Simultaneous target-mediated drug disposition model for two small-molecule compounds competing for their pharmacological target: soluble epoxide hydrolase was written by Wu, Nan;Hammock, Bruce D.;Lee, Kin Sing Stephen;An, Guohua. And the article was included in Journal of Pharmacology and Experimental Therapeutics in 2020.SDS of cas: 1222780-33-7 The following contents are mentioned in the article:
1-(1-Propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU) and 1-(4-trifluoro-methoxy-phenyl)-3-(1-cyclopropanecarbonyl-piperidin-4-yl)-urea (TCPU) are potent inhibitors of soluble epoxide hydrolase (sEH) that have much better efficacy in relieving nociceptive response than the Food and Drug Administration-approved drug gabapentin in a rodent model of diabetic neuropathy. Experiments conducted in sEH knockout mice or with coadministration of a potent sEH displacer demonstrated that the pharmacokinetics of TPPU and TCPU were influenced by the specific binding to their pharmacol. target sEH, a phenomenon known as target-mediated drug disposition (TMDD). To quant. characterize the complex pharmacokinetics of TPPU and TCPU and gain better understanding on their target occupancy, population pharmacokinetics anal. using a nonlinear mixed-effect modeling approach was performed in the current study. The final model was a novel simultaneous TMDD interaction model, in which TPPU and TCPU compete for sEH, with TCPU binding to an addnl. unknown target pool with larger capacity that we refer to as a refractory pool. The total amount of sEH enzyme in mice was predicted to be 16.2 nmol, which is consistent with the exptl. value of 10 nmol. The dissociate rate constants of TPPU and TCPU were predicted to be 2.24 and 2.67 h-1, resp., which is close to the values obtained from in vitro experiments Our simulation result predicted that 90% of the sEH will be occupied shortly after a low dose of 0.3 mg/kg TPPU administration, with ≥40% of sEH remaining to be bound with TPPU for at least 7 days. Further efficacy experiments are warranted to confirm the predicted target occupancy. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7SDS of cas: 1222780-33-7).
1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising α-glucosidase inhibitors. The former are analogs of DNJ with an improved α-glucosidase inhibitory profile than that of DNJ. Boisson et al.SDS of cas: 1222780-33-7
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem