公开(公告)号：US20180141952A1

公开(公告)日：2018-05-24

申请号：US15736202

申请日：2016-06-27

Applicant: Shawn J. STACHEL ,  Christopher J. SINZ ,  Yili CHEN ,  Jonathan E. WILSON ,  Michael P. DWYER ,  Daniel V. PAONE ,  Shimin XU ,  Merck Sharp & Dohme Corp.

Inventor： Shawn J. Stachel ,  Michael P. Dwyer ,  Christopher J. Sinz ,  Jonathan E. Wilson ,  Daniel V. Paone ,  Yili Chen ,  Shimin Xu

IPC: C07D487/04 ,  A61P25/18 ,  A61P25/22 ,  A61P25/28 ,  A61P25/06 ,  A61P25/16

CPC classification number: C07D487/04 ,  A61P25/06 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/28

Abstract: The present invention is directed to dihydropyrazolopyrimidinone compounds of formulas (I) and (II) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

公开(公告)号：US20180134712A1

公开(公告)日：2018-05-17

申请号：US15574411

申请日：2016-05-24

Applicant: Dong-Ming SHEN ,  Michael P. DWYER ,  Christopher J. SINZ ,  Deping WANG ,  Shawn J. STACHEL ,  Daniel V. PAONE ,  Ashley FORSTER ,  Richard BERGER ,  William D. SHIPE ,  Yili CHEN ,  Yimin QIAN ,  Shimin XU ,  Chunmei HU ,  Jianmin FU ,  Zhigang GUO ,  Haitang LI ,  Yingjian BO ,  Merck Sharp & Dohme Corp. ,  MSD R & D (China) Co., LTD.

Inventor： Dong-Ming Shen ,  Michael P. Dwyer ,  Christopher J. Sinz ,  Deping Wang ,  Shawn J. Stachel ,  Daniel V. Paone ,  Ashley Forster ,  Richard Berger ,  Yilli Chen ,  Yimin Qian ,  Shimin Xu ,  Chunmel Hu ,  William D. Shipe ,  Jianmin Fu ,  Zhigang Guo ,  HAITANG LI ,  Yingjian Bo

IPC: C07D487/04 ,  A61P25/18 ,  A61P25/00 ,  A61P25/14 ,  A61P25/28 ,  A61P25/16

CPC classification number: C07D487/04 ,  A61K31/519 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28

Abstract: The present invention is directed to 6-alkyl dihydropyrazolopyrimidinone compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypo-function or basal ganglia dysfunction.

公开(公告)号：US08314131B2

公开(公告)日：2012-11-20

申请号：US12681823

申请日：2008-09-19

Applicant: Liping H. Pettus ,  Kelvin K. C. Sham ,  Andrew Tasker ,  Shimin Xu

Inventor： Liping H. Pettus ,  Kelvin K. C. Sham ,  Andrew Tasker ,  Shimin Xu

IPC: A61K31/4192 ,  C07D249/06

CPC classification number: C07D249/18 ,  C07D401/04 ,  C07D403/04 ,  C07D403/12 ,  C07D409/04 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D471/04

Abstract: The present invention comprises a new class of compounds useful for modulating the activity of p38 MAP kinase. The compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, R1 and R5 are defined herein. The invention further provides pharmaceutical compositions including one or more compounds of Formula I, use of such compounds and compositions for treatment of p38 MAP kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammatory disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

Abstract translation: 本发明包括一类可用于调节p38 MAP激酶活性的化合物。 该化合物具有通式I，其中A1，A2，A3，A4，A5，A6，R1和R5如本文所定义。 本发明进一步提供包含一种或多种式I化合物的药物组合物，使用这些化合物和组合物用于治疗p38MAP激酶介导的疾病，包括类风湿性关节炎，牛皮癣和其它炎症性疾病，以及可用于制备 式Ⅰ的化合物。

公开(公告)号：US08101612B2

公开(公告)日：2012-01-24

申请号：US11899363

申请日：2007-09-04

Applicant: Andrew Tasker ,  Dawei Zhang ,  Liping H. Pettus ,  Rob M. Rzasa ,  Kelvin K. C. Sham ,  Shimin Xu ,  Partha Chakrabarti

Inventor： Andrew Tasker ,  Dawei Zhang ,  Liping H. Pettus ,  Rob M. Rzasa ,  Kelvin K. C. Sham ,  Shimin Xu ,  Partha Chakrabarti

IPC: C07D237/30 ,  C07D413/04 ,  A61K31/502 ,  A61K31/5355 ,  A61P29/00 ,  A61P19/02 ,  A61P19/10 ,  A61P17/06 ,  A61P17/00 ,  A61P31/00 ,  A61P31/16 ,  A61P31/22 ,  A61P37/08 ,  A61P21/00 ,  A61P3/10 ,  A61P9/10 ,  A61P33/06

CPC classification number: C07D403/12 ,  C07D237/30 ,  C07D237/34 ,  C07D403/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of p38 kinase mediated diseases and related inflammatory conditions. The compounds have a general Formula II wherein L1, L2, R1a, R1b, R1c, R2, R3, R3a, R4, R5 and p are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of p38 kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

