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
• Article Data: 13

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

Description

Benzamidine hydrochloride is a reversible inhibitor of trypsin, trypsin-like enzymes, and serine proteases. A concentration of approximately 1 mM is used for general protease inhibition. To inhibit proteases from yeast, a range of 0.5 to 4.0 mM is used and it is for the most part interchangeable with pepstatin A.In addition to being a strong competitive inhibitor of trypsin, benzamidine HCl has been also shown to be a strong competitive inhibitor of thrombin and plasmin. It was also found to be as effective as aprotinin in the prevention of glucagon degradation in human plasma.

Chemical Properties

white to off-white powder

Uses

Benzamidine is a reversible inhibitor of serine proteases, including trypsin, plasmin, and thrombin (Kis = 35, 350, and 220 μM, respectively). In addition to its use as a general serine protease inhibitor, benzamidine is used, when immobilized, to purify novel proteases.

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

• 100869-87-2 2-phenyl-5,6,7,8-tetrahydroquinazoline 
• 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 

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.

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.

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.

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.