The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia.

Department of Medicinal Chemistry, Merck Research Laboratories, Kenilworth, NJ 07033, United States. ginny.ho@merck.com

Bioorganic & medicinal chemistry letters 2012 Apr 1

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The identification of potent and orally active dihydroimidazoisoquinolines as PDE 10A inhibitors is reported. The SAR development led to the discovery of compound 35 as a potent, selective, and orally active PDE10A inhibitor. Compound 35 inhibited MK-801-induced hyperactivity at 3mg/kg and displayed a 10-fold separation between the minimal effective doses for inhibition of MK-801-induced hyperactivity and hypolocomotion in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Ginny D Ho, W Michael Seganish, Ana Bercovici, Deen Tulshian, William J Greenlee, Rachel Van Rijn, Alan Hruza, Li Xiao, Diane Rindgen, Deborra Mullins, Mario Guzzi, Xiaoping Zhang, Carina Bleickardt, Robert Hodgson. The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorganic & medicinal chemistry letters. 2012 Apr 1;22(7):2585-9