Mavatrep

• CAT Number: I005663
• CAS Number: 956274-94-5
• Molecular Formula: C25H21F3N2O
• Molecular Weight: 422.44
• Purity: ≥95%
• Synonyms: (E)-2-(2-(2-(4-(trifluoromethyl)styryl)-1H-benzo[d]imidazol-6-yl)phenyl)propan-2-ol
• Target: TRPV1
• Solubility: DMSO:30mg/mL
• Storage: Store at -20°C
• IC50: 6.5 nM (Ki, for TRPV1)
• IUPAC Name: 2-[2-[2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-3H-benzimidazol-5-yl]phenyl]propan-2-ol
• InChI: InChI=1S/C25H21F3N2O/c1-24(2,31)20-6-4-3-5-19(20)17-10-13-21-22(15-17)30-23(29-21)14-9-16-7-11-18(12-8-16)25(26,27)28/h3-15,31H,1-2H3,(H,29,30)/b14-9+
• InChIKey: ORDHXXHTBUZRCN-NTEUORMPSA-N
• SMILES: CC(C)(C1=CC=CC=C1C2=CC3=C(C=C2)N=C(N3)C=CC4=CC=C(C=C4)C(F)(F)F)O

Mavatrep (CAT: I0056635) is a selective antagonist of the transient receptor potential vanilloid 4 (TRPV4) ion channel. TRPV4 channels are involved in various physiological processes, including the regulation of cellular osmolarity, calcium homeostasis, and mechanosensation. By blocking TRPV4 channels, mavatrep reduces calcium influx and dampens the response to mechanical stress and inflammation. This compound has shown potential therapeutic applications in conditions such as pulmonary edema, cystic fibrosis, and pain disorders associated with TRPV4 channel dysfunction. Mavatrep’s specificity for TRPV4 and its modulatory effects on cellular responses make it a promising target for drug development in various disease areas.

Reference

1:J Med Chem. 2015 May 14;58(9):3859-74. doi: 10.1021/acs.jmedchem.5b00132. Epub 2015 Apr 15. 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 WH,Calvo RR,Cheung W,Lee YK,Patel S,Liu J,Youngman MA,Dax SL,Stone D,Qin N,Hutchinson T,Lubin ML,Zhang SP,Finley M,Liu Y,Brandt MR,Flores CM,Player MR, PMID: 25850459 DOI: 10.1021/acs.jmedchem.5b00132
Abstract: 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 Ca(2+) 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.