Nitration of Indoles. IV. The Nitration of 2-Phenylindole<sup>1</sup>

Noland, Wayl­and E.; Rush, Kent R.; Smith, Lowell R.

doi:10.1021/jo01339a013

Cited by 30 publications

(12 citation statements)

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“…Acid-catalyzed condensation of phenyl hydrazine 27 with bromoacetophenone 15 provided an intermediate hydrazone that was cyclized 44 in a Fischer indole synthesis in the presence of P 2 O 5 and H 3 PO 4 to give indole 28. Nitration was selective for the C-5 position of the indole 45 and was followed by Pd(0)-catalyzed cross-coupling with Boc-protected tetramine 17. TFA-mediated removal of the Boc-group yielded nitro-indole 23.…”

Section: Acs Medicinal Chemistry Lettersmentioning

confidence: 99%

Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

Alverez

Arkin

Bulfer

et al. 2015

ACS Med. Chem. Lett.

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Exploratory SAR studies of a new phenyl indole chemotype for p97 inhibition revealed C-5 indole substituent effects in the ADPGlo assay that did not fully correlate with either electronic or steric factors. A focused series of methoxy-, trifluoromethoxy-, methyl-, trifluoromethyl-, pentafluorosulfanyl-, and nitro-analogues was found to exhibit IC 50 s from low nanomolar to double-digit micromolar. Surprisingly, we found that the trifluoromethoxy-analogue was biochemically a better match of the trifluoromethyl-substituted lead structure than a pentafluorosulfanyl-analogue. Moreover, in spite of their almost equivalent strongly electron-depleting effect on the indole core, pentafluorosulfanyl-and nitro-derivatives were found to exhibit a 430-fold difference in p97 inhibitory activities. Conversely, the electronically divergent C-5 methyl-and nitro-analogues both showed low nanomolar activities.

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Section: Acs Medicinal Chemistry Lettersmentioning

confidence: 99%

Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

Alverez

Arkin

Bulfer

et al. 2015

ACS Med. Chem. Lett.

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“…INF55 ( 5 ) was obtained in 91% yield via regioselective nitration of 2-phenylindole ( 10 ) using the literature method. [11] N -Methyl-INF55 ( 6 ) was prepared in 80% yield by stirring INF55 ( 5 ) for 2 h at room temperature with K 2 CO 3 and CH 3 I in anhydrous DMF. N -Methyl-2-phenylindole ( 7 ) was prepared in 80% yield by stirring 2-phenylindole ( 10 ) for 2 h in anhydrous THF at room temperature with NaH and CH 3 I.…”

Section: Chemistrymentioning

confidence: 99%

On the Mechanism of Berberine–INF55 (5-Nitro-2-phenylindole) Hybrid Antibacterials

et al. 2014

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Berberine–INF55 hybrids are a promising class of antibacterials that combine berberine and the NorA multidrug resistance pump inhibitor INF55 (5-nitro-2-phenylindole) together in one molecule via a chemically stable linkage. Previous studies demonstrated the potential of these compounds for countering efflux-mediated antibacterial drug resistance but they didn’t establish whether the compounds function as originally intended, i.e. with the berberine moiety providing antibacterial activity and the attached INF55 component independently blocking multidrug resistance pumps, thereby enhancing the activity of berberine by reducing its efflux. We hypothesised that if the proposed mechanism is correct, then hybrids carrying more potent INF55 pump inhibitor structures should show enhanced antibacterial effects relative to those bearing weaker inhibitors. Two INF55 analogues showing graded reductions in NorA inhibitory activity compared with INF55 were identified and their corresponding berberine–INF55 hybrids carrying equivalent INF55 inhibitor structures synthesised. Multiple assays comparing the antibacterial effects of the hybrids and their corresponding berberine–INF55 analogue combinations showed that the three hybrids all show very similar activities, leading us to conclude that the antibacterial mechanism(s) of berberine–INF55 hybrids is different from berberine–INF55 combinations.

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“…The nitration procedure was adapted from the method reported by Noland et al for the nitration of 2-phenylindole. [12] The modified procedure involved dissolving a stoichiometric quantity of NaNO 3 in conc. H 2 SO 4 and adding this solution via syringe pump over 2 h to a dilute solution of the indoles 4 and 5 in conc.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Berberine—Efflux Pump Inhibitor Hybrid Antibacterials

Bremner

Kelso

2010

Synthetic Communications

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Nitration of Indoles. IV. The Nitration of 2-Phenylindole¹

Cited by 30 publications

References 0 publications

Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

On the Mechanism of Berberine–INF55 (5-Nitro-2-phenylindole) Hybrid Antibacterials

Synthesis of Berberine—Efflux Pump Inhibitor Hybrid Antibacterials

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Nitration of Indoles. IV. The Nitration of 2-Phenylindole1

Cited by 30 publications

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Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

Structure–Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97

On the Mechanism of Berberine–INF55 (5-Nitro-2-phenylindole) Hybrid Antibacterials

Synthesis of Berberine—Efflux Pump Inhibitor Hybrid Antibacterials

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Nitration of Indoles. IV. The Nitration of 2-Phenylindole¹