公开(公告)号：WO2012118945A3

公开(公告)日：2014-04-10

申请号：PCT/US2012027237

申请日：2012-03-01

Applicant: MERCK SHARP & DOHME ,  BENNETT CHAD E ,  BURNETT DUANE A ,  LI HONGMEI ,  CHEN YONGGANG ,  MCCRACKEN TROY ,  VICAREL MONICA

Inventor： BENNETT CHAD E ,  BURNETT DUANE A ,  LI HONGMEI ,  CHEN YONGGANG ,  MCCRACKEN TROY ,  VICAREL MONICA

IPC: A01N43/54 ,  C07D239/42 ,  C07D471/22

CPC classification number: C07D487/04 ,  A61K31/155 ,  A61K31/427 ,  A61K31/519 ,  A61K31/522 ,  A61K31/64 ,  A61K45/06 ,  C07D473/18 ,  C07D473/28 ,  A61K2300/00

Abstract: The present invention is directed to novel bicyclic 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.

Abstract translation: 本发明涉及结构式（I）的新型双环杂环，其是二肽基肽酶-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：WO2010054067A1

公开(公告)日：2010-05-14

申请号：PCT/US2009/063385

申请日：2009-11-05

Applicant: SCHERING CORPORATION ,  ZHU, Zhaoning ,  GREENLEE, William, J. ,  COLE, David, James ,  PISSARNITSKI, Dmitri, A. ,  GALLO, Gioconda, V. ,  LI, Hongmei ,  JOSIEN, Hubert, B. ,  QIN, Jun ,  KNUTSON, Chad, E. ,  MANDAL, Mihirbaran ,  VICAREL, Monica, L. ,  RAJAGOPALAN, Murali ,  DHONDI, Pawan, Kumar ,  XU, Ruo ,  SUN, Zhong-Yue ,  BARA, Thomas, A. ,  HUANG, Xianhai ,  ZHU, Xiaohong ,  ZHAO, Zhiqiang ,  CLADER, John, W. ,  PALANI, Anandan ,  ASBEROM, Theodros ,  MCCRACKEN, Troy ,  BENNETT, Chad, E.

Inventor： ZHU, Zhaoning ,  GREENLEE, William, J. ,  COLE, David, James ,  PISSARNITSKI, Dmitri, A. ,  GALLO, Gioconda, V. ,  LI, Hongmei ,  JOSIEN, Hubert, B. ,  QIN, Jun ,  KNUTSON, Chad, E. ,  MANDAL, Mihirbaran ,  VICAREL, Monica, L. ,  RAJAGOPALAN, Murali ,  DHONDI, Pawan, Kumar ,  XU, Ruo ,  SUN, Zhong-Yue ,  BARA, Thomas, A. ,  HUANG, Xianhai ,  ZHU, Xiaohong ,  ZHAO, Zhiqiang ,  CLADER, John, W. ,  PALANI, Anandan ,  ASBEROM, Theodros ,  MCCRACKEN, Troy ,  BENNETT, Chad, E.

IPC: C07D403/10 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D491/20 ,  C07D498/04 ,  C07D498/20 ,  C07D513/04 ,  C07F7/10 ,  A61K31/53 ,  A61P25/28

CPC classification number: C07D471/04 ,  C07D413/10 ,  C07D498/04 ,  C07D498/20 ,  C07F7/0812

Abstract: In its many embodiments, the present invention provides a novel class of heterocyclic compounds of the formula: as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Abstract translation: 在其许多实施方案中，本发明提供了一类新的下式杂环化合物：作为γ分泌酶的调节剂，制备这些化合物的方法，含有一种或多种此类化合物的药物组合物， 制备包含一种或多种此类化合物的药物制剂，以及使用这些化合物或药物组合物治疗，预防，抑制或改善与中枢神经系统相关的一种或多种疾病的方法。

公开(公告)号：WO2008033456A1

公开(公告)日：2008-03-20

申请号：PCT/US2007/019918

申请日：2007-09-13

Applicant: SCHERING CORPORATION ,  MCKITTRICK, Brian ,  SMITH, Elizabeth, M. ,  BENNETT, Chad, E. ,  HARRIS, Joel, M. ,  KISELGOF, Eugenia, Y. ,  KNUTSON, Chad, E. ,  KORAKAS, Peter ,  TULSHIAN, Deen ,  KIM, Hyunjin

