Intra-cellular Therapies, Inc.

National Institutes of Health, a Component of the US Dept. of Health & Human Services

1ntra-cellular Therap1es, 1nc.

Wei Yao

Peng Li

Andrew S Thompson

Qiang Zhang

John Charles Tomesch

James David Beard

Hua Cheng

Robert E Davis

Lawrence P Wennogle

Sharon Mates

Kimberly Vanover

Gretchen Snyder

Maria Michejda, Legal Representative

Brian I Carr

Siddhartha Kar

The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, 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-HTreceptor, the serotonin transporter (SERT), pathways involving the dopamine Dand Dreceptor signaling system, and/or the μ-opioid receptor.

Organic compounds

The disclosure provides new transmucosal and subcutaneous pharmaceutical compositions comprising 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 or 1-(4-fluoro-phenyl)-4-((6bR,10aS)-2,2-d-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 or comprising -(4-fluoro-phenyl)-4-((6bR,10aS)-1,1,2,2-d-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, in free base, co-crystal or salt form, together with methods of making and using them.

Transmucosal methods for treating psychiatric and neurological conditions

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

The present invention provides methods for the preparation of substituted heterocycle fused gamma-carbolines, such as the compound of Formula 2J, as shown below, intermediates useful in producing them and methods for producing such intermediates and such heterocycle fused gamma-carbolines, and as further defined herein.

Process for preparing 1-(4-fluorophenyl)-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)butan-1-one

The disclosure provides new transmucosal and subcutaneous pharmaceutical compositions comprising 1-(4-fluoro-phenyl)-4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3',4&#x2032;:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one or 1-(4-fluoro-phenyl)-4-((6bR,10aS)-2,2-d-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3&#x2032;,4&#x2032;:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one or comprising -(4-fluoro-phenyl)-4-((6bR,10aS)-1,1,2,2-d-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3&#x2032;,4&#x2032;:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one, in free base, co-crystal or salt form, together with methods of making and using them.

The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, 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-HTreceptor, the serotonin transporter (SERT), pathways involving the dopamine Dand Dreceptor signaling system, and/or the &#x3bc;-opioid receptor.

The present invention provides methods for the preparation of certain optionally substituted heterocycle fused gamma-carbolines of Formula 2F, as shown below and as further defined herein: 

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New Milford, NJ, United States of America

Wei Yao