Intra-cellular Therapies, Inc.

Qualcomm Incorporated

Takeda Pharmaceutical Company Limited

The Rockefeller University

1ntra-cellular Therap1es, 1nc.

Peng Li

Lawrence P Wennogle

Robert E Davis

Qiang Zhang

Jun Zhao

Hailin Zheng

Wei Yao

Sharon Mates

Kimberly Vanover

John Charles Tomesch

Gretchen Snyder

Andrew S Thompson

James David Beard

Hua Cheng

Edwin Aret

Joseph Hendrick

Youyi Peng

Francesco Grilli

Khaled Helmi El-Maleh

David J Maldonado

Yair Karmi

MaryBeth Selby

Haiyan Wu

Sandip S Minhas

Hailin Zeng

Robert Davis

Stein Arne Lundby

Danlu Zhang

Arungundram C Mahendran

Srinivas Raghavan

Mark Hooper

Graham Buckton

Tom Chin

Kuo-Chun Lee

Stefano M Faccin

Saumitra Mohan Das

Guangming Shi

Chung Lung Chang

Amer Catovic

Ernest Tadashi Ozaki

Jeremy Darren Dunworth

Alkinoos Hector Vayanos

Raymond T Hsu

Paul Greengard

William H Von Novak

Alireza Mohammadian

Waqar Zia

Yuhei Yamamoto

Rinat Burdo

Takashi Abe

Dario Serafino Tonesi

Ian J Fevrier

Hideaki Maruyama

Roger Wayne Martin

Jennifer O'Brien

Hironori Yamashita

Wenjie Luo

Masahiro Takasuga

Gen He

William Paul Findlay

Sophie Dutheil

Yupu Qiao

J David Beard

Sanjay Singhal

Jonathan T Velasco

Richard A Lerner

Marybeth Selby

Rodney Marlow

Yu Weng

Ziyang Li

Boguslaw Wiecek

Scott Wentzell

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 present invention relates to crystals of (6aR, 9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(phenylamino)-2-((4-(6-fluoropyridin-2-yl)phenyl)methyl)-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrazolo[4,3-e]pyrimidin-4(2H)-one, and methods of making and using such crystals.

Free base crystals

The disclosure provides methods the treatment of psychiatric disorders caused by viral, bacterial, or autoimmune encephalitis, and for treatment of psychiatric symptoms of viral, bacterial, and autoimmune encephalitis, and for protecting or reinforcing the blood-brain barrier, comprising administering to a patient in need thereof, a therapeutically effective amount of a 5-HT.

Methods

The present invention relates to PDE1 inhibitory compounds useful in the treatment of diseases involving disorders of the dopamine D1 receptor intracellular pathway, such as, among others, Parkinson's disease, depression, narcolepsy, psychosis, damage to cognitive function, e.g., in schizophrenia, or disorders that may be ameliorated through enhanced progesterone-signaling pathway, as well as their use as pharmaceuticals and pharmaceutical compositions comprising them. Methods of making and methods of use related to such compounds are further described.

Compounds

The invention relates to pharmaceutical compositions comprising the compound of Formula I, and new methods and uses pertaining thereto, and pharmaceutical compositions thereof, such as methods of use in the treatment of diseases involving the 5-HT receptor, the serotonin transporter (SERT), and/or pathways involving dopamine Dreceptor signaling, sodium channel activity, and/or norepinephrine transporter activity.

Pharmaceutical compositions comprising 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-((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)phenyl)butan-1-one for treating conditions of the central nervous system and cardiac disorders

The disclosure provides new, stable, pharmaceutically acceptable hydrochloride salt forms 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.

Salts and crystals

The disclosure provides the administration of inhibitors of phosphodiesterase 1 (PDE1) for the treatment and prophylaxis of diseases or disorders characterized by inflammation, including methods of treatment and pharmaceutical compositions for use therein.

Methods of treating inflammatory disease

The invention relates to particular deuterated substituted heterocycle fused gamma-carbolines, 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.

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.

Substituted heterocycle fused gamma-carbolines synthesis

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 heterocycle fused gamma-carbolines, 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.

The invention relates to particular prodrugs and analogs of (3α,5α)-3-hydroxy-21-(1H-imidazol-1-yl)-3-methoxymethyl)-pregnan-20-one, in free or pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use as sedatives, hypnotics, anxiolytics, and/or anesthetics, and methods for treatment of depression, anxiety, insomnia, epilepsy, and other central nervous system disorders, as well as to combinations with other agents.

The disclosure provides new, stable, pharmaceutically acceptable amorphous solid dispersions 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-l-one, together with methods of making and using them, and pharmaceutical compositions comprising them.

Amorphous solid dispersions

This 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 5-HTreceptor, serotonin transporter (SERT) and/or pathways involving dopamine D/Dreceptor signaling systems, and/or the treatment of residual symptoms.

Growing community of inventors

New Milford, NJ, United States of America

Peng Li