1670-14-0

Basic information

• Product Name: Benzamidine hydrochloride
• Synonyms: amidinobenzenehydrochloride;benzamidiniumchloride;Benzenecarboximidamide,monohydrochloride;BENZAMIDINE HCL;BENZAMIDINE HYDROCHLORIDE;BENZENECARBOXIMIDAMIDE HYDROCHLORIDE;Benzamidine hydrochloride anhydrous;BENZAMIDINE HYDROCHLORIDE 99%
• CAS NO: 1670-14-0
• Molecular Formula: C₇H₈N₂*ClH
• Molecular Weight: 156.61
• EINECS: 216-795-4
• Product Categories: Pharmaceutical Intermediates;Anilines, Aromatic Amines and Nitro Compounds;Phenyls & Phenyl-Het;Phenyls & Phenyl-Het;Core Bioreagents;Enzyme InhibitorsEnzyme Inhibitors by Enzyme;R to;Research Essentials;Trypsin Inhibitors
• Mol File: 1670-14-0.mol

Chemical Properties

• Melting Point: 86-88 °C(lit.)
• Boiling Point: 208.5 °C at 760 mmHg
• Flash Point: 79.9 °C
• Appearance: White to off-white/Powder
• Density: 1.09 g/cm³
• Vapor Pressure: 5.63E-05mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: DMF: 25 mg/mlDMSO: 25 mg/mlEthanol: 10 mg/mlPBS (pH 7.2): 3 mg/ml
• Water Solubility: soluble
• Stability: Stable for 2 years from date of purchase as supplied. Solutions are not stable and must be prepared fresh daily
• BRN: 3594959
• CAS DataBase Reference: Benzamidine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Benzamidine hydrochloride(1670-14-0)
• EPA Substance Registry System: Benzamidine hydrochloride(1670-14-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39-36
• WGK Germany: 3
• RTECS: CV6260000
• F: 3-21
• Hazardous Substances Data: 1670-14-0(Hazardous Substances Data)

Usage

Uses

Used in Biochemistry Research:
Benzamidine hydrochloride is used as a general serine protease inhibitor for [application reason] in biochemical research, where it helps in the study and analysis of protease enzymes and their functions.
Used in Protease Purification:
When immobilized, benzamidine hydrochloride is used as a purifying agent for [application reason] novel proteases, enabling the isolation and identification of new protease enzymes.
Used in Yeast Protease Inhibition:
Benzamidine hydrochloride is used as a protease inhibitor for [application reason] inhibiting proteases from yeast, with a concentration range of 0.5 to 4.0 mM, and is mostly interchangeable with pepstatin A.
Used in Glucagon Degradation Prevention:
Benzamidine hydrochloride is used as an inhibitor for [application reason] preventing glucagon degradation in human plasma, and has been found to be as effective as aprotinin in this application.

Preparation

To a stainless steel rocking autoclave equipped with a stirrer is added 103.0 gm (1.0 mole) of benzonitrile, 214.0 gm (4.0 mole) of ammonium chloride, and 306.0 gm (18.0 mole) of ammonia is introduced by means of a transfer bomb. The reaction mixture is heated at 150°C for 18 hr (pressure: 1300-6500 psig), cooled, and, with appropriate precautions for the safe control of the excess ammonia, is vented to atmospheric pressure. The reaction mixture is extracted with ether to remove approximately 5% unreacted benzonitrile, and then extracted with hot acetonitrile or ethanol to separate the amidine hydrochloride from the unreacted ammonium chloride. Concentration of the latter affords 120.5 gm (77%) of benzamidine hydrochloride, m.p. 161-163°C.

Biological Activity

Benzamidine hydrochloride is an reversible competitive inhibitor of trypsin-like serine proteases, with Kis of 97 μM, 21 μM, 20 μM and 110 μM for uPA, trypsin, tryptase and factor Xa, respectively.

Safety Profile

Moderately toxic byintraperitoneal route. When heated to decomposition itemits toxic vapors of NOx, HCl, and Cl-.

in vitro

Benzamidine hydrochloride has weak inhibition for tPA and thrombin, with Kis of 750 μM and 320 μM, respectively.

References

1) Markwardt?et al. (1968)?Comparative studies on the inhibition of trypsin, plasmin, and thrombin by derivatives of benzylamine and benzamide; Eur. J. Biochem.,?6?502 2) Deutscher?et al.?(1990),?Maintaining protein stability; Methods Enzymol.,?182?83 3) Jaswinski?et al.?(1990),?Preparations of extracts from yeast; Methods Enzymol.,?182?154 4) Ensinck?et al.?(1972),?Use of Benzamidine as a proteolytic inhibitor in the radioimmunoassay of glucagon in plasma; J. Clin. Endocrinol. Metab.,?35?463 5) Jeffcoate?et al. (1974),?Use of benzamidine to prevent the destruction of thyrotropin-releasing hormone (TRH) by blood; Endocrinol. Metab,?38?155

InChI:InChI=1/C7H8N2.ClH.H2O/c8-7(9)6-4-2-1-3-5-6;;/h1-5H,(H3,8,9);1H;1H2

Upstream product

• 100-47-0 benzonitrile 
• 7664-41-7 ammonia 
• 5333-86-8 ethyl benzimidate hydrochloride 
• 7732-18-5 water 
• 5873-90-5 methyl benzimidate hydrochloride 
• 613-92-3 N-hydroxybenzenecarboximidamide 

Downstream Products

• 68906-00-3 2-phenyl-5-nitropyrimidine 
• 1722-18-5 2-phenyl-1,3,5-triazine 
• 86739-33-5 5,6-dimethyl-2-phenylpyrimidin-4(3H)-one 
• 100725-02-8 4-amino-6-(2-hydroxy-ethoxy)-2-phenyl-pyrimidine-5-carbonitrile 
• 21506-68-3 3-(4-methyl-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl)propanoic acid 
• 22814-31-9 3-(4-methyl-6-oxo-2-phenyl-1,6-dihydro-pyrimidin-5-yl)-propionic acid ethyl ester 
• 52126-76-8 4-amino-2-phenylpyrimidine-5-carbonitrile 
• 67280-51-7 N-(2,2,2-trichloro-1-hydroxy-ethyl)-benzamidine 
• 34771-50-1 5-chloro-2-phenylpyrimidine 
• 7431-45-0 2-phenylpyrimidine 
• 73514-21-3 2,2'-diphenyl-1H,1'H-[4,4']biimidazolylidene-5,5'-dione 
• 66373-27-1 acetyl-5 methyl-4 phenyl-2 pyrimidine 
• 24504-22-1 2-phenyl-4,6-bis-trichloromethyl-[1,3,5]triazine 

Relevant articles and documents

Ethylene bis-imidazoles are highly potent and selective activators for isozymes VA and VII of carbonic anhydrase, with a potential nootropic effect

A series of ethylene bis-imidazoles was synthesized via a novel microwave-mediated synthesis. Biological testing on eight isozymes of carbonic anhydrase (CA) present in the human brain revealed compounds with nanomolar potency against CA VA and CA VII, also displaying excellent selectivity against other CA isozymes present in this organ. the Partner Organisations 2014.

Synthesis, Molecular Structure and Solution Dynamics of Dimeric Benzamidinates containing a Double Diazaallyl Lithium Bridge. A Rapid Interconversion of ? and ? Bonds

Dimeric Li reacted with the nitriles 4-XC6H4CN (X = H or Me) in diethyl ether-hexane (1:10) to yield dimeric complexes 2 (X = H 1 or Me 2).Complex 2 is dimeric in the solid state with two four-co-ordinated lithium cations bound in N,N'-bidentate ? fashion to one amidine anion (chelating), forming a double diazaallyl lithium bridge, in a monodentate ? fashion to a nitrogen lone pair of a substrate molecule, and monodentrate to a nitrogen lone pair of a second amidine anion.In solution, rapid interconversion of the different lithium-amidine bonds (? to ? and vice versa) was observed by means of the NMR chemical shifts.

