SAR and species/stereo - Selective metabolism of the sorbitol dehydrogenase inhibitor, CP-470,711

被引：10

作者：

Chu-Moyer, MY ^{[1
]}

Ballinger, WE ^{[1
]}

Beebe, DA ^{[1
]}

Coutcher, JB ^{[1
]}

Day, WW ^{[1
]}

Li, JC ^{[1
]}

Oates, PJ ^{[1
]}

Weekly, RM ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton Labs, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(02)00208-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

SAR studies on the stereoisoniers of CP-470,711 suggested that in vivo epimerization was taking place in rats. Further metabolism studies revealed that no epimerization was occurring in dogs, and that no epimerization was expected in humans. A mechanism for the in vivo epimerization is proposed involving an oxidation-reduction pathway of the secondary benzylic alcohol, in contrast to an acid/base-promoted epimerization of the same center during chemical synthesis. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1477 / 1480

页数：4

共 6 条

[1] Orally-effective, long-acting sorbitol dehydrogenase inhibitors: Synthesis, structure-activity relationships, and in vivo evaluations of novel heterocycle-substituted piperazino-pyrimidines [J].

Chu-Moyer, MY ;

Ballinger, WE ;

Beebe, DA ;

Berger, R ;

Coutcher, JB ;

Day, WW ;

Li, JC ;

Mylari, BL ;

Oates, PJ ;

Weekly, RM .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (02) :511-528

[2] PREVENTION AND TREATMENT OF THE COMPLICATIONS OF DIABETES-MELLITUS [J].

CLARK, CM ;

LEE, DA .

NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (18) :1210-1217

[3] Sorbitol dehydrogenase inhibitors (SDIs):: A new potent, enantiomeric SDI, 4-[2-1R-hydroxy-ethyl)-pyrimidin-4-yl]-piperazine-1-sulfonic acid dimethylamide [J].

Mylari, BL ;

Oates, PJ ;

Beebe, DA ;

Brackett, NS ;

Coutcher, JB ;

Dina, MS ;

Zembrowski, WJ .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (17) :2695-2700

[4] LONG-TERM COMPLICATIONS OF DIABETES-MELLITUS [J].

NATHAN, DM .

NEW ENGLAND JOURNAL OF MEDICINE, 1993, 328 (23) :1676-1685

[5]

TILTON RG, 1995, DIABETES, V44, P232

[6]

0059510

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