Synthesis and Antihypertensive Activities of 1, 4-Dihydropyridine-5-phosphonate Derivatives. II

A series of 1, 4-dihydropyridine-5-cyclic phosphonate derivatives, designed as analogues of 1, 4- dihydropyridine-3, 5-dicarboxylate calcium antagonists, was synthesized and examined for antihypertensive activity. Several compounds were proved to have activities superior or comparable to that of nif...

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Published inChemical & pharmaceutical bulletin Vol. 35; no. 10; pp. 4144 - 4154
Main Authors MORITA, IWAO, KUNIMOTO, KATSUTOSHI, TSUDA, MASAMI, TADA, SHIN-ICHI, KISE, MASAHIRO, KIMURA, KIYOSHI
Format Journal Article
LanguageEnglish
Published Tokyo The Pharmaceutical Society of Japan 1987
Maruzen
Japan Science and Technology Agency
Subjects
1, 4-dihydropyridine derivative
Animals
antihypertensive activity
Antihypertensive Agents - chemical synthesis
calcium antagonist
Chemical Phenomena
Chemistry
cyclic phosphonate derivative
Dihydropyridines - chemical synthesis
Dihydropyridines - pharmacology
Exact sciences and technology
Male
nifedipine
Organic chemistry
Organometalloidal and organometallic compounds
Organophosphorus Compounds - chemical synthesis
Organophosphorus Compounds - pharmacology
P derivatives
Preparations and properties
Rats
Rats, Inbred SHR
Rats, Inbred Strains
structure-activity relationship
Nitrogen heterocycle
Six membered ring
Antihypertensive agent
Organic phosphonate
Oxygen phosphorus heterocycle
Infrared spectrum
NMR spectrum
Biological activity
Phosphorus Organic compounds
Spiran
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Summary:A series of 1, 4-dihydropyridine-5-cyclic phosphonate derivatives, designed as analogues of 1, 4- dihydropyridine-3, 5-dicarboxylate calcium antagonists, was synthesized and examined for antihypertensive activity. Several compounds were proved to have activities superior or comparable to that of nifedipine in lowering blood pressure in normotensive and spontaneously hypertensive rats (SHR). Among these compounds, methyl 2, 6-dimethyl-5- (2-oxo-1, 3, 2-dioxaphosphorinan-2-yl) -4- (2-nitrophenyl) -1, 4-dihydropyridine-3-carboxylate (31, DHP-218) was approximately 7 times more active than nifedipine in SHR and was selected for further development and clinical evaluation. The structure-activity relationships are discussed.
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ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.35.4144