- Redetermination and Density Functional Studies of N,N′-(Disulfanediyldibenzene-2,1-Diyl) Dipyridine-2-Carboxamide
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The title compound C24H18N4O2S2 is synthesized via the azide method and its structure is redetermined at 100(2) K. The title structure, N,N′-(disulfanediyldibenzene-2,1-diyl)dipyridine-2-carboxamide i
- Yildirim,Büyükmumcu,Dogan,Butcher
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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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- 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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- Synthesis and biological studies of a new series of 5- heteroarylcarbamoylaminopyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines as human A3 adenosine receptor antagonists. Influence of the heteroaryl substituent on binding affinity and molecular modeling investigations
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Some pyrazolotriazolopyrimidines bearing different heteroarylcarbamoylamino moieties at the N5-position are described. We previously reported the synthesis of a water soluble compound with high potency and selectivity versus the human A3 adenosine receptor as antagonist, and herein we present an enlarged series of compounds related to the previously mentioned one. These compounds showed A3 adenosine receptor affinity in the nanomolar range and different levels of selectivity evaluated in radioligand binding assays at human A1, A2A, A2B, and A3 adenosine receptors. In particular, the effect of the heteroaryl substituents at the N5 position has been analyzed. This study allows us to recognize that the presence of a pyridinium moiety in this position not only increases water solubility but also improves or retains potency and selectivity at the human A3 adenosine receptors. In contrast, replacement of pyridine with different heterocycles produces loss of affinity and selectivity at the human A3 adenosine receptors. A molecular modeling study has been carried out with the aim to explain these various binding profiles.
- Pastorin, Giorgia,Da Ros, Tatiana,Bolcato, Chiara,Montopoli, Christian,Moro, Stefano,Cacciari, Barbara,Baraldi, Pier Giovanni,Varani, Katia,Borea, Pier Andrea,Spalluto, Giampiero
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- Synthesis of Acyl Phosphoramidates Employing a Modified Staudinger Reaction
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A one-step synthesis of acyl phosphoramidates from a variety of functionalized acyl azides has been developed employing trimethylsilyl chloride as an activating agent in a modified Staudinger reaction. The methodology was further adapted to include the in situ generation of the acyl azides from a diverse selection of carboxylic acids and hydrazide starting synthons. The reaction scope was extended to include the synthesis of imidodiphosphates and the natural product Microcin C.
- Currie, Iain,Sleebs, Brad E.
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supporting information
p. 464 - 468
(2021/02/03)
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- Synthesis of: N -methylated amines from acyl azides using methanol
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The transformation of acyl azide derivatives into N-methylamines was developed using methanol as the C1 source via the one-pot Curtius rearrangement and borrowing hydrogen methodology. Following this protocol, various functionalised N-methylated amines were synthesized using the (NNN)Ru(ii) complex from carboxylic acids via an acyl azide intermediate. Several kinetic studies and DFT calculations were carried out to support the mechanism and also to determine the role of the Ru(ii) complex and base in this transformation.
- Chakrabarti, Kaushik,Dutta, Kuheli,Kundu, Sabuj
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supporting information
p. 5891 - 5896
(2020/08/21)
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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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- 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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- Copper-mediated amidation of alkenylzirconocenes with acyl azides: Formation of enamides
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Copper-mediated amidation of alkenylzirconocenes generated in situ from alkynes and zirconocenes with acyl azides is accomplished under mild conditions. The reaction can be used to prepare various enamides.
- Liu, Hailan,Zhou, Yiqing,Yan, Xiaoyu,Chen, Chao,Liu, Qingbin,Xi, Chanjuan
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supporting information
p. 5174 - 5177
(2013/11/06)
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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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- Oxidative amidation and azidation of aldehydes by NHC catalysis
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Figure presented N-Heterocyclic carbene catalyzed oxidative amidations of various aldehydes to the corresponding hexafluoroisopropylesters by using the readily available organic oxidant A are described. The hexafluoroisopropylesters prepared in situ are shown to be highly useful active esters for amide bond formation. In addition, oxidative azidation of aldehydes is presented. These mild organocatalytic processes do not use any transition metal.
- De Sarkar, Suman,Studer, Armido
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supporting information; experimental part
p. 1992 - 1995
(2010/07/10)
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- New and simple synthesis of acid azides, ureas and carbamates from carboxylic acids: Application of peptide coupling agents EDC and HBTU
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Conversion of carboxylic acids into acid azides using peptide coupling agents, EDC and HBTU is described. The procedure is efficient, practical and applicable to a diverse range of carboxylic acids including N-protected amino acids. Using the same reagents, one-pot synthesis of ureas, dipeptidyl urea esters and carbamates from acids has also been achieved. The Royal Society of Chemistry 2010.
- Sureshbabu, Vommina V.,Lalithamba,Narendra,Hemantha
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experimental part
p. 835 - 840
(2010/06/20)
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- Facile one step synthesis of acyl azides and Nα-Fmoc/Boc/Z protected amino acid azides employing benzotriazole-1-yl-oxy-tris- (dimethylamino)-phosphonium hexafluorophosphate (BOP)
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A simple route for the preparation of acyl azides from the corresponding carboxylic acids employing the peptide-coupling agent BOP is described. The procedure is simple, clean and high yielding. The chemistry is also extended to the preparation of several urethane protected amino acid azides (eight examples) as well.
- Vasantha,Sureshbabu, Vommina V.
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experimental part
p. 812 - 817
(2011/01/04)
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- Substituted Dihydroisoindolones As Allosteric Modulators of Glucokinase
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The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating glucokinase mediated disorders. More particularly, the compounds of the present invention are glucokinase modulators useful for treating disorders including, but not limited to, type II diabetes.
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Page/Page column 37
(2010/11/27)
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- Preparation of polyfunctional acyl azides
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(Chemical Equation Presented) A general synthesis of acyl azides from the corresponding N-acyl benzotriazoles is described. The procedure affords acyl azides in good yields and avoids the use of acid activators and NO+ equivalents typically emp
- Katritzky, Alan R.,Widyan, Khalid,Kirichenko, Kostyantyn
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p. 5802 - 5804
(2008/02/09)
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- Pyridazinones and triazinones and medicinal use thereof
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The present invention provides a novel compound exhibiting an excellent inhibitory action on AMPA receptor and/or kainate receptor. That is, it provides a compound represented by the following formula, a salt thereof or a hydrate of them. In the formula, A1, A2 and A3 are independent of each other and each represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a 5- to 14-membered non-aromatic heterocyclic group, a C6-14 aromatic hydrocarbon cyclic group or a 5- to 14-membered aromatic heterocyclic group, each of which may be substituted; Q represents O, S or NH; Z represents C or N; X1, X2 and X3 are independent of each other and each represents a single bond, an optionally substituted C1-6 alkylene group, an optionally substituted C2-6 alkenylene group, an optionally substituted C2-6 alkynylene group, —NH—, —O—, —NHCO—, —CONH—, —SO0-2, etc.; R1 and R2 are independent of each other and each represents a hydrogen atom or an optionally substituted C1-6 alkyl group, or R1 and R2 may be bound together such that CR2-ZR1 forms C═C; and R3 represents a hydrogen atom or an optionally substituted C1-6 alkyl group etc., or may be bound to any atom in A1 or A3 to form, together with the atom, an optionally substituted C5-8 hydrocarbon ring or an optionally substituted 5- to 8-membered heterocyclic ring.
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- Il-8 receptor antagonists
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This invention relates to novel compounds of Formula (I) to (VII), and compositions thereof, useful in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
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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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- Sulfonamides
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Compounds of the formula: STR1 where A, B, R1 -R8 are as described herein are endothelin inhibitors that can be used in treating diseases associated with endothelin, such as high blood pressure. Chemical synthesis of these compounds and pharmaceutical compositions containing these compounds are also useful.
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