公开(公告)号：US20230416227A1

公开(公告)日：2023-12-28

申请号：US18043357

申请日：2021-09-09

Applicant: Merck Sharp & Dohme LLC ,  Anthony Ken OGAWA ,  Christopher J. SINZ ,  Jacqueline D. HICKS ,  Alan C. CHENG ,  Song YANG ,  Jianming BAO ,  Donna A. A. W. HAYES ,  Simon B. LANG ,  Maoqun TIAN ,  Salman JABRI ,  Galen Paul SHEARN-NANCE ,  Rongze KUANG ,  Zhiqiang ZHAO ,  Zhicai WU

Inventor： Anthony Ken Ogawa ,  Christopher J. Sinz ,  Jacqueline D. Hicks ,  Alan C. Cheng ,  Song Yang ,  Jianming Bao ,  Donna A. A. W. Hayes ,  Simon B. Lang ,  Maoqun Tian ,  Salman Jabri ,  Galen Paul Shearn-Nance ,  Rongze Kuang ,  Zhiqiang Zhao ,  Zhicai Wu

IPC: C07D401/14 ,  A61K45/06 ,  A61P9/10

CPC classification number: C07D401/14 ,  A61P9/10 ,  A61K45/06

Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

公开(公告)号：US08796258B2

公开(公告)日：2014-08-05

申请号：US13812536

申请日：2012-02-23

Applicant: Rajan Anand ,  James M. Apgar ,  Tesfaye Biftu ,  Ping Chen ,  Lin Chu ,  Vincent J. Colandrea ,  Guizhen Dong ,  James F. Dropinski ,  Danqing Feng ,  Jacqueline D. Hicks ,  Jinlong Jiang ,  Alexander J. Kim ,  Kenneth J. Leavitt ,  Bing Li ,  Xiaoxia Qian ,  Iyassu Sebhat ,  Lan Wei ,  Robert R. Wilkening ,  Zhicai Wu

Inventor： Rajan Anand ,  James M. Apgar ,  Tesfaye Biftu ,  Ping Chen ,  Lin Chu ,  Vincent J. Colandrea ,  Guizhen Dong ,  James F. Dropinski ,  Danqing Feng ,  Jacqueline D. Hicks ,  Jinlong Jiang ,  Alexander J. Kim ,  Kenneth J. Leavitt ,  Bing Li ,  Xiaoxia Qian ,  Iyassu Sebhat ,  Lan Wei ,  Robert R. Wilkening ,  Zhicai Wu

IPC: A61K31/00 ,  C07D513/02

CPC classification number: A61K31/5377 ,  A61K31/351 ,  A61K31/366 ,  A61K31/397 ,  A61K31/437 ,  A61K31/4412 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/519 ,  A61K45/06 ,  C07D471/04 ,  C07D519/00 ,  A61K2300/00

Abstract: Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

Abstract translation: 结构式（I）的新型化合物是AMP-蛋白激酶的活化剂，可用于治疗，预防和抑制由AMPK激活的蛋白激酶介导的疾病。 本发明的化合物可用于治疗2型糖尿病，高血糖症，代谢综合征，肥胖症，高胆固醇血症和高血压。

公开(公告)号：US07638530B2

公开(公告)日：2009-12-29

申请号：US10554185

申请日：2004-04-20

Applicant: Mark T. Bilodeau ,  Zhicai Wu

Inventor： Mark T. Bilodeau ,  Zhicai Wu

IPC: A61K31/4745 ,  C07D498/02 ,  C07D491/02 ,  C07D471/02

CPC classification number: C07D487/04 ,  C07D471/04

Abstract: The present invention is directed to compounds which contain a five-membered heterocyclic ring fused to a substituted pyridine moiety which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

Abstract translation: 本发明涉及含有与取代的吡啶部分稠合的五元杂环的化合物，所述取代吡啶部分抑制丝氨酸/苏氨酸蛋白激酶Akt的活性。 本发明还涉及含有本发明化合物的治疗组合物和治疗癌症的方法，包括施用本发明化合物。

公开(公告)号：US07579355B2

公开(公告)日：2009-08-25

申请号：US10554001

申请日：2004-04-20

Applicant: Mark T. Bilodeau ,  Mark E. Duggan ,  John C. Hartnett ,  Craig W. Lindsley ,  Zhicai Wu ,  Zhijian Zhao

Inventor： Mark T. Bilodeau ,  Mark E. Duggan ,  John C. Hartnett ,  Craig W. Lindsley ,  Zhicai Wu ,  Zhijian Zhao

IPC: A61K31/52 ,  C07D401/14

CPC classification number: C07F9/65583 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04

Abstract: The present invention is directed to compounds which contain a substituted pyridine moeity which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

