Southern Research Institute

Merck Sharp + Dohme Corp.

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

The UAB Research Foundation (The University of Alabama at Birmingham)

The University of Arizona

The United States Government As Represented by the Department of Veterans Affairs

University of New England College of Osteopathic Medicine

Subramaniam Ananthan

Joseph A Maddry

F George Njoroge

John A Secrist, Iii

Robert C Reynolds

Cecil D Kwong

Hollis S Kezar, Iii

Neng-Yang Shih

John J Piwinski

Feng Geng

Richard B Rothman

Abhijit Roychowdhury

Frank W Bennett

Ashok Arasappan

Jeremy Clark

Anita T Fowler

Maurizio Grimaldi

Judith Varady Hobrath

Srikanth Venkatraman

Mark J Suto

Vinay M Girijavallabhan

Corinne E Augelli-Szafran

Francisco Velazquez

Vishal Verma

Yuhua Huang

Edward J Bilsky

Vandana Gupta

Omar Moukha-Chafiq

Frank Porreca

Robert Galemmo

Joseph A Kozlowski

Ling Tong

Malcolm Maccoss

Bandarpalle B Shankar

Seong Heon Kim

Ashish Kumar Pathak

George F Njoroge

Robert A Galemmo, Jr

Regina Huelgas

Zhican Qu

Anshu M Roy

Vibha Pathak

Natalia Filippova

Xiuhua Yang

Louis B Nabors

Peter King

Andrew B West

Jacob Valiyaveettil

John A Secrist

Hollis S Kezar

Robert A Galemmo

John A Iii Secrist

Hollis S Iii Kezar

Anshu Mittal Roy

Iii Hollis S Kezar

Iii John A Secrist

This disclosure provides compounds that inhibit RNA-binding proteins, such as Human antigen R protein (HuR). The compounds described herein have a high affinity for HuR multimers and inhibit the pathological processes that promote cancer and inflammation. The compounds are highly water-soluble and have good biodistribution for both systemic and central nervous system disease processes. The compounds provide a unique therapeutic option for disease processes related to neoplastic progression or acute or chronic inflammation.

RNA-binding protein multimerization inhibitors and methods of use thereof

Methods for enhancing memory and/or learning and prevent neurodegeneration by administration of certain heterocyclic and aromatic compounds are described. The methods are particularly useful for treating patients suffering from a neurodegenerative disease such as (without limitation) Alzheimer's, Parkinsons's, Lou Gehrig's (ALS) disease or memory or learning impairment. A neuronal human cell-based assay that assess NF-kB gene up-regulation using a luciferase reporter is also provided that screens for compounds useful in methods for enhancing memory or learning.

Treatment of neurodegenerative diseases, causation of memory enhancement, and assay for screening compounds for such

The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal LRRK2 kinase activity. Compounds of the present disclosure can be used to treat disorders including neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy (Hansen's disease). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Pyrrolopyrimidine compounds, use as inhibitors of the kinase LRRK2, and methods for preparation thereof

The present disclosure relates to certain amine derivatives of fused bicyclic heterocycles that inhibit the amine reuptake function of the biogenic amine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET). Compounds of the present disclosure are potent inhibitors of the reuptake of dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) with full or partial maximal efficacy. The compounds with partial maximal efficacy in inhibiting reuptake of all three biogenic amines are herein referred to as partial triple uptake inhibitors (PTRIs). Compounds of the present disclosure are useful for treating depression, pain and substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Quinazolines as biogenic amine transport modulators

The invention provides methods of enhancing memory and/or learning and prevent neurodegeneration, comprising administering therapeutically effective amounts of certain heterocyclic and aromatic compounds to a patient in need thereof. In one aspect, the invention provides methods of treating patients suffering from a neurodegenerative disease, such as but not limited to, Alzheimer's, Parkinsons's, Lou Gehrig's (ALS) disease, and/or memory or learning impairment. The invention further provides neuronal human cell-based assays that assess NF-kB gene upregulation using a luciferase reporter, wherein the assays identify compounds that are useful in enhancing memory or learning.

Provided are compounds represented by the formula: In which: The compounds can be used for treating a patient suffering from a condition that is capable of treatment with a partial agonist or antagonist of the dopamine D2/D3 receptors. The compounds are especially useful for patients suffering from schizophrenia, depressions, neurodegenerative diseases such as Parkinson's, dyskinesias, substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol, glaucoma, cognitive disorders, restless leg syndrome, attention deficit hyperactivity disorders, hyperprolactinemia, autism, motor disturbances such as akathisia, rigor, dystonias as well as various disorders of the urinary tract and other neurologic disorders. Also provided are processes for the preparation of compounds of the present disclosure.

Urea and amide derivatives of aminoalkylpiperazines and use thereof

Heterocyclic compounds as biogenic amine transport modulators

Provided are compounds represented by the formula: with Y, Ri, and R2 being defined in the present disclosure; pharmaceutically acceptable salts thereof, deuterated forms thereof, isomers thereof, solvates thereof, and mixtures thereof. The compounds can be used for treating a patient suffering from a condition capable of treatment with a partial agonist or antagonist of the dopamine D2/D3 receptors and are especially useful for patients suffering from schizophrenia, depressions, neurodegenerative diseases such as Parkinson's, dyskinesias, substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol, glaucoma, cognitive disorders, restless leg syndrome, attention deficit hyperactivity disorders, hyperprolactinemia, autism, motor disturbances such as akathisia, rigor, dystonias as well as various disorders of the urinary tract and other neurologic disorders. Also provided are processes for the preparation of compounds of the present disclosure. 

The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein each of R, R, X, Y, Z, R, R, R, R, R, R, R, R, R, Rand n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders. 

Substituted pyridine and pyrimidine derivatives and their use in treating viral infections

Provided are novel LRRK2 kinase inhibitors and methods of treating disease states using these inhibitors. Examples of LRRK2 kinase inhibitors are compounds of the formula: or derivatives thereof. An example is 1-(piperidin-1-yl)-2-((3-(thiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)thio)butan-1-one. Particular uses include treating neurodegenerative diseases, cancer, autoimmune diseases and leprosy.

Triazolopyridazine compounds, use as inhibitors of the kinase LRRK2, and methods for preparation thereof

Provided are compounds of the formula: R; R, R; R; A; X; Y and Z are defined in the present disclosure; pharmaceutically acceptable salts thereof, deuterium forms thereof, isomers thereof, and mixture thereof; and processes for their preparation. The compounds can be used for treating a patient suffering from a condition that is capable of treatment with an agonist and/or antagonist of the opioid receptors and are especially useful a patient suffering from pain, treating a patient in need of an immunosuppressant to prevent rejection in organ transplant and skin graft, in need of an anti-allergic agent, in need of an anti-inflammatory agent, in need of a brain cell protectant, for drug and/or alcohol abuse, to decrease gastric secretion, for diarrhea, for cardiovascular disease, for a respiratory disease, in need of a cough and/or respiratory depressant, for mental illness, for epileptic seizures and other neurologic disorders.

Heterocycle-fused morphinans, use thereof and preparation thereof

The present invention provides compounds of Formula (A): (Chemical formula should be inserted here as it appears on abstract in paper form) (A) and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R, X, Y, Z, R, R, R, R, R, R, R, R, R, R, R, R, and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders. 

Ethenyl-substituted pyridine and pyrimidine derivatives and their use in treating viral infections

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Birmingham, AL, United States of America

Subramaniam Ananthan