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Identification of a stable chymase inhibitor using a pharmacophore-Based database search.

Abstract：

:In general, serine protease chymase inhibitors readily decompose in plasma. We previously found that thiazolidine-2,4-dione and thiadiazole derivatives are also unstable. Using a pharmacophore-based database search, we identified a benzo[b]thiophen-2-sulfonamide derivative as a stable chymase inhibitor. Finding a lead compound with adequate activity and stability by a pharmacophore-based approach is more efficient than modifying an unstable compound to reduce its instability without simultaneously decreasing its inhibitory activity. Our pharmacophore model of chymase inhibitors suggests that the two hydrophobic interactions in the S1 and S1' regions and the two H-bonding interactions between them play important roles in chymase inhibitors.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Koide Y,Tatsui A,Hasegawa T,Murakami A,Satoh S,Yamada H,Kazayama S,Takahashi A

doi

10.1016/s0960-894x(02)00853-3

subject

Has Abstract

pub_date

2003-01-06 00:00:00

pages

25-9

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960894X02008533

journal_volume

13

pub_type

杂志文章

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