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A plastic substance deposited by insects or obtained from plants. Waxes are esters of various fatty acids with higher, usually monohydric alcohols. The wax of pharmacy is principally yellow wax (beeswax), the material of which honeycomb is made. It consists chiefly of cerotic acid and myricin and is used in making ointments, cerates, etc. (Dorland, 27th ed)
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Technetium
The first artificially produced element and a radioactive fission product of URANIUM. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. All technetium isotopes are radioactive. Technetium 99m (m=metastable) which is the decay product of Molybdenum 99, has a half-life of about 6 hours and is used diagnostically as a radioactive imaging agent. Technetium 99 which is a decay product of technetium 99m, has a half-life of 210,000 years.
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Electron Spin Resonance Spectroscopy
A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.
Quantifying GPIIb/IIIa receptor binding using 2 monoclonal antibodies: discriminating abciximab and small molecular weight antagonists. (1/203)
BACKGROUND: Dosing of glycoprotein (GP) IIb/IIIa receptor antagonists is frequently based on the inhibition of platelet aggregation, which may be influenced by the agonist used or concurrent medications. Here we describe a monoclonal antibody-based technique to quantify total and ligand-occupied GPIIb/IIIa receptors. METHODS AND RESULTS: In vitro binding of monoclonal antibodies, LYP18 (Mab1) and 4F8 (Mab2), to the GPIIb/IIIa complex, was characterized using purified receptor and to platelets by flow cytometry. Patients undergoing coronary angioplasty received a single 20 mg dose of the oral GPIIb/IIIa antagonist, xemilofiban, or matching placebo, and antibody binding was compared with inhibition of platelet aggregation. Mab1 and Mab2 were bound to purified GPIIb/IIIa and to unoccupied, inactivated receptor on platelets. Mab2 identified the beta3 subunit, whereas Mab1 was complex-specific. Neither antibody interfered with the other's binding, suggesting that they identified distinct sites. Mab1 identified 53 300+/-5423 GPIIb/IIIa sites per platelet, whereas Mab2 identified 50 120+/-5066 sites per platelet. Mab1 binding was inhibited by abciximab in a dose dependent manner (IC50, 0.85+/-0.1 microg/mL), whereas Mab2 binding was unaffected. In contrast, the 2 small molecular weight antagonists, SC-57101A (IC50, 0.22+/-0.06 micromol/L) and eptifibatide (IC50, 0.35+/-0.14 micromol/L) inhibited Mab2 but not Mab1 binding. In patients treated with xemilofiban, Mab1 binding was unaltered but Mab2 binding decreased from 37 930+/-2061 sites per platelet at baseline to 8318+/-870 sites per platelet 6 hours after dosing (P<0.0001). Platelet aggregation to adenosine diphosphate (20 micromol/L) fell to 3+/-3% of baseline in line with the inhibition of Mab2 binding (correlation coefficient 0.8, P<0.0001). CONCLUSIONS: Mab1 and Mab2 bind to GPIIb/IIIa and are differentially displaced by abciximab and small molecular weight antagonists. These antibodies may be used to monitor receptor number and occupancy during administration of a GPIIb/IIIa antagonist. (+info)Lesions and identification of crystalline precipitates of glycoprotein IIb-IIIa antagonists in the rat kidney. (2/203)
Two glycoprotein IIb-IIIa antagonists (xemilofiban, SC-54684A, and orbofiban, SC-57099B), which are platelet aggregation inhibitors, caused crystalline precipitates in the kidney tubules of rats at high dosages. Dogs were not affected. Depending on the degree of the precipitation, which was dosage dependent, and the location, which differed somewhat between the two compounds, the lesions varied from acute obstruction with tubule cell necrosis, nephron dilation, and sudden death with no inflammation to severe chronic pyogranulomatous inflammation. In order to understand the relevance of the lesions, it was important to identify the precipitates. This was technically challenging because the crystals were water soluble (dissolving in routine fixing and staining techniques) and were present in insufficient quantity to physically isolate. Techniques were devised to evaluate the crystals in situ in unstained frozen sections prepared without directly embedding the tissues in supporting medium, which interfered with the analyses. The crystals were analyzed in situ by infrared and Raman spectroscopy and time-of-flight secondary ion mass spectroscopy (TOF-SIMS). Uroliths found in the renal pelvis of one animal were analyzed by liquid chromatography/mass spectrometry. The resulting spectra showed that the crystals were the de-esterified acids of the parent compounds. This knowledge allowed us to predict that the crystalline precipitates would not be a hazard to humans because of the large multiples of the human dosage at which they occurred and because of differences in renal physiology between rats, dogs, and humans. (+info)Potent selective nonpeptidic inhibitors of human lung tryptase. (3/203)
Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure-activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented. (+info)Design and evaluation of novel bivalent thrombin inhibitors based on amidinophenylalanines. (4/203)
Two bivalent thrombin inhibitors were synthesized, which consist of a benzamidine-based active-site-blocking segment, a fibrinogen recognition exosite inhibitor and a peptidic linker connecting these fragments. BZA-1 hirulog contains an Nalpha-(2-naphthylsulfonyl)-S-3-amidinophenylalanyl-is onipecotic acid residue connected via the carboxyl group to the linker segment. The active-site-directed moiety of BZA-2 hirulog [Nalpha-(2-naphthylsulfonyl-glutamyl)-R-4-amidinophenylal anyl-piperid ide] was coupled to the linker via the side chain of the glutamic acid. Both BZA-hirulogs contain almost identical linker-exo site inhibitor parts, except for the substitution of a glycine as the first linker residue in BZA-1 hirulog by a gamma-amino butyric acid in BZA-2 hirulog, thus increasing flexibility and linker length by two additional atoms. BZA-1 hirulog showed moderate potency (Ki = 0. 50 +/- 0.14 nM), while BZA-2 hirulog was characterized as a slow, tight binding inhibitor of thrombin (Ki = 0.29 +/- 0.08 pM). The stability in human plasma of both analogs was strongly improved compared with hirulog-1. For BZA-2 hirulog a significantly reduced plasma clearance was observed after intravenous injection in rats compared with BZA-1 hirulog and hirulog-1. The X-ray structure of the BZA-2 hirulog in complex with human alpha-thrombin was solved and confirmed the expected bivalent binding mode. (+info)Draculin, the anticoagulant factor in vampire bat saliva, is a tight-binding, noncompetitive inhibitor of activated factor X. (5/203)
The kinetic mechanism of action of Draculin on activated Factor X (FXa) is established. Draculin inhibits activated Factor X within seconds of incubation at near equimolar concentration (2-6 times on molar basis). Fitting the data to the equation for a tight-binding inhibitor gives a value for K(i)(K(d)) = 14.8+/-1.5 nM. The formation of the Draculin-FXa complex can be explained by a two-step mechanism, where for the first, reversible step, k(on) = 1.117 (+/- 0.169, S.E.M.) x 10(6) M(-1)s(-1) and k(off) = 15.388 (+/- 1.672) x 10(-3) s(-1), while for the second, irreversible step, which is concentration-independent, k(2) = 0.072 s(-1). K(d) obtained from k(off)/k(on) = 13.76 nM. Lineweaver-Burk plot shows a noncompetitive behavior. This noncompetitive mode of inhibition of Draculin is supported by the observation that Draculin, at concentrations giving complete inhibition, does not impair binding of p-aminobenzamidine to FXa. Moreover, under the same conditions, Draculin induces <14% decrease of the fluorescence intensity of the p-aminobenzamidine-FXa complex. We conclude that Draculin is a noncompetitive, tight-binding inhibitor of FXa, a characteristic so far unique amongst natural FXa inhibitors. (+info)In vivo and in vitro comparison of the short-term hematopoietic toxicity between hydroxyurea and trimidox or didox, novel ribonucleotide reductase inhibitors with potential anti-HIV-1 activity. (6/203)
Inhibitors of the cellular enzyme ribonucleotide reductase (hydroxyurea, [HU]) have been proposed as a new therapeutic strategy for the treatment of HIV type-1 (HIV-1) infection. However, HU use may be limited by the frequent development of hematopoietic toxicity. We report here short-term hematopoietic toxicity in mice receiving HU when compared to either of two more potent enzyme inhibitors, didox (DX) and trimidox (TX). High dose HU, DX, and TX monotherapy (500, 460, and 220 mg/kg/day respectively) was administered by daily i.p. injection (Monday-Friday) to C57BL/6 mice for 10 weeks. Effects on hematopoiesis were established by quantitating peripheral blood indices (hematocrit, hemoglobin, mean corpuscular volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, RBC, and WBC) and numbers of colony-forming units-granulocyte-macrophage (CFU-GM) and BFU-E from bone marrow and spleen. HU produced rapid induction of a macrocytic hypochromic anemia and altered white blood cell kinetics associated with myelosuppression defined as reduced marrow organ cellularity and induction of splenic extramedullary hematopoiesis. Compared to HU, TX and DX induced fewer changes in peripheral blood indices and CFU-GM and BFU-E per hematopoietic organ. In vitro human and murine marrow CFU-GM and BFU-E colony formations were assayed in the presence of dose escalation HU, DX, or TX (0, 1, 10, 50, 100, and 200 microM). HU inhibited colony formation more than either DX or TX. These in vivo and in vitro studies suggest that novel ribonucleotide reductase inhibitors TX and DX may provide an effective alternative to HU in HIV-1 therapy because they demonstrate reduced hematopoietic toxicity. (+info)Different effects of trypsin inhibitors on intestinal gene expression of secretin and on pancreatic bicarbonate secretion in CCK-A-receptor-deficient rats. (7/203)
The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation. (+info)Glycoprotein IIb/IIIa antagonists induce apoptosis in rat cardiomyocytes by caspase-3 activation. (8/203)
The platelet integrin glycoprotein (GP) IIb/IIIa, which mediates platelet aggregation, has been the target for novel antiplatelet agents, the GPIIb/IIIa antagonists. Several GPIIb/IIIa antagonists have been developed based on the peptide RGDS present in adhesion proteins, including the principle ligand fibrinogen. The apoptosis enzyme, procaspase-3, contains an RGD-recognition sequence and is activated by RGDS. We examined the effects of RGDS and several GPIIb/IIIa antagonists on cell death and procaspase-3 activation in rat neonatal cardiomyocytes. These antagonists do not recognize rat integrins, yet RGDS, orbofiban, and xemilofiban induced dose-dependent apoptosis and procaspase-3 activation in cardiomyocytes over 72 h, particularly under hypoxic conditions. Scrambled peptide, the monoclonal antibody 7E3 or integrelin (a peptide containing a KGD sequence), had little or no effect. Immunoprecipitation of procaspase-3 followed by treatment with the compounds showed that procaspase-3 was activated directly by RGDS, orbofiban, xemilofiban, and by monoclonal 7E3 antibody, the latter demonstrating that compounds must enter cells to induce apoptosis through caspase activation. Integrelin had no effect. Binding studies with (3)H-SC52012B, a GPIIb/IIIa antagonist analogue of orbofiban, showed no specific binding to cardiomyocytes, but the radioligand accumulated intracellularly over 72 h. (3)H-SC52012B also bound directly to human recombinant caspase-3 (K(d), 59 +/- 2 nm), and this was prevented by orbofiban, xemilofiban, and the monoclonal 7E3 antibody but not by integrelin. Finally confocal microscopy showed that RGDS co-localized with caspase-3 inside the cell. These data show that RGDS and its mimetics induce cardiomyocyte apoptosis by direct activation of procaspase-3. (+info)
Propamidine isethionate | definition of propamidine isethionate by Medical dictionary
BINDING OF DAPI ANALOG 2,5-BIS(4-AMIDINOPHENYL)FURAN TO DNA
Acanthamoebic keratitis diagnosed by paracentesis and biopsy and treated with propamidine. | British Journal of Ophthalmology
4-(TRIFLUOROMETHYL)BENZAMIDOXIME 22179-86-8 Chemical Properties Physical Properties
Synthesis, biological characterisation and structure activity relationships of aromatic bisamidines active against Plasmodium...
PurKine™ Benzamidine Resin 4FF - Abbkine - Antibodies, proteins, biochemicals, assay kits for life science research
RCSB PDB
- 1M6F: Strong Binding in the DNA Minor Groove by an Aromatic Diamidine With a Shape That Does Not Match the...
RCSB PDB
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Xemilofiban
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US Patent for Tricyclic pteridinones and a process for their preparation Patent (Patent # 5,854,419 issued December 29, 1998) ...
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BMRB Entry 15721
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N-hydroxy-4- {5- [4- (5-isopropyl-2-methyl-1, 3-thiazol-4-yl) phenoxy] pentoxy} benzamidine 2 methanesulfonic acid salt -...
Pentamidine
Ligand-Free Copper-Catalyzed Arylation of Amidines
US Patent for Benzamidine derivatives substituted by amino acid and hydroxy acid derivatives and their use as anti-coagulants...
Pharmaceuticals | Free Full-Text | Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study
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CCCC 1985, Volume 50, Issue 12, Abstracts pp. 2722-2729
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Sulfonimidamides in Medicinal and Agricultural Chemistry
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Amidine | definition of amidine by Medical dictionary
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Efficient microwave access to polysubstituted amidines from imidoylbenzotriazoles. - Semantic Scholar
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Ambiphilic Ligands from the 1,4-benzenebis(amidine) Framework : Sussex Research Online
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RCSB PDB - 3GY4: A comparative study on the inhibition of bovine beta-trypsin by bis-benzamidines diminazene and pentamidine by...
