RELATIONSHIP BETWEEN STRUCTURE AND BIOAVAILABILITY IN A SERIES OF HYDROXAMATE BASED METALLOPROTEASE INHIBITORS

被引：29

作者：

SINGH, J

CONZENTINO, P

CUNDY, K

GAINOR, JA

GILLIAM, CL

GORDON, TD

JOHNSON, JA

MORGAN, BA

SCHNEIDER, ED

WAHL, RC

WHIPPLE, DA

机构：

[1] STERLING WINTHROP PHARMACEUT RES DIV, DEPT ENZYME & RECEPTOR BIOCHEM, COLLEGEVILLE, PA 19426 USA

[2] STERLING WINTHROP PHARMACEUT RES DIV, DEPT DRUG METAB & PHARMACOKINET, COLLEGEVILLE, PA 19426 USA

[3] STERLING WINTHROP PHARMACEUT RES DIV, DEPT DRUG REGULATORY AFFAIRS, COLLEGEVILLE, PA 19426 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 04期

关键词：

D O I：

10.1016/0960-894X(95)00031-N

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pharmacokinetic parameters for a series of C-terminally modified hydroxamate dipeptides were evaluated by in vitro and in vivo models. The presence of a tertiary base at the C-terminus significantly reduced biliary excretion and increased plasma half-life. Moreover, introduction of a thioether functionality produced a more favorable pharmacokinetic profile compared to the corresponding oxo- and aza-analogs.

引用

页码：337 / 342

页数：6