2-Amino-5-chlorobenzophenone

A Molecular Imprinted Polymer as a Flow-Through Optical Sensor for Oxazepam.[Pubmed:29850374]

J Anal Methods Chem. 2018 Apr 4;2018:6302609.

A flow-through optosensing system for oxazepam recognition with fluorescence detection was performed by means of a molecular imprinted polymer based on its acid hydrolysis product, 2-Amino-5-chlorobenzophenone. The synthesis was conducted via a noncovalent imprinting methodology, using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a cross-linking agent. Hydrolysis (types and concentration of acids), polymer retention capacity, binding properties, and elution (selectivity and reversibility) conditions were optimized. The selected molecular imprinted polymer had a molar ratio composition of 1 : 6 : 45 (template : functional monomer : cross-linker). The proposed method was applied to the determination of oxazepam in a pharmaceutical formulation. External standard calibration, standard additions calibration, and Youden's calibration were carried out in order to evaluate constant and proportional errors due to the matrix. The developed metabolite-based recognition system for benzodiazepines is an innovative procedure that could be followed in routine and quality control assays.

Antibiofilm potential of synthetic 2-amino-5-chlorobenzophenone Schiff bases and its confirmation through fluorescence microscopy.[Pubmed:28755874]

Microb Pathog. 2017 Sep;110:497-506.

Antibacterial/antibiofilm potential of microwave-assisted synthetic thirty-three 2-amino-5-chloro benzophenone Schiff bases have been carried out against four bacterial strains i.e. Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus and Streptococcus mutans. Among them compounds 5, 6, 8, 9, 14, 16, 22, 24, 26, and 30-32 showed antibiofilm activities against isolates at less than 100 mug/ml concentrations. These compounds showed enhanced antibiofilm activity against S. aureus as compared to cefixime used as control. However, remaining compounds were found to be active but at higher concentration. Fluorescence microscopy has been employed for confirmation of antibiofilm results. The structures of all synthetic molecules have been characterized on the basis of spectroscopic techniques including (1)H NMR, (13)C NMR, EI-MS, HREI-MS, and IR spectroscopy and their structure-activity relationship have been established.

Bacterio-plankton transformation of diazepam and 2-amino-5-chlorobenzophenone in river waters.[Pubmed:25164562]

Environ Sci Process Impacts. 2014;16(10):2227-36.

Benzodiazepines are a large class of commonly-prescribed drugs used to treat a variety of clinical disorders. They have been shown to produce ecological effects at environmental concentrations, making understanding their fate in aquatic environments very important. In this study, uptake and biotransformations by riverine bacterio-plankton of the benzodiazepine, diazepam, and 2-Amino-5-chlorobenzophenone, ACB (a photo-degradation product of diazepam and several other benzodiazepines), were investigated using batch microcosm incubations. These were conducted using water and bacterio-plankton populations from contrasting river catchments (Tamar and Mersey, UK), both in the presence and absence of a peptide, added as an alternative organic substrate. Incubations lasted 21 days, reflecting the expected water residence time in the catchments. In River Tamar water, 36% of diazepam (p < 0.001) was removed when the peptide was absent. In contrast, there was no removal of diazepam when the peptide was added, although the peptide itself was consumed. For ACB, 61% was removed in the absence of the peptide, and 84% in its presence (p < 0.001 in both cases). In River Mersey water, diazepam removal did not occur in the presence or absence of the peptide, with the latter again consumed, while ACB removal decreased from 44 to 22% with the peptide present. This suggests that bacterio-plankton from the Mersey water degraded the peptide in preference to both diazepam and ACB. Biotransformation products were not detected in any of the samples analysed but a significant increase in ammonium concentration (p < 0.038) was measured in incubations with ACB, confirming mineralization of the amine substituent. Sequential inoculation and incubation of Mersey and Tamar microcosms, for 5 periods of 21 days each, did not produce any evidence of increased ability of the microbial community to remove ACB, suggesting that an indigenous consortium was probably responsible for its metabolism. As ACB degradation was consistent, we propose that the aquatic photo-degradation of diazepam to ACB, followed by mineralization of ACB, is a primary removal pathway for these emerging contaminants. As ACB is photo-produced by several benzodiazepines, this pathway should be relevant for the removal of other benzodiazepines that enter the freshwater environment.

Aqueous phototransformation of diazepam and related human metabolites under simulated sunlight.[Pubmed:22489744]

Environ Sci Technol. 2012 May 1;46(9):4749-56.

Phototransformation of the widely used benzodiazepine pharmaceuticals diazepam and human metabolites nordiazepam, temazepam and oxazepam under simulated sunlight in water was investigated. Photolysis experiments were conducted in the presence and absence of humic acids. Half-lives for each of the benzodiazepine pharmaceuticals were <200 h (under all conditions) suggesting that phototransformation is an important process for such chemicals in the photic zone of receiving waters. Due to the observed phototransformation of the benzodiazepines, significant emphasis was placed on identification of the photoproducts. A total of fourteen photoproducts, including benzophenones, acridinones and quinazolinones or quinazolines was identified and measured by liquid chromatography-multistage mass spectrometry (LC-MS(n)). Phototransformation studies were also undertaken on authentic samples of two of the identified photoproducts, 5-chloro-methylaminobenzophenone and 2-Amino-5-chlorobenzophenone, in order to establish the phototransformation pathways. Interestingly, these two photoproducts showed relatively higher persistence than some of the benzodiazepines, suggesting that the fate and effects of photoproducts should also be incorporated into future risk assessments and environmental models of the fate of benzodiazepines.

Acid hydrolysis of diazepam. Kinetic study of the reactions of 2-(N-methylamino)-5-chlorobenzophenone, with HCl in MeOH-H2O.[Pubmed:7500287]

J Pharm Sci. 1995 Aug;84(8):998-1004.

In the acid hydrolysis of diazepam (1), several unusual products, apart from 2-(N-methylamino)-5-chlorobenzophenone (2) and glycine, were isolated. On the assumption that some of those products could arise from further degradation of 2, the reaction of this compound with 0.5-2 M HCl was studied, in 1:1 MeOH-H2O, at 60 and 80 degrees C. Several unexpected products were isolated from the reaction of 2 with HCl, namely, 2-Amino-5-chlorobenzophenone (3), 2-(N,N-dimethylamino)-5-chlorobenzophenone (4), 2-(N-methylamino)-3,5-dichlorobenzophenone (5), 2-amino-3,5-dichlorobenzophenone (6), 2,4-dichloro-10-methyl-9,10- acridinone (7), and 2,4-dichloro-9,10-acridinone (8). The methyl transfers, the chlorination, and the cyclization reactions that give rise to products 3-8 are unexpected under the present reaction conditions. The rate of reaction of 2, as well as the rate of formation of compounds 3-6, was measured at several HCl concentrations.

Chlordiazepoxide photoisomerization kinetics into oxaziridine. A HPLC study.[Pubmed:18966267]

Talanta. 1995 Apr;42(4):581-9.

It was proved that the N(4)-oxide group included in chlordiazepoxide (CDZ) is involved in its phototoxicity. At a wavelength of 350 nm, CDZ photoisomerizes only into oxaziridine (OXA) which is not available as standard. In the course of cytotoxicity investigations, the optimal CDZ irradiation conditions were established as acetonitrile as solvent, 10 degrees C as temperature of the irradiated solutions and 70-90 min as irradiation time for solutions in the range of 12.2-152.0 microg/ml. The kinetic parameters of the CDZ photodegradation reaction order have been calculated using an appropriate algorithm. In all cases, the first order reversible or irreversible was selected by Akaike's criteria. The percentage of undecomposed CDZ and OXA generated after irradiation were determined by a reversed HPLC method. The latter also permitted the separation of CDZ major impurities in aqueous solutions (demoxepam and 2-Amino-5-chlorobenzophenone) as well as the oxaziridine of demoxepam. In this study, the experimental irradiation conditions allowed us to produce 98% pure OXA from CDZ. This HPLC method could be easily extended to the analysis of the molecules in pharmaceutical studies.

[Anti-arrhythmia action of amidinohydrazone substituted benzophenones. 6. Parenteral drug forms of (Z)-2-amino-5-chlorobenzophenone amidinohydrazone acetate (G 256)].[Pubmed:7972310]

Pharmazie. 1994 Sep;49(9):653-6.

The combination of lyophilized G 256 and a solvent ampoule is recommended as an optimal variant for the application of the compound. In the lyophilized substance both the hydrolysis and the isomerisation are reduced so it is stable enough for the required period of usability.

Cytochrome P450-dependent N-hydroxylation of an aminoguanidine (amidinohydrazone) and microsomal retroreduction of the N-hydroxylated product.[Pubmed:7975731]

Xenobiotica. 1994 Jul;24(7):671-88.

1. The first example of a P450-dependent N-hydroxylation of an aminoguanidine (amidinohydrazone) is reported for 2-Amino-5-chlorobenzophenone amidinohydrazone 1 (G 256) as substrate. 2. The N-hydroxylated metabolite 2 (2-Amino-5-chlorobenzophenone N-hydroxyamidinohydrazone NOH-G256) and a further metabolite of 1, the phenol 3, were identified by tlc and ms analysis. 3. The microsomal reduction of an N-hydroxyaminoguanidine (N-hydroxy-amidino-hydrazone) was also demonstrated for the transformation of 2 to 1. 4. Both the N-hydroxylation of the aminoguanidine and the retroreduction of the N-hydroxyaminoguanidine were characterized by quantitative hplc analysis. 5. The conversion of the aminoguanidine 1 to N-hydroxyaminoguanidine 2 may be considered as an analogue of the physiological N-hydroxylation of arginine to N-hydroxyarginine by NO synthases.

