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2004
Pyridine derivatives
R 0380
Ligand Conformation Has a Definitive Effect on 5-HT1A and Serotonin Reuptake
— Cyclohexane and cyclohexene based serotonin modulators with con52- 119 Affinity.
strained conformation are synthesized. In the first series (IX) the aryl ring is fixed in a
perpendicular orientation to the cyclohexane ring via a spiro lactone providing balanced 5-HT1A antagonists possessing mid-nanomolar range serotonin-selective
reuptake inhibitor potency. The latter activity is essentially improved at the expense of
5-HT1A activity upon rotation of the aryl ring to an orthogonal, planar conformation.
Compounds (XIV) are potent serotonin-selective reuptake inhibitors. — (BOY*, K.
M.; DEE, M.; YEVICH, J.; TORRENTE, J.; GAO, Q.; IBEN, L.; STARK, A.;
MATTSON, R. J.; Bioorg. Med. Chem. Lett. 14 (2004) 17, 4467-4470; Bristol-Myers
Squibb Pharm. Res. Inst., Wallingford, CT 06492, USA; Eng.) — H. Hoennerscheid
2004
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