Abstract translation: 本发明包括一类新的可用于预防和治疗p38激酶介导的疾病和相关炎性病症的化合物。 该化合物具有通式II，其中本文定义了L1，L2，R1a，R1b，R1c，R2，R3，R3a，R4，R5和p。 本发明还包括包含一种或多种式I化合物的药物组合物，用于治疗p38激酶介导的疾病（包括类风湿性关节炎，牛皮癣和其它炎症疾病）的这些化合物和组合物的用途，以及可用于制备化合物的中间体和方法 的式

公开(公告)号：US07626030B2

公开(公告)日：2009-12-01

申请号：US11042398

申请日：2005-01-24

Applicant: Tae-Seong Kim ,  Jean-Christophe Harmange ,  David Bauer ,  Shon Booker ,  Yuan Cheng ,  Shimin Xu ,  Ning Xi ,  Joseph L. Kim ,  Andrew Tasker

Inventor： Tae-Seong Kim ,  Jean-Christophe Harmange ,  David Bauer ,  Shon Booker ,  Yuan Cheng ,  Shimin Xu ,  Ning Xi ,  Joseph L. Kim ,  Andrew Tasker

IPC: C07D215/38

CPC classification number: C07D495/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选化合物对于预防和治疗诸如HGF介导的疾病等疾病是有效的。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗疾病和其它疾病或涉及癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：US07560460B2

公开(公告)日：2009-07-14

申请号：US11116759

申请日：2005-04-27

Applicant: Christopher H. Fotsch ,  Michael G. Kelly ,  Mark H. Norman ,  Ning Xi ,  Shimin Xu

Inventor： Christopher H. Fotsch ,  Michael G. Kelly ,  Mark H. Norman ,  Ning Xi ,  Shimin Xu

IPC: A61K31/497 ,  C07D241/02 ,  C07D403/10 ,  C07D401/08 ,  C07D403/04 ,  C07D405/02 ,  C07D411/02

CPC classification number: C07D207/08 ,  A61K38/00 ,  C07D205/04 ,  C07D207/09 ,  C07D209/14 ,  C07D209/42 ,  C07D211/26 ,  C07D211/60 ,  C07D211/62 ,  C07D213/38 ,  C07D213/81 ,  C07D213/82 ,  C07D215/48 ,  C07D217/06 ,  C07D217/14 ,  C07D217/26 ,  C07D233/64 ,  C07D295/185 ,  C07D317/60 ,  C07D317/68 ,  C07D319/18 ,  C07D401/12 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D451/02 ,  C07K5/06026 ,  C07K5/06139 ,  C07K5/06147 ,  C07K5/06191

Abstract: Selected substituted piperazine compounds are effective for prophylaxis and treatment of diseases, such as obesity and the like. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving activation of the melanocortin receptor. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选的取代哌嗪化合物对于预防和治疗诸如肥胖症等疾病是有效的。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗涉及黑皮质素受体活化的疾病和其它疾病或病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：US20090176774A1

公开(公告)日：2009-07-09

申请号：US12157303

申请日：2008-06-09

Applicant: Michele Potashman ,  Tae-Seong Kim ,  Steven Bellon ,  Shon Booker ,  Yuan Cheng ,  Joseph L. Kim ,  Andrew Tasker ,  Ning Xi ,  Shimin Xu ,  Jean-Christophe Harmange ,  George Borg ,  Matthew Weiss ,  Brian L. Hodous ,  Russell Graceffa ,  William H. Buckner ,  Craig E. Masse ,  Deborah Choquette ,  Matthew W. Martin ,  Julie Germain ,  Lucian V. DiPietro ,  Stuart C. Chaffee ,  Joseph J. Nunes ,  John L. Buchanan ,  David C. McGowan ,  Douglas A. Whittington ,  Gregory J. Habgood ,  Vinod F. Patel ,  Daniel La

Inventor： Michele Potashman ,  Tae-Seong Kim ,  Steven Bellon ,  Shon Booker ,  Yuan Cheng ,  Joseph L. Kim ,  Andrew Tasker ,  Ning Xi ,  Shimin Xu ,  Jean-Christophe Harmange ,  George Borg ,  Matthew Weiss ,  Brian L. Hodous ,  Russell Graceffa ,  William H. Buckner ,  Craig E. Masse ,  Deborah Choquette ,  Matthew W. Martin ,  Julie Germain ,  Lucian V. DiPietro ,  Stuart C. Chaffee ,  Joseph J. Nunes ,  John L. Buchanan ,  David C. McGowan ,  Douglas A. Whittington ,  Gregory J. Habgood ,  Vinod F. Patel ,  Daniel La

IPC: A61K31/536 ,  A61K31/517 ,  A61K31/502 ,  A61K31/498 ,  A61K31/4709

CPC classification number: C07D213/64 ,  C07D213/81 ,  C07D215/233 ,  C07D215/38 ,  C07D215/48 ,  C07D215/54 ,  C07D237/34 ,  C07D239/34 ,  C07D239/47 ,  C07D239/84 ,  C07D239/94 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

公开(公告)号：US20090137582A1

公开(公告)日：2009-05-28

申请号：US12288950

申请日：2008-10-24

Applicant: Liping H. Pettus ,  Andrew Tasker ,  Shimin Xu ,  Ryan Wurz

Inventor： Liping H. Pettus ,  Andrew Tasker ,  Shimin Xu ,  Ryan Wurz

IPC: A61K31/5377 ,  C07D471/04 ,  A61K31/496 ,  A61K31/437

CPC classification number: C07D471/04

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of pro-inflammatory cytokine mediated diseases, and in particular, p38 activity mediated inflammation and related conditions. The compounds have a general Formula I wherein A1, A2, A3, A4, A5, R1, R2 and R3 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of inflammatory diseases including rheumatoid arthritis, psoriasis and other disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

Abstract translation: 本发明包括一类新的可用于预防和治疗促炎细胞因子介导的疾病，特别是p38活性介导的炎症和相关病症的化合物。 所述化合物具有通式I，其中A1，A2，A3，A4，A5，R1，R2和R3如本文所定义。 本发明还包括药物组合物，其包含一种或多种式I化合物，这些化合物和组合物用于治疗炎性疾病（包括类风湿性关节炎，牛皮癣和其它病症）的用途，以及可用于制备式I化合物的中间体和方法 。

公开(公告)号：US07265138B2

公开(公告)日：2007-09-04

申请号：US10775980

申请日：2004-02-09

Applicant: Elizabeth M. Doherty ,  Christopher H. Fotsch ,  Nianhe Han ,  Randall W. Hungate ,  Qingyian Liu ,  Mark H. Norman ,  Ning Xi ,  Shimin Xu

Inventor： Elizabeth M. Doherty ,  Christopher H. Fotsch ,  Nianhe Han ,  Randall W. Hungate ,  Qingyian Liu ,  Mark H. Norman ,  Ning Xi ,  Shimin Xu

IPC: A61K31/425 ,  C07D277/04

CPC classification number: C07D233/90 ,  C07D263/34 ,  C07D277/56 ,  C07D403/04 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

Abstract: Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

Abstract translation: 具有一般结构和含有它们的组合物的化合物，用于治疗急性，炎性和神经性疼痛，牙痛，一般头痛，偏头痛，丛集性头痛，混合血管和非血管综合征，紧张性头痛，一般炎症，关节炎，风湿性 疾病，骨关节炎，炎症性肠病，炎症性眼病，炎症性或不稳定性膀胱病，银屑病，皮肤炎症成分炎症，慢性炎性病症，炎性疼痛及相关的痛觉过敏和异常性疼痛，神经性疼痛及相关的痛觉过敏和异常性疼痛，糖尿病性神经病疼痛， 咳嗽痛，交感神经痛，交感综合征，哮喘，上皮组织损伤或功能障碍，单纯疱疹，呼吸系统内脏运动紊乱，泌尿生殖道，胃肠道或血管区，伤口，烧伤，过敏性皮肤反应，瘙痒，白癜风，一般胃肠道疾病， G 腹部溃疡，十二指肠溃疡，腹泻，坏死因子诱发的胃损伤，毛发生长，血管舒缩或过敏性鼻炎，支气管疾病或膀胱疾病。

公开(公告)号：US20060040956A1

公开(公告)日：2006-02-23

申请号：US11234713

申请日：2005-09-23

Applicant: Guoqing Chen ,  Jeffrey Adams ,  Jean Bemis ,  Shon Booker ,  Guolin Cai ,  Lucian Di Pietro ,  Celia Dominguez ,  Daniel Elbaum ,  Julie Germain ,  Stephanie Geuns-Meyer ,  Michael Handley ,  Qi Huang ,  Joseph Kim ,  Tae-Seong Kim ,  Alexander Kiselyov ,  Xiaohu Ouyang ,  Vinod Patel ,  Leon Smith ,  Markian Stec ,  Andrew Tasker ,  Ning Xi ,  Shimin Xu ,  Chester Yuan ,  Michael Croghan

Inventor： Guoqing Chen ,  Jeffrey Adams ,  Jean Bemis ,  Shon Booker ,  Guolin Cai ,  Lucian Di Pietro ,  Celia Dominguez ,  Daniel Elbaum ,  Julie Germain ,  Stephanie Geuns-Meyer ,  Michael Handley ,  Qi Huang ,  Joseph Kim ,  Tae-Seong Kim ,  Alexander Kiselyov ,  Xiaohu Ouyang ,  Vinod Patel ,  Leon Smith ,  Markian Stec ,  Andrew Tasker ,  Ning Xi ,  Shimin Xu ,  Chester Yuan ,  Michael Croghan

IPC: A61K31/506 ,  C07D403/02

CPC classification number: C07D213/82 ,  A61K31/443 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/538 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/00 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: Selected heterocyclic compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.