ANTIHYPERGLYCEMIC ACTIVITY OF NOVEL SUBSTITUTED 3H-1,2,3,5-OXATHIADIAZOLE 2-OXIDES

被引：44

作者：

ELLINGBOE, JW ^{[1
]}

ALESSI, TR ^{[1
]}

DOLAK, TM ^{[1
]}

NGUYEN, TT ^{[1
]}

TOMER, JD ^{[1
]}

GUZZO, F ^{[1
]}

BAGLI, JF ^{[1
]}

MCCALEB, ML ^{[1
]}

机构：

[1] WYETH AYERST RES, DIV CARDIOVASC & METAB DISORDERS, PRINCETON, NJ 08543 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 07期

关键词：

D O I：

10.1021/jm00085a002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of substituted 3H-1,2,3,5-oxathiadiazole-2-oxides (6) was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. The oxathiadiazoles 6 were synthesized by a two-step sequence: treatment of a substituted acetonitrile (4) with hydroxylamine to give the corresponding amidoxime (5) and cyclization with thionyl chloride to yield 6. In terms of potency, the 2-naphthalenylmethyl group (as in compound 3) was found to be the optimal substituent in this series. Compound 3 was approximately 5 times more potent than ciglitazone (1).

引用

页码：1176 / 1183

页数：8

共 48 条

[1] USE OF 2,3-DICHLOROPROPENE AND 1,3-DICHLOROBUT-2-ENE AS SYNTHONS FOR HETEROCYCLIC-COMPOUNDS - SYNTHESIS OF 2-METHYLBENZO[B]FURANS, 2-METHYLBENZO[B]THIOPHENS, AND 4-METHYL-2H-CHROMEN [J].

ANDERSON, WK ;

LAVOIE, EJ ;

BOTTARO, JC .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1976, (01) :1-4

[2] THE SYNTHESIS OF 5,7-DICHLOROCOUMARAN-3-ONE AND RELATED PROBLEMS [J].

ARMAREGO, WLF .

AUSTRALIAN JOURNAL OF CHEMISTRY, 1960, 13 (01) :95-102

[3] SOME DERIVATIVES ON INDAN-1-1 [J].

BELL, F ;

SPANSWIC.J .

JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC, 1966, (20) :1887-&

[4]

CAGNIANT P, 1976, CR ACAD SCI C CHIM, V282, P993

[5]

CALDWELL J, 1990, COMPREHENSIVE MED CH, V5, P144

[6] BENZO[B]THIOPHENE DERIVATIVES .7. AN ABNORMAL SUBSTITUTION PRODUCT FROM 3-CHLOROMETHYLBENZO[B]THIOPHENE [J].

CAMPAIGN.E ;

NEISS, ES .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1965, 2 (03) :231-&

[7] ANNELATED FURANS .17. WITTIG REACTION OF BENZOFURANONES [J].

CHAN, JHT ;

ELIX, JA ;

FERGUSON, BA .

AUSTRALIAN JOURNAL OF CHEMISTRY, 1975, 28 (05) :1097-1111

[8] CIGLITAZONE, A NEW HYPOGLYCEMIC AGENT .1. STUDIES IN OB/OB AND DB/DB MICE, DIABETIC CHINESE HAMSTERS, AND NORMAL AND STREPTOZOTOCIN-DIABETIC RATS [J].

CHANG, AY ;

WYSE, BM ;

GILCHRIST, BJ ;

PETERSON, T ;

DIANI, AR .

DIABETES, 1983, 32 (09) :830-838

[9] PHARMACOLOGICALLY ACTIVE BENZO[B]THIOPHEN DERIVATIVES .7. ANALOGUES OF TRYPTAMINE AND HETEROAUXIN [J].

CHAPMAN, NB ;

CLARKE, K ;

HUMPHRIES, AJ ;

SARAF, SUD .

JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC, 1969, (12) :1612-+

[10]

COLCA JR, 1990, NEW ANTIDIABETIC DRU, P255

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