Research Triangle Institute

The United States of America As Represented by the Department of Health

Virginia Commonwealth University

Dignity Health

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

Office of Technology Transfer

Dignity Health Doing Business As St. Joseph's Hospital and Medical Center and Barrow Neurological Institute

Dignity Health Doing Business As St. Joseph's Hospital Medical Center and Barrow Neurological Institute

Bruce Edward Blough

Frank Ivy Carroll

Richard B Rothman

Philip Abraham

Hernan A Navarro

S Wayne Mascarella

Ronald J Lukas

Ana Zamfira Muresan

M Imad Damaj

Samuel W Mascarella

Ann Decker

F Ivy Carroll

Antonio Landavazo

Kevin M Page

Frank J Carroll

Richard Rothman

Ann Marie Decker

The invention provides bupropion analogue compounds capable of inhibiting the reuptake of one or more monoamines. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin. Such compounds may be used to treat conditions that are responsive to inhibition of the reuptake of monoamines, including addiction, depression, and obesity.

Monoamine reuptake inhibitors

The disclosure provides monoamine neurotransmitter releaser and/or monoamine uptake inhibitor compounds having biogenic amine transporter activity but lacking substantial activity at 5-HTreceptor subtypes. The phenethylamine or vinylogous phenethylamine compounds of the disclosure are useful in treating diseases, conditions and/or disorders mediated by activity of one or more of the monoamine neurotransmitters.

Vinylogous phenethylamines as neurotransmitter releasers

Provided herein are compounds and prodrugs and methods of preparation of compounds and prodrugs that are capable of functioning as releasers and/or uptake inhibitors of one or more monoamine neurotransmitters, including dopamine, serotonin, and norepinephrine. Also provided are pharmaceutical compositions comprising one or more of these compounds or prodrugs, which may further comprise one or more additional therapeutic agents. Also provided are methods of treatment of various conditions that may be responsive to modification of monoamine neurotransmitter levels, such as pre-obesity, obesity, addiction, and depression.

Phenylmorpholines and analogues thereof

The invention provides bupropion analog compounds capable of inhibiting the reuptake of one or more monoamines. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin. Such compounds may be used to treat conditions that are responsive to inhibition of the reuptake of monoamines, including addiction, depression, and obesity.

The invention provides hydroxybupropion analogs capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.

Hydroxybupropion analogues for treating drug dependence

The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.

The present invention provides a compound having the structure: ##STR1## wherein X, Y, and Z are independently H, Cl, Br, F, OCH.sub.3, I, or an alkyl group having 1 to 6 carbon atoms; and R is ##STR2## wherein n is 0 to 6, X' and Y' are independently H, Cl, F, CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, C.sub.4 H.sub.9, OCH.sub.3, OH, CF.sub.3, OCF.sub.3, NO.sub.2, NH.sub.2, N(CH.sub.3).sub.2, NHCOCH.sub.3, NCS, NHCOCH.sub.2 Br, or N.sub.3, and (CH.sub.2).sub.n, if present, may be substituted with OH, OCH.sub.3, or an alkyl or alkenyl group having 1 to 3 carbon atoms. The present invention also provides a pharmaceutical composition comprising the compound above and a pharmaceutically acceptable carrier. The present invention further provides a method for treating a disease characterized by a dopamine deficiency which comprises administering to a subject in need of such treatment an amount of the pharmaceutical composition above effective to treat the disease.

Selective inhibitors of biogenic amine transporters

Growing community of inventors

Raleigh, NC, United States of America

Bruce Edward Blough