Orteronel

Orteronel is a non-steroidal inhibitor of the 17,20-lyase activity of the cytochrome P450 (CYP) isoform CYP17A1 (IC50s = 48 and 19 nM for the rat and human enzyme, respectively), which is the CYP17A1 activity that converts progestogens into androgens. Orteronel is selective for the 17,20-lyase activity of CYP17A1 over its 11-hydroxylase activity and CYP3A4 (IC50s = >1,000 and >10,000 nM, respectively). It decreases adrenocorticotropic hormone-induced production of DHEA, androstenedione, cortisol, and aldosterone in monkey adrenal cells (IC50s = 110, 130, 310, and 4,400 nmol/L, respectively) and inhibits DHEA production in NCI-H295R human adrenocortical tumor cells. A single oral dose of orteronel (0.3-10 mg/kg) dose-dependently decreases DHEA, cortisol, and testosterone levels in the plasma of intact cynomolgus monkeys for at least 10 hours, and chronic dosing of 15 mg/kg twice daily suppresses levels for up to seven days of treatment. It also decreases DHEA and testosterone plasma levels in castrated monkeys, indicating an effect on extra-gonadal production of testosterone.Formal Name: 6-[(7S)-6,7-dihydro-7-hydroxy-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthalenecarboxamide. CAS Number: 566939-85-3. Synonyms: TAK-700. Molecular Formula: C18H17N3O2. Formula Weight: 307.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 10 mg/ml, Ethanol: 0.2 mg/ml. lambdamax: 237, 280 nm. SMILES: O=C(NC)C(C=C1)=CC2=C1C=C([C@@]3(O)CCN4C3=CN=C4)C=C2. InChi Code: InChI=1S/C18H17N3O2/c1-19-17(22)14-3-2-13-9-15(5-4-12(13)8-14)18(23)6-7-21-11-20-10-16(18)21/h2-5,8-11,23H,6-7H2,1H3,(H,19,22)/t18-/m0/s1. InChi Key: OZPFIJIOIVJZMN-SFHVURJKSA-N.