title: Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate.
abstract: 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.
authors.affiliation: Department of Urology, New York University Medical Center, New York, New York 10021, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: Chiu
authors.forename: J M
authors.initials: JM
authors.lastname: Wetzel
authors.forename: M R
authors.initials: MR
authors.lastname: Marzabadi
authors.forename: D
authors.initials: D
authors.lastname: Nagarathnam
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Fang
authors.forename: S W
authors.initials: SW
authors.lastname: Miao
authors.forename: X
authors.initials: X
authors.lastname: Hong
authors.forename: C
authors.initials: C
authors.lastname: Forray
authors.forename: P J
authors.initials: PJ
authors.lastname: Vaysse
authors.forename: T A
authors.initials: TA
authors.lastname: Branchek
authors.forename: C
authors.initials: C
authors.lastname: Gluchowski
authors.forename: R
authors.initials: R
authors.lastname: Tang
authors.forename: H
authors.initials: H
authors.lastname: Lepor
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000503:physiopathology; D011470:Prostatic Hyperplasia / Q000503:physiopathology; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*
chemical_list: C113173:5-(aminocarbonyl)-1,4-dihydro-2,6-dimethyl-4-(4-nitrophenyl)-(3-(4,4-diphenylpiperidin-1-yl)propyl); C547713:ADRA1A protein, human; C547715:Adra1a protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D010880:Piperidines; D011725:Pyridines; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine