618-39-3

Usage

Chemical Description

Benzamidine is a molecule with biological and pharmacological relevance.

Uses

Used in Biochemical Research:
BENZAMIDINE is used as an enzyme inhibitor for preventing enzymatic degradation during the purification procedure of bovine factor XII (Hageman factor). This application is crucial in maintaining the integrity of the factor XII during the purification process, allowing for accurate study and analysis.
Used in Preparation of Proteoglycans:
In the field of cell biology, BENZAMIDINE is utilized in the preparation of heparan sulfate-rich proteoglycan from mouse mammary epithelial cells. This application highlights its importance in the study of cell surface molecules and their interactions, which are essential for understanding various biological processes and potential therapeutic targets.

Synthesis Reference(s)

The Journal of Organic Chemistry, 27, p. 1255, 1962 DOI: 10.1021/jo01051a033Tetrahedron Letters, 31, p. 1969, 1990 DOI: 10.1016/S0040-4039(00)88891-7

Biochem/physiol Actions

Benzamidine is an inhibitor of plasmin and has been used in the radioimmunoassay of glucagon in human plasma. It prevents the destruction of Thyrotropin-releasing hormone (TRH) added to whole blood in vitro before radioimmunoassay of TRH.

Purification Methods

It is liberated from its hydrochloride chloride (below) by treatment with 5M NaOH, extracted into diethyl ether, dried (Na2SO4) and sublimed in vacuo.[Beilstein 9 H 280, 9 I 123, 9 II 199, 9 1264, 9 IV 898.]

InChI:InChI=1/C7H8N2/c8-7(9)6-4-2-1-3-5-6/h1-5H,(H3,8,9)

Upstream product

• 44830-55-9 3-cyano-1-isopropylguanidine 
• 16118-22-2 benzylidenamine 
• 5333-86-8 ethyl benzimidate hydrochloride 
• 1147550-11-5 ammonium thiocyanate 
• 100-47-0 benzonitrile 
• 613-92-3 N-hydroxybenzenecarboximidamide 
• 76843-75-9 3,7-Diphenyl-1λ⁴,5,2,4,6,8-dithiatetrazocin 
• 930-69-8 sodium thiophenolate 
• 4460-46-2 3-chloro-3-phenyl-3H-diazirine 
• 4222-25-7 3-bromo-3-phenyl-3H-diazirine 
• 1670-14-0 benzamidine monohydrochloride 
• 1456-22-0 3-phenyl-4H-[1,2,4]oxadiazol-5-one 
• 10034-85-2 hydrogen iodide 
• 3663-37-4 3-phenyl-1,2,4-oxadiazol-5-amine 

Downstream Products

• 100869-87-2 2-phenyl-5,6,7,8-tetrahydroquinazoline 
• 22454-72-4 N-ethoxycarbonylbenzamidine 
• 3599-62-0 2-methyl-4,6-diphenyl-1,3,5-triazine 
• 101091-99-0 N-benzimidoyl-N'-p-tolyl-thiourea 
• 26196-28-1 N-benzylidene-benzamidine 
• 66130-05-0 N,N'-bis-phenylcarbamoyl-benzamidine 
• 861584-19-2 6-diethoxymethyl-2-phenyl-3H-pyrimidin-4-one 
• 65363-61-3 N-ethyl-benzamidine 
• 67280-51-7 N-(2,2,2-trichloro-1-hydroxy-ethyl)-benzamidine 
• 2654-31-1 4-methyl-2,5-diphenyl-1H-imidazole 
• 10104-15-1 5,5-dimethyl-2-phenyl-1H-pyrimidine-4,6-dione 
• 25286-57-1 5,5-diethyl-2-phenyl-1H-pyrimidine-4,6-dione 
• 1666-86-0 2,4,6-triphenylpyrimidine 
• 16776-73-1 N-benzoyl-benzamidine 

Relevant academic research and scientific papers

Benzamidine

Benzenecarboximidamide, C7H8N2, has been prepared and its structure shows a planar molecule with distinct C double bond N 1.294 (3) and C - N 1.344 (3) angstroms distances, and a three-dimensional hydrogen-bonding network.

NADH cytochrome b5 reductase and cytochrome b5 catalyze the microsomal reduction of xenobiotic hydroxylamines and amidoximes in humans

Hydroxylamine metabolites, implicated in dose-dependent and idiosyncratic toxicity from arylamine drugs, and amidoximes, used as pro-drugs, are metabolized by an as yet incompletely characterized NADH-dependent microsomal reductase system. We hypothesized that NADH cytochrome b5 reductase and cytochrome b5 were responsible for this enzymatic activity in humans. Purified human soluble NADH cytochrome b5 reductase and cytochrome b5 expressed in Escherichia coli, efficiently catalyzed the reduction of sulfamethoxazole hydroxylamine, dapsone hydroxylamine, and benzamidoxime, with apparent Km values similar to those found in human liver microsomes and specific activities (Vmax) 74 to 235 times higher than in microsomes. Minimal activity was seen with either protein alone, and microsomal protein did not enhance activity other than additively. All three reduction activities were significantly correlated with immunoreactivity for cytochrome b5 in individual human liver microsomes. In addition, polyclonal antibodies to both NADH cytochrome b5 reductase and cytochrome b5 significantly inhibited reduction activity for sulfamethoxazole hydroxylamine. Finally, fibroblasts from a patient with type II hereditary methemoglobinemia (deficient in NADH cytochrome b5 reductase) showed virtually no activity for hydroxylamine reduction, compared with normal fibroblasts. These results indicate a novel direct role for NADH cytochrome b5 reductase and cytochrome b5 in xenobiotic metabolism and suggest that pharmacogenetic variability in either of these proteins may effect drug reduction capacity.

