956282-72-7Relevant academic research and scientific papers
Benzo[d]imidazole transient receptor potential vanilloid 1 antagonists for the treatment of pain: Discovery of trans-2-(2-{2-[2-(4-Trifluoromethyl-phenyl)-vinyl]-1H-benzimidazol-5-yl}-phenyl)-propan-2-ol (Mavatrep)
Parsons, William H.,Calvo, Raul R.,Cheung, Wing,Lee, Yu-Kai,Patel, Sharmila,Liu, Jian,Youngman, Mark A.,Dax, Scott L.,Stone, Dennis,Qin, Ning,Hutchinson, Tasha,Lubin, Mary Lou,Zhang, Sui-Po,Finley, Michael,Liu, Yi,Brandt, Michael R.,Flores, Christopher M.,Player, Mark R.
, p. 3859 - 3874 (2015/05/27)
Reported herein is the design, synthesis, and pharmacologic characterization of a class of TRPV1 antagonists constructed on a benzo[d]imidazole platform that evolved from a biaryl amide lead. This design composes three sections: a 2-substituted 5-phenyl headgroup attached to the benzo[d]imidazole platform, which is tethered at the two position to a phenyl tail group. Optimization of this design led to the identification of 4 (mavatrep), comprising a trifluoromethyl-phenyl-vinyl tail. In a TRPV1 functional assay, using cells expressing recombinant human TRPV1 channels, 4 antagonized capsaicin-induced Ca2+ influx, with an IC50 value of 4.6 nM. In the complete Freund's adjuvant- and carrageenan-induced thermal hypersensitivity models, 4 exhibited full efficacy, with ED80 values of 7.8 and 0.5 mg/kg, respectively, corresponding to plasma levels of 270.8 and 9.2 ng/mL, respectively. On the basis of its superior pharmacologic and safety profile, 4 (mavatrep) was selected for clinical development for the treatment of pain.
Benzimidazole Modulators of VR1
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Page/Page column 167; 171, (2008/06/13)
The invention is directed to compounds of Formula (I): to pharmaceutical compositions containing such compounds and to methods of treatment using them.
