- Preparation method of Lumateperone intermediate
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The invention discloses a preparation method of a Lumateperone intermediate. The Lumateperone intermediate (6bR, 10aS)-2, 3, 6b, 9, 10, 10a-hexahydro-3-methyl-1H-pyridine[3', 4':4, 5] pyrrolo [1, 2, 3-de] quinoxaline-8 (7H) carboxylic acid ethyl ester is
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Paragraph 0019; 0045-0056
(2021/06/26)
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- 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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Paragraph 00104
(2020/07/14)
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- SOLID STATE FORMS OF LUMATEPERONE SALTS AND PROCESSES FOR PREPARATION OF LUMATEPERONE AND SALTS THEREOF
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The present disclosure relates to solid state forms of Lumateperone besylate, processes for preparation thereof and pharmaceutical compositions thereof.
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Paragraph 00303
(2020/06/19)
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- 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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Paragraph 000105
(2020/01/08)
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- ITI-007
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A great deal has been achieved in the treatment of schizophrenia in recent decades, especially the treatment of the positive symptoms by targeting dopamine D2 receptors. But the disease has a range of other symptoms which gravely affect quality of life and which require other strategies or additional targets. Among the agents gradually filling the empty therapeutic space is ITI-007, which has an unusual mechanistic profile: it targets 5-HT2A and dopamine D2 receptors, but has a much higher affinity for the former receptors. This may allow the drug's effects to be modified by dose adjustments, with effects on sleep disturbances, depression and anxiety seen with lower doses and higher doses affecting the positive symptoms of schizophrenia through dopamine D2 receptor modulation. Higher doses can also inhibit serotonin transporters and produce glutamatergic modulation which could improve positive and negative symptoms, depressive symptoms and cognitive impairments. The findings of preclinical studies have supported this view of the drug, and a phase II study found effects on positive and negative symptoms with a safety profile distinct from atypical antipsychotics. Phase III investigation in schizophrenia has begun, and clinical investigation in insomnia and dementia is also under way.
- Cole
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p. 643 - 650
(2015/11/24)
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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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- SUBSTITUTED HETEROCYCLE FUSED GAMMA-CARBOLINES SYNTHESIS
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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.
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Page/Page column 82
(2008/12/07)
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