Novel euglycemic and hypolipidemic agents. 1.
A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.
Lohray
B B
BB
Medicinal and Organic Chemistry, Pharmacology, and Clinical Research, Dr. Reddy's Research Foundation, Bollaram Road, Miyapur Hyderabad 500 050, India.
Bhushan
V
V
Rao
B P
BP
Madhavan
G R
GR
Murali
N
N
Rao
K N
KN
Reddy
A K
AK
Rajesh
B M
BM
Reddy
P G
PG
Chakrabarti
R
R
Vikramadithyan
R K
RK
Rajagopalan
R
R
Mamidi
R N
RN
Jajoo
H K
HK
Subramaniam
S
S
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045162:Thiazolidinediones; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood
C112100:5-((4-(2-(1-indolyl)ethoxy)-phenyl)methyl)thiazolidine-2,4-dione; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007211:Indoles; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone