- New acyl derivatives of 3-aminofurazanes and their antiplasmodial activities
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An N-acylated furazan-3-amine of a Medicines for Malaria Venture (MMV) project has shown activity against different strains of Plasmodium falciparum. Seventeen new derivatives were prepared and tested in vitro for their activities against blood stages of two strains of Plasmodium falciparum. Several structure–activity relationships were revealed. The activity strongly depended on the nature of the acyl moiety. Only benzamides showed promising activity. The substitution pattern of their phenyl ring affected the activity and the cytotoxicity of compounds. In addition, physicochemical parameters were calculated (log P, log D, ligand efficiency) or determined experimentally (permeability) via a PAMPA. The N-(4-(3,4-diethoxyphenyl)-1,2,5-oxadiazol-3-yl)-3(trifluoromethyl)benzamide possessed good physicochemical properties and showed high antiplasmodial activity against a chloroquine-sensitive strain (IC50 (NF54) = 0.019 μM) and even higher antiplasmodial activity against a multiresistant strain (IC50 (K1 ) = 0.007 μM). Compared to the MMV compound, the permeability and the activity against the multiresistant strain were improved.
- Dolensky, Johanna,Hermann, Theresa,Hochegger, Patrick,Kaiser, Marcel,M?ser, Pascal,Saf, Robert,Seebacher, Werner,Weis, Robert
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- Benzoheterocyclic Oxime Carbamates Active against Mycobacterium tuberculosis: Synthesis, Structure-Activity Relationship, Metabolism, and Biology Triaging
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Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies and defining a lead optimization strategy. Carbamate and free oxime frontrunner compounds with good stability in liver microsomes and no hERG channel inhibition liability were identified and evaluated in vivo for pharmacokinetic properties. Mtb-mediated permeation and metabolism studies revealed that the carbamates were acting as prodrugs. Toward mechanism of action elucidation, selected compounds were tested in biology triage assays to assess their activity against known promiscuous targets. Taken together, these data suggest a novel yet unknown mode of action for these antitubercular hits.
- Van Der Westhuyzen, Renier,Mabhula, Amanda,Njaria, Paul M.,Müller, Rudolf,Ngumbu Muhunga, Denis,Taylor, Dale,Lawrence, Nina,Njoroge, Mathew,Brunschwig, Christel,Moosa, Atica,Singh, Vinayak,Rao, Srinivasa P.S.,Manjunatha, Ujjini H.,Smith, Paul W.,Warner, Digby F.,Street, Leslie J.,Chibale, Kelly
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p. 9444 - 9457
(2021/07/19)
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- Search for the shortest intermetallic Tl—Tl contacts: Synthesis and characterization of Thallium(I) coordination polymers with several mono- and bis-cyanoximes
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Five new Tl(I) coordination compounds based on aryl monocyanoximes, such as phenylcyanoxime – HPhCO, 1, 2-fluorophenylcyanoxime – H(2F-PhCO, 2, 3-fluorophenylcyanoxime – H(3F-PhCO), 3, of TlL composition, and aryl biscyanoximes, such as 1,3-cyanoxime (benzene) – H2(1,3-BCO, 4 and 1,4-cyanoxime (benzene) – H2(1,4-BCO), 5 of Tl2L stoichiometry were synthesized and characterized using spectroscopic methods, thermal stability studies, and X-ray analysis. All obtained complexes represent coordination polymers of different complexity, ranging in dimensionality from 1D in Tl(2F-PhCO) to 3D in Tl2(1,3-BCO). The most interesting feature of all synthesized complexes is the formation of Tl2O2 rhombs: non planar and non-centrosymmetric in Tl(PhCO), and planar and centrosymmetric in the other three compounds. These rhombi are interconnected, forming zigzag and ladder-type polymers in which very short thallophilic Tl—Tl distances were observed. Thus, in the structure of Tl2(1,3-BCO) the closest distance between metal centers was found to be 3.670 ?. This is the second shortest on-record intermetallic contact in non-organometallic and non-cluster, but Werner type complexes, and is close to that in metallic thallium: 3.456 ?. In all five new coordination polymers the central atom has a stereo-active 6 s2 lone pair that significantly distorts the shape of the coordination polyhedron of Tl(I). The first time, Tl–O vibrations in Tl2O2 rhombs were observed in Raman spectra of the obtained complexes. Thermal analysis studies evidenced stability of all complexes, but Tl(PhCO), to ~200 °C. The Tl2(1,3-BCO) compound demonstrates properties of the high energy compound, and violently exothermically decomposes at ~255 °C with the release of a significant amount of kinetic energy. The final product of anaerobic decomposition of all studied Tl-cyanoximates is metallic thallium sponge.
