16689-35-3Relevant articles and documents
Versatile synthesis of chiral 6-oxoverdazyl radical ligands-new building blocks for multifunctional molecule-based magnets
Solea, Atena B.,Wohlhauser, Tobie,Abbasi, Parisa,Mongbanziama, Yvan,Crochet, Aurelien,Fromm, Katharina M.,Novitchi, Ghenadie,Train, Cyrille,Pilkington, Melanie,Mamula, Olimpia
, p. 4785 - 4789 (2018)
A versatile synthetic methodology to access the first family of chiral verdazyl N,N′-chelate ligands is described and exemplified by N,N′-dimethyl-, N,N′-di-isopropyl- and N,N′-diphenyl oxoverdazyls bearing two isomers of the pinene-pyridine functional group. Their physical properties were probed by X-band EPR spectroscopy, cyclic voltammetry and DFT calculations. Preliminary reactivity studies show they can act as N,N′-chelate ligands affording a chiral 1:1 complex (3b) with CuCl2, which was characterized by single-crystal X-ray diffraction. Variable temperature EPR studies on (3b) confirm the presence of antiferromagnetic interactions between the spins of the Cu(ii) ion and the verdazyl radical.
Novel quinoline derivative inhibitor
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Paragraph 0967; 0969-0971, (2020/03/12)
The invention provides a novel quinoline derivative inhibitor, which has a structure represented by the following general formula (I). According to the invention, the compound provided by the invention can selectively inhibit tyrosine kinase TAM family/an
Synthesis of Macrocycles Derived from Substituted Triazines
Yepremyan, Akop,Mehmood, Arshad,Asgari, Parham,Janesko, Benjamin G.,Simanek, Eric E.
, p. 241 - 246 (2018/12/11)
A triazine ring derivatized with morpholine, an N-alkyl-N′-BOC-hydrazine (alkyl=isopropyl or benzyl) and the diethylacetal of glycinylpropionaldehyde undergoes spontaneous dimerization in good yields upon acid-catalyzed deprotection. The resulting 24-member macrocycles can be characterized by NMR spectroscopy, mass spectrometry, and single crystal X-ray diffraction. In the solid state, both homodimers adopt a taco-like conformation. Although each shows π–π stacking between the triazine rings, different patterns of hydrogen bonds emerge. The crystal structure of the isopropyl dimer shows that it includes two molecules of trifluoracetic acid per macrocycle. The trifluoroacetate anion charge balances the protonated triazines, which engage in bifurcated hydrogen bonds with the carbonyl acceptor of the distant glycine. This carbonyl also forms a hydrogen bond with the NH of the proximate glycine. The crystal structure of the benzyl derivative does not include trifluoracetic acid. Instead, two hydrogen bonds form, each between a glycine NH and the lone pair of the C=N nitrogen of the hydrazine group. In the solid state, both molecules present the alkyl side chains and morpholine groups in close proximity. A heterodimer is accessible in approximately statistical yields—along with both homodimers—by mixing the two protected monomers prior to subjecting them to deprotection.
Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators
Sharma, Swagat,Kozek, Krystian A.,Abney, Kristopher K.,Kumar, Sushil,Gautam, Nagsen,Alnouti, Yazen,David Weaver,Hopkins, Corey R.
, p. 791 - 796 (2019/02/06)
The present study describes the discovery and characterization of a series of 5-aryl-2H-tetrazol-3-ylacetamides as G protein-gated inwardly-rectifying potassium (GIRK) channels activators. Working from an initial hit discovered during a high-throughput screening campaign, we identified a tetrazole scaffold that shifts away from the previously reported urea-based scaffolds while remaining effective GIRK1/2 channel activators. In addition, we evaluated the compounds in Tier 1 DMPK assays and have identified a (3-methyl-1H-pyrazol-1-yl)tetrahydrothiophene-1,1-dioxide head group that imparts interesting and unexpected microsomal stability compared to previously-reported pyrazole head groups.
