Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 4. Structure-activity relationship in the dihydropyrimidine series.
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.
Wong
W C
WC
Departments of Chemistry and Pharmacology, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
Sun
W
W
Lagu
B
B
Tian
D
D
Marzabadi
M R
MR
Zhang
F
F
Nagarathnam
D
D
Miao
S W
SW
Wetzel
J M
JM
Peng
J
J
Forray
C
C
Chang
R S
RS
Chen
T B
TB
Ransom
R
R
O'Malley
S
S
Broten
T P
TP
Kling
P
P
Vyas
K P
KP
Zhang
K
K
Gluchowski
C
C
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
C547713:ADRA1A protein, human; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D011743:Pyrimidines; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins