Discovery of liver selective non-steroidal glucocorticoid receptor antagonist as novel antidiabetic agents.
Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver selectivity. These preliminary results confirm discovery of potent and liver selective passive GR antagonist for the treatment of T2DM.
Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India.
Kiran
K
Shah
Dipam
D
Patel
Pradip
P
Jadav
Mubeen
M
Sheikh
Kalapatapu V V M
KV
Sairam
Amit
A
Joharapurkar
Mukul R
MR
Jain
Rajesh
R
Bahekar
D000284:Administration, Oral; D000818:Animals; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015696:Gene Products, tat / Q000037:antagonists & inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001593:Benzyl Compounds; D001786:Blood Glucose; D015696:Gene Products, tat; D007004:Hypoglycemic Agents; D011965:Receptors, Glucocorticoid; D051416:Focal Adhesion Protein-Tyrosine Kinases