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Aminocyclohexylsulfonamides: discovery of metabolically stable alpha(1a/1d)-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS).

Abstract：

:Benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) can be effectively treated by alpha(1) adrenergic receptor antagonists, but these drugs also produce side effects that are related to their subtype non-selective nature. To overcome this limitation, it was hypothesized that an alpha(1a/1d) subtype-selective antagonist would be efficacious while keeping side effects to a minimum. To discover alpha(1a/1d)-selective antagonists and improve metabolic stability of our previously reported compounds, we have designed and synthesized a series of (phenylpiperazinyl)- or (phenylpiperidinyl)-cyclohexylsulfonamides. By incorporating the information obtained from metabolism studies, we were able to discover several compounds that are both alpha(1a/1d) adrenoceptor subtype selective and show increased stability toward human liver microsomal metabolism. The selectivity profile of these compounds provides great improvement over the commercial drug tamsulosin, hence may pave the way to the development of new and efficacious therapeutic agents with reduced side effects.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Chiu G,Li S,Cai H,Connolly PJ,Peng S,Stauber K,Pulito V,Liu J,Middleton SA

doi

10.1016/j.bmcl.2007.09.051

subject

Has Abstract

pub_date

2007-11-15 00:00:00

pages

6123-8

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)01089-X

journal_volume

17

pub_type

杂志文章

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