2. Academic Validation
  3. Discovery of a tetracyclic quinoxaline derivative as a potent and orally active multifunctional drug candidate for the treatment of neuropsychiatric and neurological disorders

Discovery of a tetracyclic quinoxaline derivative as a potent and orally active multifunctional drug candidate for the treatment of neuropsychiatric and neurological disorders

  • J Med Chem. 2014 Mar 27;57(6):2670-82. doi: 10.1021/jm401958n.
Peng Li 1,  Qiang Zhang,  Albert J Robichaud,  Taekyu Lee,  John Tomesch,  Wei Yao,  J David Beard,  Gretchen L Snyder,  Hongwen Zhu,  Youyi Peng,  Joseph P Hendrick,  Kimberly E Vanover,  Robert E Davis,  Sharon Mates,  Lawrence P Wennogle
Affiliations

Affiliation

  • 1 Intra-Cellular Therapies, Inc. , 3960 Broadway, New York, New York 10032, United States.
PMID: 24559051 DOI: 10.1021/jm401958n
Abstract

We report the synthesis and structure-activity relationships of a class of tetracyclic butyrophenones that exhibit potent binding affinities to serotonin 5-HT(2A) and dopamine D2 receptors. This work has led to the discovery of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-1-(4-fluorophenyl)-butan-1-one 4-methylbenzenesulfonate (ITI-007), which is a potent 5-HT(2A) antagonist, postsynaptic D2 antagonist, and inhibitor of Serotonin Transporter. This multifunctional drug candidate is orally bioavailable and exhibits good antipsychotic efficacy in vivo. Currently, this investigational new drug is under clinical development for the treatment of neuropsychiatric and neurological disorders.

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