Diarylpyrazole

Diarylpyrazole compound docking into the active site of cyciooxygenase-2 (COX-2) as an inhibitor. Different orientations are tested to optimize the steric, eiectrostatic and hydrogen boding interactions. 

Figure 3.6 Docking simulations. (Source Liu H, Huang X, Shen J, et al. Inhibitory mode of 1,5-diarylpyrazole derivatives against cyclooxygenase-2 and cyclooxygenase-1 molecular docking and 3D QSAR analyses, Journal of Medicinal Chemistry 45 4816-4827 (2002). Used with permission.)...

With regard to the synthesis of celecoxib (1), several routes were described in the 1995 patent by G. D. Searle As shown in Scheme 1, dione 7 was prepared by the Claisen condensation of 4-methylacetophenone with ethyl trifluoroacetate in the presence of NaOMe in methanol under reflux. Subsequent diarylpyrazole formation from the condensation of dione 7 and 4-sulfonamidophenylhydrazine hydrochloride then delivered... 

Reaction of 2-bromoacetophenone 45 with dimethylfomiamide dimethylacetal (DMF-DMA) to the intermediate enaminoketones followed by reaction with various arylhydrazines afforded diarylpyrazoles 46, which underwent Mizoroki-Heck palladium-catalyzed intramolecular couplings to give pyrazolo[l,5-/ phenanthridines 47 <030L1095>. 

Menozzi G, Fossa P et al (2008) Rational design, synthesis and biological evaluation of new 1, 5-diarylpyrazole derivatives as CBj receptor antagonists strucmrally related to rimonabant. Eur J Med Chem 48 2627-2638... 

Humphries PS, Finefield JM (2006) Microwave-assisted synthesis utilizing supported reagents a rapid and versatile synthesis of 1, 5-diarylpyrazoles. Tetrahedron Lett 47 2443-2446... 

Tsuji, K., Nakamura, K., Konishi, N., Tojo, T., Ochi. T.. Senoh, H.. and Matsuo, M., Studies on antiinflammatory agents. Part 4. Synthesis and pharmacological properties of 1,5-diarylpyrazoles and related derivatives, Chem. Pharm. Bull., 45. 987, 1997. 

Gatley SJ, Lan R, Pyatt B, Gifford AN, Volkow ND, Makriyannis A (1997) Binding of the non-classical cannabinoid CP-55,940, and the diarylpyrazole AM251 to rodent brain cannabinoid receptors. Life Sci 61 L191-197... 

Desiraju, G.R., Gopalakrishnan, B., Jetti, R.K.R., Raveendra, D., Sarma, J.A.R.P. and Subramanya, H.S. (2000) Three-dimensional quantitative structural activity relationship (3D-QSAR) studies of some 1,5-diarylpyrazoles analogue based design of selective cyclooxygenase-2 inhibitors. Molecules, 5, 945-955. 

Cheung KM et al (2005) The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors. Bioorg Med Chem Lett 15(14) 3338-3343... 

The cannabinoid ligand can be classified according to Ooms et al [43] into six groups i) classical, ii) nonclassical, iii) bicyclic, iv) aminoalkylindoles, v) endocannabinoid analogues, vi) diarylpyrazoles. Ooms et al [43] studied the pharmacophore of 3-alkyl-5-arylimidazolidinediones as a new CBi cannabinoid receptor. Thomas et al [44] have studied SAR data on a series of 1,5-diphenylpyrazoles proposing a pharmacophoric alignment of these compounds with THC... 

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