Wyeth

Pfizer Corporation

Bayer Cropscience Ag

Fmc Corporation

Viropharma Incorporated

Affymax, Inc.

Ariamala Gopalsamy

Mengxiao Shi

Tarek Suhayl Mansour

Aranapakam Mudumbai Venkatesan

Christoph Martin Dehnhardt

Arie Zask

David James Richard

Kevin Joseph Curran

Efren Guillermo Delos Santos

Jeroen Cunera Verheijen

Joshua Aaron Kaplan

Osvaldo Dos Santos

Zecheng Chen

Semiramis Ayral-Kaloustian

Li Huang Xing

Eddine Saiah

Ivan Viktorovich Efremov

John Isidro Trujillo

Liying Zhang

Zhao-Kui Wan

Brian Stephen Gerstenberger

Andrew Fensome

Betsy Susan Pierce

Jean-Baptiste Telliez

Walter H Yeager

John W Lyga

Robert L Dow

George Theodoridis

David W Piotrowski

Thomas G Cullen

Robert N Henrie, Ii

David Hepworth

Inna Shulman

Ian R Silverman

Daniel H Cohen

Agustin Casimiro-Garcia

Paul E Rensner

Stephen F Donovan

Ping Ding

David Rosen

Y Larry Zhang

Ralph Pelton Robinson, Jr

Guozhi Wang

Shawn Cabral

Mihir D Parikh

Seong Jae Yu

Scott Lee Kincaid

Kaapjoo Park

Chulho Choi

Qun Zhang

Dennis L Warkentin

Arjun Venkat Narayanan

Hatice Gizem Yayla

Jayasankar Jasti

Ming Zhu Chen

Olugbeminiyi Omezia Fadeyi

John W Ellingboe

Lee Richard Roberts

Lyn Howard Jones

Steven Shunxiang Zhang

Hui Y Yang

Jay Edward Wrobel

Ronald W Barrett

Jeremy Ian Levin

Christopher J Burns

Joseph Walter Strohbach

Stephen M Condon

Christopher P Holmes

John Paul Mathias

Matthew G Laporte

Neelu Kaila

Xiaolun Wang

Lih-Ling Lin

Neal Green

Randall A Scheuerman

Steve Yikkai Tam

Dennis William Powell

Jason Shaoyun Xiang

Andrew Christopher Flick

Kristina Martha Kutterer

Lori Krim Gavrin

Stephen D Yanofsky

Leonard Alexander McDonald

Yonghan Hu

John William Cuozzo

Kim Timothy Arndt

Min He

Steven J Kirincich

Beatrice Ruhland

Kristin Marie Janz

Jeffrey Edwin Janso

Ker Yu

Jeffrey Scott Condon

Stephen Shunxiang Zhang

Joseph Walter Strobach

Jennifer R Thomason

Gregory Mark Ciszewski

Marc S Collett

Derek MacLean

The invention relates to pyrazole derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to HbS modulators of formula (I) HbS modulators are potentially useful in the treatment of a wide range of disorders, including sickle cell disease (SCD).

Chemical compounds

The invention relates to pyrazole derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to HbS modulators of formula (I) or tautomers thereof, or pharmaceutically acceptable salts of said modulators or tautomers thereof, wherein X, Y, Rand Rare as defined in the description. HbS modulators are potentially useful in the treatment of a wide range of disorders, including sickle cell disease (SCD).

A compound compound having the structure: or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C-Calkyl, C-Calkoxy, C-Ccycloalkyl, aryl, heteroaryl, aryl(C-Calkyl), CN, amino, alkylamino, dialkylamino, CF, or hydroxyl; A is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, &#x2014;(C&#x2550;O)NR&#x2014;, and &#x2014;(CRR)&#x2014;, where Ris H or C-Calkyl, and Rand Rare independently hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl), heteroaryl, (C-Calkyl)heteroaryl, etc.; A' is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, &#x2014;(C&#x2550;O)NR&#x2032;, &#x2014;NR&#x2032;(C&#x2550;O)&#x2014;, and &#x2014;(CR&#x2032;R&#x2032;)&#x2014;, where R&#x2032; is H or C-Calkyl, and R&#x2032; and R&#x2032; are independently hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl), heteroaryl, (C-Calkyl)heteroaryl, heteroaryl(C-Calkyl), and heterocyclic(C-Calkyl); Z is &#x2014;(CH)&#x2014; or a bond, where one or more methylene units are optionally substituted by one or more C-Calkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; Rand R&#x2032; are independently selected from the group consisting of hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, heteroaryl, aryl(C-Calkyl), CN, etc., wherein said alkyl, aryl, cycloalkyl, heterocyclic, or heteroaryl is further optionally substituted with one or more substituents selected from the group consisting of C-Calkyl, halo, CN, C-Calkylamino, C-Ccycloalkyl, etc.; Ris selected from the group consisting of hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; Ris selected from the group consisting of hydrogen, deuterium, and amino; Ris monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C-Calkyl, heterocycloalkyl, halo, C-Ccycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C-Calkyl, halo, CN, OH, alkoxy, amino, &#x2014;COH, &#x2014;(CO)NH, &#x2014;(CO)NH(C-Calkyl), or &#x2014;(CO)N(C-Calkyl), and where said alkyl may be further substituted by one or more fluorine atoms; Ris independently selected from the group consisting of hydrogen, C-Calkyl, C-Calkoxy, and hydroxyl; h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.

Aminopyrimidinyl compounds

A compound having the structure: or an acceptable salt thereof, wherein X is N or CR, where R is hydrogen, alkyl, etc.; A is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, etc.; A' is selected from the group consisting of a bond, C&#x2550;O, etc.; Z is &#x2014;(CH)&#x2014; or a bond, etc.; Rand Rare independently selected from the group consisting of hydrogen, alkyl, etc.; Ris selected from hydrogen, alkyl, etc.; Ris selected from the group consisting of hydrogen, and amino; Ris monocyclic or bicyclic, etc.; Ris independently selected from hydrogen, alkyl, etc.; h, j, k, m, n and q are integers as defined in the specification. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.

A compound having the structure: or an acceptable salt thereof, wherein X is N or CR, where R is hydrogen, alkyl, etc.; A is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, etc.; A' is selected from the group consisting of a bond, C&#x2550;O, etc.; Z is &#x2014;(CH)&#x2014; or a bond, etc.; Rand R&#x2032; are independently selected from the group consisting of hydrogen, alkyl, etc.; Ris selected from hydrogen, alkyl, etc.; Ris selected from the group consisting of hydrogen, and amino; Ris monocyclic or bicyclic, etc.; Ris independently selected from hydrogen, alkyl, etc.; h, j, k, m, n and q are integers as defined in the specification. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.

Compounds, pharmaceutically acceptable salts thereof, are disclosed wherein the compounds have the structure of as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Heterocyclic compounds as inhibitors of Vanin-1 enzyme

Compounds of formula I  and R, R, and Rare defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

Triazine compounds as PI3 kinase and mTOR inhibitors

Triazine compounds as PI3 kinase and MTOR inhibitors

Triazine compounds as P13 kinase and MTOR inhibitors

The present invention relates to compounds of formula I: methods of their use, processes for their preparation and isolated actinomycetes strains capable of preparing pyrrolo[4,3,2-de]quinolin-8-amine compounds.

Pyrrolo[4,3,2-de]quinolin-8-amine compounds and methods of their preparation and use

Compounds of formula I wherein:Ris and R, R, and Rare defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

Growing community of inventors

Mahwah, NJ, United States of America

Ariamala Gopalsamy