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Parker MA, Marona-Lewicka D, Lucaites VL, Nelson DL, Nichols DE. 
“A novel (benzodifuranyl)aminoalkane with extremely potent activity at the 5-HT2A receptor”. 
J Med Chem. 1998 Dec 17;41(26):5148-9.
Abstract
A major focus of our research for a number of years has been to understand the structure-activity relationship (SAR) of classical hallucinogens and their derivatives, the pharmacological action of which is believed to be mediated primarily by agonist activity at the serotonin 5-HT2A receptor.2,3 In particular we have sought to understand the relationship between the modes of binding of the hallucinogens containing an indole nucleus, including LSD and psilocybin, and those containing a benzene nucleus, such as mescaline and its potent structural analogue 1 (DOB).4 In pursuing this goal, we recently reported the synthesis of the tetrahydrobenzodifuran 2 as a rigid analogue of DOB.5 Rat behavioral data and human receptor binding data showed that 2 is more potent than 1, a finding that was consistent with a binding site model first postulated by Westkaemper and Glennon,6 in which two hydrogenbond- donor residues in the receptor, possibly serine residues, lie on opposite sides of the molecule and form hydrogen bonds with the ether oxygen lone pairs. It was conjectured that the increase in activity of 2 relative to 1 is due to the fact that the lone pairs in 2 are fixed in an orientation favorable for forming such hydrogen bonds.
Notes # : dragonfly
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