Discovery of novel 3,6-disubstituted 2-pyridinecarboxamide derivatives as GK activators.
A novel class of 3,6-disubstituted 2-pyridinecarboxamide derivatives was designed based on X-ray analysis of the 2-aminobenzamide lead class. Subsequent chemical modification led to the discovery of potent GK activators which eliminate potential toxicity concerns associated with an aniline group of the lead structure. Compound 7 demonstrated glucose lowering effect in a rat OGTT model.
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Okubo, Tsukuba, Ibaraki, Japan. morihiro_mitsuya@merck.com
Morihiro
M
Mitsuya
Kenji
K
Kamata
Makoto
M
Bamba
Hitomi
H
Watanabe
Yasuhiro
Y
Sasaki
Kaori
K
Sasaki
Sumika
S
Ohyama
Hideka
H
Hosaka
Yasufumi
Y
Nagata
Jun-ichi
J
Eiki
Teruyuki
T
Nishimura
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D055808:Drug Discovery; D005941:Glucokinase / Q000737:chemistry / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship
D000577:Amides; D007004:Hypoglycemic Agents; D011725:Pyridines; D005941:Glucokinase