Bioorganic & Medicinal Chemistry 2012-04-01

C-C bond formation at C-2 of a quinoline ring: synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors.

K Shiva Kumar, S Kiran Kumar, B Yogi Sreenivas, Dhilli Rao Gorja, Ravikumar Kapavarapu, D Rambabu, G Rama Krishna, C Malla Reddy, M V Basaveswara Rao, Kishore V L Parsa, Manojit Pal

Index: Bioorg. Med. Chem. 20(7) , 2199-207, (2012)

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Abstract

A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl(3)-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC(50) ∼0.89 μM) is presented.Copyright © 2012 Elsevier Ltd. All rights reserved.