Merck Sharp + Dohme Corp.

Merck Canada Inc.

Elexopharm Gmbh

Scott B Hoyt

Clare London

Yusheng Xiong

Bheemashankar A Kulkarni

Andrew John Cooke

Emma Louise Carswell

Jerry Andrew Taylor

Paul David Ratcliffe

D Jonathan Bennett

Swapan Kumar Samanta

Jaiqiang Cai

Min K Park

Ashok Arasappan

Robert R Wilkening

Iyassu Sebhat

John K MacLean

John MacLean

Amjad Ali

Duane E DeMong

Rohit Saxena

Whitney Lane Petrilli

Yongxin Han

Michael Man-Chu Lo

Robert S Meissner

James J Perkins

Zhijian Lu

Rui Liang

Peter J Manley

Timothy J Henderson

Wonsuk Chang

Christopher James Bungard

Rolf Wolfgang Hartmann

Joseph Leslie Duffy

Jessica Frie

Brent Whitehead

Kenneth J Leavitt

Jiaqiang Cai

Hyewon Youm

Andrew Cooke

Iyassu K Sebhat

Jason Eugene Imbriglio

Ralf Heim

Qingzhong Hu

Lina Yin

Emmanuel Bey

Duane Demong

Dong Ok

Zhe Feng

Archana Gupta

Michael Lo

Joseph L Duffy

William H Parsons

Bey; Emmanuel

Brent White-Head

D Jonathan Bennet

Jaiqiqang Cai

John Maclean

The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X, X, Y, R, R, R, Rand n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples. 

Substituted 1-methyl-1,2,3,4-tetrahydroisoquinoline molecules as PCSK9 allosteric binders

The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I):  and ring B, n, R, R, R, R, and Rare as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

Chromane, isochromane and dihydroisobenzofuran derivatives as mGluR2-negative allosteric modulators, compositions, and their use

Chromane, isochromane and dihydroisobenzofuran derivatives as mGluR2&#x2014;negative allosteric modulators, compositions, and their use

The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R, R, L, X, X, and X, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders. 

Tetrahydronaphthyridine derivatives as mGluR2-negative allosteric modulators, compositions, and their use

This invention relates to pyrazolopyridyl compounds of the structural formula: or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthase.

Pyrazolopyridyl compounds as aldosterone synthase inhibitors

This invention relates to triazolopyridyl compounds of the structural formula: or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthase.

Triazolopyridyl compounds as aldosterone synthase inhibitors

This invention relates to indazole compounds of the structural formula: (structure represented) or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment or amelioration of conditions that could be treated by inhibiting aldosterone synthase. 

Indazole compounds as aldosterone synthase inhibitors

This invention relates to imidazopyridyl compounds of the structural formula: or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthase.

Imidazopyridyl compounds as aldosterone synthase inhibitors

The invention involves compounds of structural Formula (I) and the pharmaceutically acceptable salts thereof. The compounds of the invention are effective at selectively inhibiting CYP11B2, and are therefore useful for the treatment or prophylaxis of disorders that are associated with elevated aldosterone levels, including, but not limited to, hypertension and heart failure. 

Aldosterone synthase inhibitors

This invention relates to tricyclic triazole analogs of the formula I or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthetase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthetase. 

A series of N-substituted oxindole derivatives represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, calcium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, diabetic neuropathy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, sleep disorder, bipolar disorder and stroke, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.

N-substituted oxindoline derivatives as calcium channel blockers

Benzazepinone compounds represented by Formula (I), or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, sodium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, epilepsy, irritable bowel syndrome, urinary incontinence, pruritis, itchiness, allergic dermatitis, depression, anxiety, multiple sclerosis, and bipolar disorder, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds. A method of administering local anesthesia comprises administering an effective amount of a compound of the instant invention, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier.

Benzaepinones as sodium channel blockers

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Scott B Hoyt