公开(公告)号：US11466047B2

公开(公告)日：2022-10-11

申请号：US16611624

申请日：2018-05-07

申请人： Merck Sharp & Dohme Corp. ,  Wen-Lian Wu ,  Jongwon Lim ,  Jared N. Cumming ,  Benjamin Wesley Trotter ,  Wonsuk Chang

发明人： Wen-Lian Wu ,  Jongwon Lim ,  Jared N. Cumming ,  Benjamin Wesley Trotter ,  Wonsuk Chang

IPC分类号： C07H21/00 ,  C07H21/04 ,  A61P35/00 ,  A61P37/02 ,  C07H21/02

摘要： A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

公开(公告)号：US10414774B2

公开(公告)日：2019-09-17

申请号：US16324596

申请日：2017-08-10

申请人： Merck Sharp & Dohme Corp. ,  Jared N. Cumming ,  Kevin D. Dykstra ,  Alan Hruza ,  Derun Li ,  Hong Liu ,  Haiqun Tang ,  Brandon M. Taoka ,  Andreas Verras ,  Shawn P. Walsh ,  Wen-Lian Wu

发明人： Jared N. Cumming ,  Kevin D. Dykstra ,  Alan Hruza ,  Derun Li ,  Hong Liu ,  Haiqun Tang ,  Brandon M. Taoka ,  Andreas Verras ,  Shawn P. Walsh ,  Wen-Lian Wu

IPC分类号： C07D487/04 ,  C07D519/00 ,  A61P3/10 ,  C07D498/04 ,  C07D513/04 ,  C07D471/04

摘要： Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.

公开(公告)号：US09051329B2

公开(公告)日：2015-06-09

申请号：US14125116

申请日：2012-07-02

申请人： Wen-Lian Wu

发明人： Wen-Lian Wu

IPC分类号： A61K31/505 ,  C07D491/00 ,  C07D487/14 ,  A61K31/519 ,  A61K31/529

CPC分类号： C07D487/14 ,  A61K31/519 ,  A61K31/529

摘要： The present invention is directed to novel tricyclic heterocycles of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及结构式（I）的新型三环杂环，其为二肽基肽酶-IV酶的抑制剂，其可用于治疗或预防涉及二肽基肽酶-IV酶的疾病，例如糖尿病 特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。

公开(公告)号：US08067621B2

公开(公告)日：2011-11-29

申请号：US11654821

申请日：2007-01-18

申请人： Theodros Asberom ,  Thomas A. Bara ,  Chad E. Bennett ,  Duane A. Burnett ,  Mary Ann Caplen ,  John W. Clader ,  David J. Cole ,  Martin S. Domalski ,  Hubert B. Josien ,  Chad E. Knutson ,  Hongmei Li ,  Mark D. McBriar ,  Dmitri A. Pissarnitski ,  Li Qiang ,  Murali Rajagopalan ,  Thavalakulamgara K. Sasikumar ,  Jing Su ,  Haiqun Tang ,  Wen-Lian Wu ,  Ruo Xu ,  Zhiqiang Zhao

发明人： Theodros Asberom ,  Thomas A. Bara ,  Chad E. Bennett ,  Duane A. Burnett ,  Mary Ann Caplen ,  John W. Clader ,  David J. Cole ,  Martin S. Domalski ,  Hubert B. Josien ,  Chad E. Knutson ,  Hongmei Li ,  Mark D. McBriar ,  Dmitri A. Pissarnitski ,  Li Qiang ,  Murali Rajagopalan ,  Thavalakulamgara K. Sasikumar ,  Jing Su ,  Haiqun Tang ,  Wen-Lian Wu ,  Ruo Xu ,  Zhiqiang Zhao

IPC分类号： C07D493/00 ,  A61K31/35

CPC分类号： C07D311/22 ,  C07C317/14 ,  C07C317/20 ,  C07C317/44 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/12 ,  C07D311/80 ,  C07D311/92 ,  C07D311/94 ,  C07D313/08 ,  C07D335/06 ,  C07D405/12 ,  C07D409/12 ,  C07D491/04 ,  C07D493/04

摘要： This invention discloses novel gamma secretase inhibitors of the formula: R2 and R3, or R2 and R4, or R3 and R4, together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substitutents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

摘要翻译： 本发明公开了具有下式的新型γ分泌酶抑制剂：R2和R3，或R2和R4，或R3和R4与它们所连接的原子一起可以形成稠合的环烷基或稠合的杂环烷基环。 环烷基环或杂环烷基环可任选被一个或多个取代基取代。 一种或多种式（I）化合物或包含这些化合物的制剂可以是有用的，例如， 治疗阿尔茨海默病。

