Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Scott C Berk

Sander G Mills

Malcolm MacCoss

Jeffrey John Hale

Christopher L Lynch

Christopher Alan Willoughby

Kevin Tyler Chapman

Charles G Caldwell

Arthur A Patchett

Lihu Yang

Matthew G Stanton

Alexander Pasternak

Thomas Allen Miller

David L Sloman

Joey Lee Methot

Dooseop Kim

Solomon D Kattar

Joshua Close

Richard Wayne Heidebrecht, Jr

Paul A Tempest

Christopher Hamblett

Anna A Zabierek

Dawn M Mampreian

Richard J Budhu

Edward Holson

Laura T Kliman

Ravi P Nargund

David B Johnston

Liangqin Guo

Ronald M Kim

James R Tata

Meng Hsin Chen

Keith Rosauer

Thomas Miller

Paul Tempest

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. 

Spirocyclic compounds

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.

Pyrrolidine modulators of chemokine receptor activity

The present invention is directed to pyrrolidine compounds of the formula 1:

The present invention is directed to pyrrolidine and piperidine compounds of the formula I: ##STR1## (wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4a, R.sup.4b, R.sup.4c, R.sup.4d, R.sup.4e, R.sup.4f, R.sup.4g, R.sup.4h, m, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.

Pyrrolidine and piperidine modulators of chemokine receptor activity

This invention relates to somatostatin agonist compounds which are potent with high selectivity toward the receptor subtype 2. Compounds of the formula: ##STR1## including pharmaceutically acceptable salts and hydrates thereof are disclosed. These compounds are useful in the treatment of diabetes, cancer, acromegaly, restenosis, depression, irritable bowel syndrome, pain and diabetic retinopathy. Many of the compounds are also orally active.

Somatostatin agonists

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Cambridge, MA, United States of America

Scott C Berk