Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 827-832 |
| Number of pages | 6 |
| Journal | Journal of Heterocyclic Chemistry |
| Volume | 40 |
| Issue number | 5 |
| State | Published - Sep 1 2003 |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Synthesis, Lipophilicity and Structure of 2,5-Disubstituted 1,3,5-Dithiazine Derivatives. / Winfield, Leyte; Zhang, Chunming; Reid, Christy A.; Stevens, Edwin D.; Trudell, Mark L.; Izenwasser, Sari E; Wade, Dean.
In: Journal of Heterocyclic Chemistry, Vol. 40, No. 5, 01.09.2003, p. 827-832.Research output: Contribution to journal › Article
}
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 E
AU - Wade, Dean
PY - 2003/9/1
Y1 - 2003/9/1
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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UR - http://www.scopus.com/inward/citedby.url?scp=0242330276&partnerID=8YFLogxK
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 -