Simplified method for simultaneous determination of diazepam and its metabolites in urine by thin-layer chromatography and direct densitometry.[Pubmed:8335718]

J Chromatogr. 1993 Jun 2;615(2):365-8.

A direct densitometric method for determination of diazepam and its metabolites in urine was developed. The proposed procedure involves acid hydrolysis of urine specimens, thereby converting diazepam and its metabolites into benzophenones [2-methylamino-5-chlorobenzophenone (MACB) and 2-Amino-5-chlorobenzophenone (ACB)]. It is followed by extraction with chloroform-isopropanol (3:1, v/v). The two benzophenones were separated on thin-layer chromatography plates using hexane-diethyl ether-acetic acid (80:10:10) as a mobile phase. Quantitation of the MACB and ACB spots was achieved by direct ultraviolet densitometry. The limit of detection was 0.5 micrograms per ml of urine for both benzophenones. The proposed method is simple, rapid, reproducible and has been found to be effective for direct determination of diazepam and its metabolites in urine.

[The development of mass-screening method for benzodiazepines by radioimmunoassay].[Pubmed:8315856]

Nihon Hoigaku Zasshi. 1993 Feb;47(1):18-28.

For the mass-screening of benzodiazepines in urine, radioimmunoassays (RIAs) for two benzophenones (metabolites of the drugs) were established, and an animal experiment was carried out to verify their usefulness. Immunogens were prepared by condensing 2-hemisuccinyl derivatives of 2-Amino-5-chlorobenzophenone (A-CBP) or 2-amino-5-nitrobenzophenone (A-NBP) to bovine serum albumin (BSA). Antisera were produced in rabbits by immunization with the individual antigens. Two kinds of RIA were established separately for A-CBP and A-NBP using each antiserum, and their sensitivities were 150 pg/tube and 30 pg/tube, respectively. The antisera had broad cross-reactivity with many chlorbenzophenone and nitrobenzophenone derivatives, respectively. Diazepam or nitrazepam was administered to rats, and the total amounts of each in urine (benzodiazepines plus their metabolites such as benzophenones) were determined relative to time using the RIAs after acid hydrolysis of the specimen. The benzophenones were positive in urine even 9 h after administration, whereas diazepam was undetectable using a RIA against diazepam. The characterization of the antisera and the results of the animal experiments indicate that these RIAs will be very useful for mass-screening of benzodiazepines.

[Antiarrhythmia active amidinohydrazone substituted benzophenones. 5. The stability of (Z)-2-amino-5-chlorobenzophenone amidinohydrazone acetate in solution].[Pubmed:8460174]

Pharmazie. 1993 Jan;48(1):33-7.

The aqueous solution of the title compound can be used for injection for one year if it is stored at room temperature and under light protection. Under these conditions 8% of the E-isomer are produced. The reaction is reversible at day light. Red coloured products of decomposition are formed by long lasting influence of light. At higher temperatures or at sterilisation several products of decomposition are formed which structure is elucidated. For these decomposition a scheme is proposed.

Stability-indicating method for the determination of clorazepate dipotassium-I. Via its final degradation products.[Pubmed:18965571]

Talanta. 1992 Dec;39(12):1569-73.

A sensitive spectrophotometric procedure is described for the determination of 1,4-benzodiazepine (clorazepate dipotassium) in the presence of its degradation products. The procedure is based on acid hydrolysis of clorazepate dipotassium to yield its final degradation products viz., 2-Amino-5-chlorobenzophenone and glycine. The amino-chlorobenzophrenone is extracted from the neutralized hydrolysate with diethyl ether, the extract is evaporated, the residue is dissolved in methanol and its absorbance measured at about 240 nm or 380 nm. Glycine, left in the aqueous layer after etherial extraction of aminochlorobenzophenone, is treated with ninhydrin reagent in the presence of pyridine and the bluish violet colour formed is measured at about 560 nm. The suggested procedures determine 20-100 mg of clorazepate dipotassium via its degradation products aminochlorobenzophenone and glycine with mean accuracies of 100.0 +/- 0.5% at 560 nm, 100.2 +/- 0.6% at 380 nm and 99.8 +/- 0.5%. The suggested procedures are suitable for stability-testing of clorazepate dipotassium in bulk powder and in pharmaceutical preparations.

[Antiarrhythmic active amidinohydrazones of substituted benzophenones. 4. The photoisomerization of (Z)- and (E)-2-amino-5-chlorobenzophenone amidinohydrazones and the corresponding (E)-N-phenylamidinohydrazone].[Pubmed:1293615]

Pharmazie. 1992 Dec;47(12):916-8.

The title compounds undergo a photoisomerization by irradiation. If the E-isomers are irradiated by light of a wavelength of an absorption maximum typical for them, they can be converted quantitatively to the corresponding Z-isomers. In case that the synthesis of analogs of the title compounds give only one configurational isomer, sometimes the missing one can be obtained by photoisomerization.