18465-11-7

Basic information

• Product Name: 4-METHYL-BENZAMIDINE
• Synonyms: 4-methylbenzimidamide
• CAS NO: 18465-11-7
• Molecular Formula: C₈H₁₀N₂
• Molecular Weight: 134.18
• Mol File: 18465-11-7.mol

Chemical Properties

• Boiling Point: 225°C at 760 mmHg
• Flash Point: 89.9°C
• Appearance: /
• Density: 1.07g/cm³
• Vapor Pressure: 0.0884mmHg at 25°C
• Refractive Index: 1.559
• CAS DataBase Reference: 4-METHYL-BENZAMIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-METHYL-BENZAMIDINE(18465-11-7)
• EPA Substance Registry System: 4-METHYL-BENZAMIDINE(18465-11-7)

Safety Data

• Hazardous Substances Data: 18465-11-7(Hazardous Substances Data)

Usage

InChI:InChI=1/C8H10N2/c1-6-2-4-7(5-3-6)8(9)10/h2-5H,1H3,(H3,9,10)

Upstream product

• 104-85-8 para-methylbenzonitrile 
• 108-88-3 toluene 
• 930-69-8 sodium thiophenolate 
• 95911-62-9 3-Bromo-3-(p-methylphenyl)diazirine 
• 31827-28-8 4,5-dihydro-3-(p-tolyl)-1,2,4-oxadiazol-5-one 
• 10034-85-2 hydrogen iodide 
• 7664-93-9 sulfuric acid 
• 19227-13-5 p-toluamidoxime 
• 52093-58-0 N'-methoxy-4-methylbenzimidamide 
• 420-04-2 CYANAMID 
• 19227-13-5 N'-hydroxy-4-methyl-benzamidine 
• 6326-27-8 p-methylbenzamidine hydrochloride 
• 89108-49-6 1-(1-azidovinyl)-4-methyl benzene 
• 766-97-2 4-n-methylphenylacetylene 

Downstream Products

• 30377-13-0 2-methyl-4,6-di-p-tolyl-1,3,5-triazine 
• 46297-10-3 2-p-tolyl-1H-imidazole-4,5-dione 
• 92579-98-1 ethyl 4-methyl-2-(p-tolyl)pyrimidine-5-carboxylate 
• 49773-39-9 N-chloro-4-methyl-benzamidine 
• 21036-72-6 4-furan-2-yl-2-p-tolyl-1⁽³⁾H-imidazole 
• 21036-77-1 4-thiophen-2-yl-2-p-tolyl-1⁽³⁾H-imidazole 
• 21036-92-0 4-benzofuran-2-yl-2-p-tolyl-1⁽³⁾H-imidazole 
• 67565-26-8 4-p-tolyl-2,2,6,6-tetrakis-trifluoromethyl-3,6-dihydro-2H-[1,3,5]oxadiazine 
• 82805-38-7 2,2-Diphenyl-4,6-di-p-tolyl-1,2-dihydro-[1,3,5]triazine 
• 82805-40-1 2-Phenyl-4,6-di-p-tolyl-2-trifluoromethyl-1,2-dihydro-[1,3,5]triazine 
• 95674-99-0 N,N,N'-tris(4-tolylthio)-4-toluenecarboximidamide 

Relevant articles and documents

Novel Allosteric Inhibitors of Deoxyhypusine Synthase against Malignant Melanoma: Design, Synthesis, and Biological Evaluation

Based on the novel allosteric site of deoxyhypusine synthase (DHPS), two series of 30 novel 5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-amine derivatives as DHPS inhibitors were designed and synthesized. Among them, compound8m, with the best DHPS inhibitory potency (IC50= 0.014 μM), exhibited excellent inhibition against melanoma cells, which was superior to that of GC7. Besides, molecular docking and molecular dynamics (MD) simulations further proved that compound8mwas tightly bound to the allosteric site of DHPS. Flow cytometric analysis and enzyme-linked immunosorbent assay (ELISA) showed that compound8mcould inhibit the intracellular reactive oxygen species (ROS) level. Furthermore, by western blot analysis, compound8meffectively activated caspase 3 and decreased the expressions of GP-100, tyrosinase, eIF5A2, MMP2, and MMP9. Moreover, both Transwell analysis and wound healing analysis showed that compound8mcould inhibit the invasion and migration of melanoma cells. In thein vivostudy, the tumor xenograft model showed that compound8meffectively inhibited melanoma development with low toxicity.

Direct Transformation of Terminal Alkynes into Amidines by a Silver-Catalyzed Four-Component Reaction

An unprecedented conversion of terminal alkynes into N-sulfonimidamides (amidines) is reported by a silver-catalyzed, one-pot, four-component reaction with TMSN3, sodium sulfinate, and sulfonyl azide. The reaction scope includes both aromatic and aliphatic alkynes. A possible cascade reaction mechanism, consisting of alkyne hydroazidation, sulfonyl radical addition, 1,3-dipolar cycloaddition by TMSN3, and retro-1,3-dipolar cycloaddition, is proposed. TMSN3 is found to play an essential role in each step of the reaction.