Abstract translation: 本发明涉及含有抑制Akt（丝氨酸/苏氨酸蛋白激酶）活性的取代吡啶甲氧基化合物。 本发明还涉及含有本发明化合物的治疗组合物和治疗癌症的方法，包括施用本发明化合物。

公开(公告)号：US07544677B2

公开(公告)日：2009-06-09

申请号：US11659606

申请日：2005-08-19

Applicant: Mark T. Bilodeau ,  Nicholas D. P. Cosford ,  John C. Hartnett ,  Yiwei Li ,  Jun Liang ,  Peter J. Manley ,  Lou Anne Neilson ,  Tony Siu ,  Zhicai Wu

Inventor： Mark T. Bilodeau ,  Nicholas D. P. Cosford ,  John C. Hartnett ,  Yiwei Li ,  Jun Liang ,  Peter J. Manley ,  Lou Anne Neilson ,  Tony Siu ,  Zhicai Wu

IPC: A61K31/541 ,  A61K31/5355 ,  A61K31/519 ,  C07D471/04 ,  C07D519/00 ,  A61P35/00

CPC classification number: C07D471/04

Abstract: The present invention is directed to compounds which contain substituted 5-deazapteridine moieties which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

Abstract translation: 本发明涉及含有抑制Akt（丝氨酸/苏氨酸蛋白激酶）活性的取代的5-取代哌啶部分的化合物。 本发明还涉及含有本发明化合物的治疗组合物和治疗癌症的方法，包括施用本发明化合物。

公开(公告)号：US20090069312A1

公开(公告)日：2009-03-12

申请号：US12223353

申请日：2007-01-29

Applicant: B. Wesley Trotter ,  Richard C.A. Isaacs ,  Zhicai Wu ,  Jacob M. Hoffman ,  Mark T. Bilodeau ,  Ahren Iver Green

Inventor： B. Wesley Trotter ,  Richard C.A. Isaacs ,  Zhicai Wu ,  Jacob M. Hoffman ,  Mark T. Bilodeau ,  Ahren Iver Green

IPC: A61K31/538 ,  C07D413/14 ,  A61P9/06

CPC classification number: C07D413/14

Abstract: The present invention relates to dipyridin-3-ylmethoxy compounds and derivatives thereof having the structure I useful as potassium channel inhibitors to treat cardiac arrhythmias, and the like.

Abstract translation: 本发明涉及具有用作治疗心律失常的钾通道抑制剂的结构I的二吡啶-3-基甲氧基化合物及其衍生物等。

公开(公告)号：US20090030043A1

公开(公告)日：2009-01-29

申请号：US12223356

申请日：2007-01-29

Applicant: Jacob M. Hoffman ,  Anthony M. Smith ,  John Hartnett ,  Zhicai Wu ,  Mark T. Bilodeau

Inventor： Jacob M. Hoffman ,  Anthony M. Smith ,  John Hartnett ,  Zhicai Wu ,  Mark T. Bilodeau

IPC: A61K31/444 ,  C07D401/14

CPC classification number: C07D213/74

Abstract: The present invention relates to tetraaryl methyl amine compounds and derivatives thereof having the structure (I) useful as potassium channel inhibitors to treat cardiac arrhythmias, and the like.

Abstract translation: 本发明涉及具有用作治疗心律失常的钾通道抑制剂的结构（I）的四芳基甲胺化合物及其衍生物等。

公开(公告)号：US20060270673A1

公开(公告)日：2006-11-30

申请号：US10554187

申请日：2004-04-20

Applicant: Mark Duggan ,  Craig Lindsley ,  Zhicai Wu ,  Zhijian Zhao ,  John Hartnett

Inventor： Mark Duggan ,  Craig Lindsley ,  Zhicai Wu ,  Zhijian Zhao ,  John Hartnett

IPC: A61K31/5377 ,  A61K31/4439 ,  C07D417/02 ,  C07D403/02 ,  C07D413/02

CPC classification number: C07D213/85 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

Abstract: The present invention is directed to compounds which contain a substituted pyridine moiety which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention.

