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.
Discovery of acylguanidine oseltamivir carboxylate derivatives as potent neuraminidase inhibitors
Li, Zhaoliang,Meng, Yanchun,Xu, Shengtao,Shen, Wang,Meng, Zhaoqing,Wang, Zhenzhong,Ding, Gang,Huang, Wenzhe,Xiao, Wei,Xu, Jinyi
, p. 2772 - 2781 (2017)
In search of novel anti-influenza agents with higher potency, a series of acylguanidine oseltamivir carboxylate analogues were synthesized and evaluated against influenza viruses (H1N1 and H3N2) in vitro. The representative compounds with strong inhibitory activities (IC50 40?nM) against neuraminidase (NA) were further tested against the NA from oseltamivir-resistant strain (H259Y). Among them, compounds 9 and 17 were potent NA inhibitors that exhibited a 5 and 11-fold increase in activity comparing with oseltamivir carboxylate (2, OC) against the H259Y mutant, respectively. Furthermore, the effect against influenza virus H259Y mutant (H1N1) replication and cytotoxicity assays indicated that compounds 9 and 17 exhibited a 20 and 6-fold increase than the parent compound 2, and had no obvious cytotoxicity in vitro. Moreover, the molecular docking studies revealed that the docking modes of compounds 9 and 17 were different from that of oseltamivir, and the new hydrogen bonds and hydrophobic interaction were formed in this case. This work provided unique insights in the discovery of potent inhibitors against NAs from wild-type and oseltamivir-resistant strains.
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.
METHODS OF TREATING CREATINE TRANSPORTER DEFICIENCY
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Paragraph 0383-0384, (2021/10/02)
Disclosed are methods of treating creatine transporter deficiency, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound that increases transport of a substrate by a mutant or wild-type creatine transporter. Also disclosed are methods of increasing transport of guanidinoacetic acid or a salt thereof across the blood-brain barrier of a mammal, and methods of decreasing accumulation or the concentration of guanidinoacetic acid or a salt thereof in a mammalian cell.
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.
ANALGESIC AND ANTI-ADDICTIVE COMPOSITIONS FOR TREATMENT OF CHRONIC PAIN AND OPIOID ADDICTION
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Page/Page column 28-30, (2020/06/10)
The invention provides a compound of formula I and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments t
Regioselective microwave synthesis and derivatization of 1,5-diaryl-3-amino-1,2,4-triazoles and a study of their cholinesterase inhibition properties
Santos, Sabrina Neves,Alves De Souza, Gabriela,Pereira, Thiago Moreira,Franco, Daiana Portella,De Nigris Del Cistia, Catarina,Sant'anna, Carlos Mauricio R.,Lacerda, Renata Barbosa,Kümmerle, Arthur Eugen
, p. 20356 - 20369 (2019/07/09)
Herein we describe the development of an efficient one-pot regioselective synthesis protocol to obtain N-protected or N-deprotected 1,5-diaryl-3-amino-1,2,4-triazoles from N-acyl-N-Boc-carbamidothioates. This improved protocol using microwave irradiation and low reaction times (up to 1 h) furnished desired compounds in yields ranging from 50 to 84%. This chemistry is useful for a variety of aromatic groups with electronically diverse substituents. The design and correct derivation of the amino group led to compounds able to inhibit cholinesterases with good IC50 of up to 1 μM. Also, the mode of action (mixed-type) and SAR analysis for this series of compounds was described by means of kinetic and molecular modelling evaluations, showing potential for this class of compounds as new scaffolds for this biological activity.
GUANIDINE DERIVATIVE AND MEDICAL USE THEREOF
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Paragraph 0503-0505, (2019/08/22)
A compound has a guanidine skeleton that inhibits the protease activity of MALT1 and exerts a therapeutic or prophylactic effect on autoimmune disease such as psoriasis or allergic disease such as atopic dermatitis. The guanidine derivative is typified by the following formula or a pharmacologically acceptable salt thereof.
Compound, and preparation method and application thereof
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Paragraph 0058; 0060; 0067, (2020/04/02)
The invention provides a compound, and a preparation method and an application thereof. The compound can be used as a neuraminidase inhibitor. Experimental results show that the compound has a stronginhibitory effect on neuraminidases of H1N1, H3N2 and H259Y(H1N1) influenza viruses, and especially has a better or same inhibitory effect on the neuraminidase of the H259Y(H1N1) influenza virus thana positive drug oseltamivir carboxylate. The compound has a high activity, and can be used for preparing a neuraminidase inhibitor, and the preparation method of the compound has the advantages of simplicity, easily available raw materials and low cost.
