TY - JOUR
T1 - Synthesis, Lipophilicity and Structure of 2,5-Disubstituted 1,3,5-Dithiazine Derivatives
AU - Winfield, Leyte
AU - Zhang, Chunming
AU - Reid, Christy A.
AU - Stevens, Edwin D.
AU - Trudell, Mark L.
AU - Izenwasser, Sari
AU - Wade, Dean
PY - 2003/1/1
Y1 - 2003/1/1
N2 - A series of 2,5-disubstituted 1,3,5-dithiazine derivatives were synthesized as potential analogues of the potent dopamine uptake inhibitor GBR 12909. The lipophilic character of the 1,3,5-dithiazine derivatives were experimentally (log P) and computationally (clog P) determined. The in vitro binding affinities of the 2,5-disubstituted 1,3,5-dithiazine derivatives at the dopamine transporter were determined to be much less potent than the binding affinity of GBR 12909 due to steric and electronic effects inherent to the 1,3,5-dithiazine ring system. The X-ray crystal structure of 2-(2-[bis(4-fluorophenyl)methoxy]ethyl)-5-(3-phenylpropyl)-1,3,5-dithiazine (7) revealed that the 5-(3-phenylpropyl) group is in a pseudo-axial orientation and syn to the 2-ethoxybenzhydryl moiety.
AB - A series of 2,5-disubstituted 1,3,5-dithiazine derivatives were synthesized as potential analogues of the potent dopamine uptake inhibitor GBR 12909. The lipophilic character of the 1,3,5-dithiazine derivatives were experimentally (log P) and computationally (clog P) determined. The in vitro binding affinities of the 2,5-disubstituted 1,3,5-dithiazine derivatives at the dopamine transporter were determined to be much less potent than the binding affinity of GBR 12909 due to steric and electronic effects inherent to the 1,3,5-dithiazine ring system. The X-ray crystal structure of 2-(2-[bis(4-fluorophenyl)methoxy]ethyl)-5-(3-phenylpropyl)-1,3,5-dithiazine (7) revealed that the 5-(3-phenylpropyl) group is in a pseudo-axial orientation and syn to the 2-ethoxybenzhydryl moiety.
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U2 - 10.1002/jhet.5570400512
DO - 10.1002/jhet.5570400512
M3 - Article
AN - SCOPUS:0242330276
VL - 40
SP - 827
EP - 832
JO - Journal of Heterocyclic Chemistry
JF - Journal of Heterocyclic Chemistry
SN - 0022-152X
IS - 5
ER -