910303-55-8Relevant academic research and scientific papers
2-Hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl] -1-benzenesulfonamide (DRF-4367): An orally active COX-2 inhibitor identified through pharmacophoric modulation
Singh, Sunil Kumar,Vobbalareddy, Saibaba,Kalleda, Srinivasa Rao,Rajjak, Shaikh Abdul,Casturi, Seshagiri Rao,Datla, Srinivasa Raju,Mamidi, Rao N.V.S.,Mullangi, Ramesh,Bhamidipati, Ravikanth,Ramanujam, Rajagopalan,Akella, Venkateswarlu,Yeleswarapu, Koteswar Rao
, p. 2442 - 2450 (2004)
Analogs of 1,5-diarylpyrazoles with a novel pharmacophore at N1 were designed, synthesized and evaluated for the in-vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The variations at/around position-4 of the C-5 phenyl ring in conjunction with a CF3 and CHF2 groups at C-3 exhibited a high degree of potency and selectivity index (SI) for COX-2 inhibition. The in-vivo evaluation of these potent compounds with a few earlier ones indicated the 4-OMe-phenyl analog 6 and the 4-NHMe-phenyl analog 9 with a CF3, and the 4-OEt-phenyl analog 19 with a CHF2 group at C-3 to possess superior potency than celecoxib. In addition to its impressive anti-inflammatory, antipyretic, analgesic and anti-arthritic properties, compound 6 (DRF-4367) was found to possess an excellent pharmacokinetic profile, gastrointestinal (GI) safety in the long-term arthritis study and COX-2 potency in human whole blood assay. Thus, compound 6 was selected as an orally active anti-inflammatory candidate for pre-clinical evaluation.
Structure–Activity Relationships of UTX-121 Derivatives for the Development of Novel Matrix Metalloproteinase-2/9 Inhibitors
Asada, Chikako,Endo, Yoshio,Komiya, Yuki,Takino, Takahisa,Uto, Yoshihiro,Yamada, Hisatsugu,Yamahana, Hirari
, p. 1017 - 1028 (2021/10/12)
Celecoxib, a nonsteroidal anti-inflammatory drug, has been reported to have antitumor and antimetastatic activities, and it has potential for application in cancer treatments. The expression of matrix metalloproteinase (MMP)-2/9 is strongly correlated wit
Synthesis and biological evaluation of salicylic acid analogues of celecoxib as a new class of selective cyclooxygenase-1 inhibitor
Yoon, Sung-Hwa,Cho, Duk-Yeon,Choi, Seoung-Ryoung,Lee, Joo-Young,Choi, Dong-Kug,Kim, Eunha,Park, Ju-Young
, p. 1230 - 1238 (2021/09/06)
A series of salicylic acid analogues of celecoxib where the phenylsulfonamide moiety in the structure of celecoxib is replaced by salicylic acid moiety was synthesized and tested for in vitro cyclooxygenase (COX)-1 and COX-2 enzyme inhibition. Among the series, 5-substituted-2-hydroxy-benzoic acid analogues (7a–7h) generally showed better inhibitory activities on both enzymes than 4-substituted-2-hydroxy-ben-zoic acid analogues (12a–12h). In particular, the chloro analogue 7f which had the highest inhibitory effect (IC50=0.0057μM) to COX-1 with excellent COX-1 selectivity (SI=768) can be classified as a new potent and selective COX-1 inhibitor. The high inhibitory potency of 7f was rationalized through the docking simulation of this analogue in the active site of COX-1 enzyme.
