Conformational analysis of tandospirone in aqueous solution: lead evolution of potent dopamine D4 receptor ligands.
The significant contribution of folded conformation (2) of the anxiolytic tandospirone (1) in aqueous solution was verified by dynamic 1H NMR. A structurally rigid mimic of 2 was designed and synthesized to evaluate the implication of 2 towards neuroleptic receptor binding. The designed structures provided a new rigid scaffold for dopamine D4 ligands.
Nishimura
T
T
Sumitomo Pharmaceuticals Research Division, Osaka, Japan.
Igarashi
J
J
Sunagawa
M
M
D015195:Drug Design; D007202:Indicators and Reagents; D054833:Isoindoles; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D010879:Piperazines / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050638:Receptors, Dopamine D4; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000737:chemistry*; D012996:Solutions
D007202:Indicators and Reagents; D054833:Isoindoles; D008024:Ligands; D010879:Piperazines; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012996:Solutions; D050638:Receptors, Dopamine D4; C055267:tandospirone