2-methoxyphenoxy pyrimidine antitumor compound as well as preparation method and application thereof

The invention belongs to the technical field of medicines, relates to a compound with anti-tumor activity and a specific chemical structure, and particularly relates to a 2-methoxyphenoxy pyrimidine compound as well as a preparation method and application thereof. The structural general formula of the 2-methoxyphenoxy pyrimidine compound is shown in the specification, wherein an R group is a hydrogen atom, or a 2-position monosubstituted fluorine atom, or 3-position and 4-position monosubstituted methyl, methoxy, fluorine atom, chlorine atom, bromine atom and iodine atom. Experimental research shows that the prepared 2-methoxyphenoxy pyrimidine compound shows a good result in an in-vitro anti-tumor activity test, has certain inhibitory activity on human malignant melanoma A375 cells, can be used for preparing anti-tumor drugs, and opens up a new way for developing new anti-tumor drugs. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.

Phenyl pyrimidinamine anti-tumor compound as well as preparation method and application thereof

The invention belongs to the technical field of medicines, relates to a compound with anti-tumor activity and a specific chemical structure, and particularly relates to a phenyl pyrimidinamine compound as well as a preparation method and application thereof. The structural general formula of the phenyl pyrimidinamine compound is shown in the specification, wherein an R group is a hydrogen atom, a 2-position monosubstituted fluorine atom, or 3-position and 4-position monosubstituted methyl, a fluorine atom, a chlorine atom and a bromine atom. Experimental research shows that the prepared phenyl pyrimidinamine compound shows a good result in an in-vitro anti-tumor activity test, can be used for preparing anti-tumor drugs, and opens up a new way for developing the anti-tumor drugs with an endothelin receptor as a new target. The preparation method provided by the invention is simple and feasible, higher in yield and easy for large-scale production.

Synthesis method of benzamidine hydrochloride

The invention discloses a synthesis method of benzamidine hydrochloride, and belongs to the field of chemical synthesis. Benzonitrile and hydroxylamine hydrochloride carry out addition reactions under the effect of an acid-binding agent and a phase transfer agent to obtain benzamidoxime; obtained benzamidoxime carries out reduction reactions at first and then is acidified to obtain a coarse product of benzamidine hydrochloride; then the coarse product is heated and dissolved in a solvent, active carbon is added into the solution to carry out color removal, then the solution is filtered, and the filtrate is dried to obtain pure benzamidine hydrochloride. The preparation method has the advantages of simpleness, green, environmental friendliness, and suitability for industrial production.

'Green' synthesis of 2-substituted 6-hydroxy-[3H]-pyrimidin-4-ones and 4,6-dichloropyrimidines: Improved strategies and mechanistic study

An improved route to 2-substituted 6-hydroxy-[3H]-pyrimidin-4-ones 4 and to 2-substituted 4,6-dichloropyrimidines 5 is reported. Without using highly toxic reactants, compounds 4 can be prepared conveniently in a one pot synthesis on a one mol scale with average yields up to 80%. 4,6-Dichloropyrimidines 5, which are usually prepared in small quantities, are synthesized with average yields of 80%, using up to 80g of starting material. The mechanism of the chlorination of 4 is investigated computationally for the first time. The results suggest that the chlorination with phosphoryl chloride occurs in an alternating phosphorylation-chlorination manner (pathway 1) which is preferred over a sequence which starts with two phosphorylations. The investigated 4,6-dichloropyrimidines described herein form strong complexes with dichlorophosphoric acid but weak complexes with hydrochloric acid (generated during workup). These latter complexes explain the necessity of using aqueous sodium carbonate during the working up. In order to prevent possible formation of pyrimidinium salts between intermediates or the final dichloropyrimidines and unreacted hydroxypyrimidone, the latter could be deactivated with a strong acid such as dichlorophosphoric acid, thus allowing chlorination but prohibiting salt formation. Because of its general applicability to all nitrogen heterocycle chlorinations with phosphoryl chloride, the proposed route to dichloropyrimidines without solvent or side products, using less toxic reactants, is of general synthetic interest.