Inventor： MCKITTRICK, Brian ,  SMITH, Elizabeth, M. ,  BENNETT, Chad, E. ,  HARRIS, Joel, M. ,  KISELGOF, Eugenia, Y. ,  KNUTSON, Chad, E. ,  KORAKAS, Peter ,  TULSHIAN, Deen ,  KIM, Hyunjin

IPC: C07D471/08 ,  A61K31/438 ,  A61P3/00

CPC classification number: C07D471/08

Abstract: Disclosed are compounds of the formula (I): and compounds of the formula (IIA): wherein R 1 , R 2 , R 3 , R 4 , R 5 , u and v are as defined herein. These compounds can be used in methods of treating pain (e.g., inflammatory pain, chronic pain, and neuropathic pain), methods of treating diabetes, and methods of inhibiting the absorption of cholesterol.

Abstract translation: 公开了式（I）的化合物：和式（IIA）的化合物：其中R 1，R 2，R 3， R 4，R 5，u和v如本文所定义。 这些化合物可以用于治疗疼痛（例如炎性疼痛，慢性疼痛和神经性疼痛）的方法，治疗糖尿病的方法和抑制胆固醇吸收的方法。

公开(公告)号：WO2007032854A1

公开(公告)日：2007-03-22

申请号：PCT/US2006/031944

申请日：2006-08-16

Applicant: SCHERING CORPORATION ,  BENNETT, Chad, E. ,  GREENLEE, William, J. ,  KNUTSON, Chad, E. ,  BURNETT, Duane, A.

Inventor： BENNETT, Chad, E. ,  GREENLEE, William, J. ,  KNUTSON, Chad, E. ,  BURNETT, Duane, A.

IPC: C07D495/14 ,  A61P25/00 ,  A61P13/00 ,  A61P25/06 ,  A61P25/22 ,  A61P25/04

CPC classification number: C07D487/22 ,  C07D495/14

Abstract: In its many embodiments, the present invention provides tricyclic compounds of formula (I) (wherein J 1 -J 3 , X, Z, and R 1 , R 3 , and R 4 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.

Abstract translation: 在其许多实施方案中，本发明提供式（I）的三环化合物（其中J 1，X 3，X 3，Z 1和R 1） 可用作代谢型谷氨酸受体（mGluR）拮抗剂，特别是作为选择性代谢型谷氨酸受体1拮抗剂的药物组合物，其包含用于作为代谢型谷氨酸受体（mGluR）拮抗剂的组合物，其中R 3，R 3和R 4如本文所定义） 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：WO2007024593A1

公开(公告)日：2007-03-01

申请号：PCT/US2006/031972

申请日：2006-08-16

Applicant: SCHERING CORPORATION ,  BENNETT, Chad, E. ,  WU, Wen-Lian ,  BURNETT, Duane, A.

Inventor： BENNETT, Chad, E. ,  WU, Wen-Lian ,  BURNETT, Duane, A.

IPC: C07D495/14 ,  A61K31/519 ,  A61P25/00

CPC classification number: C07D495/14 ,  C07D471/14 ,  C07D487/14

Abstract: In its many embodiments, the present invention provides tricyclic compounds of formula I (wherein J 1 -J 3 , X, Z, and R 1 -R 4 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., mGluRI ) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimer's disease.

Abstract translation: 在其许多实施方案中，本发明提供式I的三环化合物（其中J 1，X 3，X，Z和R 1） 可用作代谢型谷氨酸受体（mGluR）拮抗剂，特别是作为选择性代谢型谷氨酸受体1拮抗剂的药物组合物，以及使用该化合物和组合物的治疗方法 治疗与代谢型谷氨酸受体（例如，mGluRI）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氏病。

公开(公告)号：WO2012118945A2

公开(公告)日：2012-09-07

申请号：PCT/US2012/027237

申请日：2012-03-01

Applicant: MERCK SHARP & DOHME CORP. ,  BENNETT, Chad E. ,  BURNETT, Duane A. ,  LI, HongmeI ,  CHEN, Yonggang ,  MCCRACKEN, Troy ,  VICAREL, Monica

Inventor： BENNETT, Chad E. ,  BURNETT, Duane A. ,  LI, HongmeI ,  CHEN, Yonggang ,  MCCRACKEN, Troy ,  VICAREL, Monica

IPC: A61K31/519 ,  C07D487/04

CPC classification number: C07D487/04 ,  A61K31/155 ,  A61K31/427 ,  A61K31/519 ,  A61K31/522 ,  A61K31/64 ,  A61K45/06 ,  C07D473/18 ,  C07D473/28 ,  A61K2300/00

Abstract: The present invention is directed to novel bicyclic 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.

Abstract translation: 本发明涉及结构式（I）的新型双环杂环，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：WO2010056849A1

公开(公告)日：2010-05-20

申请号：PCT/US2009/064190

申请日：2009-11-12

Applicant: SCHERING CORPORATION ,  ZHU, Zhaoning ,  GREENLEE, William J. ,  HUANG, Xianhai ,  QIN, Jun ,  LIU, Xiaoxiang ,  LI, Hongmei ,  ZHOU, Wei ,  PALANI, Anandan ,  ZHU, Xiaohong ,  VICAREL, Monica L. ,  MANDAL, Mihirbaran ,  SUN, Zhong-Yue ,  BENNETT, Chad E. ,  MCCRACKEN, Troy M. ,  GALLO, Gioconda

Inventor： ZHU, Zhaoning ,  GREENLEE, William J. ,  HUANG, Xianhai ,  QIN, Jun ,  LIU, Xiaoxiang ,  LI, Hongmei ,  ZHOU, Wei ,  PALANI, Anandan ,  ZHU, Xiaohong ,  VICAREL, Monica L. ,  MANDAL, Mihirbaran ,  SUN, Zhong-Yue ,  BENNETT, Chad E. ,  MCCRACKEN, Troy M. ,  GALLO, Gioconda

IPC: C07D471/04 ,  C07D498/04 ,  A61K31/5395 ,  A61P25/28

CPC classification number: C07D471/04 ,  C07D498/04

Abstract: In its many embodiments, the present invention provides a novel class of heterocyclic compounds of Group A or Group, as defined herein, as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Abstract translation: 在其许多实施方案中，本发明提供了一类新颖的本文所定义的组A或组的杂环化合物作为γ-分泌酶的调节剂，制备此类化合物的方法，含有一种或多种此类化合物的药物组合物，制备药物的方法 包含一种或多种这样的化合物的制剂，以及使用这些化合物或药物组合物治疗，预防，抑制或改善与中枢神经系统相关的一种或多种疾病的方法。

公开(公告)号：WO2009045314A1

公开(公告)日：2009-04-09

申请号：PCT/US2008/011112

申请日：2008-09-25

Applicant: SCHERING CORPORATION ,  ZHU, Zhaoning ,  GREENLEE, William, J. ,  CALDWELL, John, P. ,  MAZZOLA, JR., Robert, D. ,  MCKITTRICK, Brian ,  BENNETT, Chad, E. ,  BURNETT, Duane, A.

Inventor： ZHU, Zhaoning ,  GREENLEE, William, J. ,  CALDWELL, John, P. ,  MAZZOLA, JR., Robert, D. ,  MCKITTRICK, Brian ,  BENNETT, Chad, E. ,  BURNETT, Duane, A.