Crystallographic Insights into the Synthesis and Magnetic Properties of Oxoverdazyl Radicals Functionalized by Benzoic Acid
Kumar, Varun,Shova, Sergiu,Maurel, Vincent,Novitchi, Ghenadie,Train, Cyrille
supporting information, p. 517 - 524 (2017/11/28)
The synthesis and crystallization of two verdazyl radicals, 1,5-dimethyl-3-(4′-carboxyphenyl)-6-oxoverdazyl HIMe and 1,5-diisopropyl-3-(4′-carboxyphenyl)-6-oxoverdazyl HIiPr, are described. The electrochemical studies reveal that the oxidation of the two radicals is reversible, whereas their reduction is irreversible. The EPR spectrum of both radicals essentially exhibits a nine-line pattern related to the mean hyperfine interaction of the unpaired electron with the nitrogen atoms of the verdazyl cycle. The single-crystal X-ray diffraction of the intermediates towards HIiPr allows a fine description of the cyanoborane adduct, which is the key intermediate of this synthesis. The verdazyl radicals themselves are obtained as single crystals. In the case of HIiPr, depending on the solvent, two polymorphs are crystallized. The structure resolution reveals that, in the solid state, the organization of the verdazyl radicals is governed by both H-bonding and π–π interactions and is reminiscent of the H-bonded structures that can be present in solution. Within the 1D π stacks observed in the three compounds, the verdazyl–verdazyl distance varies from 4.88 ? in HIMe to 7.90 ? in HaIiPr. This modulation of the distance strongly influences the antiferromagnetic intermolecular exchange interaction between π-stacked radicals, which goes from J = –90 cm–1 (H = –JΣSiSi+1) for HIMe to –12.96(3) cm–1 for HbIiPr and –0.92 cm–1 for HaIiPr.
Synthesis of Highly Substituted 1,2-Diazetidin-3-ones, Small-Ring Scaffolds for Drug Discovery
Santos, Marilia S.,Nortcliffe, Andrew,Lewis, William,Bradshaw, Tracey D.,Moody, Christopher J.
supporting information, p. 8325 - 8330 (2018/06/21)
1,2-Diazetidin-3-ones are readily accessible, small ring scaffolds that upon functionalization have the potential to produce diverse 3-dimensional structures for drug discovery. Thus, treatment of diazo hydrazides, obtained from simple hydrazides and malonyl half ester derivatives, followed by diazo transfer, with catalytic amounts of rhodium(II) acetate dimer results in intramolecular carbenoid N?H insertion to give 1,2-diazetidin-3-ones. Although subsequent functionalization reactions could be hampered by the lability of the 4-membered ring, a wide range of new derivatives was available by deprotection at N-1, and subsequent amide or urea formation. The structures of four four-membered rings was confirmed by X-ray crystallography; the compounds showed modest growth inhibitory activity in mammary carcinoma cells.
Antiviral drug and drug composition thereof
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Paragraph 0106, (2019/01/08)
The invention relates to an antiviral drug and a drug composition thereof, specially relates to a drug against human immunodeficiency virus (HIV) and a drug composition thereof, and particularly relates to a drug capable of serving as a retrovirus proteas
Towards a general synthesis of di-aza-amino acids containing peptides
Bizet, Faustine,Tonali, Nicolo,Soulier, Jean-Louis,Oliva, Agostino,Kaffy, Julia,Crousse, Benoit,Ongeri, Sandrine
, p. 17062 - 17072 (2018/10/23)
While the incorporation of one aza-amino acid in peptides has been proved to be beneficial for inducing a structure constraint, increasing the resistance towards proteolysis and improving the biological activity, only very rare examples of the incorporation of two or more consecutive aza-amino acids have been reported. In this work, we demonstrate that this fact is probably due to the unsuspected difficulty in synthesizing such peptide analogues, as illustrated by the synthesis of tripeptide derivatives containing two consecutive aza-amino acids. Herein, we report some general guidelines regarding the activation and the coupling of alkyl-hydrazides either mutually or with a natural amino acid, taking into account their nucleophilicity and the nature of their side chains.
1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones and 1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-ones as PDE1 Inhibitors
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Paragraph 0194; 0195; 0196, (2017/10/30)
The present invention provides 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones and 1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-ones of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
Antiviral drug and its pharmaceutical composition
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Paragraph 0182-0184, (2017/03/21)
The invention relates to an antiviral medicine and a medicine composition thereof, in particular relates to an anti-human immunodeficiency virus (HIV) medicine and a medicine composition thereof, and especially relates to a medicine which can be taken as
