- Complexation of phosphates by 1,3-bis(3-(2-pyridylureido)propyl)-1,1,3,3-tetramethyldisiloxane
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Rationale Compounds containing a urea or thiourea moiety form complexes with anions thanks to the ability to form quite strong hydrogen bonds. We have synthesized 1,3-bis(3-(2-pyridylureido)propyl)-1,1,3,3-tetramethyldisiloxane (1). Compound 1 contains two urea moieties connected by a long flexible linker; thus, it should be able to adopt a structure suitable for formation of quite stable complexes with anions. Methods The ability to form complexes of compound 1 with phosphates was tested by electrospray ionization mass spectrometry (ESI-MS). Full scan ESI mass spectra and collision-induced dissociation tandem mass (CID-MS/MS) spectra of the ions of interest were obtained on a quadrupole time-of-flight (QTOF) mass spectrometer. Results It has been found that compound 1 is not only much more prone to form complexes with the phosphate anion than with other inorganic anions, but it is also able to form complexes with organic phosphates, namely nucleotides and phospholipids. However, compound 1 is not able to form complexes with organic compounds not containing a phosphate group (e.g. nucleosides, sugars, glycerolipids). Conclusions Compound 1 can be regarded as selective towards phosphate-containing organic compounds. Formation of such complexes may have some interesting applications for identification of organic phosphates in crude extracts from biological materials.
- Frański, Rafa?,Gierczyk, B?azej,Markiewicz, Grzegorz,Kozik, Tomasz
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Read Online
- A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade
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A diastereoselective approach to axially chiral imidazopyridine-containing biaryls has been developed. The reactions proceed through a radical cyclization cascade to construct the biaryls with good to excellent central-to-axial chirality transfer.
- Yan, Hong,Mao, Zhong-Yi,Hou, Zhong-Wei,Song, Jinshuai,Xu, Hai-Chao
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Read Online
- UREA INHIBITORS OF MICRO-RNA
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The present disclosure relates to compounds and methods which may be useful as inhibitors of the expression of miRNA, for use in the treatment or prevention of cancer.
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Paragraph 0209-0210
(2022/02/09)
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- Selective host-guest interactions in metal-organic frameworks: Via multiple hydrogen bond donor-acceptor recognition sites
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Targeted recognition of medium sized molecules with mixed hydrogen bond units is essential for using porous materials for molecular separation, sensing and drug delivery. One promising way to achieve selectivity, is to make use of the key-and-lock principle guiding the design of hydrogen bond receptors matching the chemical signature of the target molecules. Among the class of porous materials metal-organic frameworks are particularly well suited for this purpose, as they allow for functionalizing the inner surfaces with various pending groups. Here we report the successful incorporation of 2-pyridyl urea (URPy) side groups with hydrogen bond donor-donor-acceptor (DDA) patterns into the framework MIL-101 with pores in the mesoporous range. Their influence on the sorption properties was investigated by competitive adsorption of 2-aminopyridine (2-AP) and 3-aminopyridine (3-AP) on MIL-101-URPy (Al, Cr) derivatives and comparison to the behaviour of a single donor function within MIL-101-NH2 (Al, Cr) derivatives. Grafting the coordinatively unsaturated sites at the inorganic building units (IBUs) with diethylamine, additionally allowed the adsorption at these sites to be suppressed and thus to focus on the hydrogen bond receptors. Compared to the single D sites the selectivity of 2-AP over 3-AP is enhanced by a factor of five for the DDA pending groups. Based on 15N NMR spectroscopy and DFT calculations this observation is explained by forming double hydrogen bonds between the pyridyl urea groups and the 2-AP molecules, while 3-AP exhibits a single hydrogen bond only. At the D site of MIL-101-NH2 both 2-AP and 3-AP form single hydrogen bonds only.
- Wittmann,Tschense,Zappe,Koschnick,Siegel,St?glich,Lotsch,Senker
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p. 10379 - 10388
(2019/05/06)
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- Electrochemical Synthesis of Imidazo-Fused N-Heteroaromatic Compounds through a C?N Bond-Forming Radical Cascade
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We have developed a unified strategy for preparing a variety of imidazo-fused N-heteroaromatic compounds through regiospecific electrochemical (3+2) annulation reaction of heteroarylamines with tethered internal alkynes. The electrosynthesis employs a novel tetraarylhydrazine as the catalyst, has a broad substrate scope, and obviates the need for transition-metal catalysts and oxidizing reagents.
- Hou, Zhong-Wei,Mao, Zhong-Yi,Melcamu, Yared Yohannes,Lu, Xin,Xu, Hai-Chao
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supporting information
p. 1636 - 1639
(2018/02/06)
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- Synthesis and nematicidal activity of piperazinedione derivatives based on the natural product Barettin
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Nematodes are serious constraints of crop production worldwide. However, the traditional nematicides suffer from the side-effects, including environmental and human toxicity. Herein, more than 70 novel piperazinedione derivatives based on the natural product Barettin were synthesized and evaluated against the root-knot nematode Meloidogyne incognita (M. incognita). While most of synthesized compounds exhibited certain nematicidal activity at high concentration, the best one showed a nematicidal activity of 75% at 2.4 μmol/L.
- Sun, Haiyang,Li, Hui,Wang, Jiayi,Song, Gonghua
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p. 977 - 980
(2017/11/16)
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- Azine-imidazole aza-BODIPY analogues with large Stokes shift
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A series of azine-imidazole aza-BODIPY analogues has been prepared by a simple synthesis from 2-azinecarboxylic acids and imidazole N-oxides. The new fluorescent complexes exhibit large Stokes shifts (up to 10?000?cm?1), fluorescence in crystal
- Bukowska, Patrycja,Piechowska, Joanna,Loska, Rafa?
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p. 312 - 321
(2016/11/21)
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- Ketenes from N-(2-Pyridyl)amides
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Methoxycarbonylketene 4a, methoxycarbonyl(methyl)ketene 4b, chloroketene 4c, cyanoketene 4d, diphenylketene 4e, and 2-pyridylketene 4f have been generated by flash vacuum thermolysis of the corresponding 2-pyridylacetamide derivatives 3a-f and isolated in Ar matrices for FT-IR spectroscopic characterisation. The N-(2-pyridyl)-2-pyridylacetamide 3f yielded 2-pyridyl isocyanate in addition to 2-pyridylketene.
- Plüg, Carsten,Kanaani, Hussein,Wentrup, Curt
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p. 687 - 692
(2015/04/27)
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- TRIAZOLONE COMPOUNDS AND USES THEREOF
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The invention disclosed herein is directed to compounds of Formula (la) and (lb) and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocyticδ leukemia, melanoma and other cancers. The invention also comprises pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula (la) or (lb), or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, colon, pancreatic, chronic lymphocytic leukemia, melanoma and other cancers comprising administration of a therapeutically effective amount of a compound which is a dual antagonist of PPARα and PPARδ. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections. The invention disclosed herein is also directed to a methods of preventing the onset of and/or recurrence of acute and chronic myeloid leukemia, as well as other cancers, comprising administration of a herapeutically effective amount of a dual antagonist of PPARα and PPARδ.
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Paragraph 00173
(2015/03/28)
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- Advances in tetrahydropyrido[1,2-a]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors
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Abstract An efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine isoindolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSK3 as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro kinase activities and the best effects were obtained with lung and colon cell lines.
- Boulahjar, Rajaa,Ouach, Aziz,Bourg, Stéphane,Bonnet, Pascal,Lozach, Olivier,Meijer, Laurent,Guguen-Guillouzo, Christiane,Le Guevel, Rémy,Lazar, Sa?d,Akssira, Mohamed,Troin, Yves,Guillaumet, Gérald,Routier, Sylvain
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p. 274 - 287
(2015/07/08)
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- Photolysis and thermolysis of pyridyl carbonyl azide monolayers on single-crystal platinum
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The photochemical and thermal reactivity of a number of acyl azide-substituted pyridine compounds, namely nicotinyl azide, isonicotinyl azide, picolinyl azide and dinicotinyl azide with investigated as saturated monolayers on a single-crystal Pt(111) surface in an ultrahigh vacuum chamber. Multilayers of the substrates exhibited a maximum rate of desorption at 270 K, above which, stable saturated monolayers formed as characterized by reflection-absorption infrared spectroscopy by observation of C=O and N 3 bands at 1700 cm-1, and 2100 and 1300 cm-1 respectively. The monolayers were stable up to 400 K. Photolysis of the monolayer (or heating above 400 K) results in the formation of the respective isocyanate intermediate after loss of nitrogen as evidenced by the appearance of a new infrared band at 2260 cm-1 with concomitant loss of the azide bands. The resulting isocyanate saturated monolayer is stable in absence of nucleophiles, but can be quenched with appropriate nucleophiles. Saturated monolayers of a number of acyl azide-substituted pyridine compounds, namely nicotinyl azide, isonicotinyl azide, picolinyl azide and dinicotinyl azide, were formed on single-crystal Pt(111) surfaces in a UHV chamber. These monolayers were characterized by RAIR and thermal programmed desorption. Photolysis or thermolysis of these saturated monolayers leads to the corresponding isocyanate via a Curtius rearrangement.
- Adkinson, Dana K.,Magri, David C.,Pitters, Jason L.,Griffiths, Keith,Norton, Peter R.,Workentin, Mark S.
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p. 1020 - 1028
(2013/09/24)
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- DERIVATIVES OF 10-AMINO-1,2,3,4-TETRAHYDROPYRIDO[2,1-A]ISOINDOL-6(10BH)-ONES, METHOD FOR PREPARATION THEREOF AND THERAPEUTIC USES THEREOF
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The present invention relates to compounds having the following general formula (I): wherein: A represents a SO2 or CX group, X representing O or S;R1, R2, R″, R4 represent in particular H,R represents in particular an alkyl group or an aryl group, as well as to the pharmaceutically acceptable salts thereof, the compound of formula (I) taking the form of a pure stereoisomer or an enantiomer and/or diastereoisomer mixture, including racemic mixtures.
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Page/Page column 17
(2012/04/23)
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- Palladium-catalyzed aromatic azidocarbonylation
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Aryl iodides smoothly react with NaN3 and CO in the presence of a Pd/Xantphos catalyst to give aroyl azides (ArCON3) in 75-92 % yield. The reaction occurs under mild reaction conditions (1 atm, 20-50 °C) and exhibits high functional-group tolerance. (Xantphos=9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene)
- Miloserdov, Fedor M.,Grushin, Vladimir V.
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supporting information; experimental part
p. 3668 - 3672
(2012/05/20)
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- Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): Potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts
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The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents.
- Boulahjar, Rajaa,Ouach, Aziz,Matteo, Chiurato,Bourg, Stephane,Ravache, Myriam,Guével, Rémy Le,Marionneau, Séverine,Oullier, Thibauld,Lozach, Olivier,Meijer, Laurent,Guguen-Guillouzo, Christiane,Lazar, Sa?d,Akssira, Mohamed,Troin, Yves,Guillaumet, Gérald,Routier, Sylvain
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p. 9589 - 9606
(2013/01/16)
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- PROLYL HYDROXYLASE INHIBITORS
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The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I), (I) which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.
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Page/Page column 30-31
(2008/06/13)
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- 2-Arylureidobenzoic Acids: Selective Noncompetitive Antagonists for the Homomeric Kainate Receptor Subtype GluR5
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A series of 2-arylureidobenzoic acids (AUBAs) was prepared by a short and effective synthesis, and the pharmacological activity at glutamate receptors was evaluated in vitro and in vivo. The compounds showed noncompetitive antagonistic activity at the kainate receptor subtype GluR5. The most potent compounds showed more than 50-fold selectivity for GluR5 compared to GluR6 and the AMPA receptor subtypes GluR1-4. The structure-activity relationships for the AUBAs showed distinct structural requirements for the substituents on the two aromatic ring systems. Only para-substituents were tolerated on the benzoic acid moiety (ring A), whereas ring B tolerated a variety of substituents, but with a preference for lipophilic substituents. The most potent compounds had a 4-chloro substituent on ring A and 3-chlorobenzene (6b), 2-naphthalene (8h), or 2-indole (8k) as ring B and had IC50 values of 1.3, 1.2, and 1.2 μM, respectively, in a functional GluR5 assay. Compound 6c (IC50 = 4.8 μM at GluR5) showed activity in the in vivo ATPA rigidity test, indicating that 6c has better pharmacokinetic properties than 8h, which was inactive in this test. The AUBAs are the first example of a series of noncompetitive GluR5-selective antagonists and may prove to be important pharmacological tools and leads in the search for therapeutic glutamatergic agents.
- Valgeirsson, Jon,Nielsen, Elsebet ?.,Peters, Dan,Varming, Thomas,Mathiesen, Claus,Kristensen, Anders S.,Madsen, Ulf
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p. 5834 - 5843
(2007/10/03)
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- Structure-based generation of a new class of potent Cdk4 inhibitors: New de novo design strategy and library design
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As a first step in structure-based design of highly selective and potent Cdk4 inhibitors, we performed structure-based generation of a novel series of Cdk4 inhibitors. A Cdk4 homology model was constructed according to X-ray analysis of an activated form of Cdk2. Using this model, we applied a new de novo design strategy which combined the de novo design program LEGEND with our in-house structure selection supporting system SEEDS to generate new scaffold candidates. In this way, four classes of scaffold candidates including diarylurea were identified. By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N′-pyridin-2-ylurea 15 (IC50 = 0.10 μM), together with preliminary SAR. We performed a docking study between 15 and the Cdk4 model and selected a reasonable binding mode which is consistent with the SAR. Further modification based on the proposed binding mode provided a more potent compound, N-[(9bR)-5-oxo2,3,5,9b-tetrahydro-1H-pyrrolo[2,1-a]isoindol-9-yl]-N′ -pyridin-2-ylurea 26a (IC50 = 0.042 μM), X-ray analysis of which was accomplished by the soaking method. The predicted binding mode of 15 in Cdk4 was validated by X-ray analysis of the Cdk2-26a complex.
- Honma,Hayashi,Aoyama,Hashimoto,Machida,Fukasawa,Iwama,Ikeura,Ikuta,Suzuki-Takahashi,Iwasawa,Hayama,Nishimura,Morishima
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p. 4615 - 4627
(2007/10/03)
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- Mesoions and ketene valence isomers. Three types of rearrangement of mesoionic pyridopyrimidinylium olates involving ketene intermediates
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The ketene valence isomers of mesoionic pyrimidinylium olates undergo (i) a retro-ene type fragmentation to C3O2 16 and 2-aminopyridine 15, (ii) an electrocyclisation to form a naphthyridine (19→20→21), or (iii) a cycloreversion to 2-pyridyl isocyanate 26 and a ketene 25.
- Fiksdahl, Anne,Plueg, Carsten,Wentrup, Curt
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p. 1841 - 1845
(2007/10/03)
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- 1H and 13C NMR spectra of some unsymmetric N,N′-dipyridyl ureas: Spectral assignments and molecular conformation
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The 1H NMR spectra of N-(2-pyridyl), N′-(3-pyridyl)ureas and N-(2-pyridyl), N′-(4-pyridyl)ureas in CDCl3 and (CD3)2CO have been assigned with the aid of COSY and NOE experiments and chemical shift and coupling constant correlations. The 13C NMR spectra in CDCl3 were analysed utilizing the HETCOR and proton coupled spectra. The 1H NMR spectra, NOE effects and MINDO/3 calculations have been utilized to show that the molecular conformation of these compounds has the 2-pyridyl ring coplanar with the urea plane with the N-H group hydrogen bonded to the nitrogen of the 2-pyridyl group on the other urea nitrogen while the 3/4-pyridyl group rotates rapidly about the N-C3TN-C4 bond.
- Singha, Netai C.,Sathyanarayana, Dixit N.
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p. 157 - 162
(2007/10/03)
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- Reaction of 2,2-dimethyl-1,3-dioxin-4-ones with Imines, Carbodiimides, and Isocyanates
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The ring transformation of 2,2-dimethyl-1,3-dioxin-4-ones (1) to nitrogen heterocycles was studied.Heating of 1 whith imines such as Schiff bases gave rise to cycloadducts of imines to acylketenes (2), i.e., 3,4-dihydro-1,3-oxazin-4-one derivatives
- Sato, Masayuki,Ogasawara, Hiromichi,Kato, Tetsuzo
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p. 2602 - 2608
(2007/10/02)
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- Formation of Cycloadducts from Heterocyclic Formamidines and Phenyl Isocyanate
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Heterocyclic formamidines react with phenyl isocyanate at room temperature to give a cycloadduct which decomposes at elevated temperatures in two different ways; phenyl isocyanate reacts with the heterocyclic isocyanate formed in situ to form a new cycloadduct, a fused 1,3,5-triazine-2,4-dione derivative.
- Tisler, Miha,Stanovnik, Branko
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p. 313 - 314
(2007/10/02)
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