Silver-catalyzed [3+2+1] annulation of aryl amidines with benzyl isocyanide

A silver-catalyzed [3+2+1] annulation of amidines with benzyl isocyanide toward 2,4-diaryl-1,3,5-triazines was developed. A variety of symmetrical and unsymmetrical products were obtained in moderate to good yields. This work also features an oxidant-free approach to 2,4-disubstituted triazines.

Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases

Abstract The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl)ate their target proteins using NAD+ as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with β-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused >1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2.

Electrochemical and mARC-catalyzed enzymatic reduction of para-substituted benzamidoximes: Consequences for the prodrug concept "amidoximes instead of amidines"

The mitochondrial amidoxime reducing component (mARC) activates amidoxime prodrugs by reduction to the corresponding amidine drugs. This study analyzes relationships between the chemical structure of the prodrug and its metabolic activation and compares its enzyme-mediated vs. electrochemical reduction. The enzyme kinetic parameters KM and Vmax for the N-reduction of ten para-substituted derivatives of the model compound benzamidoxime were determined by incubation with recombinant proteins and subcellular fractions from pig liver followed by quantification of the metabolites by HPLC. A clear influence of the substituents at position 4 on the chemical properties of the amidoxime function was confirmed by correlation analyses of 1H NMR chemical shifts and the redox potentials of the 4-substituted benzamidoximes with Hammett's σ. However, no clear relationship between the kinetic parameters for the enzymatic reduction and Hammett's σ or the lipophilicity could be found. It is thus concluded that these properties as well as the redox potential of the amidoxime can be largely ignored during the development of new amidoxime prodrugs, at least regarding prodrug activation.

TANKYRASE INHIBITORS

The present invention relates to a compound of formula I wherein X is C(R6) or N, Y is C or N, and ring A, ring B, R1 and R2 have the meanings defined herein, provided that when ring B is carbocyclic, X is C(R6); or a pharmaceutically acceptable salt or solvate thereof. The compounds are tankyrase-1 and tankyrase-2 inhibitors and are useful in the treatment of a number of conditions, including cancer.

Direct palladium(II)-catalyzed synthesis of arylamidines from aryltrifluoroborates

A fast and convenient synthesis of arylamidines starting from readily available potassium aryltrifluoroborates and cyanamides is reported. The coupling was achieved by Pd(II)-catalysis in a one step 20 min microwave protocol using Pd(O2CCF

Unsymmetrical 1α3-1,2,4,6-thiatriazinyls with aryl and trifluoromethyl substituents: Synthesis, crystal structures, EPR spectroscopy, and voltammetry

A general synthetic route to 3-trifluoromethyl-5-aryl-1α3- 1,2,4,6-thiatriazinyl radicals was developed. X-ray structures were obtained for all five neutral radicals and show that they exist in the solid state as cofacial dimers linked by S...S contacts. X-ray structures were also obtained for two of the precursor chlorothiatriazines along with several aryl N-imidoylamidines, p-methoxybenzamidine, and N-chlorosulfonyl- N,N'-benzamidine. Cyclic voltammetric studies were performed on the [R2C 2N3S]. radicals in CH3CN and CH 2Cl2 with [nBu4N][PF6] as the supporting electrolyte under vacuum conditions in an all-glass electrochemical cell. The results provide quasi-reversible formal potentials for the [R2C2N3S]-/0 process in the range of -0.61 to -0.47 V, irreversible peak potentials for the [R2C 2N3S]0/+ process from 0.59 to 0.91 V at lower concentrations, and the appearance of a second, reversible oxidation process from 0.69 to 0.94 V at higher concentrations (versus the Fc0/+ couple; Fc = ferrocene). This behavior was indicative of monomer-dimer equilibrium in solution, as ascertained from digital models of the voltammograms. There is a small but measurable trend in both the oxidation and reduction potentials with varying remote aryl substituents. EPR spectra were obtained for all five neutral radicals in CH2Cl2 solutions, which confirm the concentration of the unpaired electron density on the heterocyclic core. Trends were also seen in the hyperfine splitting constants aN with varying remote aryl substituents. Calculations were performed for all three oxidation states of the [R2C2N3S]-/./+ monomeric rings; the resulting theoretical redox energies correlate well with solution phase voltammetric data.

Direct Conversion of Amidoximes to Amidines via Transfer Hydrogenation

Amidoximes, O-alkylamidoximes, and O-acylamidoximes are directly converted to amidines by reaction with ammonium formate and Pd/C in acetic acid.

Pyridine and pyrimidine derivatives

The present invention provides compounds of formula (I) wherein R1, R2, R3, R4 and X are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment