3586-15-0Relevant articles and documents
Uptake and transformation of pesticide metabolites by duckweed (Lemna gibba)
Fujisawa, Takuo,Kurosawa, Motohiro,Katagi, Toshiyuki
, p. 6286 - 6293 (2006)
Uptake and transformation of 14C-labeled metabolites from several pesticides, 3-methyl-4-nitrophenol (1), 3,5-dichloroaniline (2), 3-phenoxybenzoic acid (3), (R,S)-2-(4-chlorophenyl)-3-methylbutanoic acid (4), and (1RS)-trans-3-(2,2-dichlorovin
Design and synthesis of N-(3-sulfamoylphenyl)amides as Trypanosoma brucei leucyl-tRNA synthetase inhibitors
Li, Zezhong,Xin, Weixiang,Wang, Qing,Zhu, Mingyan,Zhou, Huchen
, (2021/03/16)
The protozoan parasite Trypanosoma brucei (T. brucei) causes human African trypanosomiasis (HAT), which is a fatal and neglected disease in the tropic areas, and new treatments are urgently needed. Leucyl-tRNA synthetase (LeuRS) is an attractive target for the development of antimicrobial agents. In this work, starting from the hit compound thiourea ZCL539, we designed and synthesized a series of amides as effective T. brucei LeuRS (TbLeuRS) synthetic site inhibitors. The most potent compounds 74 and 91 showed IC50 of 0.24 and 0.25 μM, which were about 700-fold more potent than the starting hit compound. The structure-activity relationship was also discussed. These compounds provided a new scaffold and lead compounds for further development of antitrypanosomal agents.
Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the Treatment of Inflammatory Acne
Fournier, Jean-Fran?ois,Clary, Laurence,Chambon, Sandrine,Dumais, Laurence,Harris, Craig Steven,Millois, Corinne,Pierre, Romain,Talano, Sandrine,Thoreau, étienne,Aubert, Jérome,Aurelly, Michèle,Bouix-Peter, Claire,Brethon, Anne,Chantalat, Laurent,Christin, Olivier,Comino, Catherine,El-Bazbouz, Ghizlane,Ghilini, Anne-Laurence,Isabet, Tatiana,Lardy, Claude,Luzy, Anne-Pascale,Mathieu, Céline,Mebrouk, Kenny,Orfila, Danielle,Pascau, Jonathan,Reverse, Kevin,Roche, Didier,Rodeschini, Vincent,Hennequin, Laurent Fran?ois
supporting information, p. 4030 - 4051 (2018/05/23)
The use of an interleukin β antibody is currently being investigated in the clinic for the treatment of acne, a dermatological disorder affecting 650M persons globally. Inhibiting the protease responsible for the cleavage of inactive pro-IL1β into active IL-1β, caspase-1, could be an alternative small molecule approach. This report describes the discovery of uracil 20, a potent (38 nM in THP1 cells assay) caspase-1 inhibitor for the topical treatment of inflammatory acne. The uracil series was designed according to a published caspase-1 pharmacophore model involving a reactive warhead in P1 for covalent reversible inhibition and an aryl moiety in P4 for selectivity against the apoptotic caspases. Reversibility was assessed in an enzymatic dilution assay or by using different substrate concentrations. In addition to classical structure-activity-relationship exploration, topical administration challenges such as phototoxicity, organic and aqueous solubility, chemical stability in solution, and skin metabolic stability are discussed and successfully resolved.
Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus
Eissa, Ibrahim H.,Mohammad, Haroon,Qassem, Omar A.,Younis, Waleed,Abdelghany, Tamer M.,Elshafeey, Ahmed,Abd Rabo Moustafa, Mahmoud M.,Seleem, Mohamed N.,Mayhoub, Abdelrahman S.
supporting information, p. 73 - 85 (2017/03/02)
A new class of diphenylurea was identified as a novel antibacterial scaffold with an antibacterial spectrum that includes highly resistant staphylococcal isolates, namely methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA & VRSA). Starting with a lead compound 3 that carries an aminoguanidine functionality from one side and a n-butyl moiety on the other ring, several analogues were prepared. Considering the pharmacokinetic parameters as a key factor in structural optimization, the structure-activity-relationships (SARs) at the lipophilic side chain were rigorously examined leading to the discovery of the cycloheptyloxyl analogue 21n as a potential drug-candidate. This compound has several notable advantages over vancomycin and linezolid including rapid killing kinetics against MRSA and the ability to target and reduce the burden of MRSA harboring inside immune cells (macrophages). Furthermore, the potent anti-MRSA activity of 21n was confirmed in?vivo using a Caenorhabditis elegans animal model. The present study provides a foundation for further development of diphenylurea compounds as potential therapeutic agents to address the burgeoning challenge of bacterial resistance to antibiotics.
