Emory University

Neurop, Inc.

Harvard College

Raymond J Dingledine

Dennis C Liotta

James P Snyder

Stephen F Traynelis

Lawrence J Wilson

Thota Ganesh

Yesim Altas Tahirovic

Scott James Myers

Cara Mosley

R John Collier

Haian Fu

Jianxiong Jiang

Shabber Mohammed

Scott Myers

Lawrence Wilson

Yesim Altas

David D Mott

James J Doherty, Jr

Radhika Amaradahi

The disclosure relates to Prostnglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, epilepsy, neuroinflammation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.

Prostaglandin receptor EP2 antagonists, derivatives, and uses related thereto

The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflammation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.

Prostaglandin receptor EP2 antagonists, derivatives, compositions, 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.

pH-dependent NMDA receptor antagonists

The invention provides a cytotoxicity-based genetic selection (TOXSEL) method and related testing kit for the identification and positive selection of molecules or mutations that are capable of disrupting a specific protein--protein interaction. The invention enables positive selection of molecules disruptive of specific protein--protein interactions by virtue of the presence in the TOXSEL system of a toxin reporter gene. A disrupted protein--protein interaction precludes expression of the toxin reporter gene and, consequently, allows survival of the host cell. TOXSEL technology enables large-scale screening for drugs or small molecules capable of disrupting specific protein--protein interactions critical in processes such as cellular signalling, carcinogenesis, etc. The positive selection of molecules or mutations capable of interfering with specific protein--protein interactions permits the identification of amino acid residues or motifs critical in the protein--protein interactions and permits the design of drugs for therapeutic or diagnostic applications.

Cytotoxicity-based genetic selection system (TOXSEL)

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Atlanta, GA, United States of America

Raymond J Dingledine