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

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A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: discovery of a potential atypical antipsychotic agent.

As part of a program to develop dopamine D4 antagonists for the treatment of schizophrenia, we discovered a series of 6- and 7-(phenylpiperazinyl)- and -(phenylpiperidinyl)methylbenzoxazinones through mass screening of our compound library. A structure-activity relationship SAR study was carried out involving substituents on the phenyl ring, and several selective D4 antagonists were identified. The 7-substituted benzoxazinones showed more activity in neurochemical and behavioral tests than the 6-substituted series. One of the most potent and selective compounds (26) was found to have potent activity in animal tests predictive of antipsychotic activity in humans after oral administration. This paper describes the SAR of the benzoxazinone series and the preclinical characterization of 26.[1]

References

  1. A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: discovery of a potential atypical antipsychotic agent. Belliotti, T.R., Wustrow, D.J., Brink, W.A., Zoski, K.T., Shih, Y.H., Whetzel, S.Z., Georgic, L.M., Corbin, A.E., Akunne, H.C., Heffner, T.G., Pugsley, T.A., Wise, L.D. J. Med. Chem. (1999) [Pubmed]
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