Studies on non-thiazolidinedione antidiabetic agents. 1. Discovery of novel oxyiminoacetic acid derivatives

被引：15

作者：

Imoto, H ^{[1
]}

Imamiya, E ^{[1
]}

Momose, Y ^{[1
]}

Sugiyama, Y ^{[1
]}

Kimura, H ^{[1
]}

Sohda, T ^{[1
]}

机构：

[1] Takeda Chem Ind Ltd, Div Pharmaceut Res, Yodogawa Ku, Osaka 5328686, Japan

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2002年 / 50卷 / 10期

关键词：

antidiabetic agent; oxyiminoacetic acid; type; 2; diabetes; peroxisome proliferator-activated receptor; KKA(y) mice;

D O I：

10.1248/cpb.50.1349

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of oxyiminoacetic acid derivatives were synthesized in an effort to develop a potent antidiabetic agent, which does not contain the 2,4-thiazolidinedione moiety. These compounds were evaluated for glucose and lipid lowering effects in genetically obese and diabetic KKA(y) mice. Several of the compounds showed strong antidiabetic activity, including functional potency at peroxisome proliferator-activated receptor (PPAR)-gamma. (Z)-2-[4-[(5-Methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyloxyimino]-2-(4-phenoxyphenyl)acetic acid (25) significantly reduced plasma glucose (33%, p<0.01) and plasma triglycelide levels (43%, p<0.01) even at a dosage of 0.001% in diet. Pharmacokinetic analyses of 25 are also reported.

引用

页码：1349 / 1357

页数：9

共 40 条

[1] [[OMEGA-(HETEROCYCLYLAMINO)ALKOXY]BENZYL]-2,4-THIAZOLIDINEDIONES AS POTENT ANTIHYPERGLYCEMIC AGENTS [J].

CANTELLO, BCC ;

CAWTHORNE, MA ;

COTTAM, GP ;

DUFF, PT ;

HAIGH, D ;

KINDLEY, RM ;

LISTER, CA ;

SMITH, SA ;

THURLBY, PL .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (23) :3977-3985

[2] 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

[3] SUBSTITUTED DIHYDROBENZOPYRAN AND DIHYDROBENZOFURAN THIAZOLIDINE-2,4-DIONES AS HYPOGLYCEMIC AGENTS [J].

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 .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (01) :319-325

[4] N-(2-benzoylphenyl)-L-tyrosine PPARγ agonists.: 3.: Structure-activity relationship and optimization of the N-aryl substituent [J].

Cobb, JE ;

Blanchard, SG ;

Boswell, EG ;

Brown, KK ;

Charifson, PS ;

Cooper, JP ;

Collins, JL ;

Dezube, M ;

Henke, BR ;

Hull-Ryde, EA ;

Lake, DH ;

Lenhard, JM ;

Oliver, W ;

Oplinger, J ;

Pentti, M ;

Parks, DJ ;

Plunket, KD ;

Tong, WQ .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (25) :5055-5069

[5] N-(2-benzoylphenyl)-L-tyrosine PPARγ agonists.: 2.: Structure-activity relationship and optimization of the phenyl alkyl ether moiety [J].

Collins, JL ;

Blanchard, SG ;

Boswell, GE ;

Charifson, PS ;

Cobb, JE ;

Henke, BR ;

Hull-Ryde, EA ;

Kazmierski, WM ;

Lake, DH ;

Leesnitzer, LM ;

Lehmann, J ;

Lenhard, JM ;

Orband-Miller, LA ;

Gray-Nunez, Y ;

Parks, DJ ;

Plunkett, KD ;

Tong, WQ .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (25) :5037-5054

[6] EFFECT OF NEAR NORMOGLYCEMIA FOR 2 YEARS ON PROGRESSION OF EARLY DIABETIC-RETINOPATHY, NEPHROPATHY, AND NEUROPATHY - THE OSLO STUDY [J].

DAHLJORGENSEN, K ;

BRINCHMANNHANSEN, O ;

HANSSEN, KF ;

GANES, T ;

KIERULF, P ;

SMELAND, E ;

SANDVIK, L ;

AAGENAES, O .

BRITISH MEDICAL JOURNAL, 1986, 293 (6556) :1195-1199

[7]

DEFRONZO RA, 1988, DIABETES, V37, P255

[8]

Depres JP, 1996, NEW ENGL J MED, V334, P952

[9]

FELDTRASMUSSEN B, 1986, LANCET, V2, P1300

[10] REDUCTION OF INSULIN RESISTANCE IN OBESE AND OR DIABETIC ANIMALS BY 5-[4-(1-METHYLCYCLOHEXYLMETHOXY)BENZYL]-THIAZOLIDINE-2,4-DIONE (ADD-3878, U-63,287, CIGLITAZONE), A NEW ANTI-DIABETIC AGENT [J].

FUJITA, T ;

SUGIYAMA, Y ;

TAKETOMI, S ;

SOHDA, T ;

KAWAMATSU, Y ;

IWATSUKA, H ;

SUZUOKI, Z .

DIABETES, 1983, 32 (09) :804-810

← 1 2 3 4 →