67448-15-1Relevant academic research and scientific papers
Conformationally constrained 1,4-DHPs. A convenient route to bis-1,4-DHPs as a novel class of nitrogen compounds
Marchalín, ?tefan,Chudík, Miloslav,Cvopová, Katarína,Kozí?ek, Jozef,Le?ko, Ján,Da?ch, Adam
, p. 5747 - 5754 (2002)
2-Formyl-1,4-DHP derivatives 2 undergo the tandem Knoevenagel condensation/amino-nitrile cyclisation with activated methylene reagents to afford high functionalised indolizines. However, in the absence of this tandem, the Knoevenagel condensation intermediate leads to bis-1,4-DHPs as a new class of nitrogen compounds.
Chemistry of Hantzsch Cyclization: Stereochemistry of the 2-Hydroxy-1,2,3,4-tetrahydropyridine Intermediate of Hantzsch Cyclization. X-Ray Molecular Structure of Diastereoisomers of 5-(2-Cyanoethyl) 3-Methyl 2-Dimethoxymethyl-2-hydroxy-6-methyl-4-(3-nitrophenyl)-1,2,3,4-tetrahydropyri...
Ogawa, Toshihisa,Matsumoto, Keita,Hatayama, Katsuo,Kitamura, Kunihiro
, p. 3033 - 3040 (2007/10/02)
Hantzsch cyclization of cyanoethyl 3-aminocrotonate and (E,Z)-4,4-dialkoxy-2-benzylideneacetoacetonates 12a-h afforded the corresponding 3,4-trans-2-hydroxy-1,2,3,4-tetrahydropyridines 14a-h with high stereoselectivity. 1H NMR and X-ray analyses of compound 14a established the configuration of 3-H and 4-H as trans and that of 3-H and 2-OH as trans also.
Studies on nilvadipine. III. Synthesis of metabolites of nilvadipine and their related compounds
Satoh,Okumura,Shiokawa
, p. 1799 - 1807 (2007/10/02)
Nilvadipine (I), isopropyl 2-cyano-3-methoxycarbonyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridi ne-5-carboxylate, has a unique 1,4-dihydropyridine structure in that the substituents at all five positions of the nucleus differ from one another. It is an exellent calcium antagonist drug in terms of its potency, its duration of action and its selectivity in the blood vascular system. During the development of I, some metabolites were isolated from the urine and bile of both rats and dogs after oral administration. With data obtained from the metabolism of known 1,4-dihydropyridines at hand, we proposed the synthesis of a series of compounds (1-11) for comparison with the metabolites isolated from I as a method for structure determination. Indeed, of the compounds synthesized five of them (3-7) were found to coincide with the metabolites from both rat and dog urine and bile isolates.
Studies on nilvadipine. I. Synthesis and structure-activity relationships of 1,4-dihydropyridines containing novel substituents at the 2-position
Satoh,Ichihashi,Okumura
, p. 3189 - 3201 (2007/10/02)
The synthesis of new 1,4-dihydropyridine derivatives containing novel substituent at the 2-position of the nucleus via the key intermediate 2-formyl-1,4-dihydropyridines (X), is described. The aldehydes (X) were prepared by hydrolysis of the acetals (IX) which were obtained from aryl aldehyde (V) and alkyl 4,4-dialkoxyacetoacetate (VI) by the Knoevenagel reaction and treatment with alkyl 3-aminocrotonate (VIII) according to the modified Hantzsch method. The formyl group of the aldehydes (X) was reactive enough to be converted to a variety of functional groups such as hydroxymethyl, cyano, substituted iminomethyl, carbamoyl, semicarbazone, substituted vinyl, ethynyl, and so on. In all of the novel compounds we prepared, 2-hydroxymethyl- and 2-cyano-1,4-dihydropyridines (IV and XXII) were found to possess potent activities in preliminary biological evaluations on hypotension in normotensive rats and on an increase in coronary blood flow in pentobarbital-anesthetized dogs. Optimization research in order to obtain a more potent compound was accomplished in the 2-hydroxymethyl- and 2-cyano-1,4-dihydropyridine series. We selected isopropyl 2-cyano-3-methoxycarbonyl-4-(3-nitrophenyl)-6-methyl-1,4-dihydropyridin e-5-carboxylate (XXIIj) as a candidate compound for further biological evaluation studies. Fortunately, XXIIj (nilvadipine) has been accepted in clinical use for the treatment of hypertension.