IPC: C07D233/76 ,  C07D233/86 ,  C07D233/88 ,  C07D403/04 ,  A61K31/4178 ,  A61P25/28

CPC classification number: C07D233/86 ,  C07D233/76 ,  C07D233/88 ,  C07D403/04

Abstract: In its many embodiments, the present invention provides a novel class of 5-membered, nitrogen-containing heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Abstract translation: 在其许多实施方案中，本发明提供了一类新颖的5元含氮杂环化合物作为γ-分泌酶的调节剂，制备这种化合物的方法，含有一种或多种这类化合物的药物组合物，制备药物制剂的方法，包括一种 或更多这样的化合物，以及使用这些化合物或药物组合物治疗，预防，抑制或改善与中枢神经系统相关的一种或多种疾病的方法。

公开(公告)号：WO2008033464A3

公开(公告)日：2008-05-15

申请号：PCT/US2007019930

申请日：2007-09-13

Applicant: SCHERING CORP ,  ASLANIAN ROBERT G ,  BENNETT CHAD E ,  BURNETT DUANE A ,  CHAN TIN-YAU ,  KISELGOF EUGENIA Y ,  KNUTSON CHAD E ,  HARRIS JOEL M ,  MC KITTRICK BRIAN A ,  PALANI ANANDAN ,  SMITH ELIZABETH M ,  VACCARO HENRY M ,  XIAO DONG ,  KIM HYUNJIN M

Inventor： ASLANIAN ROBERT G ,  BENNETT CHAD E ,  BURNETT DUANE A ,  CHAN TIN-YAU ,  KISELGOF EUGENIA Y ,  KNUTSON CHAD E ,  HARRIS JOEL M ,  MC KITTRICK BRIAN A ,  PALANI ANANDAN ,  SMITH ELIZABETH M ,  VACCARO HENRY M ,  XIAO DONG ,  KIM HYUNJIN M

IPC: C07D471/10 ,  A61K31/438 ,  A61P3/00

CPC classification number: C07D471/10

Abstract: The present invention relates to Azetidinone Derivatives, compositions comprising an Azetidinone Derivative and methods for treating or preventing a disorder of lipid metabolism, pain, diabetes, a vascular condition, demyelination or nonalcoholic fatty liver disease, comprising administering to a patient an effective amount of an Azetidinone Derivative.

Abstract translation: 本发明涉及氮杂环丁酮衍生物，包含氮杂环丁酮衍生物的组合物和用于治疗或预防脂质代谢紊乱，疼痛，糖尿病，血管病症，脱髓鞘或非酒精性脂肪性肝病的方法，包括向患者施用有效量的 氮杂环丁酮衍生物。

公开(公告)号：WO2007084595A3

公开(公告)日：2007-09-07

申请号：PCT/US2007001302

申请日：2007-01-18

Applicant: SCHERING CORP ,  ASBEROM THEODROS ,  BARA THOMAS ,  BENNETT CHAD E ,  BURNETT DUANE A ,  CAPLEN MARY ANN ,  CLADER JOHN W ,  COLE DAVID J ,  DOMALSKI MARTIN S ,  JOSIEN HUBERT B ,  KNUTSON CHAD E ,  LI HONGMEI ,  MCBRIAR MARK D ,  PISSARNITSKI DMITRI A ,  QIANG LI ,  RAJAGOPALAN MURALI ,  SASIKUMAR THAVALAKULAMGAR K ,  SU JING ,  TANG HAIQUN ,  WU WEN-LIAN ,  XU RUO ,  ZHAO ZHIQIANG

Inventor： ASBEROM THEODROS ,  BARA THOMAS ,  BENNETT CHAD E ,  BURNETT DUANE A ,  CAPLEN MARY ANN ,  CLADER JOHN W ,  COLE DAVID J ,  DOMALSKI MARTIN S ,  JOSIEN HUBERT B ,  KNUTSON CHAD E ,  LI HONGMEI ,  MCBRIAR MARK D ,  PISSARNITSKI DMITRI A ,  QIANG LI ,  RAJAGOPALAN MURALI ,  SASIKUMAR THAVALAKULAMGAR K ,  SU JING ,  TANG HAIQUN ,  WU WEN-LIAN ,  XU RUO ,  ZHAO ZHIQIANG

IPC: C07D311/22 ,  C07D311/80 ,  C07D311/92 ,  C07D311/94 ,  C07D313/08 ,  C07D335/06

CPC classification number: 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

Abstract: This invention discloses novel gamma secretase inhibitors of the formula: R 2 and R 3 , or R 2 and R 4 , or R 3 and R 4 , 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 substituents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

Abstract translation: 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以及它们所结合的原子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。