39075-92-8Relevant academic research and scientific papers
Halogen Bonding Increases the Potency and Isozyme Selectivity of Protein Arginine Deiminase 1 Inhibitors
Mondal, Santanu,Gong, Xuefeng,Zhang, Xiaoqian,Salinger, Ari J.,Zheng, Li,Sen, Sudeshna,Weerapana, Eranthie,Zhang, Xuesen,Thompson, Paul R.
supporting information, p. 12476 - 12480 (2019/08/07)
Protein arginine deiminases (PADs) hydrolyze the side chain of arginine to form citrulline. Aberrant PAD activity is associated with rheumatoid arthritis, multiple sclerosis, lupus, and certain cancers. These pathologies established the PADs as therapeutic targets and multiple PAD inhibitors are known. Herein, we describe the first highly potent PAD1-selective inhibitors (1 and 19). Detailed structure–activity relationships indicate that their potency and selectivity is due to the formation of a halogen bond with PAD1. Importantly, these inhibitors inhibit histone H3 citrullination in HEK293TPAD1 cells and mouse zygotes with excellent potency. Based on this scaffold, we also developed a PAD1-selective activity-based probe that shows remarkable cellular efficacy and proteome selectivity. Based on their potency and selectivity we expect that 1 and 19 will be widely used chemical tools to understand PAD1 biology.
Further investigation of inhibitors of MRSA pyruvate kinase: Towards the conception of novel antimicrobial agents
Labrière, Christophe,Gong, Huansheng,Finlay, B. Brett,Reiner, Neil E.,Young, Robert N.
supporting information, p. 1 - 13 (2016/09/23)
Several novel series of compounds were synthesized and evaluated as inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK). PK has been identified as a highly interconnected essential ‘hub’ protein in MRSA, with structural features distinct from the human homologs which makes it a novel antimicrobial target. Several MRSA PK inhibitors (including the hydrazide 1) were identified using in silico screening combined with enzyme assays and were found to be selective for bacterial enzyme compared to human PK isoforms. Structure–activity relationship (SAR) studies were carried out on the replacement of the hydrazide linker with 3-atoms, 2-atoms and 0-atom linkers and led us to discover more potent compounds with enzyme inhibiting activities in the low nanomolar range and some were found to effectively inhibit bacteria growth in culture with minimum inhibitory concentrations (MIC) as low as 1?μg/mL.
Design, synthesis, and biological activities of closantel analogues: Structural promiscuity and its impact on onchocerca volvulus
Garner, Amanda L.,Gloeckner, Christian,Tricoche, Nancy,Zakhari, Joseph S.,Samje, Moses,Cho-Ngwa, Fidelis,Lustigman, Sara,Janda, Kim D.
experimental part, p. 3963 - 3972 (2011/08/05)
Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3moltingwas investigated. Structure-activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.
Identification of halosalicylamide derivatives as a novel class of allosteric inhibitors of HCV NS5B polymerase
Liu, Yaya,Donner, Pamela L.,Pratt, John K.,Jiang, Wen W.,Ng, Teresa,Gracias, Vijaya,Baumeister, Steve,Wiedeman, Paul E.,Traphagen, Linda,Warrior, Usha,Maring, Clarence,Kati, Warren M.,Djuric, Stevan W.,Molla, Akhteruzzaman
scheme or table, p. 3173 - 3177 (2009/04/11)
Halosalicylamide derivatives were identified from high-throughput screening as potent inhibitors of HCV NS5B polymerase. The subsequent structure and activity relationship revealed the absolute requirement of the salicylamide moiety for optimum activity. Methylation of either the hydroxyl group or the amide group of the salicylamide moiety abolished the activity while the substitutions on both phenyl rings are acceptable. The halosalicylamide derivatives were shown to be non-competitive with respect to elongation nucleotide and demonstrated broad genotype activity against genotype 1-3 HCV NS5B polymerases. Inhibitor competition studies indicated an additive binding mode to the initiation pocket that is occupied by the thiadiazine class of compounds and an additive binding mode to the elongation pocket that is occupied by diketoacids, but a mutually exclusive binding mode with respect to the allosteric thumb pocket that is occupied by the benzimidazole class of inhibitors. Therefore, halosalicylamides represent a novel class of allosteric inhibitors of HCV NS5B polymerase.
Synthetic study of substituted arylsulfonylphenylbenzamides
Gong, Denghuang,Li, Jiafeng,Yuan, Chengye,Yuan, Junying
, p. 55 - 66 (2007/10/03)
For the structure-activity relationship, a series of substituted arylsulfonyl-phenylbenzamides is reported.
Acyl derivatives of 2-aminobenzimidazole and their fungicide activity
Pilyugin,Sapozhnikov,Sapozhnikova
, p. 738 - 743 (2007/10/03)
Procedures have been developed for the preparation of methyl 2-benzimidazolylcarbamate, 2-acetylaminobenzimidazole, 2- benzoylaminobenzimidazole, 2-(3,5-dibromo-2-hydroxybenzoylamino)benzimidazole, 1-(3,6-dichloro-2-methoxybenzoyl)-2-aminobenzimidazole, 2-(3,5-dichloro-2- hydroxybenzoylamino)benzimidazole, 2-(3,5-dichloro-2-methoxybenzoylamino) benzimidazole, and 1-(3,5,6-trichloro-2-methoxybenzoyl)-2-aminobenzimidazole. The synthesized compounds have been tested for fungicide activity.
