Merck Sharp + Dohme Corp.

Msd R&d (china) Co., Ltd.

Other

Msd International Gmbh

Elexopharm Gmbh

Merck Msd (r&d) China Co., Ltd.

Msd R&d Co., Ltd.

Timothy J Henderson

Michael Man-Chu Lo

Ryan D Otte

Jared N Cumming

Michael D Altman

Andrew M Haidle

James Patrick Jewell

Benjamin Wesley Trotter

Min Lu

Amjad Ali

Jongwon Lim

Tony Siu

Wonsuk Chang

David L Sloman

Rui Liang

Matthew A Larsen

Brandon D Cash

Anandan Palani

Yongxin Han

Jianming Bao

Ling Tong

Thomas H Graham

Robert D Mazzola, Jr

Rongze Kuang

David M Tellers

Matthew Lloyd Childers

Yeon-Hee Lim

Heping Wu

Brent Whitehead

Chunsing Li

Edward Metzger

Sriram Tyagarajan

Indu T Bharathan

Symon Gathiaka

Andrew William Stamford

Shrenik K Shah

Melissa S Egbertson

Dong Xiao

Alan B Northrup

Michael T Rudd

Pauline C Ting

Lin Yan

Brian M Andresen

Xiaolei Gao

Manuel De Lera Ruiz

Qiaolin Deng

Paul Tempest

Quang T Truong

John J Acton, Iii

Fengqi Zhang

Scott T Harrison

Oleg B Selyutin

Zhiqiang Guo

Jae-Hun Kim

Gioconda V Gallo

David James Witter

Xianhai Huang

Kevin D McCormick

Michael Berlin

Younong Yu

Phieng Siliphaivanh

Michelle R Machacek

Christopher W Boyce

Robert K Baker

Yusheng Xiong

Duane E DeMong

Hong Liu

Shawn P Walsh

Purakkattle J Biju

Michael Hale Reutershan

Craig R Gibeau

Bheemashankar A Kulkarni

Tao Yu

Junying Zheng

Clare London

Takao Suzuki

Jayaram R Tagat

Tanweer A Khan

Rolf Wolfgang Hartmann

Sandra Lee Knowles

Yonglian Zhang

Zhaoyang Meng

James J Mulhearn

Jean-Laurent Paparin

Scott B Hoyt

Nicolas Zorn

Walter Won

Yingchun Ye

Gang Zhou

Xiaohong Zhu

Eric B Daniels

Jerry Andrew Taylor

Jianhua Cao

Houcine Rahali

Vanessa L Rada

Kake Zhao

Chunhui Huang

Swapan Kumar Samanta

Joe F Lee

Ralf Heim

The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W, W, Y, Z, M, L, C, C, R, R, R, R, R, R, R, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Small molecule inhibitors of KRAS G12C mutant

The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.

PRMT5 inhibitors

The present invention is directed to cinnolinyl and quinolinyl 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.

3-(1H-pyrazol-4-yl)pyridine allosteric modulators of the M4 muscarinic acetylcholine receptor

The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W, W, Y, Z, M, L, C, C, R, R, R, R, R, R, Rand the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

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.

The present invention is directed to 2,2-difluorodioxolo compounds that are antagonists of Areceptor. The present invention is also directed to uses of the 2,2-difluorodioxolo compounds described herein in the potential treatment or prevention of neurological disorders and diseases in which Areceptor are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds and to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which Areceptors are involved.

2,2-difluorodioxolo Areceptor antagonists

The present invention is directed to 5-(pyridine-3-yl)oxaxole 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.

5-(pyridin-3-yl)oxazole allosteric modulators of the M4 muscarinic acetylcholine receptor

Compounds of general formula (I), of general formula (II), of general formula (III), of general formula (IV), of general formula (V), of general formula (VI), and their pharmaceutically acceptable salts, wherein all variables are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are compositions comprising such compounds, processes for the synthesis of such compounds, and to uses of such compounds, including administration of such compounds to induce immune response, to induce STING-dependent type I interferon production, and/or to treat a cell proliferation disorder, such as cancer. 

Sting agonist compounds

A class of polycyclic compounds of general formula (I), of general formula (I'), or of general formula (I&#x2033;), wherein Base, Base, Y, Y, X, X, X, X, X, X, X, X, R, R, R, R, R, R, R, R, R, R, R, R, R, and Rare 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. 

Cyclic di-nucleotide compounds as sting agonists

A class of polycyclic compounds of general formula (II), of general formula (II'), or of general formula (II&#x2033;), wherein Base, Base, Y, Y, X, X, X, X, X, X, X, X, R, R, R, R, R, R, R, R, R, R, R, R, R, and Rare 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. 

Cyclic di-nucleotide compounds as STING agonists

Compounds of general formula (Ia), compounds of general formula (Ia'), compounds of general formula (Ib), compounds of general formula (Ib&#x2032;), compounds of general formula (I), compounds of general formula (I&#x2032;), and their pharmaceutically acceptable salts, wherein R, R, R, R, R, R, R, R, X, X, and Xare 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 of the disclosure.

Benzo[b]thiophene compounds as STING agonists

Benzo[b]thiophene compounds as sting agonists

The problem of evenly cooking a food item so that all sides cook and brown evenly is solved by the use of a roasting platform that raises above rendered substances that can cause a steam and wetness to the surface of a food item. The roasting platform can be foldable or compressed, so that it takes up minimal storage space and can be deployed for use. Drain holes allow rendered substances to be more quickly separated from the surface of a food item. The same drain holes can be used as visual indicators when deploying the roasting platform to show when he folds of a roasting platform are sufficiently separated for maximum usable area and support for a weight placed thereon.

Expandable roasting platform

Growing community of inventors

Natick, MA, United States of America

Timothy J Henderson