title: Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 4. Structure-activity relationship in the dihydropyrimidine series.
abstract: We have previously disclosed dihydropyridines such as 1a,b as selective alpha(1a) antagonists as a potential treatment for benign prostatic hyperplasia (BPH). The propensity of dihydropyridines toward an oxidation led us to find suitable replacements of the core unit. The accompanying papers describe the structure-activity relationship (SAR) of dihydropyrimidinones 2a,b as selective alpha(1a) antagonists. We report herein the SAR of dihydropyrimidines such as 4 and highlight the similarities and differences between the dihydropyrimidine and dihydropyrimidinone series of compounds.
authors.affiliation: Departments of Chemistry and Pharmacology, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Wong
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.forename: B
authors.initials: B
authors.lastname: Lagu
authors.forename: D
authors.initials: D
authors.lastname: Tian
authors.forename: M R
authors.initials: MR
authors.lastname: Marzabadi
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Nagarathnam
authors.forename: S W
authors.initials: SW
authors.lastname: Miao
authors.forename: J M
authors.initials: JM
authors.lastname: Wetzel
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.forename: C
authors.initials: C
authors.lastname: Forray
authors.forename: R S
authors.initials: RS
authors.lastname: Chang
authors.forename: T B
authors.initials: TB
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Ransom
authors.forename: S
authors.initials: S
authors.lastname: O'Malley
authors.forename: T P
authors.initials: TP
authors.lastname: Broten
authors.forename: P
authors.initials: P
authors.lastname: Kling
authors.forename: K P
authors.initials: KP
authors.lastname: Vyas
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Gluchowski
mesh_terms: D000284:Administration, Oral; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001682:Biological Availability; D004285:Dogs; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011467:Prostate / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C547713:ADRA1A protein, human; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011743:Pyrimidines; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins