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

Thesis/Dissertation · Wed Jan 01 00:00:00 EST 1986

OSTI ID:7003307

Joslyn, A F

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
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

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