- Curtis, Scott,Lottes, Brett,Robertson, Daniel,Lindeman, Sergey V.,Gerasimchuk, Nikolay
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- Cu-Mediated Stereoselective [4+2] Annulation between N-Hydroxybenzimidoyl Cyanide and Norbornene
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A Cu-mediated stereoselective [4+2] annulation between N-hydroxybenzimidoyl cyanides and norbornene (NBE) has been developed for the synthesis of 4H-1,2-oxazin-4-ones. The reaction proceeds through sequentially forming C-O/C-C bonds. The advantage of this reaction includes high stereoselectivity, excellent yields, as well as simple and mild reaction conditions. A total of 26 examples are presented along with some control experiments.
- Liu, Kui,Chen, Zhen-Bang,Zhang, Fang-Ling,Qian, Chun,Tao, Shou-Wei,Xu, Qiong-Ming,Zhu, Yong-Ming
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p. 8457 - 8463
(2018/06/25)
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- Synthesis, crystallographic characterization, DFT and TD-DFT studies of Oxyma-sulfonate esters
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Abstract: Three oxyma sulfonate esters were prepared using dichloromethane-water (two-phase method) in the presence of sodium carbonate for scavenging HCl. The products were characterized by FT-IR, NMR (1H and 13C), UV-Vis spectra and elemental analysis. X-ray single crystal diffraction experiments proved the molecular structures of three esters. Their molecular structures were also calculated using DFT/B3LYP method. The optimized structures agreed well with the X-ray structures. Time-dependent density functional theory (TD-DFT) was used to assign the electronic absorption bands observed experimentally. Pyridine derivative showed two bands at shorter λ max compared to the others, both experimentally and theoretically. The NMR chemical shifts were computed for protons and carbons using GIAO method, which correlated well with the experimental data. Natural charges, dipole moments and chemical reactivity of these molecules, as well as their non-linear optical activity, were computed and compared. Graphical Abstract:: SYNOPSIS An eco-friendly method was used to synthesise three oxyma-sulfonate esters using two-phase (dichloromethane-water) method in presence of sodium carbonate for scavenging HCl. The oxyma sulfonate esters were characterized using different spectroscopic techniques (FT-IR, NMR, UV-Vis) as well as X-ray single crystal diffraction analysis. The electronic and spectroscopic properties of these esters were computed using DFT/B3LYP method[Figure not available: see fulltext.].
- Soliman, Saied M.,Ghabbour, Hazem A.,Khattab, Sherine N.,Siddiqui, Mohammed R.H.,El-Faham, Ayman
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p. 1469 - 1481
(2017/09/27)
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- Synthesis of N-Aryl Oxindole Nitrones through a Metal-Free Selective N-Arylation Process
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An efficient selective N-arylation of 3-(hydroxyimino)indolin-2-ones with diaryliodonium salts to prepare (Z)-N-aryl oxindole nitrones has been achieved under simple base-mediated conditions. The reaction tolerated a variety of diaryliodonium salts with diverse and sensitive functional groups. Studies on the oxime structures revealed that the pyrroline ring and carbonyl group in 3-(hydroxyimino)indolin-2-ones played important roles in the selective N-arylation process. The N-aryl oxindole nitrones could be prepared rapidly and easily at the gram scale.
