SUBSTITUTED DIHYDROBENZOPYRAN AND DIHYDROBENZOFURAN THIAZOLIDINE-2,4-DIONES AS HYPOGLYCEMIC AGENTS

被引：88

作者：

CLARK, DA

GOLDSTEIN, SW

VOLKMANN, RA

EGGLER, JF

HOLLAND, GF

HULIN, B

STEVENSON, RW

KREUTTER, DK

GIBBS, EM

KRUPP, MN

MERRIGAN, P

KELBAUGH, PL

ANDREWS, EG

TICKNER, DL

SULESKE, RT

LAMPHERE, CH

RAJECKAS, FJ

KAPPELER, WH

MCDERMOTT, RE

HUTSON, NJ

JOHNSON, MR

机构：

[1] Central Research, Pfizer, Inc., Eastern Point Road, Groton

[2] NC 27709, Research Triangle Park

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 01期

关键词：

D O I：

10.1021/jm00105a050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of dihydrobenzofuran and dihydrobenzopyran thiazolidine-2,4-diones (compounds 3-26) was synthesized from the corresponding aryl aldehydes 1 in two steps. These compounds represent conformationally restricted analogues of the novel hypoglycemic ciglitazone. The series was evaluated by hypoglycemic effects in vitro by measuring stimulation of 2-deoxyglucose uptake in L6 myocytes and stimulation of expression of the glucose transporter protein in 3T3-L1 adipocytes. In vivo hypoglycemic effects were evaluated in the genetically obese ob/ob mouse, and structure-activity relationships are discussed. On the basis of this in vivo potency, we have selected the 2(R)-benzylbenzopyran derivative to be further studied in a clinical setting.

引用

页码：319 / 325

页数：7