- N′-3-(Trifluoromethyl)phenyl Derivatives of N-Aryl-N′-methylguanidines as Prospective PET Radioligands for the Open Channel of the N-Methyl- d -aspartate (NMDA) Receptor: Synthesis and Structure-Affinity Relationships
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N-Methyl-d-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain NMDA receptors in the activated "open channel" state would be useful for research on such disorders and for the development of novel therapies. To date, no radioligands have shown well-validated efficacy for imaging NMDA receptors in human subjects. In order to discover improved radioligands for PET imaging, we explored structure-affinity relationships in N′-3-(trifluoromethyl)phenyl derivatives of N-aryl-N′-methylguanidines, seeking high affinity and moderate lipophilicity, plus necessary amenability for labeling with a positron-emitter, either carbon-11 or fluorine-18. Among a diverse set of 80 prepared N′-3-(trifluoromethyl)phenyl derivatives, four of these compounds (13, 19, 20, and 36) displayed desirable low nanomolar affinity for inhibition of [3H](+)-MK801 at the PCP binding site and are of interest for candidate PET radioligand development.
- Naumiec, Gregory R.,Jenko, Kimberley J.,Zoghbi, Sami S.,Innis, Robert B.,Cai, Lisheng,Pike, Victor W.
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p. 9722 - 9730
(2016/01/12)
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- Regioselective one-pot synthesis of 5-CHLORO-3-METHYL8-TRIFLUOROMETHYL-4H- l,4-BENZOTHIAZINES
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5-Chloro-3-methyl-8-trifluoromethyl-4H-l, 4-benzothiazines have been synthesized by an efficient synthetic method in a single step involving heterocyclization of 2amino-3-chloro-6-trifluoromethylbenzenethiol with D-ketoesters or D-diketones. 2Amino-3-chloro-6-trifluoromethylbenzenethiol was prepared by hydrolytic cleavage of 2-amino-4-chloro-7- trifluoromethylbenzothiazole which in turn was prepared by brominative cyclization of 2-chloro-5-trifluoromethylphenylthiourea. The phenylthiourea was prepared by the reaction of 2-chloro-5-trifluoromethylaniline with ammonium thiocyantate. The structures of the synthesized 4H-1,4-benzothiazines have been characterized by their elemental analyses and spectral characteristics.
- Ankodia, Vandana,Sharma, Praveen Kumar,Sharma, Kailash,Kumar,Gupta, Archana
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p. 127 - 133
(2010/07/04)
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