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A conformationally constrained inhibitor with an enhanced potency for β-tryptase and stability against semicarbazide-sensitive amine oxidase (SSAO).

Abstract：

:A novel β-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so that entropic penalty was decreased. More importantly, this constrained conformation limited the accessibility of this molecule to anti-targets, especially SSAO, so that an enhanced metabolic profile was achieved.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Liang G,Choi-Sledeski YM,Poli G,Chen X,Shum P,Minnich A,Wang Q,Tsay J,Sides K,Cairns J,Stoklosa G,Nieduzak T,Zhao Z,Wang J,Vaz RJ

doi

10.1016/j.bmcl.2010.08.141

subject

Has Abstract

pub_date

2010-11-15 00:00:00

pages

6721-4

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)01287-4

journal_volume

20

pub_type

杂志文章

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