Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate

A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3-(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human alpha adrenoceptors as well as the rat L-type calcium channe...

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Published in:Journal of medicinal chemistry 1998-07, Vol.41 (14), p.2643-2650
Main Authors: Wong, W C, Chiu, G, Wetzel, J M, Marzabadi, M R, Nagarathnam, D, Wang, D, Fang, J, Miao, S W, Hong, X, Forray, C, Vaysse, P J, Branchek, T A, Gluchowski, C, Tang, R, Lepor, H
Format: Article
Language:English
Subjects:
Adrenergic alpha-Agonists - pharmacology
Adrenergic alpha-Antagonists - pharmacology
Aged
Aged, 80 and over
Animals
Brain - drug effects
Brain - metabolism
Calcium Channels - drug effects
Humans
In Vitro Techniques
Male
Middle Aged
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Muscle, Smooth - physiopathology
Phenylephrine - pharmacology
Piperidines - chemical synthesis
Piperidines - metabolism
Piperidines - pharmacology
Prostate - drug effects
Prostate - physiopathology
Prostatic Hyperplasia - physiopathology
Pyridines - chemical synthesis
Pyridines - metabolism
Pyridines - pharmacology
Rats
Receptors, Adrenergic, alpha-1 - drug effects
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Summary:A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3-(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human alpha adrenoceptors as well as the rat L-type calcium channel. Within this compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73) and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the human prostate.
ISSN:0022-2623