5-{[(2S,3R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-2,3-dihydro-1H-1,2,4-triazol-3-one

• ChemBase ID: 555
• Molecular Formular: C23H21F7N4O3
• Molecular Mass: 534.4266624
• Monoisotopic Mass: 534.15018809
• SMILES: Fc1ccc([C@H]2N(CCO[C@H]2O[C@@H](c2cc(cc(c2)C(F)(F)F)C(F)(F)F)C)Cc2[nH][nH]c(=O)n2)cc1
• Canonical SMILES: Fc1ccc(cc1)[C@@H]1[C@@H](OCCN1Cc1[nH][nH]c(=O)n1)O[C@@H](c1cc(cc(c1)C(F)(F)F)C(F)(F)F)C
• InChI: InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19-,20+/m1/s1
• InChIKey: ATALOFNDEOCMKK-BYYRLHKVSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-{[(2S,3R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-2,3-dihydro-1H-1,2,4-triazol-3-one
• IUPAC Traditional name: emend
• Brand Name: Emend
• Synonyms: aprepitant; MK-869; MK-0517; Aprepitant

Database IDs

• CAS Number: 170729-80-3
• PubChem SID: 160964018
• PubChem CID: 151165

CALCULATED PROPERTIES

JChem

• Acid pKa: 2.269396
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 3.5673702
• LogD (pH = 7.4): 3.5806317
• Log P: 3.3180022
• Molar Refractivity: 127.3431 cm^3
• Polarizability: 43.315456 Å^3
• Polar Surface Area: 75.19 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 3.37
• LOG S: -4.39
• Solubility (Water): 2.18e-02 g/l

PROPERTIES

Physical Property

• Solubility: Practically insoluble
• Hydrophobicity(logP): 4.5

DETAILS

DrugBank - DB00673

• Drug Groups: approved; investigational
• Description: Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).
• Indication: For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including high-dose cisplatin (in combination with other antiemetic agents).
• Pharmacology: Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT₃), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV).
• Affected Organisms: Humans and other mammals
• Biotransformation: Aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19. Seven metabolites of aprepitant, which are only weakly active, have been identified in human plasma.
• Absorption: The mean absolute oral bioavailability of aprepitant is approximately 60 to 65%.
• Half Life: 9-13 hours
• Protein Binding: >95%
• Elimination: Aprepitant is eliminated primarily by metabolism; aprepitant is not renally excreted. Aprepitant is excreted in the milk of rats. It is not known whether this drug is excreted in human milk.
• Distribution: * 70 L
• Clearance: * Apparent plasma cl=62-90 mL/min
• External Links: Wikipedia; RxList; Drugs.com