Synthesis and evaluation of S-4-(3-thienyl)phenyl-alpha-methylacetic acid

Shilpi Mittal; Alpeshkumar Malde; C Selvam; K H S Arun; P S Johar; Sanjay M Jachak; P Ramarao; P V Bharatam; H P S Chawla

doi:10.1016/j.bmcl.2003.11.066

Synthesis and evaluation of S-4-(3-thienyl)phenyl-alpha-methylacetic acid

Bioorg Med Chem Lett. 2004 Feb 23;14(4):979-82. doi: 10.1016/j.bmcl.2003.11.066.

Authors

Shilpi Mittal¹, Alpeshkumar Malde, C Selvam, K H S Arun, P S Johar, Sanjay M Jachak, P Ramarao, P V Bharatam, H P S Chawla

Affiliation

¹ Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062, India.

PMID: 15013005
DOI: 10.1016/j.bmcl.2003.11.066

Abstract

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.

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / pharmacology
Isoenzymes / antagonists & inhibitors
Models, Molecular
Molecular Structure
Prostaglandin-Endoperoxide Synthases
Thiophenes / chemical synthesis*
Thiophenes / pharmacology

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
S-4-(3-thienyl)phenyl-alpha-methylacetic acid
Thiophenes
Cyclooxygenase 1
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases