Merck Sharp + Dohme Corp.

Schering Corporation

Pharmacopeia Drug Discovery, Inc.

Pharmacopeia Inc.

Ulrich Iserloh

Andrew William Stamford

Jared N Cumming

Yusheng Wu

Zhaoning Zhu

Corey Strickland

Tao Guo

Suresh D Babu

Kurt William Saionz

Ying Huang

Lingyan Wang

Johannes H Voigt

Zhong-Yue Sun

Brian Alexander McKittrick

William J Greenlee

John P Caldwell

Thuy X H Le

Elizabeth M Smith

Yuanzan C Ye

Guoqing Li

Robert D Mazzola, Jr

Rachael Catherine Hunter

Jack D Scott

Gang Qian

Michelle Lee Morris

Dawit Tadesse

Jianping Pan

Huizhong Gu

Eric J Gilbert

Xiaoxiang Liu

Douglas Walsh Hobbs

Johannes H Voight

Jeffrey A Misiaszek

Samuel Chackalamannil

Yan Xia

Yuefei Shao

Gaifa Lai

Jingqi Duo

Chuanxing Qu

Robert Mazzola

Thuy X E Le

Jeffrey F Lowrie

Younong Yu

Jeffrey H Lowrie

Xiaoiang Liu

Santhosh Francis Neelamkavil

Pengcheng Patrick Shao

Mihirbaran Mandal

Jonathan E Wilson

Wei Li

David Earl Kaelin, Jr

Thuy Xe Le

Rachel C Hunter

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R, R, R, R, R, R, ring A, ring B, m, n, p, -L-, L-, and L- 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 &#x3b2;-amyloid (A&#x3b2;) 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 (A&#x3b2;) protein, including Alzheimers disease, are also disclosed. 

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): (structurally represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds, wherein R1, R2, R3, X, Y, s, 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. 

C6-spiro iminothiadiazine dioxides as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain C2-ring-substituted thiadiazine compounds, including compounds Formula (I): (structure represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R, R, ring A, R, m, -L-, R, and ring C 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. 

C6-azaspiro iminothiadiazine dioxides as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): 

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions and their use

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein the middle ring (referred to herein as 'ring B') of the tricyclic substituent is an optionally substituted 5-membered ring, and each of the remaining variables shown in the formula 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 Alzheimer's disease, are also disclosed. 

Tricyclic substituted thiadiazine dioxide compounds as BACE inhibitors, compositions and their use

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein the middle ring (referred to herein as 'ring B') of the tricyclic substituent is an optionally substituted 6-membered ring, and each of the remaining variables shown in the formula 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 Alzheimer's disease, are also disclosed. 

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein  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 &#x3b2;-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.

Cyclic amide BACE-1 inhibitors having a benzamide substituent

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula 1 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods 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 magonist or mantagonist.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein 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 magonist or mantagonist.

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula I are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods 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 magonist or mantagonist.

Disclosed are compounds of formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, U, W, X, R, R, R, R, Rand Rare as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. 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 magonist or mantagonist.

Aspartyl protease inhibitors

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein Ris  R is &#x2014;C(O)&#x2014;N(R)(R) 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 &#x3b2;-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.

Cyclic amine BACE-1 inhibitors having a benzamide substituent

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 (A&#x3b2;) protein, including Alzheimers Disease, are also disclosed. 

Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions and their use

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Hoboken, NJ, United States of America

Ulrich Iserloh