Discovery of Clinical Candidate N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915): A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders.

@article{Mikami2017DiscoveryOC,
  title={Discovery of Clinical Candidate N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915): A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders.},
  author={Satoshi Mikami and Shinji Nakamura and Tomoko Ashizawa and Izumi Nomura and Masanori Kawasaki and Shigekazu Sasaki and Hideyuki Oki and Hironori Kokubo and Isaac Dylan Hoffman and Hua Song Zou and Noriko Uchiyama and Kosuke Nakashima and Naomi Kamiguchi and Haruka Imada and Noriko Suzuki and Hiroki Iwashita and Takahiko Taniguchi},
  journal={Journal of medicinal chemistry},
  year={2017},
  volume={60 18},
  pages={
          7677-7702
        }
}
Phosphodiesterase (PDE) 2A inhibitors have emerged as a novel mechanism with potential therapeutic option to ameliorate cognitive dysfunction in schizophrenia or Alzheimer's disease through upregulation of cyclic nucleotides in the brain and thereby achieve potentiation of cyclic nucleotide signaling pathways. This article details the expedited optimization of our recently disclosed pyrazolo[1,5-a]pyrimidine lead compound 4b, leading to the discovery of clinical candidate 36 (TAK-915), which… CONTINUE READING
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