دورية أكاديمية
Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones.
| العنوان: | Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones. |
|---|---|
| المؤلفون: | Nagarathnam D; Departments of Chemistry and Pharmacology, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA., Miao SW, Lagu B, Chiu G, Fang J, Murali Dhar TG, Zhang J, Tyagarajan S, Marzabadi MR, Zhang F, Wong WC, Sun W, Tian D, Wetzel JM, Forray C, Chang RS, Broten TP, Ransom RW, Schorn TW, Chen TB, O'Malley S, Kling P, Schneck K, Bendesky R, Harrell CM, et. al. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 1999 Nov 18; Vol. 42 (23), pp. 4764-77. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print Cited Medium: Print ISSN: 0022-2623 (Print) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Adrenergic alpha-1 Receptor Antagonists*, Adrenergic alpha-Antagonists/*chemical synthesis , Pyrimidinones/*chemical synthesis, Adrenergic alpha-Antagonists/chemistry ; Adrenergic alpha-Antagonists/metabolism ; Adrenergic alpha-Antagonists/pharmacology ; Animals ; Binding, Competitive ; Blood Pressure/drug effects ; Dogs ; Drug Design ; Drug Evaluation, Preclinical ; Humans ; In Vitro Techniques ; Male ; Prostate/metabolism ; Pyrimidinones/chemistry ; Pyrimidinones/metabolism ; Pyrimidinones/pharmacology ; Radioligand Assay ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, alpha-1/metabolism ; Stereoisomerism ; Urethra/drug effects ; Urethra/physiology |
| مستخلص: | Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds. |
| المشرفين على المادة: | 0 (ADRA1A protein, human) 0 (Adra1a protein, rat) 0 (Adrenergic alpha-1 Receptor Antagonists) 0 (Adrenergic alpha-Antagonists) 0 (Pyrimidinones) 0 (Receptors, Adrenergic, alpha-1) 0 (SNAP 6201) |
| تواريخ الأحداث: | Date Created: 19991202 Date Completed: 19991217 Latest Revision: 20190709 |
| رمز التحديث: | 20240627 |
| DOI: | 10.1021/jm990200p |
| PMID: | 10579840 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society كن أول من يترك تعليقا!