Emory University

Neurop, Inc.

Children's Healthcare of Atlanta, Inc.

Stephen F Traynelis

Dennis C Liotta

Yao Jing

James P Snyder

Ethel Garnier

Yesim Altas Tahirovic

Raymond J Dingledine

David Menaldino

Lawrence J Wilson

Scott James Myers

Timothy M Acker

Rose M Santangelo

Matthew Epplin

Cara Mosley

Lanny Steven Liebeskind

Yesim Altas

Katie L Strong

David D Mott

James J Doherty, Jr

PavanKumar Reddy Gangireddy

Praseeda Mullasseril

Ethel C Garnier-Amblard

Kamalesh Poornachary

Sommer Zimmerman

Scott Myers

Rose M Freel

Lawrence Wilson

Compounds that selectively inhibit GluN2B-containing N-methyl-D-aspartic acid receptors (NM/DARs) are disclosed. In some cases, the compounds selectively target GluN2B over GluN2A, GluN2C, and/or GluN2D. Generally, the compounds possess an enhanced potency to GluN2B at a pH that is more acidic compared to the physiological pH. Pharmaceutical formulations containing one or more of the compounds are also disclosed. Additionally, methods of treating a condition, disorder or disease using the compounds or their pharmaceutical formulations thereof are disclosed. Exemplary conditions, disorders, and diseases relevant to this disclosure include stroke, subarachnoid hemorrhage, cerebral ischemia, cerebral vasospasm, hypoxia, acute CNS injury, spinal cord injury, traumatic brain injury, coronary artery bypass graft, persistent or chronic cough, substance abuse disorder, opiate withdrawal, opiate tolerance, bipolar disorder, suicidal ideation, pain, fibromyalgia, depression, postpartum depression, resting tremor, dementia, epilepsy, seizure disorder, movement disorder, and neurodegenerative disease.

GluN2B-subunit selective antagonists of the N-methyl-D-aspartate receptors with enhanced potency at acidic pH

A compound according to Formula (I) or salts or prodrugs thereof and pharmaceutical formulations comprising the compound are provided herein for the treatment of neurological disorders. The disorders may include providing neuroprotection, preventing neurodegeneration, treating neuropathic pain or treating schizophrenia, psychoses or depression. Furthermore, the compounds may be used in combination with another active ingredient.

GluN2C/D subunit selective antagonists of the N-methyl-D-aspartate receptor

This disclosure relates to pyrazoline dihydroquinolone derivatives, pharmaceutical compositions, and uses. In certain embodiments, the compounds are selective NMDA receptor inhibitors and are useful in therapeutic methods related thereto. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a compound of the following formula:

Pyrazoline dihydroquinolones, pharmaceutical compositions, and uses

The disclosure relates thieno[2,3-d]pyrimidin-4-one derivatives as modulators of NMDA receptors and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing conditions related to cognition, typically prevention or treatment of neurological conditions related to the NMDA receptor.

Thieno[2,3-d]pyrimidin-4-one derivatives as NMDAR modulators and uses related thereto

A series of subunit selective allosteric modulators of NMDA receptor function according to Formula (I) is provided herein. Also provided is a method of treating neurological disorders such as Alzheimer's disease Parkinson's disease, schizophrenia, depression, stroke, psychosis and the like using compounds of Formula (I), optionally in combination with one or more further active agent. Pharmaceutical compositions containing a compound of Formula (I) and optionally one or more active agent for treating such disorders may be provided in the form of a tablet, capsule, pill, gel, granules, aerosol, aqueous buffer or a nanoparticle formulation, emulsion, liposome, etc. (I)

N-methyl-D-aspartic acid receptor modulators

This disclosure relates to pyrazoline dihydroquinolone derivatives, pharmaceutical compositions, and uses. In certain embodiments, the compounds are selective NMDA receptor inhibitors and are useful in therapeutic methods related thereto. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a compound of the following formula: 

This disclosure relates to tetrahydroisoquinolines, salts, and derivatives useful for managing mental or cognitive diseases or conditions of the brain or central nervous system. In certain embodiments, the disclosure relates to compounds and compositions having formula I: prodrugs, esters, or salts thereof, wherein the substituents are described herein. 

N-methyl-D-aspartate receptor (NMDAR) potentiators, pharmaceutical compositions, and uses related thereto

Provided are compounds, pharmaceutical compositions and methods of treating or preventing disorders associated with NMDA receptor activity, including schizophrenia, Parkinson's disease, cognitive disorders, depression, neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds of the general Formulas A-J, and pharmaceutically acceptable salts, esters, prodrugs or derivatives thereof are disclosed.

Subunit selective NMDA receptor potentiators for the treatment of neurological conditions

This disclosure relates to NMDA modulators and used related thereto such as for treatment of central nervous system disorders. In certain embodiments, compounds disclosed herein are NR2C subunit-selective NMDA potentiators. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions. In certain embodiments, the disclosure contemplates compounds disclosed herein as prodrugs, optionally substituted with one or more substituents, derivatives, or salts thereof. In certain embodiments, the disclosure relates to methods of treating or preventing nervous system disorders comprising administering an effective amount of a composition comprising compound disclosed herein to a subject in need thereof.

NMDA receptor modulators and uses related thereto

Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein:

NMDA receptor antagonists for neuroprotection

Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein:each (L)-Aris a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NRor O and each Rand Ris independently H, alkyl, alkenyl or aralkyl or Rand Rtaken together form a 5-8 membered ring; RRare selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO, CH, NH, N(alkyl), or NHC(&#x2550;O); and Z is OH, NRR, NRSO(alkyl), NRC(O)NRR, NRC(O)O(alkyl), NR-dihydrothiazole, or NR-dihydroimidazole or wherein Z can fuse with Arto form selected heterocycles.

NMDA receptor blockers, including pH-sensitive NMDA receptor blockers, are provided as neuroprotective drugs that are useful in stroke, traumatic brain injury, epilepsy, and other neurologic events that involve acidification of brain or spinal cord tissue. Compositions and methods of this invention are used for treating neurodegeneration resulting from NMDA receptor activation. The compounds described herein have enhanced activity in brain tissue having lower-than normal pH due to pathological conditions such as hypoxia resulting from stroke, traumatic brain injury, global ischemia that may occur during cardiac surgery, hypoxia that may occur following cessation of breathing, pre-eclampsia, spinal cord trauma, epilepsy, chronic pain, vascular dementia and glioma tumors. Compounds described herein are also useful in preventing neurodegeneration in patients with Parkinson's Alzheimer's, Huntington's chorea, ALS, and other neurodegenerative conditions known to the art to be responsive to treatment using NMDA receptor blockers. Preferably the compounds provided herein are allosteric NMDA inhibitors.

Growing community of inventors

Decatur, GA, United States of America

Stephen F Traynelis