QSAR studies on some thiophene analogs as anti-inflammatory agents: enhancement of activity by electronic parameters and its utilization for chemical lead optimization.
Small molecule heterocycle is an integral part of new drug discovery in anti-inflammatory research. In our previous papers we reported the synthesis of thiophene analogs substituted at the fifth position with alpha-oximino propionic ester moiety and the fact that such new chemical entities exhibit anti-inflammatory activity in male/female Sprague-Dawley rats. In this paper we report the quantitative structure activity relationship (QSAR) studies of a series of 43 thiophene analogs. The analogs when subjected to cluster analysis technique led to the formation of four homogeneous groups. The cluster analysis technique grouped the 2-anilino-5-substituted-4-methyl-thiophene-3-carboxylic acid methyl esters as one homogeneous group. The clusters were individually taken up for a Hansch type of QSAR study with 10 molecular descriptors. The QSAR equations generated were cross validated by the leave out one method. The studies gave an insight into the dominant role played by electronic properties like energy of the lowest unoccupied molecular orbital (ELUMO) and dipole moment (dipole) in modulating the anti-inflammatory activity. From the QSAR studies a three point pharmacophore has been established for designing novel anti-inflammatory molecules.
Pillai
Ajay D
AD
Department of Pharmaceutical Chemistry, M.S Ramaiah College of Pharmacy, M.S Ramaiah Nagar, Mathikere, Bangalore 560 054, Karnataka, India.
Rani
Shubha
S
Rathod
Parendu D
PD
Xavier
Franklin P
FP
Vasu
Kamala K
KK
Padh
Harish
H
Sudarsanam
Vasudevan
V
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D008297:Male; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013876:Thiophenes