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Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: part II
Sanjib Das1, Dnyaneshwar E Shelke1, Rajendra L Harde1
1Glenmark Research Centre, Glenmark Pharmaceuticals Ltd, MIDC, Mahape, Navi Mumbai 400 709, India.
Abstract:
We report the design and synthesis of novel pyrrolo[3,2-b]quinoline containing heteroarene ethers as PDE10A inhibitors with good to excellent potency, selectivity and metabolic stability. Further optimization of this primary series resulted in the identification of 1-methyl-3-(4-{[3-(pyridine-4-yl)pyrazin-2-yl]oxy}phenyl)-1H-pyrrolo[3,2-b]pyridine 13a with good hPDE10A potency (IC50: 6.3 nM), excellent selectivity over other related PDEs and desirable physicochemical properties. The compound exhibited high peripheral and adequate brain levels upon oral dosing in rodents. The compound also showed excellent efficacy in multiple preclinical animal models related to psychiatric disorders, particularly schizophrenia.
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