The author of 《Synthesis and pharmacology of site-specific cocaine abuse treatment agents: the role of the phenyl group in highly modified methylphenidate analogs as dopamine uptake inhibitors》 were Deutsch, Howard M.; Dunn, Travis; Ye, Xiaocong; Schweri, Margaret M.. And the article was published in Medicinal Chemistry Research in 1999. Reference of Methyl 2-(piperidin-3-yl)acetate hydrochloride The author mentioned the following in the article:
A series of modified methylphenidate derivatives was synthesized and tested for inhibitory potency in [3H]WIN 35,428 binding and [3H]dopamine uptake assays using rat striatal tissue. In these compounds the role of the Ph ring was investigated by its removal from the position adjacent to the ester function. The des-Ph analogs were then subsequently modified by reintroduction of the Ph ring in the form of N-benzyl, N-(2-phenylethyl) or N-(3-phenylpropyl). The des-Ph analogs had no significant affinity for the [3H]WIN 35,428 binding site and almost no ability to inhibit [3H]dopamine uptake, indicating the primary importance of the Ph group. All N-benzyl analogs had very low affinity, with IC50 values against [3H]WIN 35,428 binding in the range of 40-100 μM. Interestingly, among the N-(2-phenylethyl) analogs, the one with the carboxymethyl group in the 2-position (like methylphenidate) was much more potent (IC50=2.24 μM) than the analogs with the ester group in the 3- or 4-positions. A derivative of Me N-(2-phenylethyl)-2-piperidylacetate (I), with 3,4-dichloro substituents, was less potent than the parent compound Me N-(3-phenylpropyl)-2-piperidylacetate was also less potent than I. Although I is only some 27-fold less potent than methylphenidate, it appears that its Ph group does not interact with the normal aromatic ring binding region of the dopamine transporter. In the experiment, the researchers used many compounds, for example, Methyl 2-(piperidin-3-yl)acetate hydrochloride(cas: 247259-31-0Reference of Methyl 2-(piperidin-3-yl)acetate hydrochloride)
Methyl 2-(piperidin-3-yl)acetate hydrochloride(cas: 247259-31-0) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.Reference of Methyl 2-(piperidin-3-yl)acetate hydrochloride
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem