Design, synthesis, and activity of novel cis- and trans-3,6-disubstituted pyran biomimetics of 3,6-disubstituted piperidine as potential ligands for the dopamine transporter.
In our effort to develop novel molecules for the dopamine transporter, we converted our previously designed dopamine transporter specific 3,6-disubstituted piperidine template into corresponding pyran derivatives. cis-Pyran derivative 7b, like their piperidine counterparts, exhibited greater activity for the dopamine transporter compared to the trans-isomer. Further molecular modifications of the cis derivative led to the development of potent analogues which indicated successful bioisosteric replacement of the piperidine ring by a pyran moiety in these 3,6-disubstituted derivatives.
Zhang
Shijun
S
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
Reith
Maarteen E A
ME
Dutta
Aloke K
AK
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010880:Piperidines; D011714:Pyrans; D004298:Dopamine