Columbia University

Albany Molecular Research, Inc.

Agenebio, Inc.

University of Michigan

Emily Elizabeth Freeman

Graham Johnson

Konstantin Petrukhin

Christopher Cioffi

Lei Zhu

Michael Conlon

Ping Chen

Nicoleta Dobri

Rando L Allikmets

Peter Guzzo

Matthew Surman

Qin Jiang

Nicholas James Mayhew

John Anthony Butera

Robert Jason Herr

Jianxing Huang

Belew Mekonnen

Hemantbhai Patel

Neil Moss

James A Shayman

Scott D Larsen

Alan John Henderson

Mark Hadden

Kim Hutchings

Zohreh Sajjadi Hashemi

James Francis Grabowski, Jr

Peter R Guzzo

The present invention provides a compound having the structure:

4-phenylpiperidines, their preparation and use

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

Substituted 4-phenylpiperidines, their preparation and use

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with CNS disorders. It also relates to the use of an α5-containing GABAreceptor agonist (e.g., an α5-containing GABAreceptor positive allosteric modulator) in treating cognitive impairment associated with CNS disorders in a subject in need or at risk thereof, including age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI, Age-Associated Memory Impairment, Age Related Cognitive Decline, dementia, Alzheimer's Disease (AD), prodromal AD, PTSD, schizophrenia, bipolar disorder, ALS, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease, autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of an α5-containing GABAreceptor agonist (e.g., an α5-containing GABAreceptor positive allosteric modulator) in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment

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

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with CNS disorders. It also relates to the use of an &#x3b1;5-containing GABAreceptor agonist (e.g., an &#x3b1;5-containing GABAreceptor positive allosteric modulator) in treating cognitive impairment associated with CNS disorders in a subject in need or at risk thereof, including age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI, Age-Associated Memory Impairment, Age Related Cognitive Decline, dementia, Alzheimer's Disease (AD), prodromal AD, PTSD, schizophrenia, bipolar disorder, ALS, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease, autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of an &#x3b1;5-containing GABAreceptor agonist (e.g., an &#x3b1;5-containing GABAreceptor positive allosteric modulator) in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

Glucosylceramide synthase inhibitors and therapeutic methods using the same

The present invention provide a compound having the structure: (structurally represented) wherein R, R, R, R, and Rare each independently H, halogen, CFor C-Calkyl; Ris H, OH, or halogen; B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole, wherein the heterocycle is other than chloro substituted indole; and the pyrazole, when substituted, is substituted with other than trifluoromethyl, or a pharmaceutically acceptable salt thereof.

The present invention provides compounds comprising variously substituted octahydropyrrolopyrroles, their synthesis, methods of making, methods of using, compositions and formulations thereof.

Octahydropyrrolopyrroles their preparation and use

The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is alkyl; A is absent or present, and when present is &#x2014;C(O)&#x2014; or &#x2014;C(O)NH&#x2014;; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is &#x2014;C(O)&#x2014;, or a pharmaceutically acceptable salt thereof.

N-alkyl-2-phenoxyethanamines, their preparation and use

The present invention provides Octahydrocyclopentapyrrole compounds having the structure: (structurally represented) wherein psi is absent or present, and when present is a bond; R1, R2, R3, R4, and R5 are each independently H, halogen, CF, or C1-C4 alkyl; R6 is absent or present, and when present is H, OH, or halogen; A is absent or present, and when present is C(O) or C(O)NH; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is C(O); and when psi is present, then R6 is absent and when psi is absent, then R6 is present, or a pharmaceutically acceptable salt thereof, for treatment of diseases characterized by excessive lipofuscin accumulation in the retina.

Octahydrocyclopentapyrroles, their preparation and use

The present invention provides a compound having the structure: (structurally represented) wherein R, R, R, R, and Rare each independently H, halogen, CFor C-Calkyl; Ris H, OH, or halogen; B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole, wherein the heterobicycle is other than chloro substituted indole; and the pyrazole, when substituted, is substituted with other than trifluoromethyl, or a pharmaceutically acceptable salt thereof.

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Voorheesville, NY, United States of America

Emily Elizabeth Freeman