Disease relevance of difluorophosphorylmethane

• Most of the benzimidazole heterocycles, but not the difluoro analog, were active against human cytomegalovirus (HCMV) (IC50's = 3-40 microM) and herpes simplex virus type 1 (HSV-1) (IC50's = 50-90 microM) [1].
• Temafloxacin, a new difluoro quinolone, inhibited the majority of Enterobacteriaceae at less than or equal to 1 microgram/ml [2].

High impact information on difluorophosphorylmethane

• When incubated with Krebs' bicarbonate solution (pH 7.4) at 37 degrees C, the biological half-life of the difluoro analog was about 24 hr compared to the 10- to 15-min half-life of PGI2 under similar conditions [3].
• The difluoro analog was 3- to 4-fold more active than PGI2 in causing relaxation of both types of strips and appeared at least equipotent to PGI2 in its blood pressure lowering effect in dogs [3].
• The decomposition of diradicals resulting from a cleavage of C-C and Si-C bonds in 2 is exothermic by 24.3-3.3 kcal/mol (apart from the difluoro derivative which is endothermic by 5.1 kcal/mol) and 27.0-13.3 kcal/mol, respectively [4].
• Mono- or difluoro substitution at meta position(s), as in 22c and 22h, was advantageous for both in vitro COX-2 potency and selectivity (e.g., COX-2 IC(50) for 22c = 1 microM and COX-1 IC(50) for 22c = 20 microM in HWB assay) [5].
• Previous studies in our laboratory using substrate-based difluoro ketone and difluoro alcohol transition-state analogue inhibitors suggest that gamma-secretase is an aspartyl protease with loose sequence specificity [6].

Biological context of difluorophosphorylmethane

• To further characterize the active site of gamma-secretase, we prepared a series of difluoro ketone peptide analogues with varying steric bulkiness in the P1 position and tested the ability of these compounds to inhibit Abeta production in APP-transfected cells [6].
• The inhibition of rat and guinea pig cholinesterases by anionic hydrolysis products of methylphosphonic difluoride (difluoro) [7].
• Rats were exposed by both inhalation and noninhalation routes to carbon-14-labeled methylphosphonic difluoride (difluoro) or its hydrolysis products [8].
• The deposition of inhaled difluoro was mainly in the maxillo- and ethmoturbinates, and clearance was mainly by mucociliary clearance and swallowing [8].
• The diol derivative (6) and the difluoro nitrogen mustard (5) were not cytotoxic against L1210 cells and did not show any detectable DNA alkylation [9].

Anatomical context of difluorophosphorylmethane

• These constants indicate that the maxilloturbinates in the anterior of the nose receive more than four times the dose of difluoro than do the ethmoturbinates, whereas the trachea and lung receive much lower doses than do the nasal tissues [8].
• Of interest, the slopes of the concentration-dependence lines of the difluoro- and dibromo-acetates were markedly dissimilar from the other di- and tri-haloacetates, suggesting either a marked difference in the way they activate the PPARalpha receptor or a substantial difference in the way they are metabolized or transported by the hepatocytes [10].
• 7. These results indicate the difluoro and 4-fluoro analogues of ciprofibrate and clofibric acid are hypolipidaemic agents and peroxisome proliferators but with reduced potencies relative to the parent molecules [11].
• Flunarizine, a difluoro derivative of cinnarizine, has been used to study its antivasoconstrictor effects on isolated perfused rat mesentery [12].

Associations of difluorophosphorylmethane with other chemical compounds

• Quinazoline antifolate thymidylate synthase inhibitors: difluoro-substituted benzene ring analogues [13].
• Methylphosphonic difluoride (difluoro) and its hydrolysis products, methylphosphonofluoridate (MF) and fluoride, were examined for cholinesterase-inhibiting ability in rats and guinea pigs by both inhalation and intraperitoneal exposure routes [7].
• In vitro activity of temafloxacin, a new difluoro quinolone antimicrobial agent [2].
• The in vitro activity of temafloxacin, a new difluoro quinolone agent, against 725 bacterial isolates representing 32 species was evaluated in comparison with that of ciprofloxacin [14].
• Flunarizine, a difluoro derivative of cinnarizine, is a potent inhibitor of Ca2+-induced constriction of isolated arteries; this inhibition has a gradual onset and a prolonged duration [15].

Gene context of difluorophosphorylmethane

• The difluoro analog dFdG was an efficient substrate for recombinant dGK with an apparent Km of 16 microM with ATP as phosphate donor [16].
• We report herein that, like camptothecins, homocamptothecin and its difluoro derivative BN80915 are substrates for ABCG2 [17].
• Compared to their nonfluorinated parent compounds all the difluoro analogues were poorer inhibitors of TS [13].
• The combination of CyA with RAPA, a macrolide which inhibits lymphokine signal transduction, and with BQR, a difluoro quinoline carboxylic acid analog that inhibits pyrimidine biosynthesis, permits at least a 20-fold reduction of the CyA dose in rat allograft models as well as prevents the activation of some CyA-resistant rejection pathways [18].

Analytical, diagnostic and therapeutic context of difluorophosphorylmethane

• The representative Pt(II) and Pt(IV) difluoro complexes were characterized by X-ray crystallography [19].
• After oral administration of the radioactive difluoro analog in oil to rats, difluororetinol , difluororetinyl palmitate and related esters, 4- oxoretinol , 4- oxoretinoic acid and polar conjugated derivatives were identified in the intestine, liver, kidney and/or blood [20].

References