Identification of novel and potent 2-amino benzamide derivatives as allosteric glucokinase activators

Teruyuki Nishimura; Tomoharu Iino; Morihiro Mitsuya; Makoto Bamba; Hitomi Watanabe; Daisuke Tsukahara; Kenji Kamata; Kaori Sasaki; Sumika Ohyama; Hideka Hosaka; Mayumi Futamura; Yasufumi Nagata; Jun-Ichi Eiki

doi:10.1016/j.bmcl.2009.01.053

Identification of novel and potent 2-amino benzamide derivatives as allosteric glucokinase activators

Bioorg Med Chem Lett. 2009 Mar 1;19(5):1357-60. doi: 10.1016/j.bmcl.2009.01.053. Epub 2009 Jan 21.

Authors

Teruyuki Nishimura¹, Tomoharu Iino, Morihiro Mitsuya, Makoto Bamba, Hitomi Watanabe, Daisuke Tsukahara, Kenji Kamata, Kaori Sasaki, Sumika Ohyama, Hideka Hosaka, Mayumi Futamura, Yasufumi Nagata, Jun-Ichi Eiki

Affiliation

¹ Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo-3, Tsukuba, 300-2611 Ibaraki, Japan.

PMID: 19188063
DOI: 10.1016/j.bmcl.2009.01.053

Abstract

The identification and structure-activity-relationships (SARs) of novel 2-amino benzamide glucokinase activators are described. Compounds in this series were developed to be potent GK activators, and their binding mode to the GK protein was determined by crystal structure analysis. In vivo pharmacokinetic and acute in vivo efficacy studies of compound 18 are also described.

Publication types

Comparative Study

MeSH terms

Allosteric Regulation / drug effects
Allosteric Regulation / physiology
Animals
Benzamides / chemistry*
Benzamides / pharmacology
Binding Sites / drug effects
Binding Sites / physiology
Enzyme Activation / drug effects
Enzyme Activation / physiology
Glucokinase / metabolism*
Male
Rats
Rats, Wistar
Structure-Activity Relationship

Substances

Benzamides
Glucokinase