公开(公告)号：WO2019074810A1

公开(公告)日：2019-04-18

申请号：PCT/US2018/054790

申请日：2018-10-08

Applicant: MERCK SHARP & DOHME CORP. ,  ACTON, John ,  CANDITO, David Annunziato ,  ELLIS, J. Michael ,  FULLER, Peter, H. ,  GUNAYDIN, Hakan ,  LAPOINTE, Blair, T. ,  LIU, Weiguo ,  METHOT, Joey, L. ,  NEELAMKAVIL, Santhosh, F. ,  PIO, Barbara ,  SIMOV, Vladimir ,  WOOD, Harold, B.

Inventor： ACTON, John ,  CANDITO, David Annunziato ,  ELLIS, J. Michael ,  FULLER, Peter, H. ,  GUNAYDIN, Hakan ,  LAPOINTE, Blair, T. ,  LIU, Weiguo ,  METHOT, Joey, L. ,  NEELAMKAVIL, Santhosh, F. ,  PIO, Barbara ,  SIMOV, Vladimir ,  WOOD, Harold, B.

IPC: A01N43/42 ,  C07D487/04

CPC classification number: C07D401/14 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/5386 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D498/04 ,  C07D498/10

Abstract: The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R 1A , R 1B , X, Y, R Z and R 2 are as defined herein, which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. 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 LRRK-2 kinase is involved.

公开(公告)号：WO2019074809A1

公开(公告)日：2019-04-18

申请号：PCT/US2018/054789

申请日：2018-10-08

Applicant: MERCK SHARP & DOHME CORP. ,  CANDITO, David Annunziato ,  GRAHAM, Thomas, H. ,  ACTON, John ,  CHAU, Ryan Wing-Kun ,  CHEN, Joanna, L. ,  ELLIS, J. Michael ,  FULLER, Peter, H. ,  GULATI, Anmol ,  GUNAYDIN, Hakan ,  KATTAR, Solomon ,  KEYLOR, Mitchell Henry ,  LAPOINTE, Blair, T. ,  LIU, Ping ,  LIU, Weiguo ,  METHOT, Joey, L. ,  NEELAMKAVIL, Santhosh, F. ,  SIMOV, Vladimir ,  TONG, Ling ,  WOOD, Harold, B.

Inventor： CANDITO, David Annunziato ,  GRAHAM, Thomas, H. ,  ACTON, John ,  CHAU, Ryan Wing-Kun ,  CHEN, Joanna, L. ,  ELLIS, J. Michael ,  FULLER, Peter, H. ,  GULATI, Anmol ,  GUNAYDIN, Hakan ,  KATTAR, Solomon ,  KEYLOR, Mitchell Henry ,  LAPOINTE, Blair, T. ,  LIU, Ping ,  LIU, Weiguo ,  METHOT, Joey, L. ,  NEELAMKAVIL, Santhosh, F. ,  SIMOV, Vladimir ,  TONG, Ling ,  WOOD, Harold, B.

IPC: A01N43/42 ,  C07D487/04

CPC classification number: C07D403/14 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D413/14 ,  C07D487/08 ,  C07D487/10 ,  C07D491/10 ,  C07D498/04 ,  C07D498/10

Abstract: The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. 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 LRRK-2 kinase is involved.

公开(公告)号：WO2022197577A1

公开(公告)日：2022-09-22

申请号：PCT/US2022/020110

申请日：2022-03-14

Applicant: MERCK SHARP & DOHME LLC ,  CHILDERS, Kaleen Konrad ,  ELLIS, J. Michael ,  FULLER, Peter, J. ,  GUNAYDIN, Hakan ,  SCOTT, Jack, D. ,  TANG, Haiqun ,  YEUNG, Charles, S.

Inventor： CHILDERS, Kaleen Konrad ,  ELLIS, J. Michael ,  FULLER, Peter, J. ,  GUNAYDIN, Hakan ,  SCOTT, Jack, D. ,  TANG, Haiqun ,  YEUNG, Charles, S.

