{"id":10501,"date":"2022-10-21T06:59:36","date_gmt":"2022-10-20T22:59:36","guid":{"rendered":"https:\/\/www.pyrazoles-derivatives.com\/?p=10501"},"modified":"2022-10-21T06:59:36","modified_gmt":"2022-10-20T22:59:36","slug":"ehmke-veronikas-team-published-research-in-chemmedchem-in-2013-cas-20154-03-4","status":"publish","type":"post","link":"https:\/\/www.pyrazoles-derivatives.com\/?p=10501","title":{"rendered":"Ehmke, Veronika’s team published research in ChemMedChem in 2013 | CAS: 20154-03-4"},"content":{"rendered":"

\u300aOptimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal Structure Analysis with Human Cathepsin L\u300b was written by Ehmke, Veronika; Winkler, Edwin; Banner, David W.; Haap, Wolfgang; Schweizer, W. Bernd; Rottmann, Matthias; Kaiser, Marcel; Freymond, Celine; Schirmeister, Tanja; Diederich, Francois. COA of Formula: C4H3F3N2<\/a>This research focused onTrypanosoma rhodesain inhibitor triazine nitrile structure activity relationship. The article conveys some information:<\/p>\n

The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 substituent led to high-affinity ligands with inhibition constants down to 2 nM for compounds bearing cyclohexyl substituents. Systematic investigations on the S3 pocket revealed its potential to achieve high activities with aromatic vectors that undergo stacking interactions with the planar peptide backbone forming part of the pocket. X-ray crystal structure anal. with the structurally related enzyme human cathepsin L confirmed the binding mode of the triazine ligand series as proposed by mol. modeling. Sub-micromolar inhibition of the proliferation of cultured parasites was achieved for ligands decorated with the best substituents identified through the optimization cycles. In cell-based assays, the introduction of a basic side chain on the inhibitors resulted in a 35-fold increase in antitrypanosomal activity. Finally, bioisosteric imidazopyridine nitriles were studied to prevent off-target effects with unselective nucleophiles by decreasing the inherent electrophilicity of the triazine nitrile headgroup. Using this ligand, the stabilization by intramol. hydrogen bonding of the thioimidate intermediate, formed upon attack of the catalytic cysteine residue, compensates for the lower reactivity of the headgroup. The imidazopyridine nitrile ligand showed excellent stability toward the thiol nucleophile glutathione in a quant. in vitro assay and fourfold lower cytotoxicity than the parent triazine nitrile. After reading the article, we found that the author used 3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4COA of Formula: C4H3F3N2<\/a>)<\/p>\n

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.COA of Formula: C4H3F3N2<\/a><\/p>\n

Referemce:
Pyrazole – Wikipedia<\/a>,
Pyrazoles – an overview | ScienceDirect Topics<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

3-(Trifluoromethyl)-1H-pyrazole(cas: 20154-03-4) belongs to pyrazoles. Pyrazole derivatives have been reported to exhibit a wide range of applications in medicinal chemistry and pharmacology. A large number of drugs incorporating pyrazole structure have been utilized as partial agonists for nicotinic acid receptors, antidepressants, antimicrobial agents, antiviral agents, and antifungal agents solely or along with the combination of other structural motifs.COA of Formula: C4H3F3N2<\/a><\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[205,131],"tags":[128],"class_list":["post-10501","post","type-post","status-publish","format-standard","hentry","category-20154-03-4","category-pyrazoles-derivatives","tag-100-200"],"yoast_head":"\nEhmke, Veronika's team published research in ChemMedChem in 2013 | CAS: 20154-03-4 | pyrazoles-derivatives<\/title>\n<meta name=\"description\" content=\"\u300aOptimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal Structure Analysis with Human Cathepsin L\u300b was written by Ehmke, Veronika; Winkler, Edwin; Banner, David W.; Haap, Wolfgang; Schweizer, W. Bernd; Rottmann, Matthias; Kaiser, Marcel; Freymond, Celine; Schirmeister, Tanja; Diederich, Francois. COA of Formula: C4H3F3N2This research focused onTrypanosoma rhodesain inhibitor triazine nitrile structure activity relationship. The article conveys some information:\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.pyrazoles-derivatives.com\/?p=10501\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Ehmke, Veronika's team published research in ChemMedChem in 2013 | CAS: 20154-03-4 | pyrazoles-derivatives\" \/>\n<meta property=\"og:description\" content=\"\u300aOptimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal Structure Analysis with Human Cathepsin L\u300b was written by Ehmke, Veronika; Winkler, Edwin; Banner, David W.; Haap, Wolfgang; Schweizer, W. Bernd; Rottmann, Matthias; Kaiser, Marcel; Freymond, Celine; Schirmeister, Tanja; Diederich, Francois. COA of Formula: C4H3F3N2This research focused onTrypanosoma rhodesain inhibitor triazine nitrile structure activity relationship. 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Bernd; Rottmann, Matthias; Kaiser, Marcel; Freymond, Celine; Schirmeister, Tanja; Diederich, Francois. COA of Formula: C4H3F3N2This research focused onTrypanosoma rhodesain inhibitor triazine nitrile structure activity relationship. 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