| Autor: |
Nagarathnam, D., Miao, S. W., Lagu, B., Chiu, G., Fang, J., Dhar, T. G. Murali, Zhang, J., Tyagarajan, S., Marzabadi, M. R., Zhang, F., Wong, W. C., Sun, W., Tian, D., Wetzel, J. M., Forray, C., Chang, R. S. L., Broten, T. P., Ransom, R. W., Schorn, T. W., Chen, T. B., O'Malley, S., Kling, P., Schneck, K., Bendesky, R., Harrell, C. M., Vyas, K. P., Gluchowski, C. |
| Zdroj: |
Journal of Medicinal Chemistry; November 18, 1999, Vol. 42 Issue: 23 p4764-4777, 14p |
| Abstrakt: |
Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human α1a receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (Ki = 0.2 nM) for α1a receptor and greater than 1500-fold selectivity over α1b and α1d 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 (Kb(DBP)/Kb(IUP) = 40) suggesting uroselectivity for α1a-selective compounds. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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