IPC: A61K31/415 ,  A61K31/4155 ,  A61K31/427 ,  C07D231/10 ,  C07D231/12 ,  C07D231/14

Abstract: The present invention is directed to certain (hetero)aroyl 4-aminopyrazole derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, R1, R2, and R3 are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. 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 LRRK-2 kinase is involved.

公开(公告)号：WO2022197575A1

公开(公告)日：2022-09-22

申请号：PCT/US2022/020108

申请日：2022-03-14

Applicant: MERCK SHARP & DOHME LLC ,  CHILDERS, Kaleen Konrad ,  ELLIS, J. Michael ,  FULLER, Peter, H. ,  GULATI, Anmol ,  GUNAYDIN, Hakan ,  KATTAR, Solomon, D. ,  KURUKULASURIYA, Ravi ,  METHOT, Joey, L. ,  MORRIELLO, Gregori, J. ,  NEELAMKAVIL, Santhosh ,  LAPOINTE, Blair, T. ,  SIMOV, Vladimir ,  YEUNG, Charles, S.

Inventor： CHILDERS, Kaleen Konrad ,  ELLIS, J. Michael ,  FULLER, Peter, H. ,  GULATI, Anmol ,  GUNAYDIN, Hakan ,  KATTAR, Solomon, D. ,  KURUKULASURIYA, Ravi ,  METHOT, Joey, L. ,  MORRIELLO, Gregori, J. ,  NEELAMKAVIL, Santhosh ,  LAPOINTE, Blair, T. ,  SIMOV, Vladimir ,  YEUNG, Charles, S.

IPC: A61K31/166 ,  A61K31/167 ,  A61K31/4155 ,  C07D231/12 ,  C07D401/00 ,  C07D401/14

Abstract: The present invention is directed to certain 2-aminoquinzaoline derivatives of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, R1, R2, and R3 are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. 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 LRRK-2 kinase is involved.

公开(公告)号：WO2016089830A1

公开(公告)日：2016-06-09

申请号：PCT/US2015/063127

申请日：2015-12-01

Applicant: MERCK SHARP & DOHME CORP. ,  FISCHER, Christian ,  BOGEN, Stephane, L. ,  CHILDERS, Matthew, L. ,  LLINAS, Francesc Xavier Fradera ,  ELLIS, J. Michael ,  ESPOSITE, Sara ,  HOFFMAN, Dawn, M. ,  HUANG, Chunhui ,  KATTAR, Solomon ,  KIM, Alexander, J. ,  LAMPE, John, W. ,  MACHACEK, Michelle, R. ,  MCMASTERS, Daniel, R. ,  PARKER, Dann, L., Jr. ,  REUTERSHAN, Michael ,  SCIAMMETTA, Nunzio ,  SHAO, Pengcheng, P. ,  SLOMAN, David, L. ,  SUN, Wanying ,  UJJAINWALLA, Feroze ,  WU, Zhicai ,  YU, Yang ,  GIBEAU, Craig

Inventor： FISCHER, Christian ,  BOGEN, Stephane, L. ,  CHILDERS, Matthew, L. ,  LLINAS, Francesc Xavier Fradera ,  ELLIS, J. Michael ,  ESPOSITE, Sara ,  HOFFMAN, Dawn, M. ,  HUANG, Chunhui ,  KATTAR, Solomon ,  KIM, Alexander, J. ,  LAMPE, John, W. ,  MACHACEK, Michelle, R. ,  MCMASTERS, Daniel, R. ,  PARKER, Dann, L., Jr. ,  REUTERSHAN, Michael ,  SCIAMMETTA, Nunzio ,  SHAO, Pengcheng, P. ,  SLOMAN, David, L. ,  SUN, Wanying ,  UJJAINWALLA, Feroze ,  WU, Zhicai ,  GIBEAU, Craig

IPC: A01N43/00

CPC classification number: C07D471/04 ,  C07D471/14 ,  C07D519/00

Abstract: The present invention is directed to tricyclic compounds of formula (I) which are inhibitors of one or more mutant IDH enzymes (I); wherein A is -C(R 1 )= or -N=; and X is selected from the group consisting of: (II-i), and (II-ii). The present invention is also directed to uses of the tricyclic compounds described herein in the potential treatment or prevention of cancers in which one or more mutant IDH enzymes are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such cancers.

