公开(公告)号：US20190218223A1

公开(公告)日：2019-07-18

申请号：US16324596

申请日：2017-08-10

Applicant: Jared N. CUMMING ,  Kevin D. DYKSTRA ,  Alan HRUZA ,  Derun LI ,  Hong LIU ,  Haiqun TANG ,  Brandon M. TAOKA ,  Andreas VERRAS ,  Shawn P. WALSH ,  Wen-Lian WU ,  Merck Sharp & Dohme Corp.

Inventor： Jared N. Cumming ,  Kevin D. Dykstra ,  Alan Hruza ,  Derun Li ,  Hong Liu ,  Haiqun Tang ,  Brandon M. Taoka ,  Andreas Verras ,  Shawn P. Walsh ,  Wen-Lian Wu

IPC: C07D487/04 ,  C07D519/00 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  A61P3/10

CPC classification number: C07D487/04 ,  A61P3/10 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07D519/00

Abstract: Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula I act as Cyp8b1 inhibitors and can be useful in preventing, treating or acting as a remedial agent for diabetes and cardiovascular disease.

公开(公告)号：US10238743B2

公开(公告)日：2019-03-26

申请号：US15516076

申请日：2015-09-28

Applicant: Merck Sharp & Dohme Corp. ,  Shuwen He ,  Jared N. Cumming ,  Jack D. Scott

Inventor： Shuwen He ,  Jared N. Cumming ,  Jack D. Scott

IPC: A61K45/06 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04 ,  C07D519/00 ,  A61K31/54 ,  A61K31/549 ,  C07D519/06

Abstract: In its many embodiments, the present invention provides certain C5-C6 fused tricyclic iminothiadiazine compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R2, R3, RA, ring A, RA, m, -L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

公开(公告)号：US20180230178A1

公开(公告)日：2018-08-16

申请号：US15752144

申请日：2016-08-11

Applicant: Michael D. ALTMAN ,  Brian ANDRESEN ,  Wonsuk CHANG ,  Matthew Lloyd CHILDERS ,  Jared N. CUMMING ,  Andrew Marc HAIDLE ,  Timothy J. HENDERSON ,  James P. JEWELL ,  Min LU ,  Alan B. NORTHRUP ,  Ryan D. OTTE ,  Tony SIU ,  Benjamin Wesley TROTTER ,  Quang T TRUONG ,  Merck Sharp & Dohme Corp.

Inventor： Michael D. Altman ,  Brian Andresen ,  Wonsuk Chang ,  Matthew Lloyd Childers ,  Jared N. Cumming ,  Andrew Marc Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Min Lu ,  Alan B. Northrup ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Quang T. Truong

IPC: C07H21/04 ,  C07H21/02 ,  C07H19/23 ,  C07H19/20 ,  A61P35/00

Abstract: A class of polycyclic compounds of general formula (II), of general formula (II′), or of general formula (II″), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3a, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

公开(公告)号：US20160016975A1

公开(公告)日：2016-01-21

申请号：US14774204

申请日：2014-03-11

Applicant: Eric J. GILBERT ,  Jared N. CUMMING ,  Jack D. SCOTT ,  Wen-Lian WU ,  Duane A. BURNETT ,  Andrew W. STAMFORD ,  MERCK SHARP & DOHME CORP.

Inventor： Eric J. Gilbert ,  Jared N. Cumming ,  Jack D. Scott ,  Wen-Lian Wu ,  Duane A. Burnett ,  Andrew W. Stamford

IPC: C07D513/10

CPC classification number: C07D513/10

Abstract: In its many embodiments, the present invention provides certain C2-azaspiro substituted iminothiazine dioxide compounds. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供某些C2-氮杂螺环取代的亚氨基噻嗪二氧化物化合物。 本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与其相关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和使用方法，包括用于治疗阿尔茨海默氏病的药物组合物。

公开(公告)号：US09221839B2

公开(公告)日：2015-12-29

申请号：US14009883

申请日：2012-04-04

Applicant: Jared N. Cumming ,  Eric J. Gilbert ,  Andrew W. Stamford

Inventor： Jared N. Cumming ,  Eric J. Gilbert ,  Andrew W. Stamford

IPC: C07D513/04 ,  A61K31/549 ,  A61K31/54 ,  A61K45/06

CPC classification number: C07D513/04 ,  A61K31/54 ,  A61K31/549 ,  A61K45/06 ,  A61K2300/00

Abstract: In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein each of ring A, ring B, ring C, R2, R3, R4, m, n, p, and -L1- is as defined herein. The novel compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了某些亚氨基二嗪二氧化物化合物，包括其化学式及互变异构体及其立体异构体，以及所述化合物，所述互变异构体和所述立体异构体的药学上可接受的盐，其中环A，环B，环C， ，R3，R4，m，n，p和-L1-如本文所定义。 本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与其相关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和使用方法，包括阿尔茨海默氏病。

公开(公告)号：US20140296222A1

公开(公告)日：2014-10-02

申请号：US14221644

申请日：2014-03-21

Applicant: Jack D. Scott ,  Andrew W. Stamford ,  Eric J. Gilbert ,  Jared N. Cumming ,  Ulrich Iserloh

Inventor： Jack D. Scott ,  Andrew W. Stamford ,  Eric J. Gilbert ,  Jared N. Cumming ,  Ulrich Iserloh

IPC: C07D417/12 ,  C07C309/30

CPC classification number: A61K31/549 ,  A61K31/00 ,  A61K31/495 ,  A61K31/54 ,  A61K45/06 ,  C07C309/30 ,  C07D213/26 ,  C07D213/89 ,  C07D239/14 ,  C07D285/18 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D417/04 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  A61K2300/00

Abstract: In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, -L2-, and -L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (“Aβ”) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's disease, are also disclosed.

公开(公告)号：US08778980B2

公开(公告)日：2014-07-15

申请号：US13551315

申请日：2012-07-17

Applicant: Zhaoning Zhu ,  Brian A McKittrick ,  Zhong-Yue Sun ,  Yuanzan C Ye ,  Johannes H Voigt ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert Mazzola ,  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 ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

Inventor： Zhaoning Zhu ,  Brian A McKittrick ,  Zhong-Yue Sun ,  Yuanzan C Ye ,  Johannes H Voigt ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert Mazzola ,  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 ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

IPC: A01N43/82 ,  A61K31/41 ,  C07D271/06

CPC classification number: C07D233/46 ,  C07D233/70 ,  C07D233/88 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D401/04 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/10 ,  C07D409/04 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06

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 m1 agonist or m2 antagonist.

公开(公告)号：US20140128382A1

公开(公告)日：2014-05-08

申请号：US14110363

申请日：2012-04-12

Applicant: Wen-Lian Wu ,  Duane A. Burnett ,  Andrew W. Stamford ,  Jared N. Cumming ,  Chad E. Bennett ,  Eric J. Gilbert ,  Jack D. Scott ,  Younong Yu ,  Xuanjia Peng

Inventor： Wen-Lian Wu ,  Duane A. Burnett ,  Andrew W. Stamford ,  Jared N. Cumming ,  Chad E. Bennett ,  Eric J. Gilbert ,  Jack D. Scott ,  Younong Yu ,  Xuanjia Peng

IPC: C07D279/12 ,  A61K45/06 ,  C07D417/04 ,  A61K31/541 ,  C07D498/04 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  A61K31/54 ,  C07D417/14

CPC classification number: C07D279/12 ,  A61K31/54 ,  A61K31/541 ,  A61K45/06 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  C07D513/04

Abstract: The present invention discloses certain iminothiazine compounds and mono- and dioxides thereof, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein each of variables shown in the formula are as defined herein. The compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and uses, including Alzheimer's disease, are also disclosed.

Abstract translation: 本发明公开了某些亚氨基噻嗪化合物及其单 - 和二氧化物，包括式（I）化合物及其互变异构体和立体异构体，以及所述化合物，所述互变异构体和所述立体异构体的药学上可接受的盐，其中式 如本文所定义。 本发明的化合物可用作BACE抑制剂和/或用于治疗和预防与其相关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物，及其制备和用途的方法，包括阿尔茨海默氏病。

公开(公告)号：US08623867B2

公开(公告)日：2014-01-07

申请号：US13610162

申请日：2012-09-11

Applicant: Jared N. Cumming ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voight ,  Yusheng Wu ,  Ying Huang ,  Yan Xia ,  Samuel Chackalamannil ,  Tao Guo ,  Douglas W. Hobbs ,  Thuy X. H. Le ,  Jeffrey H. Lowrie ,  Kurt W. Saionz ,  Suresh D. Babu

Inventor： Jared N. Cumming ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voight ,  Yusheng Wu ,  Ying Huang ,  Yan Xia ,  Samuel Chackalamannil ,  Tao Guo ,  Douglas W. Hobbs ,  Thuy X. H. Le ,  Jeffrey H. Lowrie ,  Kurt W. Saionz ,  Suresh D. Babu

IPC: A61K31/445 ,  A61K31/4458 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/5377 ,  C07D295/027 ,  C07D401/06 ,  C07D401/12 ,  C07D413/12

CPC classification number: C07D243/08 ,  C07D205/04 ,  C07D207/08 ,  C07D207/09 ,  C07D207/12 ,  C07D207/26 ,  C07D209/52 ,  C07D211/26 ,  C07D211/46 ,  C07D217/18 ,  C07D233/32 ,  C07D241/04 ,  C07D241/08 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D409/06 ,  C07D409/12 ,  C07D413/06

Abstract: Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is —C(O)—N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

Abstract translation: 公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中R1是R是-C（O）-N（R27）（R28），或其余的变量如说明书中所定义。 还公开了包含式I化合物的药物组合物。还公开了治疗认知或神经变性疾病如阿尔茨海默病的方法。 还公开了治疗认知或神经变性疾病的药物组合物和方法，其包含式I化合物与除式I以外的β-分泌酶抑制剂，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂， 甾族抗炎剂，N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂或抗淀粉样蛋白抗体。

公开(公告)号：US08569310B2

公开(公告)日：2013-10-29

申请号：US13391441

申请日：2010-10-06

Applicant: Ulrich Iserloh ,  Andrew W. Stamford ,  Jared N Cumming

Inventor： Ulrich Iserloh ,  Andrew W. Stamford ,  Jared N Cumming

IPC: A01N43/54 ,  C07D239/42 ,  C07D401/04

CPC classification number: C07D239/22 ,  C07D405/04

Abstract: In its many embodiments, the present invention provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (a) and pharmaceutically acceptable salts thereof. Compounds of Formula (a) have the general structure: (a) wherein each variable is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供某些五氟硫亚氨基杂环化合物，包括式（a）化合物及其药学上可接受的盐。 式（a）的化合物具有通式结构：（a）其中每个变量是独立选择的，如本文所定义。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和用于治疗与包括阿尔茨海默病在内的淀粉样蛋白β（Abeta）蛋白相关的病理学的方法。