公开(公告)号：US09493440B2

公开(公告)日：2016-11-15

申请号：US14772295

申请日：2014-02-27

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael Miller ,  Kallol Basu ,  Duane DeMong ,  Jack Scott ,  Wei Li ,  Andrew Stamford ,  Marc Poirer ,  Paul Tempest

IPC: C07D403/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D403/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/107 ,  C07D498/04 ,  C07D498/08 ,  C07D498/10

CPC classification number: C07D403/04 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/107 ,  C07D498/04 ,  C07D498/08 ,  C07D498/10

Abstract: The present invention is directed to indazole compounds 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. 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：US11584724B2

公开(公告)日：2023-02-21

申请号：US17048833

申请日：2019-04-18

Applicant: Merck Sharp & Dohme Corp. ,  Werthenstein BioPharma GmbH

Inventor： Kevin M. Maloney ,  Kallol Basu ,  Michael James Di Maso ,  Guy R. Humphrey ,  Alfred Y. Lee ,  Feng Peng ,  Hong Ren ,  Siwei Zhang

IPC: C07D239/48 ,  C07C41/09 ,  C07C41/30 ,  C07C253/30 ,  C07D487/18

Abstract: Disclosed herein is a novel process for preparing Compound A free base, 5-((2,4-diaminopyrimidin-5-yl)oxy)-4-iso-propyl-2-methoxybenzenesulfonamide, and a citrate salt of Compound A with simplified chemistry and a high overall yield: Compound A. In one embodiment, the overall yield from the starting material 2-isopropylphenol to Compound A citrate salt is greater than 50%. In another embodiment, the overall yield is greater than 60%. Also disclosed herein are novel salts and solvates of Compound A.

公开(公告)号：US20160009696A1

公开(公告)日：2016-01-14

申请号：US14772290

申请日：2014-02-27

Applicant: Michael MILLER ,  Kallol BASU ,  Duane DEMONG ,  Jack SCOTT ,  Wei LI ,  Joel HARRIS ,  Andrew STAMFORD ,  Marc POIRIER ,  Paul TEMPEST ,  MERCK SHARP & DOHME CORP.

Inventor： Michael Miller ,  Kallol Basu ,  Duane DeMong ,  Jack Scott ,  Wei Li ,  Joel Harris ,  Andrew Stamford ,  Marc Poirier ,  Paul Tempest

IPC: C07D403/14 ,  C07D401/14 ,  C07D491/107 ,  C07D417/14 ,  C07D471/10 ,  C07D413/14 ,  C07D498/08

CPC classification number: C07D403/14 ,  A61K31/505 ,  A61K31/506 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/10 ,  C07D491/107 ,  C07D498/08

Abstract: The present invention is directed to indazole compounds 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. 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：US20180230152A1

公开(公告)日：2018-08-16

申请号：US15507577

申请日：2015-08-28

Applicant: Merck Sharp & Dohme Corp.

Inventor： Xing Dai ,  Kallol Basu ,  Duane DeMong ,  Sarah W. Li ,  Michael Miller ,  Jack D. Scott ,  Andrew W. Stamford

IPC: C07D487/04 ,  C07D413/14 ,  C07D403/14 ,  C07D401/14 ,  A61P25/16

CPC classification number: C07D487/04 ,  A61P25/16 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/14

Abstract: The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R9, and A 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. 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：US09440952B2

公开(公告)日：2016-09-13

申请号：US14772589

申请日：2014-02-27

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael Miller ,  Kallol Basu ,  Duane DeMong ,  Jack Scott ,  Hong Liu ,  Xing Dai ,  Joel M. Harris ,  Bernard Neustadt ,  Andrew Stamford ,  Marc Poirier ,  John A. McCauley ,  Thomas Greshock ,  Heather Stevenson ,  John Sanders ,  Jonathan Kern

IPC: C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/10 ,  C07D451/02 ,  C07D487/10 ,  C07D491/04 ,  C07D491/08 ,  C07D491/056 ,  C07D498/04 ,  C07D498/08 ,  C07D403/04 ,  C07D491/10 ,  C07D487/04 ,  C07D491/107 ,  C07D491/113

CPC classification number: C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D451/02 ,  C07D471/10 ,  C07D487/04 ,  C07D487/10 ,  C07D491/04 ,  C07D491/056 ,  C07D491/08 ,  C07D491/10 ,  C07D491/107 ,  C07D491/113 ,  C07D498/04 ,  C07D498/08

Abstract: The present invention is directed to indazole compounds 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. 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：US09416126B2

公开(公告)日：2016-08-16

申请号：US14772290

申请日：2014-02-27

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael Miller ,  Kallol Basu ,  Duane DeMong ,  Jack Scott ,  Wei Li ,  Joel Harris ,  Andrew Stamford ,  Marc Poirier ,  Paul Tempest

IPC: A61K31/505 ,  C07D403/14 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D409/14 ,  C07D417/14 ,  A61K31/506 ,  C07D471/10 ,  C07D491/107 ,  C07D498/08 ,  C07D403/04

CPC classification number: C07D403/14 ,  A61K31/505 ,  A61K31/506 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/10 ,  C07D491/107 ,  C07D498/08

Abstract: The present invention is directed to indazole compounds 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. 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.

Abstract translation: 本发明涉及作为LRRK2激酶的有效抑制剂的吲唑化合物，可用于治疗或预防其中涉及LRRK2激酶的疾病，例如帕金森病。 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LRRK-2激酶的疾病中的用途。

公开(公告)号：US20160009681A1

公开(公告)日：2016-01-14

申请号：US14772525

申请日：2014-02-27

Applicant: Michael MILLER ,  Kallol BASU ,  Duane MONG ,  Jack SCOTT ,  Hong LIU ,  Xing DAI ,  Andrew STAMFORD ,  Marc POIRIER ,  Paul TEMPEST ,  MERCK SHARP & DOHME CORP.

Inventor： Michael Miller ,  Kallol Basu ,  Duane DeMong ,  Jack Scott ,  Hong Liu ,  Xing Dai ,  Andrew Stamford ,  Marc Poirier ,  Paul Tempest

IPC: C07D401/04 ,  C07D498/08 ,  C07D401/14 ,  C07D495/08 ,  C07D498/04 ,  C07D487/04 ,  C07D413/14 ,  C07D405/14 ,  C07D417/14

CPC classification number: C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D491/08 ,  C07D495/08 ,  C07D498/04 ,  C07D498/08

Abstract: The present invention is directed to indazole compounds 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. 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 LRRK2 kinase is involved.

Abstract translation: 本发明涉及作为LRRK2激酶的有效抑制剂的吲唑化合物，可用于治疗或预防其中涉及LRRK2激酶的疾病，例如帕金森病。 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LRRK2激酶的疾病中的用途。

公开(公告)号：US09718818B2

公开(公告)日：2017-08-01

申请号：US14912761

申请日：2014-08-18

Applicant: MERCK SHARP & DOHME CORP. ,  Duane DeMong ,  Thomas J. Greshock ,  Ronald K. Chang ,  Xing Dai ,  Hong Liu ,  John A. McCauley ,  Wei Li ,  Kallol Basu ,  Jack D. Scott ,  Michael Miller

Inventor： Duane DeMong ,  Thomas J. Greshock ,  Ronald K. Chang ,  Xing Dai ,  Hong Liu ,  John A. McCauley ,  Wei Li ,  Kallol Basu ,  Jack D. Scott ,  Michael Miller

IPC: A61K31/44 ,  C07D471/04 ,  C07D498/04 ,  C07D519/00 ,  C07D487/04

CPC classification number: C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00

Abstract: The present invention is directed to azaindazole compounds 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. 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：US09688654B2

公开(公告)日：2017-06-27

申请号：US14772525

申请日：2014-02-27

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael Miller ,  Kallol Basu ,  Duane DeMong ,  Jack Scott ,  Hong Liu ,  Xing Dai ,  Andrew Stamford ,  Marc Poirier ,  Paul Tempest

IPC: C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D491/08 ,  C07D495/08 ,  C07D498/04 ,  C07D498/08

CPC classification number: C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D491/08 ,  C07D495/08 ,  C07D498/04 ,  C07D498/08

Abstract: The present invention is directed to indazole compounds 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. 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 LRRK2 kinase is involved.

公开(公告)号：US09422266B2

公开(公告)日：2016-08-23

申请号：US14347268

申请日：2012-09-24

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael W. Miller ,  Andrew W. Stamford ,  Kallol Basu ,  Scott Edmondson ,  Zhiqiang Guo ,  William B. Geiss

IPC: C07D401/12 ,  C07D401/14 ,  C07D211/96

CPC classification number: C07D401/12 ,  C07D211/96 ,  C07D401/14

Abstract: Substituted cyclopropyl compounds of the formula I and the pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the g-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included. Another aspect of the invention that is of interest relates to compounds of formula 1a.

Abstract translation: 公开了取代的式I的环丙基化合物及其药学上可接受的盐，用于治疗或预防2型糖尿病和类似病状。 该化合物可用作g-蛋白偶联受体GPR-119的激动剂。 还包括药物组合物和治疗方法。 感兴趣的本发明的另一方面涉及式1a的化合物。