Abstract translation: 本发明涉及含有抑制Akt（丝氨酸/苏氨酸蛋白激酶）活性的取代的吡啶部分的化合物。 本发明还涉及含有本发明化合物的治疗组合物和治疗癌症的方法，包括施用本发明化合物。

公开(公告)号：US06867323B2

公开(公告)日：2005-03-15

申请号：US09875777

申请日：2001-06-06

Applicant: Scott E. Denmark ,  Jun Young Choi ,  Daniel Wehrli ,  Zhicai Wu ,  Luc Neuville ,  Weitao Pan ,  Ramzi F. Sweis ,  Zhigang Wang ,  Shyh-Ming Yang

Inventor： Scott E. Denmark ,  Jun Young Choi ,  Daniel Wehrli ,  Zhicai Wu ,  Luc Neuville ,  Weitao Pan ,  Ramzi F. Sweis ,  Zhigang Wang ,  Shyh-Ming Yang

IPC: C07B37/04 ,  C07C1/32 ,  C07C29/36 ,  C07C29/44 ,  C07C41/30 ,  C07C45/68 ,  C07C45/72 ,  C07C67/343 ,  C07C205/06 ,  C07F7/08 ,  C07F7/12 ,  C07F7/18 ,  C07F7/21 ,  C07C67/00

CPC classification number: C07C29/36 ,  C07B37/04 ,  C07C1/325 ,  C07C29/44 ,  C07C41/30 ,  C07C45/68 ,  C07C45/72 ,  C07C67/343 ,  C07C201/12 ,  C07C2527/13 ,  C07C2531/22 ,  C07F7/0827 ,  C07F7/083 ,  C07F7/0836 ,  C07F7/0838 ,  C07F7/0896 ,  C07F7/12 ,  C07F7/1804 ,  C07F7/21 ,  C07C33/28 ,  C07C33/30 ,  C07C33/02 ,  C07C49/835 ,  C07C49/796 ,  C07C49/794 ,  C07C69/76 ,  C07C205/06 ,  C07C205/19 ,  C07C205/35 ,  C07C43/215 ,  C07C43/15 ,  C07C43/225 ,  C07C43/23 ,  C07C43/164

Abstract: Improved methods for generating a —C—C— bond by cross-coupling of a transferable group with an acceptor group. The transferable group is a substituent of an organosilicon nucleophile and the acceptor group is provided as an organic electrophile. The reaction is catalyzed by a Group 10 transition metal complex (e.g., Ni, Pt or Pd), particularly by a palladium complex. Certain methods of this invention use improved organosilicon nucleophiles which are readily prepared, can give high product yields and exhibit high stereoselectivity. Methods of this invention employ activating ions such as halides, hydroxide, hydride and silyloxides. In specific embodiments, organosilicon nucleophilic reagents of this invention include siloxanes, particularly cyclic siloxanes. The combination of the cross-coupling reactions of this invention with ring-closing metathesis, hydrosilylation and intramolecular hydrosilylation reactions provide useful synthetic strategies that have wide application.

Abstract translation: 通过可转移基团与受体基团的交叉偶联产生-C-C键的改进方法。 可转移基团是有机硅亲核试剂的取代基，并且受体基团作为有机亲电试剂提供。 该反应由第10族过渡金属络合物（例如，Ni，Pt或Pd）催化，特别是由钯络合物催化。 本发明的某些方法使用易于制备的改进的有机硅亲核试剂，可以提供高产物产率并显示高立体选择性。 本发明的方法使用活化离子如卤化物，氢氧化物，氢化物和甲硅烷氧基。 在具体实施方案中，本发明的有机硅亲核试剂包括硅氧烷，特别是环状硅氧烷。 本发明的交叉偶联反应与闭环复分解，氢化硅烷化和分子内氢化硅烷化反应的组合提供了广泛应用的有用的合成策略。

公开(公告)号：US20190352294A1

公开(公告)日：2019-11-21

申请号：US16461849

申请日：2017-11-13

Applicant: Ashwin RAO ,  Brian Alexander MCKITTRICK ,  Matthew LOMBARDO ,  Jacqueline D. HICKS ,  Amy Bittner MCCRACKEN ,  Hong Dong CHU ,  Sung-Sau SO ,  Peter ORTH ,  Zhicai WU ,  Ping LAN ,  John S. DEBENHAM ,  Brent R. WHITEHEAD ,  Jerry A. TAYLOR ,  Zhongxiang SUN ,  Revathi Reddy KATIPALLY ,  Jonathan E. GABLE ,  Markus K. DAHLGREN ,  Sathesh P. BHAT ,  Merck Sharp & Dohme Corp.

Inventor： Ashwin U. Rao ,  Brian Alexander McKittrick ,  Matthew Lombardo ,  Jacqueline D. Hicks ,  Amy Bittner McCracken ,  Hong Dong Chu ,  Sung-Sau So ,  Peter Orth ,  Zhicai Wu ,  Ping Lan ,  John S. Debenham ,  Brent R. Whitehead ,  Jerry A. Taylor ,  Zhongxiang Sun ,  Revathi Reddy Katipally ,  Jonathan E. Gable ,  Markus K. Dahlgren ,  Sathesh P. Bhat

IPC: C07D413/14 ,  C07D495/04 ,  A61P7/02

Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIIa inhibitors.