Iloperidone

Base Information

• Chemical Name: Iloperidone
• CAS No.: 133454-47-4
• Molecular Formula: C24H27FN2O4
• Molecular Weight: 426.488
• Hs Code.: 29349990
• UNII: VPO7KJ050N
• DSSTox Substance ID: DTXSID6049060
• Nikkaji Number: J550.684K
• Wikipedia: Iloperidone
• Wikidata: Q4199443
• NCI Thesaurus Code: C83784
• RXCUI: 73178
• Pharos Ligand ID: 9ZDKPF9CNB3U
• Metabolomics Workbench ID: 63741
• ChEMBL ID: CHEMBL14376
• Mol file: 133454-47-4.mol

Synonyms:Fanapt;HP 873;HP-873;iloperidone;Zomaril

Chemical Property of Iloperidone

Chemical Property:

• Vapor Pressure: 4.6E-14mmHg at 25°C
• Melting Point: 118-120°C
• Refractive Index: 1.57
• Boiling Point: 593.7 °C at 760 mmHg
• PKA: 8.43±0.20(Predicted)
• Flash Point: 312.8 °C
• PSA: 64.80000
• Density: 1.204 g/cm³
• LogP: 4.76450
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility.: DMSO: soluble5mg/mL, clear
• XLogP3: 4.1
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 8
• Exact Mass: 426.19548551
• Heavy Atom Count: 31
• Complexity: 586

Purity/Quality:

99.9% ^*data from raw suppliers

Iloperidone ^*data from reagent suppliers

Safty Information:

• Pictogram(s): F,T
• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 16-36/37-45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antipsychotic Agents
• Canonical SMILES: CC(=O)C1=CC(=C(C=C1)OCCCN2CCC(CC2)C3=NOC4=C3C=CC(=C4)F)OC
• Recent ClinicalTrials: Safety and Tolerability of Open-Labeled Iloperidone in Adolescents
• Recent EU Clinical Trials: A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of iloperidone for 4 weeks in the treatment of patients with acute manic episodes associated with Bipolar I Disorder
• Drug Interactions: 1. This product is not the substrate of CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or CYP2E1, so this product won’t have interaction when combined with either inducers or inhibitors of these enzymes. This product is mainly metabolized by CYP3A4 and CYP2D6. The inhibitors of either CYP3A4 (e.g., ketoconazole) or CYP2D6 (such as fluoxetine, paroxetine) can inhibit the metabolism of the product and increase its plasma concentration. 2. In vivo test of the human liver microsomes have showed that this product has on inhibitory effects on the drugs which are metabolized by the CYP1A1, CYP1A2, CYP2A 6, CYP2B6, CYP2C8, CYP2C9, or CYP2E1 enzyme; It also has no induction effect on CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 enzymes. 3. This product should be avoided being combined with QT-prolonging drugs including class IA antiarrhythmics drugs (quinidine, procainamide) or Class III antiarrhythmic drugs (amiodarone, sotalol); antipsychotics drugs (chlorpromazine, thioridazine); antibacterial drugs (gatifloxacin, moxifloxacin); other drugs (pentamidine, acetyl L-methadone). This product should be avoided from being used in congenital prolonged-QT phase patients and patients with arrhythmia history.
• Description: Iloperidone is an atypical antipsychotic and adrenergic, dopamine, and serotonin (5-HT) receptor antagonist. It binds to several receptors, including the α1-adrenergic receptor (α1-AR), α2-AR, and dopamine D2 receptor (Kis = 0.31, 3, and 3.3 nM, respectively), as well as the 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C receptors (Kis = 33, 15, 0.2, and 14 nM, respectively) in radioligand binding assays using human post-mortem brain tissue. Iloperidone also binds to human D1, D3, D4, D5, and rat 5-HT2 receptors (Kis = 216, 7.1, 25, 319, and 3.1 nM, respectively, in CHO cells) and the histamine H1 receptor (Ki = 12.3 nM in human post-mortem brain tissue). Iloperidone (1-3 mg/kg) prevents the reduction in prepulse inhibition induced by apomorphine , phencyclidine (PCP), and cirazoline in rats. It also increases the time rats spend in the open arms of the elevated plus maze and the number of social interactions when administered at a dose of 0.5 mg/kg. Formulations containing iloperidone have been used in the treatment of schizophrenia.
• Uses: Iloperidone (Fanapt, Fanapta, Zomaril) is an atypical antipsychotic for the treatment of schizophrenia. Iloperidone is a monoamine directed towards acting upon and antagonizing specific neurotransmitters, particularly multiple dopamine and serotonin recep Combined dopamine (D2) and serotonin (5HT2) receptor antagonist. Antipsychotic.
• Clinical Use: Acting as an antagonist on serotonin (5-HT2) and dopamine receptor subtypes, iloperidone is an antipsychotic indicated for the treatment of acute schizophrenia in adults. Based on its in vitro and in vivo binding properties against both serotonin and dopamine receptors, it is expected that iloperidone will show fewer extrapyramidal symptoms than currently marketed antipsychotics such as haloperidol and clozapine. The original discovery was made by Hoechst-Roussel Pharmaceuticals who passed the developing rights to Vanda Pharmaceuticals and subsequently Novartis for marketing in the U.S. and Canada. While this drug was originally approved in the U.S. in 2009, the marketing was only initiated in the U.S. in 2010.

