- Conformationally constrained 1,4-DHPs. A convenient route to bis-1,4-DHPs as a novel class of nitrogen compounds
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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.
- Marchalín, ?tefan,Chudík, Miloslav,Cvopová, Katarína,Kozí?ek, Jozef,Le?ko, Ján,Da?ch, Adam
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p. 5747 - 5754
(2007/10/03)
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- A simple and expeditious synthesis of substituted 3-aminoindolizines
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Treatment of easily available 2-formyl-1,4-dihydropyridines with 3-oxo-3-phenylpropanenitrile offers a simple and efficient one-pot method for the preparation of substituted 3-amino-indolizines.
- Chudik, Miloslav,Marchalin, Stefan,Pham-Huu, Duy-Phong,Humpa, Otakar,Friedl, Zdenek
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p. 1241 - 1252
(2007/10/03)
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- Studies on nilvadipine. I. Synthesis and structure-activity relationships of 1,4-dihydropyridines containing novel substituents at the 2-position
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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.
- Satoh,Ichihashi,Okumura
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p. 3189 - 3201
(2007/10/02)
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