EST64454 HCl

• CAS: 1950569-11-5
• Catalog Number: ACM1950569115
• Category: Antagonists
• Molecular Weight: 400.85
• Molecular Formula: C18H23ClF2N4O2
• Description: EST64454 is a Highly Soluble σ1 Receptor Antagonist Clinical Candidate for Pain Management. EST64454 shows an outstanding aqueous solubility, which together with its high permeability in Caco-2 cells will allow its classification as a BCS class I compound. It also shows high metabolic stability in all species, linked to an adequate pharmacokinetic profile in rodents, and antinociceptive properties in the capsaicin and partial sciatic nerve ligation models in mice.
• Synonyms: EST64454 HCl; EST64454 hydrochloride; EST64454; EST-64454; EST 64454
• IUPAC Name: 1-(4-(2-((1-(3,4-difluorophenyl)-1H-pyrazol-3-yl)methoxy)ethyl)piperazin-1-yl)ethan-1-one hydrochloride
• Canonical SMILES: CC(N1CCN(CCOCC2=NN(C3=CC=C(F)C(F)=C3)C=C2)CC1)=O.[H]Cl
• InChI: InChI=1S/C18H22F2N4O2.ClH/c1-14(25)23-8-6-22(7-9-23)10-11-26-13-15-4-5-24(21-15)16-2-3-17(19)18(20)12-16;/h2-5,12H,6-11,13H2,1H3;1H
• InChI Key: YJZGDOPAALDWAT-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1351438-26-0 (free base); 1950569-11-5 (HCl)
• Biological Target: EST64454 hydrochloride is a selective and orally active sigma-1 receptor antagonist with a Ki of 22 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 53.93; H, 5.78; Cl, 8.84; F, 9.48; N, 13.98; O, 7.98
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: EST64454 is a selective sigma-1 receptor ligand intended for orally administered pain treatment that showed a promising profile in the lead optimization process. As part of the preliminary compound profiling, the potential for future drug-drug interactions was explored in vitro. Both direct and time-dependent CYP inhibition for CYP1A2, 2C9, 2C19, 2D6 and 3A4 was studied in human liver microsomes. EST64454 showed a low potential for CYP inhibition (IC50 between 100 and 1000 µM) and as time-dependent inhibitor (IC50 shift mainly around 1). CYP induction studies with HepaRG™ cells revealed no CYP induction at concentrations ≤50 µM, as shown by the CYP1A2, 3A4 and 2B6 activities measured. EST64454 was not a P-glycoprotein (P-gp) substrate and was highly permeable in Caco-2 cells.; Reference: Biol Pharm Bull. 2020;43(1):68-76. https://pubmed.ncbi.nlm.nih.gov/31902934/
• In Vivo Activity: The compound 9k (EST64454) showed in vivo efficacy after oral administration in two different pain models in mice: intraplantar capsaicin-induced mechanical hypersensitivity and partial sciatic nerve ligation (PSNL)-induced mechanical hypersensitivity, a model representative of neuropathic pain. In the capsaicin test, the antiallodynic potency of 9k was similar to that of the compound 1 (ED50 33 vs 28 mg/kg, respectively, Figure 3, Table 2). In the PSNL model, oral administration of 9k at 80 mg/kg, revealed an increased antiallodynic efficacy when comparing with the same dose of the compound 1 (95% vs 54%, respectively).; Reference: J Med Chem. 2020 Dec 10;63(23):14979-14988. https://pubmed.ncbi.nlm.nih.gov/31902934/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).