Synthesis and evaluation of some novel isochroman carboxylic acid derivatives as potential anti-diabetic agents.
A series of novel isochroman mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Analysis of structure-activity relationships led to the identification of potent compound 4n which inhibited PTP1B with IC(50) value of 51.63+/-0.91 nM. In general, high potency was associated with a dithiolane ring with a spacer of five carbons to the isochroman ring. Compound 4n has been selected for in vivo evaluation as drug candidate for anti-diabetic activity.
Lakshminarayana
N
N
Medicinal Chemistry Division, Glenmark Research Center, Mahape, Navi Mumbai, India.
Rajendra Prasad
Y
Y
Gharat
Laxmikant
L
Thomas
Abraham
A
Ravikumar
P
P
Narayanan
Shridhar
S
Srinivasan
C V
CV
Gopalan
Balasubramanian
B
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D007004:Hypoglycemic Agents; D017027:Protein Tyrosine Phosphatases