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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Aminopyrimidines with high affinity for both serotonin and dopamine receptors.

A series of [4-[2(4-arylpiperazin-1-yl)alkyl]cyclohexyl]pyrimidin-2-ylamine s was prepared and found to have receptor binding affinity for D2 and D3 dopamine (DA) receptors and serotonin 5-HT1A receptors. The structural contributions to D2/D3 and 5-HT1A receptor binding of the aminopyrimidine, cycloalkyl, and phenylpiperazine portions of the molecule were examined. From these studies compounds 14, 39, 42, 43, having potent affinity for both DA D2 and 5-HT1A receptors, were evaluated for intrinsic activity at these receptors, in vitro and in vivo. Compound 14 (PD 158771) had a profile indicative of partial agonist activity at both D2 and 5-HT1A receptors causing partially decreased synthesis of the neurotransmitters DA and 5-HT and their metabolites. This compound has a profile in behavioral tests that is predictive of antipsychotic activity, suggesting that mixed partial agonists such as 14 may have utility as antipsychotic agents with increased efficacy and decreased side effects.[1]

References

  1. Aminopyrimidines with high affinity for both serotonin and dopamine receptors. Wustrow, D., Belliotti, T., Glase, S., Kesten, S.R., Johnson, D., Colbry, N., Rubin, R., Blackburn, A., Akunne, H., Corbin, A., Davis, M.D., Georgic, L., Whetzel, S., Zoski, K., Heffner, T., Pugsley, T., Wise, L. J. Med. Chem. (1998) [Pubmed]
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