公开(公告)号：US20200069671A1

公开(公告)日：2020-03-05

申请号：US16674546

申请日：2019-11-05

Applicant: Merck Sharp & Dohme Corp.

Inventor： John J. Acton, III ,  Jianming Bao ,  Melissa Egbertson ,  Xiaolei Gao ,  Scott T. Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, JR. ,  Zhaoyang Meng ,  Michael T. Rudd ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Jenny Miu-Chun Wai

IPC: A61K31/4439 ,  A61P25/28 ,  A61P25/18 ,  A61P25/16 ,  A61K31/437 ,  C07D401/14 ,  C07D405/14 ,  C07D471/04

Abstract: The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors 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 diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US20150105354A1

公开(公告)日：2015-04-16

申请号：US14575418

申请日：2014-12-18

Applicant: Merck Sharp & Dohme Corp. ,  Pharmacopeia, LLC

Inventor： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voigt ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, JR. ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X.H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter

IPC: C07D233/88 ,  C07D401/04 ,  A61K31/4439 ,  C07D405/06 ,  A61K31/4178 ,  C07D401/06 ,  A61K31/454 ,  C07D407/06 ,  C07D403/06 ,  A61K31/5377 ,  C07D235/02 ,  A61K31/4184 ,  A61K31/655 ,  C07D405/14 ,  C07D401/14 ,  A61K31/4545 ,  A61K31/4725 ,  A61K45/06 ,  A61K31/4168

CPC classification number: C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/655 ,  A61K45/06 ,  C07D233/46 ,  C07D233/70 ,  C07D235/02 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D295/15 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D407/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  Y02A50/411

Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes.Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.