Distribution of furamidine analogues in tumor cells: influence of the number of positive charges
MEDLINE - Resultado p gina 1
0 (Benzamidines); 0 (Ophthalmic Solutions); 7T9IJ84C42 (propamidine isethionate); R4KO0DY52L (Chlorhexidine). [Em] M s de ... 0 (Benzamidines); 0 (Biomarkers, Tumor); 0 (LCN2 protein, human); 0 (Lipocalin-2); 9005-49-6 (Heparin); EC 3.4.- (Serine ... Eleven compounds of substituted 4-(5-arylthiophen-2-yl)benzamidines 4a-k were synthesized from their corresponding mononitriles ... 0 (Amino Acid Chloromethyl Ketones); 0 (Benzamidines); 0 (Caspase Inhibitors); 0 (Macrolides); 0 (Reactive Oxygen Species); 0 ( ...
Ewa Daniela Raczyńska
Corinne Beinat | Stanford Medicine
A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic ... A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic ... A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic ... "Structure-Activity Relationships of N-Substituted 4-(Trifluoromethoxy) Benzamidines with Affinity for GluN2B-Containing NMDA ...
Refereed academic publications
of 2001 | Zernike (ZIAM) | Onderzoek | Rijksuniversiteit Groningen
John A McCauley
Cyclic benzamidines as orally efficacious NR2B-selective NMDA receptor antagonists. Kevin T Nguyen. Department of Medicinal ... Cyclic benzamidines as orally efficacious NR2B-selective NMDA receptor antagonists. Kevin T Nguyen. Department of Medicinal ... A novel series of cyclic benzamidines was synthesized and shown to exhibit NR2B-subtype selective NMDA antagonist activity. ...
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Patent US6432892 - Cleaning of fruit, vegetables, and meats comprising alkyl-polyglycoside - Google Patents
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Evaluation of oral Xemilofiban in Controlling Thrombotic Events - American College of Cardiology
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Crystals and structures of spleen tyrosine kinase SYKKD - ATWELL SHANE
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Andrew Thompson
- the University of Bath's research portal
Studies on the DNA Duplex Adducts of Anti-cancer agents by High Field NMR. The central target of my research is aimed at determining the molecular basis for the anti-tumour activity of DNA interactive anti-cancer ligands. It is hoped that we will be able relate the structural changes in local DNA structure which are induced or entrapped by these ligands to the biochemical and biological effects and incorporate these findings into the design of future DNA interactive anti-cancer ligands.. A number of methods are available to study the structure and nature of ligand-DNA adducts, these include X-ray diffraction, high-field NMR, circular dichroism, Raman spectroscopy, UV, IR, gel electrophoresis and enzymatic probes. My research has concentrated on the use of high-field NMR coupled with molecular modelling to closely study the duplex adducts formed in the reactions of DNA alkylating ligands and DNA duplexes.. High field NMR studies are performed on the in-house Varian 600MHz and 400Mhz NMR ...
US6989342B2 - Catalyst for polymerization and copolymerization of ethylene
- Google Patents
Ligand-Free Copper-Catalyzed Arylation of Amidines
Imide synthesis by oxidation or hydrolysis
Benzamidines/metabolism
Humans , Receptors, GABA-A/chemistry , Binding Sites , Benzamidines/chemistry , Benzamidines/metabolism , Benzamidines/ ... Benzamidines/metabolism , Trypsin/metabolism , Benzamidines/chemistry , Binding Sites , Chromatography, Affinity , Mathematics ... Benzamidines/metabolism , Spectrophotometry, Atomic , Thermodynamics , Trypsin/metabolism , Protein Conformation , Trypsin ...
DI-fusion Reaction of 1,3,5-oxadiazinium salts with amines; formation...
DeCS
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Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. - PubMed - NCBI
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Pentamidine | REACH
Benzamidines/chemistry
Humans , Receptors, GABA-A/chemistry , Binding Sites , Benzamidines/chemistry , Benzamidines/metabolism , Benzamidines/ ... Benzamidines/metabolism , Trypsin/metabolism , Benzamidines/chemistry , Binding Sites , Chromatography, Affinity , Mathematics ... Animals , Cattle , Benzamidines/chemistry , Diminazene/analogs & derivatives , Trypsin Inhibitors/chemistry , Trypsin/chemistry ...
Amidines1
- DMF was the superior solvent for the N -arylation of benzamidines, while MeCN was used in the formation of N -aryl amidines in good yield. (organic-chemistry.org)
Ketones1
- An iodine-catalyzed oxidative C-H/N-H cross-coupling enables an efficient construction of α-ketoimides in good to excellent yields from methyl ketones and benzamidines hydrochloride under metal-free and peroxide-free conditions. (organic-chemistry.org)