Merck Sharp + Dohme Corp.

Other

Merck + Co., Inc.

Christopher Hamblett

Thomas Allen Miller

Joey Lee Methot

Matthew G Stanton

David L Sloman

Solomon D Kattar

Paul A Tempest

Anna A Zabierek

Dawn M Mampreian

David James Witter

Joshua Close

Sandro Belvedere

Richard Wayne Heidebrecht, Jr

Scott C Berk

Jed Hubbs

Jiaming Yan

Laura T Kliman

Timothy Harrison

Benito Munoz

Andrew Madin

Mark Peter Ridgill

Paul Tempest

Michelle Martinez

Joanne Clare Hannam

Yudith Garcia

Janusz Josef Kulagowski

Thomas Miller

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

Compounds of formula I: I wherein at least one of R4 and R5 comprises Si(R6)3 as a substituent selectively attenuate production of A&#x3b2;(1-42) and hence find use in treatment of Alzheimer's disease and related conditions.

Silylated piperidine derivatives

Compounds of formula (I) are modulators of gamma-secretase, and hence are useful in treatment of Alzheimer's disease. 

Piperidines and related compounds for the treatment of Alzheimer's disease

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 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 invention relates to hydroxamic acid derivatives having carbamate linkage with the structural formula that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous systems (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.

Histone deacetylase inhibitors

This invention relates to hydroxamic acid derivatives having a urea linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.

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Boston, MA, United States of America

Christopher Hamblett