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Structure-activity studies on 1,4-dihydropyridine calcium channel antagonists and activators

Thesis/Dissertation ·
OSTI ID:7003307
Four series of 1,4-dihydropyridine Ca{sup 2+} channel antagonists related to mifedipine were synthesized by a modified Hantzsch procedure to determine the effects of ester (C{sub 3} = CO{sub 2}Me, C{sub 5} = CO{sub 2}R) and phenyl (C{sub 4}) substituents on pharmacological and radioligand binding ((H)nitrendipine) activities in guinea pig ileal longitudinal smooth muscle. Two series of Ca{sup 2+} channel activator 1,4-dihydropyridines, BAY K 8644 (C{sub 3} = NO{sub 2}, C{sub 5} = CO{sub 2}Me) and CGP 28392 (C{sub 2,3} = lactone, C{sub 5} = CO{sub 2}Me) were biochemically evaluated by inhibition of ({sup 3}H)nitrendipine binding in guinea pig ileal longitudinal smooth muscle membranes to establish fundamental structure-activity requirements. A homologous series of bis-1,4-dihydropyridines were synthesized, pharmacologically and biochemically evaluated in an attempt to explore the distribution of the 1,4-dihydropyridine receptor in guinea pig ileal longitudinal smooth muscle membranes. Several potential affinity labels including ester substituted 3- and 4-fluorosulfonyl benzoyl and isothiocyanate derivatives were synthesized and evaluated by inhibition of ({sup 3}H)nitrendipine binding.
Research Organization:
State Univ. of New York, Buffalo, NY (USA)
OSTI ID:
7003307
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL PREPARATION
DIGESTIVE SYSTEM
ESTERS
GASTROINTESTINAL TRACT
GUINEA PIGS
HYDROGEN COMPOUNDS
INHIBITION
INTESTINES
ISOTOPE APPLICATIONS
KINETICS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MUSCLES
ORGANIC COMPOUNDS
ORGANS
PORINS
PROTEINS
REACTION KINETICS
RECEPTORS
RODENTS
SMALL INTESTINE
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES