An efficient aldol-type direct reaction of isatins with TMSCH<sub>2</sub>CN

Rao, V. U. Bhaskara; Kumar, Krishna; Singh, Ravi P.

doi:10.1039/c5ob01560j

Cited by 9 publications

(3 citation statements)

References 93 publications

(3 reference statements)

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“…S1). Further, 25 compounds from isatin in-house library [39] were docked and scored against HAV 3C protease to check for their inhibitory potential. All isatin compounds showed low binding potential computationally; hence iterative modifications in their structure were undertaken.…”

Section: Computational Methodologymentioning

confidence: 99%

“…An indole backbone, with various substituents on the core structure, has the ability to display a spectrum of functionalities. In particular, and due to their broad structural diversity, isatins have been shown to affect a wide range of biological targets [35][36][37][38][39]. We computationally screened a variety of isatin derivatives against HAV 3C protease, and found that two modifications in the protecting groups of isatins (in compounds 8 and 9; Table 1) resulted in better interactions with the target, as reflected in docking studies as well as in the 100 ns molecular dynamics simulations.…”

Section: Novel Isatin-based Compounds Against Hav 3cmentioning

confidence: 99%

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Toward development of generic inhibitors against the 3C proteases of picornaviruses

Banerjee¹,

Bhat

Rao

et al. 2018

The FEBS Journal

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Development of novel antivirals, which requires knowledge of the viral life cycle in molecular detail, is a daunting task, involving extensive investments, and frequently resulting in failure. As there exist significant commonalities among virus families in the manner of host interaction, identifying and targeting common rather than specific features may lead to the development of broadly useful antivirals. Here, we have targeted the 3C protease of Hepatitis A Virus (HAV), a feco‐orally transmitted virus of the family Picornaviridae, for identification of potential antivirals. The 3C protease is a viable drug target as it is required by HAV, as well as by other picornaviruses, for post‐translational proteolysis of viral polyproteins and for inhibiting host innate immune pathways. Computational screening, followed by chemical synthesis and experimental validation resulted in identification of a few compounds which, at low micromolar concentrations, could inhibit HAV 3C activity. These compounds were further tested experimentally against the 3C protease of Human Rhinovirus, another member of the Picornaviridae family, with comparable results. Computational studies on 3C proteases from other members of the picornavirus family have indicated that the compounds identified could potentially be generic inhibitors for picornavirus 3C proteases.

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Section: Computational Methodologymentioning

confidence: 99%

Section: Novel Isatin-based Compounds Against Hav 3cmentioning

confidence: 99%

Toward development of generic inhibitors against the 3C proteases of picornaviruses

Banerjee¹,

Bhat

Rao

et al. 2018

The FEBS Journal

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“…Recently, aryl- and trifluoromethyl-substituted tertiary alcohols were synthesized by the aldol reaction of ketones as donor and aryl trifluoromethyl ketone as acceptor in the presence of DBU as catalyst . Recently, our group as well as others have demonstrated the cyanomethylation by using TMSAN (trimethylsilyl acetonitrile) as the cyanomethylating agent . Here, we report DBU-mediated direct alkylnitrile addition to isatins, a facile access to 3-hydroxy-3-cyanomethyl oxindoles.…”

mentioning

confidence: 99%

DBU-Mediated Diastereoselective Aldol-Type Cyanomethylation of Isatins

et al. 2017

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An efficient, metal-free approach to 3-substituted 3-hydroxyoxindole by DBU-mediated highly diastereoselective addition of aryl acetonitrile to N-protected isatin under mild conditions has been developed. The reaction proceeds smoothly to produce respective cyanomethylated adducts in good yield and excellent diastereoselectivity. Further transformation of the cyanide group allowed the synthesis of an advance intermediate of corresponding (±) CPC analogue. The mechanistic insight toward the aldol-type cyanomethylation of N-tritylisatin with benzyl cyanide was obtained by DFT calculations.

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