National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Department of Health

Other

University of Connecticut

The United States of America As Represented by the Secretary of

Saint Louis University

University of Pennsylvania

Duke University

Universiteit Leiden

University of Texas System

Institut National De La Sante Et De La Recherche Medicale

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

Universitá Degli Studi Di Padova

National Institutes of Health (nih)

National Institute of Health

Kenneth Alan Jacobson

Bruce T Liang

Kenneth L Kirk

John W Daly

Dilip K Tosh

Harvey B Pollard

Daniela Salvemini

Yishai Karton

Gary L Stiles

Philip J Van Galen

Michel G Maillard

Barton J Bradbury

Bhalchandra V Joshi

Lak Shin Jeong

Hea Ok Kim

Victor E Marquez

Adriaan Pieter Ijzerman

Johannes Brussee

Artem Melman

Yong-Chul Kim

Zhan-Guo Gao

Heaok Kim Jeong

Carola Gallo-Rodriguez

Bilha Fischer

John A Secrist, Iii

Joel M Linden

John L Neumeyer

Richard A Stone

Kamal N Tiwari

Carl R Johnson

James D Lechleiter

Jesse Baumgold

Theodore E Liston

William S Korinek

Susanna Tchilibon

Markku I Linnoila

R Tyler McCabe

Phil Skolnick

Christian Gachet

Yoonkyung Kim

Santhosh Kumar Thatikonda

Giampiero Spalluto

Claire Mitchell

Detlev Boison

Albert M Van Rhee

Daniel L Boring

Oksana Gavrilova

Marc L Reitman

Dag K Von Lubitz

Kazunori Mine

Thomas Miller

David C Furlano

Yechiel Shai

Suhaib M Siddiqi

Beatrice Hechler

Wolfgang Pfleidover

Dag K J E Von Lubitz

Rajkumar Verma

Anna Junker

Elisa Uliassi

Evgeny Kiselev

Kiran Shambhu Toti

Anikó Göblyös

Eszter Erika Kozma

Stefano Moro

Stephanie Federico

Thatikonda Santhosh Kumar

Ben Bih-Ren Wang

Aniko Goblyos

Athena Klutz

Jinha Yu

Antonella Ciancetta

Zhiwei Wen

Young-Hwan Jung

Mortimer M Civan

An-Hu Li

Hyung Ryong Moon

Seung Ah Choe

Ji-Long Jiang

Harvey Pollard

Disclosed are compounds of the formulas (I), (II), and (II): which are Aadenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein Y, R-R, R-R, and R-Rare as defined in the specification. These compounds are selective to the Aadenosine receptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, for inducing and/or maintaining a hypothermic and/or hypometabolic state for treatment of a mammal.

A1 adenosine receptor agonists and methods of use thereof

The present invention relates to compounds and methods of use thereof for treatment of certain disorders and conditions, for example brain injuries such as stroke or traumatic brain injuries.

Compounds and methods for treating neurological and cardiovascular conditions

Disclosed herein are methods for treating neuropathic pain in a subject in need thereof. The methods include: administering to a subject in need thereof a therapeutically effective amount of an antagonist of P2Y14.

Treatment and prevention of neuropathic pain with P2Y14 antagonists

Disclosed are compounds of formulas (I)-(IX) for treating or preventing a disease or disorder responsive to antagonism of a P2YR receptor agonist in a mammal in need thereof, wherein R-R, X, Y, Z, X', Y&#x2032;, Z&#x2032;, and A are as defined herein, that are useful in treating an inflammatory such as asthma, cystic fibrosis, and sterile inflammation of the kidney. 

Heterocyclic P2Yreceptor antagonists

Described herein are methods for the treatment of a human subject who has had a stroke by administering to the subject a pharmaceutical composition including an antagonist of the P2X4 receptor. The antagonist of the P2X4 receptor can be administered in the acute phase of stroke, optionally in combination with a thrombolytic therapeutic or a procedure on the subject involving a clot-removal device.

Methods for pharmacologic treatment of stroke

Described are compounds, which are antagonists of the P2Yreceptor, for example, a compound of formula (I) in which ring A, R, R, R, and n are as described herein. Also provided are dendron conjugates comprising the compounds, and methods of using the compounds, including a method of treating a disorder, such as inflammation, diabetes, insulin resistance, hyperglycemia, a lipid disorder, obesity, a condition associated with metabolic syndrome, and asthma, and a method of antagonizing P2receptor activity in a cell. 

Triazole derivatives as P2Yreceptor antagonists

Disclosed are compounds of the formula (I) and (II): which are Aadenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R-R, and R-Rare as defined in the specification. These compounds are selective to the Areceptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain.

A3 adenosine receptor agonists

Adenosine kinase inhibitors, including pharmaceutical compositions containing the adenosine kinase inhibitors, and their use for preventing epilepsy and its progression in patients. The adenosine kinase inhibitors have the formula: where the moieties J and K, considered in combination, are &#x2014;CH&#x2014;, or K and L, considered in combination, are &#x2014;CH&#x2014;. The Rmoiety can be &#x2014;NH, C-Calkyl, C-Calkoxy, or C-Chydroxyalkyl. The Rand Rmoieties are each independently C-Calkyl. The Rmoiety is hydrogen or C-Calkyl. The Rand Rmoieties are each independently C-Caryl, C-Ccycloalkyl, or C-Cheteroaryl, that is optionally further substituted.

Methanocarba derivatives of pseudoribose that inhibit adenosine kinase

Disclosed are compounds of the formula (I) and (II) which are Aadenosine receptor agonists, pharmaceutical compositions comprising such compounds, and a method of use of these compounds, wherein X, Y, Z, R-R, and R-Rare as defined in the specification. These compounds are selective to the Areceptor, and are contemplated for use in the treatment or prevention of a number of diseases or conditions, for example, neuropathic pain. 

Phosphonate and phosphinate N-methanocarba derivatives of AMP including their prodrug analogs are described. MRS2339, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) ring system in place of ribose, activates P2X receptors, ligand-gated ion channels. Phosphonate analogues of MRS2339 were synthesized using Michaelis-Arbuzov and Wittig reactions, based on the expectation of increased half-life in vivo due to the stability of the C&#x2014;P bond. When administered to calsequestrin-overexpressing mice (a genetic model of heart failure) via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in vivo, as assessed by echocardiography-derived fractional shortening (FS) as compared to vehicle-infused mice. The range of carbocyclic nucleotide analogues for treatment of heart failure has been expanded.

Compositions and methods to treat cardiac diseases

The claimed subject matter relates to allosteric modulation of Aadenosine receptor (AAR) and provides for the use of an Aadenosine receptor modulator (ARM), for the preparation of pharmaceutical compositions for modulating the AAR in a subject, as well as pharmaceutical compositions including the same and therapeutic methods including administering to a subject an amount of an ARM, the amount being effective to modulate AAR activity. The ARM according to claimed subject matter are 1H-Imidazo-[4,5-c]quinolin-4-amine derivatives. Also provided are 1H-Imidazo-[4,5-c]quinolin-4-amine derivatives.

A3 adenosine receptor allosteric modulators

Phosphonate and phosphinate N-methanocarba derivatives of AMP including their prodrug analogs are described. MRS2339, a 2-chloro-AMP derivative containing a (N)-methanocarba(bicyclo[3.1.0]hexane) ring system in place of ribose, activates P2X receptors, ligand-gated ion channels. Phosphonate analogues of MRS2339 were synthesized using Michaelis-Arbuzov and Wittig reactions, based on the expectation of increased half-life in vivo due to the stability of the C&#x2014;P bond. When administered to calsequestrin-overexpressing mice (a genetic model of heart failure) via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in vivo, as assessed by echocardiography-derived fractional shortening (FS) as compared to vehicle-infused mice. The range of carbocyclic nucleotide analogues for treatment of heart failure has been expanded.

Disclosed are compounds of the formula (I) which are fluorescently labeled antagonists of the Aadenosine receptor: wherein A, R, R, and Y are as described herein. Also disclosed are diagnostic compositions and a method of diagnosis of a patient for a possible treatment by an antagonist of the Aadenosine receptor, involving the use of one or more of these compounds as diagnostic agents.

Fluorescent antagonists of the A3 adenosine receptor

Disclosed are Aadenosine receptor antagonists and/or partial agonists and Aadenosine receptor agonists and/or partial agonists of formula (I): wherein Rto Rare as described herein, as well as pharmaceutical compositions thereof and methods of use thereof. The AAR antagonists or partial agonists find use in treating a number of diseases such as cancer, glaucoma, and inflammatory diseases, as well as in preventing cardiac ischemia. Also disclosed are radiolabeled compounds of formula (I) and the use thereof in diagnostic imaging of tissues and organs. The AAR agonists and partial agonists find use in treating diseases such as seizures, convulsion, stroke, diabetes, pain, arrhythmias, depression, and anxiety and in cardioprotection or neuroprotection.

Adenosine receptor agonists, partial agonists, and antagonists

Disclosed are adenosine derivatives, methods for the synthesis thereof, and pharmaceutical compositions for the prevention and treatment of inflammatory diseases, comprising the same as an active ingredient. The adenosine derivatives have high binding affinity and selectivity for adenosine receptors, especially for Aadenosine receptors and act as Aadenosine receptor antagonists, and exhibit anti-inflammatory activity. Thus, the adenosine derivatives are useful in the prevention and treatment of inflammatory diseases.

Adenosine derivatives, method for the synthesis thereof, and the pharmaceutical compositions for the prevention and treatment of the inflammatory diseases containing the same as an active ingredient

Growing community of inventors

Silver Spring, MD, United States of America

Kenneth Alan Jacobson