Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: Oxadiazolyl ketones

被引：14

作者：

Koo, Ki Dong ^{[1
]}

Kim, Min Jung ^{[1
]}

Kim, Sungsub ^{[1
]}

Kim, Kyoung-Hee ^{[1
]}

Hong, Sang Yong ^{[1
]}

Hur, Gwong-Cheung ^{[1
]}

Yim, Hyeon Joo ^{[1
]}

Kim, Geun Tae ^{[1
]}

Han, Hee Oon ^{[1
]}

Kwon, O. Hwan ^{[1
]}

Kwon, Tae Sik ^{[1
]}

Koh, Jong Sung ^{[1
]}

Lee, Chang-Seok ^{[1
]}

机构：

[1] LG Life Sci, Taejon 305380, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 15期

关键词：

oxadiazolyl ketones; DPPIV inhibitors;

D O I：

10.1016/j.bmcl.2007.05.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure-activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described. (c) 2007 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4167 / 4172

页数：6

相关论文

共 19 条

[1] Inhibitors of proline-specific a dipeptidyl peptidases: DPP IV inhibitors as a novel approach for the treatment of Type 2 diabetes [J].

Augustyns, K ;

Van der Veken, P ;

Haemers, A .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (10) :1387-1407

[2] Inhibitors of dipeptidyl peptidase IV:: a novel approach for the prevention and treatment of Type 2 diabetes? [J].

Deacon, CF ;

Ahrén, B ;

Holst, JJ .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2004, 13 (09) :1091-1102

[3] Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes [J].

Drucker, DJ .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2003, 12 (01) :87-100

[4] Glucagon-like peptides [J].

Drucker, DJ .

DIABETES, 1998, 47 (02) :159-169

[5]

EDUARDS PD, 1995, J MED CHEM, V38, P76

[6] Ketopyrrolidines and ketoazetidines as potent dipeptidyl peptidase IV (DPP IV) inhibitors [J].

Ferraris, D ;

Ko, YS ;

Calvin, D ;

Chiou, T ;

Lautar, S ;

Thomas, B ;

Wozniak, K ;

Rojas, C ;

Kalish, V ;

Belyakov, S .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (22) :5579-5583

[7] Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes [J].

Gautier, JF ;

Fetita, S ;

Sobngwi, E ;

Salaün-Martin, C .

DIABETES & METABOLISM, 2005, 31 (03) :233-242

[8]

KIFFER TJ, 1995, ENDOCRINOLOGY, V136, P3585

[9] (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-α]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine:: A potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes [J].

Kim, D ;

Wang, LP ;

Beconi, M ;

Eiermann, GJ ;

Fisher, MH ;

He, HB ;

Hickey, GJ ;

Kowalchick, JE ;

Leiting, B ;

Lyons, K ;

Marsilio, F ;

McCann, ME ;

Patel, RA ;

Petrov, A ;

Scapin, G ;

Patel, SB ;

Roy, RS ;

Wu, JK ;

Wyvratt, MJ ;

Zhang, BB ;

Zhu, L ;

Thornberry, NA ;

Weber, AE .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (01) :141-151

[10] Glucagon-like peptide-1: The basis of a new class of treatment for type 2 diabetes [J].

Knudsen, LB .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (17) :4128-4134