889676-34-0Relevant academic research and scientific papers
Synthesis and structure-activity relationship of novel bisindole amidines active against MDR Gram-positive and Gram-negative bacteria
Liu, Yonghua,Hu, Xinxin,Wu, Yanbin,Zhang, Weixing,Chen, Xiaofang,You, Xuefu,Hu, Laixing
, p. 771 - 782 (2018)
A series of novel diamidines with N-substituents on an amidine N-atom were synthesized and evaluated for their cytotoxicity and in vitro antibacterial activity against a range of Gram-positive and Gram-negative bacterial strains. Based on structure-activity relationship, N-substituents with a branched chain and a shorter carbon chain on the amidine N-atom exhibited more promising activity against Gram-negative and MDR-Gram-positive bacteria; compounds 5c and 5i were the most powerful candidate compounds. Compound 5c showed greater efficacy than levofloxacin against most drug-resistant Gram-positive bacteria and exhibited broad-spectrum antibacterial activity against Gram-negative bacteria, with MIC values in the range of 2–16 μg/mL. Slightly more potent antibacterial activity against Klebsiella pneumoniae, Acinetobacter calcoaceticus, Enterobacter cloacae, and Proteus mirabilis was observed for 5i in comparison with 5c. Compound 5i also showed remarkable antibacterial activity against NDM-1-producing Gram-negative bacteria, with MIC values in the range of 2–4 μg/mL, and was superior to the reference drugs meropenem and levofloxacin. Effective antibacterial activity of 5i was also shown in vivo in a mouse model of Staphylococcus aureus MRSA strain, with an ED50values of 2.62 mg/kg.
Exploration of DAPI analogues: Synthesis, antitrypanosomal activity, DNA binding and fluorescence properties
Farahat, Abdelbasset A.,Kumar, Arvind,Say, Martial,Wenzler, Tanja,Brun, Reto,Paul, Ananya,Wilson, W. David,Boykin, David W.
, p. 70 - 78 (2017/02/18)
The DAPI structure has been modified by replacing the phenyl group with substituted phenyl or heteroaryl rings. Twelve amidines were synthesized and their DNA binding, fluorescence properties, in?vitro and in?vivo activities were evaluated. These compounds are shown to bind in the DNA minor groove with high affinity, and exhibit superior in?vitro antitrypanosomal activity to that of DAPI. Six new diamidines (5b, 5c, 5d, 5e, 5f and 5j) exhibit superior in?vivo activity to that of DAPI and four of these compounds provide 100% animal cure at a low dose of 4?×?5?mg/kg i.p. in T.?b. rhodesiense infected mice. Generally, the fluorescence properties of the new analogues are inferior to that of DAPI with the exception of compound 5i which shows a moderate increase in efficacy while compound 5k is comparable to DAPI.
Indolyne experimental and computational studies: Synthetic applications and origins of selectivities of nucleophilic additions
Im, G-Yoon J.,Bronner, Sarah M.,Goetz, Adam E.,Paton, Robert S.,Cheong, Paul H.-Y.,Houk,Garg, Neil K.
supporting information; experimental part, p. 17933 - 17944 (2011/02/26)
Efficient syntheses of 4,5-, 5,6-, and 6,7-indolyne precursors beginning from commercially available hydroxyindole derivatives are reported. The synthetic routes are versatile and allow access to indolyne precursors that remain unsubstituted on the pyrrole ring. Indolynes can be generated under mild fluoride-mediated conditions, trapped by a variety of nucleophilic reagents, and used to access a number of novel substituted indoles. Nucleophilic addition reactions to indolynes proceed with varying degrees of regioselectivity; distortion energies control regioselectivity and provide a simple model to predict the regioselectivity in the nucleophilic additions to indolynes and other unsymmetrical arynes. This model has led to the design of a substituted 4,5-indolyne that exhibits enhanced nucleophilic regioselectivity.
Palladium-catalyzed benzylation of N-Boc indole boronic acids
Kearney, Aaron M.,Landry-Bayle, Adrienne,Gomez, Laurent
scheme or table, p. 2281 - 2283 (2010/05/18)
The direct benzylation of indole 2-boronic acid can be efficiently achieved using trans-PdBr(N-Succ)(PPh3)2, alleviating the need for strong bases or toxic organotin reagents. Under these reaction conditions substituted indole-2-boro
Synthesis, DNA binding, fluorescence measurements and antiparasitic activity of DAPI related diamidines
Farahat, Abdelbasset A.,Kumar, Arvind,Say, Martial,Barghash, Alaa El-Din M.,Goda, Fatma E.,Eisa, Hassan M.,Wenzler, Tanja,Brun, Reto,Liu, Yang,Mickelson, Leah,Wilson, W. David,Boykin, David W.
experimental part, p. 557 - 566 (2010/04/29)
A novel series of extended DAPI analogues were prepared by insertion of either a carbon-carbon triple bond (16a-d) or a phenyl group (21a,b and 24) at position-2. The new amidines were evaluated in vitro against both Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.). Five compounds (16a, 16b, 16d, 21a, 21b) exhibited IC50 values against T. b. r. of 9 nM or less which is two to nine folds more effective than DAPI. The same five compounds exhibited IC50 values against P. f. of 5.9 nM or less which is comparable to that of DAPI. The fluorescence properties of these new molecules were recorded, however; they do not offer any advantage over those of DAPI.
Synthesis of new substituted 2-(trimethylstannyl)indoles
Kumar, Arvind,Say, Martial,Boykin, David W.
, p. 707 - 710 (2008/09/21)
Synthesis of the previously unreported 2-(trimethylstannyl)indole derivatives, 5-bromo-1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole, 6-bromo-1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole, 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole-5-carbonitrile, 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole-6-carbonitrile and 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-pyrrolo[2,3-b] pyridine-6-carbonitrile, is described. Georg Thieme Verlag Stuttgart.
