Evaluation of glycolamide esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors.
A number of novel indomethacin glycolamide esters were synthesized and tested for their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of these compounds proved to be selective COX-2 inhibitors, and subtle structural changes in the substituents on the glycolamide ester moiety altered the inhibitory properties as well as potencies significantly. Their in vitro data were rationalized through molecular modeling studies. Few of them displayed anti-inflammatory activity in vivo. Compound 32, [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid 2-morpholin-4-yl-2-oxo ethyl ester, was identified as a promising compound in this class and its good anti-inflammatory activity was demonstrated in the in vivo model.
Department of Chemistry, Discovery Research, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad 500049, India.
Smriti
S
Khanna
Manjula
M
Madan
Akhila
A
Vangoori
Rahul
R
Banerjee
Ram
R
Thaimattam
S K
SK
Jafar Sadik Basha
Mullangi
M
Ramesh
Seshagiri Rao
SR
Casturi
Manojit
M
Pal
D000818:Animals; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D012669:Seminal Vesicles / Q000187:drug effects / Q000201:enzymology; D012756:Sheep; D013276:Stomach Ulcer / Q000139:chemically induced
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D051546:Cyclooxygenase 2; D007213:Indomethacin