公开(公告)号：US20110236400A1

公开(公告)日：2011-09-29

申请号：US12665580

申请日：2008-07-01

申请人： Wen-Lian Wu ,  Thomas A. Bara ,  Duane A. Burnett ,  John W. Clader ,  Martin S. Domalski ,  Yan Jin ,  Hubert B. Josien ,  Hongmei Li ,  Xian Liang ,  Dmitri A. Pissarnitski ,  Thavalakulamgara K. Sasikumar ,  Jesse K. Wong ,  Ruo Xu ,  Zhiqiang Zhao ,  Paul E. McNamara

发明人： Wen-Lian Wu ,  Thomas A. Bara ,  Duane A. Burnett ,  John W. Clader ,  Martin S. Domalski ,  Yan Jin ,  Hubert B. Josien ,  Hongmei Li ,  Xian Liang ,  Dmitri A. Pissarnitski ,  Thavalakulamgara K. Sasikumar ,  Jesse K. Wong ,  Ruo Xu ,  Zhiqiang Zhao ,  Paul E. McNamara

IPC分类号： A61K39/395 ,  C07D493/04 ,  C07D311/80 ,  C07D407/12 ,  A61K31/35 ,  A61K31/352 ,  A61K31/381 ,  A61P25/28 ,  A61P29/00 ,  A61P31/00 ,  C07C201/12 ,  C07C67/343

CPC分类号： C07D493/04 ,  C07D311/78 ,  C07D407/12

摘要： Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)—O—C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)—O—C(O)-heteroaryl and a basic tertiary amine.

摘要翻译： 公开了下式的新型γ-分泌酶抑制剂。 还公开了抑制γ-分泌酶，治疗神经变性疾病的方法和治疗阿尔茨海默氏病的方法。 还公开了在一个反应​​步骤中使用醛（或酮）和被两个吸电子基团取代的烷基的混合物制备烯烃的方法，并使该混合物与：（a）磺酰卤（例如磺酰氯） 和（b）磺酰基酐和碱性胺，或（c）芳基-C（O） - 卤化物和碱式叔胺，或（d）芳基-C（O） - （O） - 芳基和碱式叔胺，或（e）杂芳基-C（O） - 卤化物和碱式叔胺，或（f）杂芳基-C（O）-O-C（O ） - 杂芳基和碱性叔胺。

公开(公告)号：US20090082336A1

公开(公告)日：2009-03-26

申请号：US12264676

申请日：2008-11-04

申请人： Julius J. Matasi ,  Deen Tulshian ,  Duane A. Burnett ,  Wen-Lian Wu ,  Peter Korakas ,  Lisa S. Silverman ,  Thavalakulamgara K. Sasikumar ,  Li Qiang ,  Martin S. Donalski

发明人： Julius J. Matasi ,  Deen Tulshian ,  Duane A. Burnett ,  Wen-Lian Wu ,  Peter Korakas ,  Lisa S. Silverman ,  Thavalakulamgara K. Sasikumar ,  Li Qiang ,  Martin S. Donalski

IPC分类号： A61K31/55 ,  C07D495/14 ,  A61K31/519 ,  C12N5/06 ,  A61K31/5377

CPC分类号： C07D471/14 ,  C07D491/14 ,  C07D495/04 ,  C07D495/14 ,  C09B57/00

摘要： In its many embodiments, the present invention provides tricyclic compounds of formula I (wherein J1-J4, X, and R1-R5 are as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimer's disease.

摘要翻译： 在其许多实施方案中，本发明提供用作代谢型谷氨酸受体（mGluR）拮抗剂的式I（其中J1-J4，X和R1-R5如本文所定义）的三环化合物，特别是作为选择性代谢型谷氨酸受体1拮抗剂， 含有该化合物的药物组合物，以及使用该化合物和组合物治疗与代谢型谷氨酸受体（例如，mGluR1）相关的疾病例如疼痛，偏头痛，焦虑症，尿失禁和神经变性疾病如阿尔茨海默病的治疗方法。

公开(公告)号：US20080312218A1

公开(公告)日：2008-12-18

申请号：US11524867

申请日：2006-09-21

申请人： Duane A. Burnett ,  Wen-Lian Wu

发明人： Duane A. Burnett ,  Wen-Lian Wu

IPC分类号： A61K31/549 ,  A61K31/538 ,  A61K31/519 ,  A61K31/504 ,  C07D498/02 ,  C07D491/02

CPC分类号： C07D495/14

摘要： In its many embodiments, the present invention provides tetracyclic compounds of formula I or formula II (wherein the various moieties are as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimers disease.