Abstract translation: 本发明涉及作为一种或多种突变体IDH酶（I）的抑制剂的式（I）的三环化合物; 其中A是-C（R 1）=或-N =; 并且X选自：（II-i）和（II-ii）。 本发明还涉及本文所述的三环化合物在潜在的治疗或预防涉及一种或多种突变体IDH酶的癌症中的用途。 本发明还涉及包含这些化合物的组合物。 本发明还涉及这些组合物在这种癌症的潜在预防或治疗中的用途。

公开(公告)号：WO2016089797A1

公开(公告)日：2016-06-09

申请号：PCT/US2015/063061

申请日：2015-12-01

Applicant: MERCK SHARP & DOHME CORP. ,  FISCHER, Christian ,  BOGEN, Stephane, L. ,  CHILDERS, Matthew, L. ,  LLINAS, Francesc Xavier Fradera ,  ELLIS, J. Michael ,  ESPOSITE, Sara ,  HONG, Qingmei ,  HUANG, Chunhui ,  KIM, Alexander, J. ,  LAMPE, John, W. ,  MACHACEK, Michelle, R. ,  MCMASTERS, Daniel, R. ,  OTTE, Ryan, D. ,  PARKER, Dann, L., Jr. ,  REUTERSHAN, Michael ,  SCIAMMETTA, Nunzio ,  SHAO, Pengcheng, P. ,  SLOMAN, David, L. ,  UJJAINWALLA, Feroze ,  WHITE, Catherine ,  WU, Zhicai ,  YU, Yang ,  ZHAO, Kake ,  GIBEAU, Craig ,  BIFTU, Tesfaye ,  BIJU, Purakkattle ,  CHEN, Lei ,  CLOSE, Joshua ,  FULLER, Peter, H. ,  HUANG, Xianhai ,  PARK, Min, K. ,  SIMOV, Vladimir ,  WITTER, David, J. ,  ZHANG, Hongjun

Inventor： FISCHER, Christian ,  BOGEN, Stephane, L. ,  CHILDERS, Matthew, L. ,  LLINAS, Francesc Xavier Fradera ,  ELLIS, J. Michael ,  ESPOSITE, Sara ,  HONG, Qingmei ,  HUANG, Chunhui ,  KIM, Alexander, J. ,  LAMPE, John, W. ,  MACHACEK, Michelle, R. ,  MCMASTERS, Daniel, R. ,  OTTE, Ryan, D. ,  PARKER, Dann, L., Jr. ,  REUTERSHAN, Michael ,  SCIAMMETTA, Nunzio ,  SHAO, Pengcheng, P. ,  SLOMAN, David, L. ,  UJJAINWALLA, Feroze ,  WHITE, Catherine ,  WU, Zhicai ,  ZHAO, Kake ,  GIBEAU, Craig ,  BIFTU, Tesfaye ,  BIJU, Purakkattle ,  CHEN, Lei ,  CLOSE, Joshua ,  FULLER, Peter, H. ,  HUANG, Xianhai ,  PARK, Min, K. ,  SIMOV, Vladimir ,  WITTER, David, J. ,  ZHANG, Hongjun

IPC: A01N43/00

CPC classification number: C07D498/08 ,  A01N43/00 ,  C07D471/04 ,  C07D471/08 ,  C07D498/04 ,  C07D498/10

Abstract: The present invention is directed to tricyclic compounds of formula (I) which are inhibitors of one or more mutant IDH enzymes: (I). The present invention is also directed to uses of the tricyclic compounds described herein in the potential treatment or prevention of cancers in which one or more mutant IDH enzymes are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such cancers.

Abstract translation: 本发明涉及作为一种或多种突变体IDH酶的抑制剂的式（I）的三环化合物：（I）。 本发明还涉及本文所述的三环化合物在潜在的治疗或预防涉及一种或多种突变体IDH酶的癌症中的用途。 本发明还涉及包含这些化合物的组合物。 本发明还涉及这些组合物在这种癌症的潜在预防或治疗中的用途。