当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones.

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Nagarathnam D,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,Sch

doi

10.1021/jm990200p

keywords:

subject

Has Abstract,Author List Incomplete

pub_date

1999-11-18 00:00:00

pages

4764-77

issue

23

eissn

0022-2623

issn

1520-4804

pii

jm990200p

journal_volume

42

pub_type

杂志文章

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