Assembly of 5-Aminoimidazoles via Palladium-Catalysed Double Isocyanide Insertion Reaction

A palladium-catalysed tandem cyclisation reaction of amidoximes, isocyanides and amines to produce 5-aminoimidazoles was developed. Various 5-aminoimidazoles were prepared in good to excellent yields under mild conditions. This elegant domino process involves the effective cleavage of the N?O bond and the formation of new C?C and C?N bonds in a single operation. (Figure presented.).

Compounds for Treating Cannabinoid Toxicity and Acute Cannabinoid Overdose

The present invention relates to novel compounds that can act as antidotes for treating “Acute Cannabinoid Overdose” produced by classical cannabinoids such as Δ9-tetrahydrocannabinol (THC) and several synthetic psychoactive cannabinoids (SPCs). The cannabis constituent THC exerts its psychotropic effects via CB1 receptor activation and SPCs mimic the effects of THC with higher potency and severe neurotoxicity. Compounds disclosed in this invention, their enantiomers, diastereomers, geometric isomers, racemates, tautomers, rotamers, atropisomers, metabolites, N-oxides, salts, solvates, hydrates, isotopic variations and their polymorphic forms can be therapeutically useful in an emergency setting for counteracting the intoxicating effects of acute THC ingestion and SPC overdose. Also, aspects of the invention are concerned with pyrazoles, imidazoles, triazoles, thiazoles, oxazoles, dihydropyrazoles, pyrrolidinones, azetidines, oxyazetidines and azaspiro[3.3]heptanes with unique pharmacokinetic and pharmacodynamic properties for treating “Acute Cannabinoid Overdose”.

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.

Toward Continuous-Flow Synthesis of Biologically Interesting Pyrazole Derivatives

A two-step continuous-flow synthesis of substituted pyrazole derivatives has been developed via the formation of vinylidene keto esters as key intermediates. Heterogeneous Ni2+-montmorillonite was found to be an efficient catalyst for orthoester condensation of 1,3-dicarbonyls under flow conditions. The intermediate reacted with methylhydrazine to afford pyrazole derivatives, for which suitable selection of a solvent played a key role in achieving high yields and excellent regioselectivities of the desired products. An application of this protocol has been demonstrated by the synthesis of a key intermediate for biologically active pyrazoles such as Bixafen. (Figure presented.).

Sulfated tungstate catalyzed activation of nitriles: addition of amines to nitriles for synthesis of amidines

An efficient and mild method for the synthesis of amidines by direct nucleophilic addition of amines to nitriles using sulfated tungstate as heterogeneous catalyst is described. Highlight of the method is its applicability for the synthesis of amidines using a wide variety of amines including ammonia as ammonium acetate and nitriles. Catalyst is mildly acidic, stable, easy to prepare and separate from the reaction mass.

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.

4-Amino-3-phenylamino-6-phenylpyrazolo[3,4-d]pyrimidine derivatives, their manufacture and their use as antiviral active substances

The present invention relates to 5-amino-3-phenylamino-6-phenylpyrazolo[3,4-d]pyrimidine derivatives of the general formula I or pharmaceutically acceptable salts or propharmacons thereof, wherein at least one hydrogen atom in at least one of the phenyl groups A and B is substituted by a substituent RH, which has a Hammett constant σp greater than 0.23. The present invention also concerns the method of its manufacture. For corresponding compounds, surprisingly a particuarly high activity against viruses, in particular rhinoviruses and picornaviruses was determined. Furthermore, the compounds are tolerated very well. For these reasons the compounds are suitable for the treatment of viral infections and as drugs.

Functional characterization of protein variants encoded by nonsynonymous single nucleotide polymorphisms in MARC1 and MARC2 in healthy Caucasians

Human molybdenum-containing enzyme mitochondrial amidoxime reducing component (mARC), cytochrome b5 type B, and NADH cytochrome b5 reductase form an N-reductive enzyme system that is capable of reducing N-hydroxylated compounds. Genetic variations are known, but their functional relevance is unclear. Our study aimed to investigate the incidence of nonsynonymous single nucleotide polymorphisms (SNPs) in the mARC genes in healthy Caucasian volunteers, to determine saturation of the protein variants with molybdenum cofactor (Moco), and to characterize the kinetic behavior of the protein variants by in vitro biotransformation studies. Genotype frequencies of six SNPs in the mARC genes (c. 493A>G, c. 560T>A, c. 736T>A, and c. 739G>C in MARC1; c. 730G>A and c. 735T>G in MARC2) were determined by pyrosequencing in a cohort of 340 healthy Caucasians. Protein variants were expressed in Escherichia coli. Saturation with Moco was determined by measurement of molybdenum by inductively coupled mass spectrometry. Steady state assays were performed with benzamidoxime. The six variants were of low frequency in this Caucasian population. Only one homozygous variant (c.493A; MARC1) was detected. All protein variants were able to bind Moco. Steady state assays showed statistically significant decreases of catalytic efficiency values for the mARC-2 wild type compared with the mARC-1 wild type (P 0.05) and for two mARC-2 variants compared with the mARC-2 wild type (G244S, P 0.05; C245W, P 0.05). After simultaneous substitution of more than two amino acids in the mARC-1 protein, N-reductive activity was decreased 5-fold. One homozygous variant of MARC1 was detected in our sample. The encoded protein variant (A165T) showed no different kinetic parameters in the N-reduction of benzamidoxime. Copyright