- SUBSTITUTED HETEROCYCLE FUSED GAMMA-CARBOLINES SYNTHESIS
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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.
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- METHOD FOR THE MANUFACTURE OF LUMATEPERONE AND ITS SALTS
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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.
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- NOVEL SALTS AND CRYSTALS
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The disclosure provides a new, stable, pharmaceutically acceptable bis-tosylate salt form of 1-(4-fluoro-phenyl)-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)-butan-1-one, together with methods of making and using them, and pharmaceutical compositions comprising them.
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Paragraph 0046
(2019/12/28)
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- 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 addition salt and salt crystals
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The present invention relates to 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 tosylate salt in crystalline and in solid forms, the method of making and using such crystals.
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Page/Page column 9
(2015/12/17)
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- Discovery of a tetracyclic quinoxaline derivative as a potent and orally active multifunctional drug candidate for the treatment of neuropsychiatric and neurological disorders
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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.
- Li, Peng,Zhang, Qiang,Robichaud, Albert J.,Lee, Taekyu,Tomesch, John,Yao, Wei,Beard, J. David,Snyder, Gretchen L.,Zhu, Hongwen,Peng, Youyi,Hendrick, Joseph P.,Vanover, Kimberly E.,Davis, Robert E.,Mates, Sharon,Wennogle, Lawrence P.
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p. 2670 - 2682
(2014/04/17)
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