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Abstract

Grant Number:	1R43NS046109-01
PI Name:	SMITH, MILES P.
PI Email:	msmith@biostream.net
PI Title:
Project Title:	Halopiperidines for imaging of monoamine transporters

Abstract: DESCRIPTION (provided by applicant): The monoamine transporters are important targets for therapy, diagnosis and monitoring of a number of CNS disease states. It is expected that imaging agents that exhibit high affinity and selectivity for the dopamine transporter (DAT) would fulfill a number of unmet needs including use for Parkinson's disease (PD), ADD/ADHD, depression and cocaine abuse. Additionally, imaging agents that exhibit high affinity and selectivity for either the serotonin or norepinephrine transporters would similarly be of utility for the diagnosis and monitoring of depressive syndromes and related disorders. While, many studies have reported the design of radioligands for the DAT no agents have been disclosed that exhibit favorable imaging properties that are required for widespread utilization. Fewer reports are available on specific radioligands for the serotonin (5-HTT) and norepinephrine (NET) transporters. Herein, we propose the rational design and synthesis a series of halogenated piperidines as potential radio-tracers for imaging of the monoamine transporters utilizing PET and SPECT. These studies utilize our versatile and efficient piperidine pharmacophore for the facile preparation of highly selective monoamine transporter ligands exploiting the divergent structure activity relationships for the enantiomers/isomers of the piperidine. In this manner it is anticipated that this work will result in the identification of new radiopharmaceuticals that can be labeled with positron emitting elements for PET, or single photon emitting elements for SPECT. These radiopharmaceuticals would be of wide spread use for both the diagnosis of CNS disorders and the monitoring of therapeutic interventions.

Thesaurus Terms:
drug design /synthesis /production, halogenation, neuroimaging, neurotransmitter transport, piperidine, radiotracer, technology /technique development
chemical structure function, dopamine transporter, serotonin transporter
bioimaging /biomedical imaging, biotechnology, chemical synthesis, positron emission tomography, single photon emission computed tomography

Institution:	MOLECULAR INSIGHT PHARMACEUTICALS, INC.
	160 2ND ST
	CAMBRIDGE, MA 02142
Fiscal Year:	2003
Department:
Project Start:	01-JUL-2003
Project End:	31-DEC-2003
ICD:	NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG:	ZRG1

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