173998-77-1Relevant articles and documents
Small Cause, Great Impact: Modification of the Guanidine Group in the RGD Motif Controls Integrin Subtype Selectivity
Kapp, Tobias G.,Fottner, Maximilian,Maltsev, Oleg V.,Kessler, Horst
, p. 1540 - 1543 (2016)
Due to its unique role as a hydrogen-bond donor and its positive charge, the guanidine group is an important pharmacophoric group and often used in synthetic ligands. The chemical modification of the guanidine group is often considered to destroy its function. Herein, we show that the N-methylation, N-alkylation, or N-acylation of the guanidine group can be used to modify the receptor subtype specificity of the integrin ligand cilengitide. Using the αvβ6/α5β1-biselective ligand c(isoDGRkphg) and the αvβ6-specific ligand c(FRGDLAFp(NMe)K(Ac) as examples, we show that the binding affinities of the ligands can be fine-tuned by this method to enhance the selectivity for αvβ6. Furthermore, we describe a new strategy for the functionalization of integrin ligands. By introducing longer N-alkylguanidine and N-acylguanidine groups, we are able to simultaneously identify a hitherto unknown anchoring point and enhance the subtype selectivity of the ligand.
Design, synthesis biological activity, and docking of novel fluopyram derivatives containing guanidine group
Liang, Peibo,Shen, Shengqiang,Xu, Qingbo,Wang, Simin,Jin, Shuhui,Lu, Huizhe,Dong, Yanhong,Zhang, Jianjun
, (2020/11/17)
Succinate dehydrogenase (SDH), a crucial bridge enzyme between the respiratory electron transfer chain and tricarboxylic acid (or Krebs) cycle, has been identified as an ideal target for the development of effective fungicide. In this study, a series of 24 novel SDH inhibitors (SDHIs) were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. In vitro fungicidal activity experiments, most of the compounds exhibited broad-spectrum antifungal activities against five plant pathogenic fungi. Compounds 9j and 9k showed excellent activities against Pythium aphanidermatum with EC50 values of 9.93 mg/L and 10.50 mg/L, respectively, which were superior to the lead compound Fluopyram with an EC50 value of 19.10 mg/L. Furthermore, the toxicity of these compounds was also tested against Meloidogyne incognita J2 nematodes. The results indicated that compound 9x exhibited moderate nematicidal activity (LC50/48 h = 71.02 mg/L). Molecular docking showed that novel guanidine amide of 9j formed hydrogen bonds with crucial residues, which was crucial to the binding of an inhibitor and SDH. This present work indicates that these derivatives may serve as novel potential fungicides targeting SDH.
SMALL MOLECULES TARGETING MUTANT MAMMALIAN PROTEINS
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Paragraph 0522-0523, (2021/12/03)
Disclosed are compounds, compositions, and methods useful for treating or preventing a disease or disorder associated with a mutation in a protein.
CXCR4-TARGETED DIAGNOSTIC AND THERAPEUTIC AGENTS WITH REDUCED SPECIES SELECTIVITY
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Page/Page column 63, (2020/05/07)
The present disclosure relates to imaging and endoradiotherapy of diseases involving chemokine receptor 4 (CXCR4). Provided are compounds which bind or inhibit hCXCR4 and mCXCR4 and furthermore carry at least one moiety which is amenable to labeling. Provided are also medical uses of such compounds.