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Synthesis, Spectral and Structural Study of N -[1-( N,N,N ′ ,N ′-Tetramethylphosphoramidoyl)- 1 H -Benzimidazol-2-yl]-Propionimidic Ethyl Ether
Abstract
The preparation of N-[1-(N,N,N',N'-tetramethylphosphoramidoyl)-1H-benzimidazol-2-yl]-proponimidic ethyl ester 2 has been achieved by the reaction of N-(1H-benzimidazol-2-yl)-proponimidic acid ethyl ester 1 with N,N,N',N'-tetramethylchlorophosphoramide. The structure of compound 2 has been determined by X-ray diffraction. The results of (1H, 13C, 31P) NMR, IR, EI-MS spectral data are consistent with those obtained from the X-ray diffraction. The compound crystallizes in the triclinic system, following the EsZ conformation. In the crystal, there are two weak C3–H3·s1 and C15–H15·sO1 intermolecular hydrogen bonds.
... Raouafi et al. [68] then discuss the synthesis and structural characterization of N- [1-(N,N,N 0 ,N 0 -tetramethylphosphoramidoyl)-1H-benzimidazol-2-yl]-proponimidic ethyl ester. They used X-ray diffraction; 1 H, 13 C, and 31 P nuclear magnetic resonance spectroscopy; infrared spectroscopy; and electron impact mass spectrometry to characterize the compound. ...
In the current review, the content of the journal Structural Chemistry for the calendar year 2005 is related to thermochemistry. Papers are summarized and a thermochemical flavor added. Often
questions are asked and research topics suggested.
KeywordsStructural chemistry-Thermodynamics-Physical chemistry-Thermochemistry-Chemical reactions-Phase transitions
A series of 2-amino-(phosphonoalkyl)-1H-benzimidazole-2-alkanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H]CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Several compounds of the AP-6 type demonstrated potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular, [R(-)]-2-amino-3-(5-chloro-1-phosphonomethyl-1H-benzoimidazol-2-yl)-propionic acid (1) displayed an IC(50) value of 7.1 nM in the [3H]CPP binding assay and an ED(50) value of 0.13 mg/kg (ip) in the NMDA lethality model. Compound 1, when administered intravenously as a single bolus dose of 3 mg/kg following permanent occlusion of the middle cerebral artery in the rat, reduced the volume of infarcted brain tissue by 45%. These results support a promising therapeutic potential for compound 1 as a neuroprotective agent.
Mit Hilfe einer für ungesättigte Kohlenwasserstoffe erhaltenen HMO‐π‐Bindungsordnung‐Bindungslängen‐Beziehung werden Für CN‐Hetero‐π‐Bindungssysteme die empirischen Resonanzintegral‐Heteroparameter kCN und kCN zu 1.10 bzw. 1.00 bestimmt. Die mit diesen Parametern berechneten HMO‐π‐Bindungsordnungen ergeben mit experimentellen Bindungsabständen, die mit einer Standardabweichung von höchstens 0.015 Å bestimmt wurden, eine lineare Beziehung, deren Gleichung nach der Methode der kleinsten Fehlerquadrate zu (Formula Presented.) mit einer Standardabweichung von 0.019 Å und einem Korrelationskoeffizienten von 0.865 für 114 Punkte bestimmt wurde. Für PPP‐SCF‐π‐Bindungsordnungen beträgt die Ausgleichsgerade (Formula Presented.) mit einer Standardabweichung von 0.022 Å und einem Korrelationskoeffizienten von 0.801 für 168 Werte.
The reaction of hexamethylphosphotriamide or methylphosphonic bis(dimethylamide) compounds with amidines derived from N-Benzimidazoyl imidates 1 leads to (1,2a)benzimidazolo-1,3,5,2-tiazaphosphorine-2-oxides (4) over bar in good yields. If the condensation is realized at room temperature, N-phosphonic amidines (3) over bar can be isolated as intermediates. The isolated compounds (2) over bar, (3) over bar, and (4) over bar are identified by spectroscopic methods: IR, H-1, C-13, (31)p, NMR, and M.S.
Dehydrogenation reaction between AlH3←NMe3 and ButP[N(H)But]2 leads to ButP(NBut)2AlH←NMe3, the first neutral 1,3,2,4-diazaphosphaaluminetidine.
