40641-03-0Relevant articles and documents
Fluorescence Decay of Tryptophan Conformers in Aqueous Solution
Szabo, A. G.,Rayner, D. M.
, p. 554 - 563 (1980)
The fluorescence decay parameters of aqueous solutions of tryptophan and several tryptophan and indole derivatives are reported.The fluorescence decays of tryptophan, tryptophan ethyl ester, and 5-methyl- and 6-methyltryptophan are all described by double exponential kinetics.The relative proportions of the two components vary with emission wavelength.The fluorescence of all other derivatives obeys single exponential decay kinetics.In the case of tryptophan the two components, τ1 = 3.1 ns and τ2 = 0.51 ns, had fluorescence maxima at 350 and 335 nm, respectively.The origin of this behavior is discussed in terms of several models bur is most consistent with the assignment of the emission to different rotamers or conformers of the alanyl side chain of tryptophan.
Anhydrous Hydrogen Iodide-Mediated Reductive Indolization of in Situ-Generated Cyclopropyl Hydrazones
Yasui, Motohiro,Fujioka, Hiroki,Takeda, Norihiko,Ueda, Masafumi
supporting information, p. 43 - 47 (2021/12/17)
Fischer-type indolization of N-aryl-C-cyclopropyl hydrazones generated in situ followed by chemoselective reduction using tert-butyl iodide as an anhydrous HI generator was developed. This protocol provides indoles bearing carboxylic acid derivative units. A series of control experiments indicated the HI-mediated formation and reduction of spirocyclopropyl indolenines. Anhydrous HI functions as a Br?nsted acid as well as a reducing agent, facilitating the successful conversion of unstable reaction intermediates and iodinated mixtures in equilibrium.
4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors
Gavara, Laurent,Legru, Alice,Verdirosa, Federica,Sevaille, Laurent,Nauton, Lionel,Corsica, Giuseppina,Mercuri, Paola Sandra,Sannio, Filomena,Feller, Georges,Coulon, Rémi,De Luca, Filomena,Cerboni, Giulia,Tanfoni, Silvia,Chelini, Giulia,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
supporting information, (2021/06/15)
In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2.
COMPOUNDS FOR TREATING RAC-GTPASE MEDIATED DISORDER
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Page/Page column 33, (2019/08/08)
This disclosure relates to certain compounds that are effective in the treatment of a Rac-GTPase mediated disorder (e.g., acute lymphoblastic or chronic myelogenous leukemia), as well as methods for the manufacture of and the use of these compounds (e.g.,
