscious dogs showed that the efficacy for increasing the heart rate was at least 3-fold greater than that of II.
Chemical & Pharmaceutical Bulletin published new progress about Cardiotonics. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Computed Properties of 197638-83-8.
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics