Merck Sharp + Dohme Corp.

Amgen Inc.

Merck + Co., Inc.

Paul A Tempest

Thomas Allen Miller

Solomon D Kattar

Matthew G Stanton

David L Sloman

Joey Lee Methot

Anna A Zabierek

Dawn M Mampreian

Vinod Francis Patel

Brian Lewis Hodous

Joshua Close

Stephanie Geuns-Meyer

Richard Wayne Heidebrecht, Jr

Christopher Hamblett

Ning Xi

Joseph L Kim

Brian K Albrecht

David James Witter

Kevin J Wilson

Victor J Cee

Xiaotian Zhu

Yuan Cheng

Michelle R Machacek

Jonathan R Young

Andrew M Haidle

Vu Van Ma

Steven F Bellon

Hanh Nho Nguyen

Jonathan B Grimm

Thomas Nixey

Karina Romero

Brandon Mitsuo Taoka

Erin F DiMauro

Stuart C Chaffee

Philip R Olivieri

Holly L Deak

Scott C Berk

Guity P Balow

Christopher Hulme

Rebecca E Johnson

Laura T Kliman

Stephanie D Geuns-Meyer

Matthew W Martin

Craig E Masse

Andrew Stewart Tasker

Gang Liu

Jean-Christophe P Harmange

Michael D Altman

Benito Munoz

Jean E Bemis

Jongwon Lim

Anthony B Reed

Robert Michael Rzasa

Ryan D White

Liping H Pettus

Phieng Siliphaivanh

Dawei Zhang

Shimin Xu

Ryan D Otte

Russell Graceffa

Paul E Harrington

Tony Siu

Matthew Christopher

James Richard Falsey

Adrian Leonard Smith

Nick A Paras

Gregory J Habgood

Bradley J Herberich

Kerrie Spencer

Partha P Chakrabarti

Richard W Heidebrecht, Jr

Guo-Qiang Cao

Rachel Nicola MacCoss

Chaomin Li

Hyun Chong Woo

Karin M Otte

William H Buckner

Kaleen M Konrad

Andrew Rosenau

Maya C Thaman

Laura M Surdi

Ekundayo Osimboni

Kelvin Sham

Phillip R Olivieri

David C Mcgowan

Susan Ann Tomlinson

Frenel F Demorin

Guo-Giang Cao

John L Buchanan

Erin F Dimauro

Stephanie D Geuns-meyer

The present invention relates to compounds of Formulas I and II, wherein B, B, B, B, C, C, ring D, L, Land Rare defined herein, synthetic intermediates, and pharmaceutical compositions, comprising such compounds. The compounds and compositions are capable of modulating various protein kinase receptors such as Tie-2 and Aurora and, therefore, influencing kinase related disease states and conditions. The compounds, for example, are capable of treating cancer caused by unregulated angiogenesis, and inflammation as well as other proliferative disorders.

Multi-cyclic compounds and methods of use

The invention encompasses a novel class of cyclobutyl sulfone derivatives which inhibit the processing of APP by the putative &#x3b3;-secretase while sparing Notch signaling pathway, and thus are useful in the treatment or prevention of Alzheimer's disease without the development of Notch inhibition mediated gastrointestinal issues. Pharmaceutical compositions and methods of use are also included.

Cyclobutyl sulfones as notch sparing gamma secretase inhibitors

The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, Hand Rare defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other proliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Protein kinase modulators and method of use

The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Inhibitors of janus kinases

The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

Spirocyclic compounds

The present invention relates to a novel class of modified malonate derivatives. The modified malonate compounds can be used to treat cancer. The modified malonate compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the modified malonate derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the modified malonate derivatives in vivo.

Modified malonate derivatives

The present invention relates to a novel class of aryl-fused spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

Aryl-fused spirocyclic compounds

The present invention relates to a novel class of histone deacetylase inhibitors with aryl-pyrazolyl motifs. The compounds of this invention can be used to treat cancer. The compounds of this invention are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The present invention further provides pharmaceutical compositions comprising the compounds of this invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the compounds of this invention in vivo.

Histone deacetylase inhibitors with aryl-pyrazolyl-motifs

The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, Hand Rare defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR, NR, C(O) and O; E is selected from a bond, CR, NR, C(O) and O; wherein at least one of A, B, D or E is CR; and provided that when A is O, then E is not O; G is CR; R is selected from NHand OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo. 

The instant invention provides for tetracyclic compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R-R, and Rare as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Melanin concentrating hormone receptor antagonist

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Brookline, MA, United States of America

Paul A Tempest