1-Substituted 5,10-Dihydro[1,2]diazepino[4,5-b]indol-4(3H)-ones. Synthesis and Functionalization

Muratov, A. V.; Eresko, A. B.; Толкунов, В. С.; Толкунов, С. В.

doi:10.1134/s1070428019030126

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…We also envisioned the attachment of the 4-NO 2 -phenyl group to the C-2 position of the indole of Trp through a CO linker. To this end, Fmoc-Trp-OMe ( 10 ) reacted with 4-NO 2 -benzoyl chloride in the presence of SnCl 4 in anhydrous DCM at 0 °C, as described for a similar indole derivative, 36 to afford the C-2 substituted derivative 47 . Unexpectedly, reaction of 47 with piperidine led to the removal of the Fmoc group and concomitant cyclization and aromatization to afford the β-carboline 48 .…”

Section: Resultsmentioning

confidence: 99%

C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein

Gargantilla,

Francés,

Adhav

et al. 2023

J. Med. Chem.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound 2 as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of 2 rendered compounds 63 and 65, which also potently inhibited genuine SARS-CoV-2 cell entry. Thermofluor and microscale thermophoresis studies revealed their binding to S and to its isolated receptor binding domain (RBD), interfering with the interaction with ACE2. Highresolution cryoelectron microscopy structure of S, free or bound to 2, shed light on cell entry inhibition mechanisms by these compounds. Overall, this work identifies and characterizes a new class of SARS-CoV-2 entry inhibitors with clear potential for preventing and/or fighting COVID-19.

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Section: Resultsmentioning

confidence: 99%

C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein

Gargantilla,

Francés,

Adhav

et al. 2023

J. Med. Chem.

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“…For detailed information on the synthesis of [1,2]diazepino [4,5-b]indoles 1-3 as well as their precursors, see our recent article [9].…”

Section: Experimental Partmentioning

confidence: 99%

“…Investigations on the synthesis of indolo [1,2]diazepines are few [5][6][7][8] and limited to derivatives containing alkyl substituent's in the diazepine ring. Synthesis and structural modification of arylcontaining indolodiazepines have been demonstrated recently [9]. As a continuation of our research on the synthesis and reactivity of heterocyclic systems based on 1,2-diazepine [8,[10][11][12], this paper presents the results of molecular modeling of the structure and NMR 1 H spectra of some new indolo [1,2]diazepines.…”

Section: Introductionmentioning

confidence: 98%