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 describ...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1999-11, Vol.42 (23), p.4804-4813
Main Authors: Wong, W C, Sun, W, Lagu, B, Tian, D, Marzabadi, M R, Zhang, F, Nagarathnam, D, Miao, S W, Wetzel, J M, Peng, J, Forray, C, Chang, R S, Chen, T B, Ransom, R, O'Malley, S, Broten, T P, Kling, P, Vyas, K P, Zhang, K, Gluchowski, C
Format: Article
Language:English
Subjects:
Administration, Oral
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists - chemical synthesis
Adrenergic alpha-Antagonists - chemistry
Adrenergic alpha-Antagonists - metabolism
Adrenergic alpha-Antagonists - pharmacology
Animals
Binding, Competitive
Biological Availability
Dogs
Drug Design
Drug Evaluation, Preclinical
Humans
In Vitro Techniques
Male
Prostate - metabolism
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - metabolism
Pyrimidines - pharmacology
Rats
Receptors, Adrenergic, alpha-1 - metabolism
Recombinant Proteins - metabolism
Stereoisomerism
Structure-Activity Relationship
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm9902032