Columbia University

Cornell University

Sloan-Kettering Institute for Cancer Research

Icahn School of Medicine at Mount Sinai

Research Foundation for Mental Hygiene, Inc.

Jonathan A Javitch

Dalibor Sames

Andrew Carry Kruegel

Madalee G Wulf

Marie-Laure Rives

Scott C Blanchard

Thomas Edward Prisinzano

Marta Filizola

Harel Weinstein

Adam Henke

Madalee M Gassaway

Juraj Galeta

Vaclav Havel

Srijita Bhowmik

Susruta Majumdar

Maria Hauge Pedersen

Andrew C Kruegel

Marie-Laure Rivers

The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

Opioid receptor modulators

The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

Mitragynine alkaloids as opioid receptor modulators

The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with a pain, a depressive disorder, a mood disorder, an anxiety disorder, borderline personality disorder, opioid addiction, or opioid withdrawal symptoms by administering the compound to the subject.

Carboxylic diarythiazepineamines as mixed mu- and delta-opioid receptor agonists

Mitragynine analogs for the treatment of pain, mood disorders and substance use disorders

The current invention is methods and assays for detecting and/or measuring the modification, i.e., activation or inhibition, of a receptor of interest, without the need to modify the receptor with a label or a tag. The invention uses proteins that move, translocate, are recruited and/or bind to the receptor of interest when the receptor is modified, and proteins in proximity to and/or in the same compartment as the receptor of interest. The proteins are attached or linked to polypeptides that result from the unique cleavage of a modifiedluciferase. When the proteins are in proximity allowing the unique polypeptides to recombine, a luminescent signal is generated. The invention also includes vector encoding these proteins, cells expressing these proteins, compositions, system and kits.

Assays using arrestin recruitment and unmodified receptors

This disclosure is directed to methods of conducting dynamic single-molecule fluorescence studies such as smFRET on a membrane protein which permits observation and quantification of conformational dynamics of a membrane protein. Also disclosed herein are mutant membrane proteins in which one or more mutations have been introduced for affixing a fluorophore, as well as reagents and kits containing such mutant membrane proteins for conducting dynamic single-molecule fluorescence studies. The methods and compositions disclosed herein can be used in screening for compounds that enhance or reduce the activity of a membrane protein, useful for treating diseases associated with the malfunction of the membrane protein or alterations in membrane protein conformation.

SmFRET with membrane proteins

The present invention provides a compound having the structure of the instant invention of a pharmaceutically acceptable salt or ester thereof, methods of preparing the same, and methods of treating a subject with compounds of the instant invention in combination therapies.

Carboxylic diarylthiazepineamines as mu-opioid receptor agonists

The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof.

Class of mu-opioid receptor agonists

The present invention provides, inter alia, compounds of formula (I): (structurally represented). Also provided are pharmaceutical compositions containing such compounds and methods for treating or ameliorating the effects of a medical condition in a subject using such compounds or pharmaceutical compositions. 

Growing community of inventors

Dobbs Ferry, NY, United States of America

Jonathan A Javitch