Synthesis and evaluation of S-4-(3-thienyl)phenyl-alpha-methylacetic acid.
Herein we report an efficient procedure to synthesize S-4-(3-thienyl)phenyl-alpha-methylacetic acid, an enantiomerically pure intermediate of a recently approved nonsteroidal antiinflammatory cyclooxygenase inhibitor, atliprofen [methyl RS-4-(3-thienyl)phenyl-alpha-methylacetate]. The interactions of the active S-isomer of the acid were theoretically compared with those of S-ibuprofen through molecular docking studies using COX-1 and COX-2 protein structures. The results were corroborated by in vitro and in vivo studies.
Mittal
Shilpi
S
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062, India.
Malde
Alpeshkumar
A
Selvam
C
C
Arun
K H S
KH
Johar
P S
PS
Jachak
Sanjay M
SM
Ramarao
P
P
Bharatam
P V
PV
Chawla
H P S
HP
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; C490863:S-4-(3-thienyl)phenyl-alpha-methylacetic acid; D013876:Thiophenes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases