Merck Sharp + Dohme Corp.

Neurocycle Therapeutics, Inc.

Other

Jed Hubbs

Thomas Allen Miller

Matthew Toczko

Hua Zhou

Matthew G Stanton

David James Witter

Kevin J Wilson

Phieng Siliphaivanh

Christopher Hamblett

Timothy Harrison

Benito Munoz

Andrew Madin

Eileen Mary Seward

David L Sloman

Joey Lee Methot

Mark Peter Ridgill

Matthew H Daniels

Jonathan B Grimm

Michelle Martinez

Joanne Clare Hannam

Karin M Otte

Sam Kattar

Yudith Garcia

Janusz Josef Kulagowski

Thomas Miller

Christopher L Hamblett

Described herein are polymorphs comprising 2′,6-difluoro-5′-[3-(1-hydroxy-1-methylethyl)-imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile (TPA023B) or salts thereof. In one aspect, disclosed herein is a crystalline polymorphic salt or co-crystal of TPA023B with p-toluenesulfonic acid of the following formula: Also described herein are methods of making and using the same.

Crystalline salts or co-crystals of 2',6-difluoro-5′-[3-(1-hydroxy-1-methylethyl)-imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile with p-toluenesulofonic acid as GABAA positive allosteric modulators

Disclosed herein are GABAA positive allosteric modulators for the treatment of pruritic conditions and dermatitis. Also disclosed herein are formulations comprising the GABAA positive allosteric modulators.

GABAA positive allosteric modulator compounds for treatment of itch and/or dermatitis

Described herein are polymorphs comprising 2',6-difluoro-5&#x2032;-[3-(1-hydroxy-1-methylethyl)-imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile (TPA023B) or salts thereof. In one aspect, disclosed herein is a crystalline polymorphic salt or co-crystal of TPA023B with phosphoric acid. Also described herein are methods of making and using the same.

Crystalline salts or co-crystals of 2',6-difluoro-5&#x2032;-[3-(1-hydroxy-1-methylethyl)-imidazo[1,2-b] [1,2,4]triazin-7-yl]biphenyl-2-carbonitrile with phosphoric acid as GABAA positive allosteric modulators

The present invention is directed to a novel trifluoromethylsulfonamide derivative which inhibits the processing of APP by the putative &#x3b3;-secretase and thus is useful in the treatment or prevention of Alzheimer's disease. This compound possesses favorable pharmacokinetic properties in higher species (rhesus) and thus can be dosed on an intermittent dosing regiment (e.g., once weekly). When dosed on such a regiment the compound exhibits significant and continuous A&#x3b2; lowering without the manifestation of Notch associated gastrointestinal toxicity for extended periods, e.g., 7 days. Pharmaceutical compositions and methods of use are also included.

Trifluoromethylsulfonamide gamma secretase inhibitor

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 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.

Inhibitors of histone deacetylase

The present invention relates to a novel class of hydroxamic acid derivatives. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid 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 are also 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 hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

Benzothiophene hydroxamic acid derivatives

Growing community of inventors

Cambridge, MA, United States of America

Jed Hubbs