公开(公告)号：US12139490B2

公开(公告)日：2024-11-12

申请号：US17808836

申请日：2022-06-24

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： John Charles Tomesch ,  Peng Li ,  Wei Yao ,  Qiang Zhang ,  James David Beard ,  Andrew S. Thompson ,  Hua Cheng ,  Lawrence P. Wennogle

IPC: C07D471/16 ,  C07D471/04

Abstract: 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.

公开(公告)号：US11440911B2

公开(公告)日：2022-09-13

申请号：US16649515

申请日：2018-09-26

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： Lawrence P. Wennogle ,  Peng Li ,  Edwin Aret

IPC: C07D471/16

Abstract: 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.

公开(公告)号：US10398698B2

公开(公告)日：2019-09-03

申请号：US15709258

申请日：2017-09-19

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： Lawrence P. Wennogle ,  Robert Davis

IPC: A61K31/519 ,  A61K45/06

Abstract: The invention relates to the administration of inhibitors of phosphodiesterase 1 (PDE1) for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways. In one embodiment the invention relates to inhibitors of phosphodiesterase 1 (PDE1) for treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.

公开(公告)号：US10221176B2

公开(公告)日：2019-03-05

申请号：US15660762

申请日：2017-07-26

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： John Charles Tomesch ,  Peng Li ,  Wei Yao ,  Qiang Zhang ,  James David Beard ,  Andrew S. Thompson ,  Hua Cheng ,  Lawrence P. Wennogle

IPC: C07D471/22 ,  C07D487/22 ,  C07D471/16 ,  C07D471/04

Abstract: The present invention provides methods for the preparation of substituted heterocycle fused gamma-carbolines of Formula 2F, as shown below, intermediates useful in producing them and methods for producing such intermediates and such heterocycle fused gamma-carbolines, such methods comprising the preparation of a Compound of Formula 2F, as shown below and as further defined herein:

公开(公告)号：US10117867B2

公开(公告)日：2018-11-06

申请号：US15467867

申请日：2017-03-23

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： Sharon Mates ,  Allen Fienberg ,  Lawrence P. Wennogle

IPC: A61K31/44 ,  A61K31/4985 ,  A61K31/5383 ,  A61K45/06 ,  C07D471/14 ,  C07D498/14 ,  A61K9/00 ,  A61K31/198

Abstract: Use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals and pharmaceutical compositions comprising them for the treatment of one or more disorders involving the 5-HT2A, SERT and/or dopamine D2 pathways are disclosed. In addition, the compounds may be combined with other therapeutic agents for the treatment of one or more sleep disorders, depression, psychosis, dyskinesias, and/or Parkinson's disease or any combinations.

公开(公告)号：US10077267B2

公开(公告)日：2018-09-18

申请号：US15301912

申请日：2015-04-03

Applicant: Intra-Cellular Therapies, Inc.

Inventor： Sharon Mates ,  Peng Li ,  Lawrence P. Wennogle ,  Robert Davis

IPC: C07D471/16 ,  A61K31/4985 ,  C07D471/14 ,  A61K45/06 ,  C07B59/00

Abstract: 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 5-HT2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D1/D2 receptor signaling systems, and/or the treatment of residual symptoms.

公开(公告)号：US10072010B2

公开(公告)日：2018-09-11

申请号：US15629481

申请日：2017-06-21

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： Peng Li ,  Qiang Zhang ,  Robert Davis ,  Lawrence P. Wennogle

IPC: A61K31/4985 ,  C07D487/22 ,  C07D471/16 ,  C07D471/14 ,  A61K9/48 ,  A61K9/50 ,  A61K47/34 ,  A61K47/38

CPC classification number: C07D471/16 ,  A61K9/4825 ,  A61K9/4891 ,  A61K9/5031 ,  A61K31/4985 ,  A61K47/34 ,  A61K47/38 ,  C07D471/14

Abstract: The invention relates to substituted pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]-quinoxaline compounds, represented by Formula 1, defined herein, free base or pharmaceutically acceptable salt forms of the compounds, pharmaceutical compositions thereof, and methods of treating conditions of the central nervous system therewith:

公开(公告)号：US09956227B2

公开(公告)日：2018-05-01

申请号：US15101874

申请日：2014-12-03

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： Kimberly Vanover ,  Peng Li ,  Sharon Mates ,  Robert Davis ,  Lawrence P. Wennogle

IPC: A61K45/06 ,  A61K9/00 ,  A61K31/4985 ,  A61K31/5383 ,  A61K9/51

CPC classification number: A61K31/5383 ,  A61K9/0019 ,  A61K9/0024 ,  A61K9/5153 ,  A61K31/4985 ,  A61K45/06 ,  A61K2300/00

Abstract: The disclosure provides the use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals for the treatment of residual symptoms of psychosis or schizophrenia. The disclosure also provides novel long acting injectable formulations of particular substituted heterocycle fused gamma-carboline compounds and use of such long acting injectable formulations for the treatment of residual symptoms of psychosis or schizophrenia.

公开(公告)号：US09469647B2

公开(公告)日：2016-10-18

申请号：US14409988

申请日：2013-06-21

Applicant: INTRA-CELLULAR THERAPIES, INC.

Inventor： Peng Li ,  Lawrence P. Wennogle ,  Robert Davis ,  Graham Buckton ,  Mark Hooper

IPC: C07D487/14 ,  A61K31/519 ,  A61P35/00 ,  C07C55/02 ,  C07C57/15 ,  C07C309/04

CPC classification number: C07D487/14 ,  C07B2200/13 ,  C07C55/02 ,  C07C57/15 ,  C07C309/04

Abstract: The present invention relates to acid addition salt and salt 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]pyrimidin-4(2H)-one, composition comprising the same and the method of making and using such salt and crystal.

Abstract translation: 本发明涉及（6aR，9aS）-5,6a，7,8,9,9a-六氢-5-甲基-3-（苯基氨基）-2 - （（4-（6 - 氟吡啶-2-基）苯基）甲基） - 环戊并[4,5]咪唑并[1,2-a]吡唑并[4,3-e]嘧啶-4（2H） - 酮，包含该组合物的组合物和方法 制作和使用这种盐和水晶。

公开(公告)号：US09168258B2

公开(公告)日：2015-10-27

申请号：US14066987

申请日：2013-10-30

Applicant: INTRA-CELLULAR THERAPIES INC.

Inventor： Sharon Mates ,  Allen Fienberg ,  Lawrence P. Wennogle

IPC: A61K31/535 ,  A01N43/58 ,  A01N43/60 ,  A61K31/50 ,  A61K31/495 ,  A61K9/48 ,  A61K31/5383 ,  A61K31/44 ,  A61K31/4985 ,  A61K45/06 ,  C07D471/14 ,  C07D498/14

CPC classification number: A61K31/4985 ,  A61K9/0053 ,  A61K31/198 ,  A61K31/44 ,  A61K31/5383 ,  A61K45/06 ,  C07D471/14 ,  C07D498/14

Abstract: Use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals and pharmaceutical compositions comprising them for the treatment of one or more disorders involving the 5-HT2A, SERT and/or dopamine D2 pathways are disclosed. In addition, the compounds may be combined with other therapeutic agents for the treatment of one or more sleep disorders, depression, psychosis, dyskinesias, and/or Parkinson's disease or any combinations.

Abstract translation: 公开了使用特定的取代的杂环稠合的γ-咔啉化合物作为药物和包含它们的药物组合物用于治疗涉及5-HT2A，SERT和/或多巴胺D2途径的一种或多种病症。 此外，化合物可以与其它治疗剂组合用于治疗一种或多种睡眠障碍，抑郁症，精神病，运动障碍和/或帕金森病或任何组合。