313368-91-1

Basic information

• Product Name: ITI-722
• Synonyms: ITI-722;Lumateperone
• CAS NO: 313368-91-1
• Molecular Formula: C₂₄H₂₈FN₃O
• Molecular Weight: 393.4970232
• Product Categories: API
• Mol File: 313368-91-1.mol

Chemical Properties

• Boiling Point: 556.4±50.0 °C(Predicted)
• Appearance: /
• Density: 1.26±0.1 g/cm3(Predicted)
• PKA: 9.10±0.20(Predicted)
• CAS DataBase Reference: ITI-722(CAS DataBase Reference)
• NIST Chemistry Reference: ITI-722(313368-91-1)
• EPA Substance Registry System: ITI-722(313368-91-1)

Safety Data

• Hazardous Substances Data: 313368-91-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
ITI-722 is used as an antipsychotic agent for the treatment of schizophrenia, offering a unique mechanism of action that targets the 5-HT2A receptors.
ITI-722 is also used as a potential treatment for bipolar depression, given its unique pharmacological profile.
Used in Sleep Aid Industry:
ITI-722 is used as a sleep aid for the treatment of insomnia, as demonstrated in a Phase 2 study that showed its efficacy in improving sleep quality without affecting next-day cognition.

Upstream product

• 313369-67-4 3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline 
• 3874-54-2 4-(4-fluorophenyl)-4-oxo-n-butyl chloride 
• 313368-85-3 (6bR,10aS)-3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido-[3’,4’:4,5]-pyrrolo[1,2,3-de]quinoxaline 
• 59564-59-9 1,2,3,4-tetrahydroquinoxalin-2-one 
• 53374-52-0 1-nitroso-3-keto-1,2,3,4-tetrahydroquinoxaline 
• 313544-31-9 2-oxo-2,3,9,10-tetrahydro-1H,7H-pyrido-[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8-carboxylic acid ethyl ester 
• 87973-61-3 1-amino-3-keto-1,2,3,4-tetrahydroquinoxaline 
• 50709-33-6 2-bromophenylhydrazine hydrochloride 
• 1059630-11-3 6-bromo-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole hydrochloric acid salt 
• 40064-34-4 piperidine-4,4-diol hydrochloride 
• 40862-32-6 1-iodo-3-(p-fluorophenylcarbonyl)propane 

Downstream Products

• 1187020-80-9 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)-1-(4-fluorophenyl)-1-butanone toluenesulfonic acid salt 

Relevant articles and documents

Preparation method and intermediate of rumepirone

The invention provides a preparation method and intermediate of rumepirone. The preparation method comprises the following steps: taking a 6-bromine-2, 3, 4, 5-tetrahydro-1H-pyrido [4, 3-b] indole compound 1 as an initial raw material to obtain a compound 2, then carrying out Boc protection to obtain a compound 3, and then reacting the compound 3 with 2-chloro-N-methyl acetamide to obtain a compound 4; carrying out intramolecular Ullmann coupling reaction cyclization to obtain a compound 5; reducing the compound 5 by using borane to obtain a compound 6, then removing Boc protection and performing salifying to obtain a mepiquat key intermediate compound 7, or performing reducing and deprotecting by using a one-pot method and performing salifying to obtain an intermediate compound 7; enabling an intermediate compound 7 and a compound 8 to be subjected to reductive amination condensation to obtain a compound 9, and finally enabling the compound 9 to react with a 4-fluorophenyl Grignard reagent to obtain a rumepirone product compound 10, wherein the reaction route is shown in the specification.

ORGANIC COMPOUND

The invention relates to a particular substituted heterocycle fused gamma-carboline, in free, or pharmaceutically acceptable salt, and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), and/or pathways involving the dopamine D1 and D2 receptor signaling system.

SOLID STATE FORMS OF LUMATEPERONE SALTS AND PROCESSES FOR PREPARATION OF LUMATEPERONE AND SALTS THEREOF

The present disclosure relates to solid state forms of Lumateperone besylate, processes for preparation thereof and pharmaceutical compositions thereof.

SUBSTITUTED HETEROCYCLE FUSED GAMMA-CARBOLINES SYNTHESIS

The present invention provides improved methods for the preparation of substituted heterocycle fused gamma-carbolines, intermediates useful in producing them and methods for producing such intermediates and such heterocycle fused gamma-carbolines.

METHOD FOR THE MANUFACTURE OF LUMATEPERONE AND ITS SALTS

Method for the production of formula (I) lumateperone or its acid addition salts so that the enantiomer compound with stereochemistry 6bR, 10aS is separated form the cis racemate using resolution and the formula (II) stereoisomer is alkylated with 4-halo-4'-fluoro butyrophenone (X = I, Br, CI) to produce the formula (I) lumateperone, or optionally its acid addition salt. The object of the invention also relates to the amorphous form of the morphologically uniform p-toluenesulfonic acid salt of lumateperone and to the naphthalene-2-sulfonic acid salt of lumateperone, to the 1 :2 stoichiometry salt of lumateperone formed with naphthalene-2-sulfonic acid.

Discovery of a tetracyclic quinoxaline derivative as a potent and orally active multifunctional drug candidate for the treatment of neuropsychiatric and neurological disorders

We report the synthesis and structure-activity relationships of a class of tetracyclic butyrophenones that exhibit potent binding affinities to serotonin 5-HT2A and dopamine D2 receptors. This work has led to the discovery of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H- pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl) -1-(4-fluorophenyl)-butan-1-one 4-methylbenzenesulfonate (ITI-007), which is a potent 5-HT2A antagonist, postsynaptic D2 antagonist, and inhibitor of serotonin transporter. This multifunctional drug candidate is orally bioavailable and exhibits good antipsychotic efficacy in vivo. Currently, this investigational new drug is under clinical development for the treatment of neuropsychiatric and neurological disorders.

SUBSTITUTED HETEROCYCLE FUSED GAMMA-CARBOLINES SYNTHESIS

The present invention provides methods for the preparation of substituted heterocycle fused gamma-carbolines, intermediates useful in producing them and methods for producing such intermediates and such heterocycl fused gamma-carbolines.

Substituted heterocycle fused gamma-carbolines

The present invention is directed to methods of treating addictive behavior and sleep disorders by administering compounds represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R1, R5, R6a, R6b, R7, R8, R9, X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.