Chloro-trifluoromethyl-benzyl-piperidin-pentafluorosulfanyl-phenyl-acetamide-Cpd21y
Replacement of the urea pharmacophore of TPPU with an acetamide resulted in reduced enzyme inhibition due to the weakening of electrostatic interactions with the catalytic Asp335, but provided a clear improvement in aqueous solubility. The introduction of a pentafluorosulfanyl substituent proved crucial to restore inhibitory potency. IC50 hsEH 1.7 msEH 11.6 ratsEH 5.4 nM
General
Type : Trifluoro, Piperidine, Sulfur Compound
Chemical_Nomenclature : 2-(1-(4-chloro-2-(trifluoromethyl)benzyl)piperidin-4-yl)-N-(4-(pentafluorosulfanyl)phenyl)acetamide Hydrochloride
Canonical SMILES : C1(=CC=C(C=C1)NC(CC2CCN(CC2)CC3=CC=C(C=C3C(F)(F)F)Cl)=O)[S](F)(F)(F)(F)F
InChI : InChI=1S\/C21H21ClF8N2OS\/c22-16-2-1-15(19(12-16)21(23,24)25)13-32-9-7-14(8-10-32)11-20(33)31-17-3-5-18(6-4-17)34(26,27,28,29)30\/h1-6,12,14H,7-11,13H2,(H,31,33)
InChIKey : LEQZLWBDSROYKB-UHFFFAOYSA-N
Other name(s) : Compound 21y
Target
Families : Chloro-trifluoromethyl-benzyl-piperidin-pentafluorosulfanyl-phenyl-acetamide-Cpd21y ligand of proteins in family
Epoxide_hydrolase
Protein :
human-EPHX2
mouse-hyes
References (1)
| Title : Topliss-Guided Optimization of Acetanilide-Based Soluble Epoxide Hydrolase Inhibitors: Exploring the Pentafluorosulfanyl Group as a Potency-Enhancing Motif - Lopez-Ruiz_2026_ChemMedChem_21_e70430 |
| Author(s) : Lopez-Ruiz A , Pujol E , Ramos C , Rizzo V , Morisseau C , Val C , Ginex T , Vazquez J , Codony S , Turcu AL , Perez B , Saez E , Pineda-Lucena A , Hammock BD , Luque FJ , Loza MI , Brea J , Vazquez S |
| Ref : ChemMedChem , 21 :e70430 , 2026 |
| Abstract : |
| PubMedSearch : Lopez-Ruiz_2026_ChemMedChem_21_e70430 |
| PubMedID: 42596002 |