title: Design and synthesis of novel dihydropyridine alpha-1a antagonists.
abstract: A series of analogs of SNAP 5150 containing heteroatoms at C2 or C6 positions is described. Herein, we report that the presence of alkyl substituted heteroatoms at the C2(6)-positions of the dihydropyridine are well tolerated. In addition, 15 inhibited the phenylephrine induced contraction of dog prostate tissue with a Kb of 1.5 nM and showed a Kb (DBP, dogs, microg/kg)/Kb (IUP, dogs, microg/kg) ratio of 14.8/2.5.
authors.affiliation: Department of Chemistry, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Marzabadi
authors.forename: X
authors.initials: X
authors.lastname: Hong
authors.forename: D
authors.initials: D
authors.lastname: Nagarathnam
authors.forename: S W
authors.initials: SW
authors.lastname: Miao
authors.forename: G
authors.initials: G
authors.lastname: Chiu
authors.forename: W C
authors.initials: WC
authors.lastname: Wong
authors.forename: J M
authors.initials: JM
authors.lastname: Wetzel
authors.forename: J
authors.initials: J
authors.lastname: Fang
authors.forename: C
authors.initials: C
authors.lastname: Forray
authors.forename: T B
authors.initials: TB
authors.lastname: Chen
authors.forename: S S
authors.initials: SS
authors.lastname: O'Malley
authors.forename: R S
authors.initials: RS
authors.lastname: Chang
authors.forename: C
authors.initials: C
authors.lastname: Gluchowski
mesh_terms: D018674:Adrenergic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D011485:Protein Binding; D051381:Rats; D013237:Stereoisomerism
chemical_list: D018674:Adrenergic Antagonists; D015220:Calcium Channels; D004095:Dihydropyridines; D010656:Phenylephrine