- Wu, Si-Yi,Ma, Xiao-Pan,Liang, Cui,Mo, Dong-Liang
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p. 3232 - 3238
(2017/03/23)
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- Synthesis of 4-substituted 3-chloro-1,2,5-thiadiazoles from monosubstituted glyoximes
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One-pot synthesis of 3-chloro-1,2,5-thiadiazoles from monosubstituted glyoximes and sulfur monochloride was developed.
- Kryshenko,Knyazeva,Konstantinova,Rakitin
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p. 2678 - 2681
(2017/05/19)
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- Synthesis, characterization and anti-proliferation activities of novel cyano oximino sulfonate esters
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A series of novel cyano oximino sulfonate derivatives were prepared from the reaction of arylsulfonyl chloride with different cyanoacetamide-based oximes ranging from the simplest unsubstituted amide to analogues containing N-ethyl (mimicking the Oxyma template), N-piperidinyl and N-morpholinyl chains. In addition, the cyano oximes, N-hydroxybenzimidoyl cyanide and N-hydroxypicolinimidoyl cyanide were also used in the synthesis of the novel cyano oximino sulfonate derivatives. The structures of the prepared compounds were confirmed by 1H-NMR, 13C-NMR, and elemental analysis. The preliminary bioassays showed that some of the title compounds, such as 2-oxo-2-(piperidin-1-yl)-N-(tosyloxy)acetimidoyl cyanide (TsPipOx), N-(tosyloxy)benzimidoyl cyanide (TsPhOX), N-(naphthalen-2-ylsulfonyloxy)-2-oxo- 2-(piperidin-1-yl)acetimidoyl cyanide (NpsPipOx), 2-amino-N-(naphthalen-2- ylsulfonyloxy)-2-oxoacetimidoyl cyanide (NpsAmOx), N-(naphthalen-2- ylsulfonyloxy)benzimidoyl cyanide (NpsPhCN), and N-(naphthalen-2-ylsulfonyloxy) picolinimidoyl cyanide (NpsPyCN), showed anti-proliferation effect on the mouse fibroblast L929. The calculated IC50-values were ranging between 36.5 μg/mL and 0.235 mg/mL. However the anti-proliferation effects seem to be cytostatic rather than cytotoxic. The compounds only minimize the growth activity without completely killing the cells.
- El-Faham, Ayman,Elnakdy, Yasser Abbas,El Gazzar, Sarah Abdou Mohamed,El-Rahman, Mohamed Mokbel Abd,Khattab, Sherine Nabil
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p. 373 - 378
(2014/04/17)
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- Oxodiazonium ion generation 5. 3-(N-Nitroamino)-4-phenylfuroxan: Synthesis and reactivity
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3-(N-Nitroamino)-4-phenylfuroxan, the first representative of the furoxan series that contains the N-nitroamino group in position 3 of the furoxan ring, was obtained. This compound is not very stable; its structure was confirmed by chemical transformation
- Zelenov,Voronin,Churakov,Klenov,Strelenko, Yu. A.,Tartakovsky
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p. 351 - 354
(2013/06/05)
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- A new synthetic route to 3-Oxo-4-amino-1, 2, 3-oxadiazole from the diazeniumdiolation of benzyl cyanide: Stable sydnone iminium N-Oxides
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Treating benzylcyanide with nitric oxide in basic methanol returns 3-oxo-4-phenyl-5-amino-1, 2, 3- oxadiazole (a 5-iminium-sydnone N-oxide), 5, in addition to the known 2-(hydroxyimino)-2-phenylac-etonitrile, 6, and the bisdiazeniumdiolate imidate salt, 7. Conditions for the separation and purification of the new 1, 2, 3-oxadiazole 5 are described along with its theory, structure, spectroscopy, and reactivity which demonstrate the predominance of the amino tautomer over the N-hydroxide tautomer. New derivatives of 5 include a Schiff base, from the condensation with salicylaldehyde, 8, and a dimethylamino analogue of 5, from its reaction with methyliodide and NaH. As with other related 3-oxo-1, 2, 3-oxadiazoles 5 has pronounced acid/base stability. Theoretical calculations demonstrate that the only other prior sydnone N-oxides prepared were misformulated as the N-hydroxide imines and are better described as 3-oxo-5-amino-derivatives of 1, 2, 3-oxadiazoles.
- Scott Bohle,Perepichka, Inna
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experimental part
p. 1621 - 1626
(2009/07/11)
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- Synthesis and seed germination stimulating activity of some imino analogs of strigolactones
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Strigolactones are germination stimulants for seeds of the root parasitic weeds, Striga and Orobanche spp. The imino analog of GR24 showed moderate germination stimulating activity against the seeds of S. hermonthica. The seed germination stimulating activity of some phenyliminoacetates and phenyliminoacetonitriles was also examined. The degree of activity of the phenyliminoacetate was less than that of the phenylacrylates. On the other hand, the degree of activity of the phenyliminoacetonitrile was comparable to that of the phenylacrylonitriles. Among the tested compounds, the 3- pyridyliminoacetonitrile showed higher activity against the seeds of O. crenata than GR24. These findings demonstrate that it is not always essential to have the Michael acceptor of the C-D ring junction moiety which has been proposed to react with nucleophilic species presented at the target site to enhance the activity.
- Kondo, Yuki,Tadokoro, Eriko,Matsuura, Mayuko,Iwasaki, Kyoko,Sugimoto, Yukihiro,Miyake, Hideyoshi,Takikawa, Hirosato,Sasaki, Mitsuru
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p. 2781 - 2786
(2008/03/15)
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- 3-(substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds
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3-(Substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds are useful as insecticides and acaricides. New synthetic procedures and intermediates for preparing the compounds, pesticide compositions containing the compounds, and methods of controlling insects and mites using the compounds are also provided.
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- A convenient synthesis of α-hydroxyiminoacetonitriles from aldoximes
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Aromatic α-hydroxyiminoacetonitriles can be conveniently prepared by a facile one-pot procedure in high yields involving chlorination of the corresponding aldoximes with tert-butyl hypochlorite followed by reaction with alkali cyanide.
- Ma, Jun-An,Ma, Zhi-Hua,Ma, Hong-Min,Huang, Run-Qiu,Shao, Rui-Lian
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p. 1563 - 1567
(2007/10/03)
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- A convenient synthesis of α-hydroxyiminoacetonitriles from aldoximes
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Aromatic α-hydroxyiminoacetonitriles can be conveniently prepared by a facile one-pot procedure in high yields involving chlorination of the corresponding aldoximes with tert-butyl hypochlorite followed by reaction with alkali cyanide.
- Ma, Jun-An,Ma, Zhi-Hua,Ma, Hong-Min,Huang, Run-Qiu,Shao, Rui-Lian
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p. 3863 - 3868
(2007/10/03)
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- THE SEARCH FOR THE ETHYNYL CATION: NITROSATION OF N,N-BIS(TRIMETHYLSILYL)YNAMINES
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The reaction of bis-silylated ynamines with different nitrosyl reagents affords products derived from an electrophilic attack at the β-carbon atom and not the expected alkynyldiazonium salts.
- Alvarez, Roberto Martinez,Hanack, Michael,Schmid, Thomas,Subramanian, L. R.
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p. 191 - 194
(2007/10/02)
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- Reaction of the Silver Salts of Arylnitroacetonitriles with 9-Bromofluorene. Synthesis of 9-(α-Cyanoarylidene)fluorenes
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The silver salts 1a-d react with 9-bromofluorene to give both C- and O-alkylated products 2 and 3.The latter decompose to yield 9-fluorenone and the α-cyanooximes 5.The products 2 upon treatment with NaOH/EtOH eliminate HNO2 to afford 9-(α-cyanoarylidene)fluorenes 4 in 80percent yield. 9-Chloro-9-phenylfluorene reacts with salt 1a to give only C-alkylated product 6 in 70percent yield.
- Lianis, Pygmalion S.,Rodios, Nestor A.,Alexandrou, Nicholas E.
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p. 537 - 540
(2007/10/02)
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