The use of fungicides in agriculture, to protect plants from soil-borne pathogens, is a common practice. However, there is a dearth of information on the side-effects of fungicides on key soil ecological processes. We investigated the effects of three fungicides, benomyl, captan and chlorothalonil, on soil microbial activity (substrate-induced respiration and dehydrogenase activity), and nitrogen dynamics (NH4–N and NO3–N) in two laboratory experiments, one with captan and chlorothalonil and another with captan. In each laboratory batch incubation, soil was treated with a fungicide at approximately recommended field application rates (benomyl, 51 mg a.i. kg−1, captan,125 mg a.i. kg−1 and chlorothalonil, 37 mg a.i. kg−1) and incubated at 30°C for 8 weeks. Some soils were amended with either ground alfalfa leaves or ground wheat straw to provide additional substrates for soil microorganisms and to alter rates of nitrogen mineralization/immobilization. All three fungicides suppressed the peak soil respiration in unamended soil by 30–50%, but the three fungicides had different effects in the amended soils. Soil dehydrogenase activity was stimulated by benomyl (18–21%) and chlorothalonil (8–15%) except in the alfalfa amended soil, but was decreased by captan (40–58%) in both the straw-amended and unamended soils. The fungicide-treated soils in general had less microbial biomass N concentrations than the untreated soils. Captan-treated soils had much higher NH4 N concentrations than the control soils, with or without the organic amendments. Benomyl and chlorothalonil had little influence on soil NH4 N concentrations. Net N mineralization and nitrification rates were influenced by all fungicide treatments as well as by the addition of organic materials. N mineralization rates were significantly higher in captan-treated soils than in untreated soils. N dynamics were influenced by chlorothalonil in a similar pattern to captan but reached peak nitrification rates earlier (day 7), in the alfalfa-amended soil. The effects of the three fungicides on soil microbial activity and nitrogen dynamics depended on the quality of the organic materials added to the soil. The patterns of effects of the fungicides on soil nutrient cycling processes were not large and were specific to each fungicide. Captan appeared to have more pronounced overall effects on soil microbial activity and nitrogen dynamics than either benomyl or chlorothalonil.
We examined the effects of non-sedative histamine H1 receptor antagonists on the electrocardiogram (ECG) in conscious cynomolgus monkeys. Terfenadine (3 mg kg(-1) h(-1), i.v.) and astemizole (0.3 and 1 mg kg(-1) h(-1), i.v.) caused significant time-dependent increases in the QT interval and QTc Bazett (QTc). However, normal ECG forms were found during a 60-min infusion of epinastine (3 mg kg(-1) h(-1) i.v.). A higher dose of epinastine (10 mg kg(-1) h(-1), i.v.) increased the QTc and PR interval only 5 min after the start of the infusion. The minimum plasma concentrations of terfenadine, astemizole and epinastine which caused QTc prolongation were 85, 35 and over than 3600 ng/ml, respectively. These drugs did not alter the PQ and QRS intervals and did not cause arrhythmia or atrioventricular block. Our results are consistent with the clinical observation that prolongation of QTc is caused by terfenadine and astemizole but not by epinastine. Thus, measurement of QTc in cynomolgus monkey appears to be a useful approach for evaluating the potential cardiotoxicity of histamine H1 receptor antagonists.
Some 2-substituted benzimidazole-N-carbamates were synthesized and tested in vitro for antiviral activity. Two derivatives were active at noncytotoxic concentrations. The results confirmed the importance of the substituents at the 2-position of benzimidazole; an isopropylcarboxamide group led to the best activity.
A series of 2'-heterocyclic derivatives of 5-phenyl-2,5'-1H-bibenzimidazoles were evaluated for topoisomerase I poisoning activity and cytotoxicity. Topo I poisoning activity was associated with 2'-derivatives that possessed a hydrogen atom capable of hydrogen bond formation, suggesting that the interatomic distances between such hydrogen atoms and the heteroatoms on the adjacent benzimidazole influence activity.
A series of compounds comprising the thiocarboximidopyrazolyl 5, the phenylpyrazolyl 6, the dimethylpyrazolyl 7, the nitrophenylpyrazolyl 8, the dimethyloxazolyl 9, the benzoxazepinyl 10, and pyrimidyl 11 a-c derivatives of 3-(2-methyl-1H-benzimidazol-5-ylazo)pentane-2, 4-dione was synthesized. Moreover, 5-amino-2-methylbenzimidazole (3) was reacted with phthalic anhydride or maleic anhydride in acetic acid or in toluene to produce 12-15. Treating 5, 6-diamino-2-methylbenzimidazole (16) with ethyl cyanoacetate or diethyl malonate or acetyl acetone leads to the formation of the benzodiazepine derivatives 17-20. The cytotoxic activity of the compounds 2, 7, 9, 10, and 11 was tested against 60 types of human cancer cell lines. Compounds 7 and 9 were found to be the most potent.
Giardia intestinalis is one of the most prevalent parasites in adults and children in Mexico. Benzimidazoles have been proposed as a therapeutic alternative in the treatment of giardiasis. However, high-dose related toxicity and the development of resistance have emerged in clinical trials using this therapy. In the search of alternative drugs, we found that benzimidazole-resistant strains of fungi have shown increased sensitivity to phenyl-carbamates, hence, we developed several substituted phenyl-carbamates, two of which were tested against the protozoan parasite G. intestinalis in susceptible and albendazole-resistant Giardia strains. 4-R-ethyl-phenyl-carbamates IRE-6A and IRE-7B demonstrated antigiardial, albeit modest, activity when compared with albendazole, against susceptible and albendazole-induced resistant Giardia. However, when albendazole 0.38 microg/mL (MIC(50)) was combined with each IRE compound, a significant antigiardial synergism (fractional inhibitory concentration index (FICI < 0.5)) was obtained not only with sensitive cultures but also with resistant Giardia parasites. The results described here suggest a potential role for a combined therapy with phenyl-carbamates and sub-doses of benzimidazoles in the treatment of giardiasis.
SHELXL 97: Program for structure refinement
- G M Sheldrick
Program for structure solution
- G M Sheldrick
- Shelxs
- G. M. Sheldrick
Program for structure refinement
- G M Sheldrick
- Shelxl
- G. M. Sheldrick
PLATON: Visualization program
- A L Spek
- A. L. Spek