Technology Process of Iloperidone

There total 24 articles about Iloperidone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

4-(3-chloropropoxy)-3-methoxyacetophenone (58113-30-7) + 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride (84163-13-3) → iloperidone (133454-47-4)

Guidance literature:

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride; With sodium hydroxide; In water; at 25 - 30 ℃; for 0.25h; Industrial scale; Green chemistry;

4-(3-chloropropoxy)-3-methoxyacetophenone; In water; at 25 - 30 ℃; for 0.25h; Industrial scale; Green chemistry;

With tetrabutylammomium bromide; In n-heptane; water; at 65 - 70 ℃; Reagent/catalyst; Solvent; Temperature; Concentration; Time; Industrial scale; Green chemistry;

DOI:10.1021/op400335p

Reference yield: 70.0%

methyl magnesium iodide (917-64-6) + 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-benzonitrile → iloperidone (133454-47-4)

Guidance literature:

methyl magnesium iodide; 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-benzonitrile; With copper(l) chloride; In diethyl ether; toluene; for 2h; Reflux;

With sulfuric acid; water; In diethyl ether; toluene; at 25 ℃; for 2h; Reflux;

With sodium carbonate; In diethyl ether; water; toluene;

Reference yield: 64.0%

3-(1-(3-chloropropyl)piperidin-4-yl)-6-fluorobenzo[d]isoxazole (329977-73-3) + 1-(3-methoxy-4-hydroxyphenyl)ethanone (498-02-2) → iloperidone (133454-47-4)

Guidance literature:

With lithium hydroxide; In dichloromethane; water; at 180 ℃; under 33753.4 Torr; Solvent; Flow reactor;

DOI:10.1002/chem.201504409

upstream raw materials:

4-(3-chloropropoxy)-3-methoxyacetophenone

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride

potassium carbonate

3-(1-(3-chloropropyl)piperidin-4-yl)-6-fluorobenzo[d]isoxazole

Downstream raw materials:

Triphenylphosphine oxide

4'-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]propoxy]-3'-methoxyacetophenone phosphate

4'-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]propoxy]-3'-methoxyacetophenone bisulphate

4'-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]propoxy]-3'-methoxyacetophenone hydrochloride

Refernces

• 1、 -. "Synthesis method of iloperidone". Paragraph 0023; 0024; 0026; 0028. . Retrieved 2018/04/01.
• 2、 Hartwig, Jan,Kirschning, Andreas. "Flow Synthesis in Hot Water: Synthesis of the Atypical Antipsychotic Iloperidone". supporting information. p. 3044 - 3052. Retrieved 2016/03/23.