460356-15-4Relevant articles and documents
Synthesis and pharmacology of site specific cocaine abuse treatment agents: A new synthetic methodology for methylphenidate analogs based on the Blaise reaction
Deutsch, Howard M,Ye, Xiaocong,Shi, Qing,Liu, Zhanzhu,Schweri, Margaret M
, p. 303 - 311 (2007/10/03)
In order to make new analogs of the dopamine (DA) uptake inhibitor methylphenidate, a synthetic methodology based on the Blaise reaction was developed. The reaction between α-bromophenylacetic acid esters, zinc and α-cyano-ω-mesylates gave stable primary enamines. After reduction of the enamines with cyanoborohydride, the amines could be cyclized to methylphenidate analogs in which the amine ring size and aromatic ring were varied. These compounds were tested for inhibitory potency against [3H]WIN 35,428 binding to the cocaine recognition site and [3H]DA uptake using rat striatal tissue. When the heterocyclic ring size was varied, the six-membered ring of methylphenidate appeared to be the optimum ring size. When the aryl ring was varied the 4-trifluoromethylphenyl analog was less potent than methylphenidate, the β-naphthyl congener was considerably more potent, whereas the α-naphthyl congener was less potent. Most of the compounds tested had ratios of uptake to binding inhibition (discrimination ratio) that were similar to cocaine and were therefore not lead compounds for the development of cocaine antagonists.
