The United States of America, as Represented by the Secretary, Department of Health and Human Services

University System of Maryland

The Rockefeller University

Icahn School of Medicine at Mount Sinai

Forschungsverbund Berlin E.v.

Other

Cincinnati Children's Hospital Medical Center

Craig J Thomas

Wenwei Huang

James Inglese

Jian-kang Jiang

Matthew Brian Boxer

Patrick Joseph Morris

Douglas S Auld

Marvin C Gershengorn

Susanne Neumann

Wei Ping Zheng

Noel Terrence Southall

Min Shen

Steven Titus

Gerd Krause

Bruce M Raaka

Amanda P Skoumbourdis

Gunnar Kleinau

Barry S Coller

Carlos A Zarate

Ruin Moaddel

Marta Filizola

Todd Gould

Panos Zanos

Joshua McCoy

Daniel T Starczynowski

Garrett W Rhyasen

Adam Van Dyke

Scott Thompson

Katelyn Melgar

Morgan MacKenzie Walker

Matthew Boxer

Jian-Kang Jiang

Martin J Walsh

John A Beutler

Stuart F J LeGrice

Suhman Chung

Jennifer Wilson

Richard Andrew Castledine

Samuel Lawrence Bourne

Carlos Zarate

Patrick Morris

Wei Zheng

The disclosure provides a method for synthesizing free base foams of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal foams of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

Crystal forms and methods of synthesis of (2R, 6R)-hydroxynorketamine and (2S, 6S)-hydroxynorketamine

The present invention relates to novel alpha5 subunit-selective negative allosteric modulators of GABAreceptors that have been deuterated to improve their medicinal properties by prolonging their half-lives, rendering them useful as fast-acting pharmaceutical treatments for depression related disorders.

Deuterated Alpha5 subunit-selective negative allosteric modulators of gamma-aminobutyric acid type a receptors as fast acting treatment for depression and mood disorders

The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I)) and compositions (e.g., pharmaceutical compositions) which can be used for treating, for example, certain diseases. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as head and neck squamous cell carcinoma (HNSCC), cancer, blood disorders, etc.). Additional embodiments provide synergistic combinations of a BCL2 inhibitor with an IRAK inhibiting compound, and methods of using same. 

Substituted Imidazo[1,2-a]-pyridines as IRAK 1/4 and FLT3 inhibitors

Deuterated Alpha5 subunit-selective negative allosteric modulators of gamma-aminobutyric acid type A receptors as fast acting treatment for depression and mood disorders

Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer or blood disorders). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein. 

Substituted imidazo[1,2-A]pyridines as IRAK 1/4 and flt3 inhibitors

A process for the preparation of (2R,6R)-hydroxynorketamine is provided. The process requires no chromatography purification and affords the (2R,6R)-hydroxynorketamine in eight steps with a 26% overall yield and greater than 97% purity.

Process for synthesis and purification of (2R,6R)-hydroxynorketamine

An attachable canopy for a riding lawnmower for providing a shading mechanism for a user seated on such a lawnmower includes a harness formed from a wrap around elongated strap that has a first end that is connectable to a second end, a frame which includes two elongated rods whose proximal ends are connected to opposite sides of the harness, and a canopy which is connected to the distal ends of the rods. The harness is adjustable so as to be attachable to either the seat or seat back of a riding lawnmower. In this regard, the rods which form the frame may selectively swivel at least ninety degrees so as to remain in a perpendicular orientation relative to the seat with the canopy held over the seat regardless of which structure the harness is attached to.

Attachable canopy for riding lawnmower

Disclosed are pyruvate kinase M2 activators, which are, bis sulfonamide piperazinyl compounds of Formula (I) and 2,4-disubstituted 4H-thieno[3,2-b]pyrrole-2-(substituted benzyl)pyridazin-3(2H)ones of Formula (II), wherein L and Rto Rare as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer and anemia, 

Activators of human pyruvate kinase

Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A, A, L, R, Rto R, Xto X, k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A-NR-L-A(I). 

The present invention relates to compounds of Formula P-I where the variables (e.g. R, Y, A, R, R, R, R, R, R, R, R, R, R, or R) and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

Oxadiazolo[3,2-A]pyrimidines and thiadiazolo[3,2-A]pyrimidines

Disclosed are oxo-hydroquinazolines that are useful as selective TSHR agonists. The compounds may be used for detecting or treating thyroid cancer, or treating a bone degenerative disorder.

Low molecular weight thyroid stimulating hormone receptor (TSHR) agonists

A compound, or a pharmaceutically acceptable salt or ester thereof, of formula I:X&#x2014;Wwherein X is a caspase-selective structure and W has the structure of&#x2014;NH&#x2014;CH(Y)(Z)wherein Y is a structure that can form a reversible covalent bond with a caspase; andZ is selected from a carboxyl moiety or a carboxylic acid mimetic.

Caspase inhibitors

The present invention relates to compounds and compositions of Formula P useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The definitions of variables A, B, R, R, R, R, R', R, R&#x2032;, R, R, R&#x2032;, R, and R&#x2032; are provided in the disclosure. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-A]pyrimidin-5-ones for the treatment of thrombotic disorders

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Gaithersburg, MD, United States of America

Craig J Thomas