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

Sri International

The Cooper Health System

University System of Maryland

Ruin Moaddel

Carlos A Zarate

Craig J Thomas

Irving William Wainer

Patrick Joseph Morris

Todd Gould

Panos Zanos

Marc C Torjman

Michel Bernier

Mary Jean Tanga

Michael E Goldberg

Gregory S Keyes

Christopher E Ramsden

Jack R Collins

Luigi Ferrucci

Myriam Gorospe

Kotb Abdelmohsen

Krzysztof Jozwiak

Martina Rossi

Sarangan Ravichandran

Carlos Zarate

Patrick Morris

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

Gingerenone A prodrug compounds have a structure according to Formula I, or a pharmaceutically acceptable salt thereof wherein one of Rand Ris H or —C(O)—R and the other of Rand Ris —C(O)—R. Each R independently is Ror, where Ris C-Calkenyl, and Ris an amino acid side chain. The compounds are useful for inhibiting or eliminating senescence. The compounds may be administered to a subject having a senescence-associated disease or disorder, neuroinflammation, pain, and/or an amino acid deficiency.

Gingerenone A prodrugs as sensotherapeutics and methods of use

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.

The disclosure provides pharmaceutical preparations containing (2R,6R)-hydroxynorketamine, or (R)- or (S)-dehydronorketamine, or other stereoisomeric dehydro or hydroxylated ketamine metabolite. (2R,6R)-hydroxynorketamine The disclosure also provides novel ketamine metabolite prodrugs. The disclosure provides methods of treating, bipolar depression, major depressive disorder, neuropathic and chronic pain, including complex regional pain synthetic pain disorder (CRPD) by administering a purified ketamine metabolite or a ketamine metabolite prodrug directly to patients in need of such treatment.

Use of (2R, 6R)-hydroxynorketamine, (S)-dehydronorketamine and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine in the treatment of depression and neuropathic pain

The disclosure provides pharmaceutical preparations containing (2R,6R)-hydroxynorketamine, or (R)- or (S)-dehydronorketamine, or other stereoisomeric dehydro or hydroxylated ketamine metabolite. (2R,6R)-hydroxynorketamine The disclosure also provides novel ketamine metabolite prodrugs. The disclosure provides methods of treating, bipolar depression, major depressive disorder, neuropathic and chronic pain, including complex regional pain disorder (CRPS) by administering a purified ketamine metabolite or a ketamine metabolite prodrug directly to patients in need of such treatment. 

A computer readable medium holding data of a molecular model of a ligand-gated ion channel receptor and/or a computer system for modeling said receptor are provided by the instant invention. The molecular model can be used to design novel compounds having activity as non-competitive inhibitors of the ion channel. A preferred embodiment of the invention relates to nicotinic acetylcholine receptors. Compounds having activity as non-competitive inhibitors of ligand-gated ion channel receptors and methods for inhibiting the receptor and treating diseases or disorders mediated by function of the receptor are also disclosed.

Computer-based model for identification and characterization of non-competitive inhibitors of nicotinic acetylcholine receptors and related ligand-gated ion channel receptors

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Bel Air, MD, United States of America

Ruin Moaddel