Investigation of new 2-aryl substituted Benzothiopyrano[4,3-d[pyrimidines as kinase inhibitors targeting vascular endothelial growth factor receptor 2

Vascular Endothelial Growth Factor (VEGF) pathway has emerged as one of the most important positive modulators of Angiogenesis, a central process implicated in tumour growth and metastatic dissemination. This led to the design and development of anti-VEGF monoclonal antibodies and small-molecule ATP-competitive VEGFR-inhibitors. In this study, we describe the synthesis and the biological evaluation of novel 2-aryl substituted benzothiopyrano-fused pyrimidines 1a-i, 2a-i and 3a-i. The ability of the compounds to target the VEGF pathway was determined in vitro exploiting the compounds' antiproliferative efficacy against HUVEC cells. The VEGFR-2 inhibition was confirmed by enzymatic assays on recombinant human kinase insert domain receptor (KDR), by cell-based phospho-VEGFR-2 inhibition assays, and by ex vivo rat aortic ring tests. The selectivity profile of the best performing derivatives belonging to series 2 was further explored combining modeling studies and additional assays in a panel of human cell lines and other kinases.

A new nonpolar N-hydroxy imidazoline lead compound with improved activity in a murine model of late-stage Trypanosoma brucei brucei infection is not cross-resistant with diamidines

Treatment of late-stage sleeping sickness requires drugs that can cross the blood-brain barrier (BBB) to reach the parasites located in the brain. We report here the synthesis and evaluation of four new N-hydroxy and 12 new N-alkoxy derivatives of bisimidazoline leads as potential agents for the treatment of late-stage sleeping sickness. These compounds, which have reduced basicity compared to the parent leads (i.e., are less ionized at physiological pH), were evaluated in vitro against Trypanosoma brucei rhodesiense and in vivo in murine models of first- and second-stage sleeping sickness. Resistance profile, physicochemical parameters, in vitro BBB permeability, and microsomal stability also were determined. The N-hydroxy imidazoline analogues were the most effective in vivo, with 4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide (14d) showing 100% cures in the first-stage disease, while 15d, 16d, and 17d appeared to slightly improve survival. In addition, 14d showed weak activity in the chronic model of central nervous system infection in mice. No evidence of reduction of this compound with hepatic microsomes and mitochondria was found in vitro, suggesting that N-hydroxy imidazolines are metabolically stable and have intrinsic activity against T. brucei. In contrast to its unsubstituted parent compound, the uptake of 14d in T. brucei was independent of known drug transporters (i.e., T. brucei AT1/P2 and HAPT), indicating a lower predisposition to cross-resistance with other diamidines and arsenical drugs. Hence, the N-hydroxy bisimidazolines (14d in particular) represent a new class of promising antitrypanosomal agents.

Transition-metal-free approach to 4-ethynylpyrimidines via alkenynones

A practical approach to the synthesis of 4-ethynylpyrimidines by the condensation of arylamidines with 2-aryl-1-ethoxy-5-(trimethylsilyl)pent-1-en-4- yn-3-ones has been developed. As these latter ketones are easily accessible from bis(trimethylsilyl)acetylene and arylacetyl chlorides, the regioselective condensation reported herein provides a facile access to both TMS-protected and unprotected 4-ethynylpyrimidines in yields of up to 85%. Copyright

Hydrothermal synthesis, crystal structures and properties of zinc(2) Di-Nuclear complex and copper(1) coordination polymer based on building block 2-Phenyl-4,6-Di(pyridin-2-yl)pyrimidine

A tetradentate ligand of 2-phenyl-4,6-di(pyridin-2-yl)pyrimidine (L) has been synthesized and its complexes with ZnI2 and CuI have been obtained by hydrothermal method. single crystal X-ray diffraction analysis indicates that ligand L coordinates with Zn(2) ions to form a simple four-coordinate di-nuclear complex, while the complexation of L with Cu(1) constructs a one-dimensional chain polymer. The existence of I-ion hampers the L to assemble grid-type complexes with Zn(2) and Cu(1). Fluorescence spectra show that the L emits blue fluorescence while its Cu(1) polymer decrease the fluorescence intensity and Zn(2) complex quenches the fluorescence.