摘要翻译： 在其许多实施方案中，本发明提供了可用作代谢型谷氨酸受体（mGluR）拮抗剂的式I或式II（其中各种部分如本文所定义）的四环化合物，特别是作为选择性代谢型谷氨酸受体1拮抗剂，含有 化合物和使用化合物和组合物治疗与代谢型谷氨酸受体（例如，mGluR1）相关的疾病例如疼痛，偏头痛，焦虑症，尿失禁和神经变性疾病如阿尔茨海默病的治疗方法。

公开(公告)号：US20070197581A1

公开(公告)日：2007-08-23

申请号：US11654821

申请日：2007-01-18

申请人： Theodros Asberom ,  Thomas Bara ,  Chad Bennett ,  Duane Burnett ,  Mary Ann Caplen ,  John Clader ,  David Cole ,  Martin Domalski ,  Hubert Josien ,  Chad Knutson ,  Hongmei Li ,  Mark McBriar ,  Dmitri Pissarnitski ,  Li Qiang ,  Murali Rajagopalan ,  Thavalakulamgara Sasikumar ,  Jing Su ,  Haiqun Tang ,  Wen-Lian Wu ,  Ruo Xu ,  Zhiqiang Zhao

发明人： Theodros Asberom ,  Thomas Bara ,  Chad Bennett ,  Duane Burnett ,  Mary Ann Caplen ,  John Clader ,  David Cole ,  Martin Domalski ,  Hubert Josien ,  Chad Knutson ,  Hongmei Li ,  Mark McBriar ,  Dmitri Pissarnitski ,  Li Qiang ,  Murali Rajagopalan ,  Thavalakulamgara Sasikumar ,  Jing Su ,  Haiqun Tang ,  Wen-Lian Wu ,  Ruo Xu ,  Zhiqiang Zhao

IPC分类号： A61K31/4741 ,  A61K31/473 ,  A61K31/353 ,  A61K31/19

CPC分类号： C07D311/22 ,  C07C317/14 ,  C07C317/20 ,  C07C317/44 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/12 ,  C07D311/80 ,  C07D311/92 ,  C07D311/94 ,  C07D313/08 ,  C07D335/06 ,  C07D405/12 ,  C07D409/12 ,  C07D491/04 ,  C07D493/04

摘要： This invention discloses novel gamma secretase inhibitors of the formula: R2 and R3, or R2 and R4, or R3 and R4, together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substitutents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

摘要翻译： 本发明公开了下式的新型γ分泌酶抑制剂：R 2和R 3，或R 2和R 4 O / >或R 3和R 4与它们所连接的原子一起可以形成稠合的环烷基或稠合的杂环烷基环。 环烷基环或杂环烷基环可任选被一个或多个取代基取代。 一种或多种式（I）化合物或包含这些化合物的制剂可以是有用的，例如， 治疗阿尔茨海默病。

公开(公告)号：US20200062798A1

公开(公告)日：2020-02-27

申请号：US16611624

申请日：2018-05-07

申请人： Wen-Lian WU ,  Jongwon LIM ,  Jared N. CUMMING ,  Benjamin Wesley TROTTER ,  Wonsuk CHANG ,  Merck Sharp & Dohme Corp.

发明人： Wen-Lian WU ,  Jongwon LIM ,  Jared N. Cumming ,  Benjamin Wesley TROTTER ,  Wonsuk CHANG

IPC分类号： C07H21/00

摘要： A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

公开(公告)号：US09499502B2

公开(公告)日：2016-11-22

申请号：US14110363

申请日：2012-04-12

申请人： Wen-Lian Wu ,  Duane A. Burnett ,  Andrew W. Stamford ,  Jared N. Cumming ,  Chad E. Bennett ,  Eric J. Gilbert ,  Jack D. Scott ,  Younong Yu ,  Xuanjia Peng

发明人： Wen-Lian Wu ,  Duane A. Burnett ,  Andrew W. Stamford ,  Jared N. Cumming ,  Chad E. Bennett ,  Eric J. Gilbert ,  Jack D. Scott ,  Younong Yu ,  Xuanjia Peng

IPC分类号： C07D279/12 ,  A61K45/06 ,  C07D417/04 ,  A61K31/541 ,  C07D417/12 ,  C07D417/14 ,  A61K31/54 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  C07D513/04

CPC分类号： C07D279/12 ,  A61K31/54 ,  A61K31/541 ,  A61K45/06 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  C07D513/04

摘要： The present invention discloses certain iminothiazine compounds and mono- and dioxides thereof, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein each of variables shown in the formula are as defined herein. The compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and uses, including Alzheimer's disease, are also disclosed.