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.

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Kumar KS, Kiran Kumar S, Yogi Sreenivas B, Gorja DR, Kapavarapu R, Rambabu D, Rama Krishna G, Reddy CM, Basaveswara Rao MV, Parsa KV, Pal M

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.

Bioorg Med Chem. 2012 Apr 1;20(7):2199-207. doi: 10.1016/j.bmc.2012.02.027. Epub 2012 Feb 16.

PubMed ID

22386978 [ View in PubMed

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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) approximately 0.89 muM) is presented.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
(R)-Rolipram	cAMP-specific 3',5'-cyclic phosphodiesterase 4B	EC 50 (nM)	220	N/A	N/A	Details