Microwave-assisted synthesis of salicylamide via BCl3 mediated coupling.
A novel and efficient microwave-assisted, BCl3-mediated coupling reaction to synthesize salicylamide structures from phenols and isocyanates is described.
Boranes↗
SEARCH · Search PubMed
Results for “SALICYLAMIDE”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Potential salicylamide antiplaque agents: in vitro antibacterial activity against Actinomyces viscosus.
A series of 55 salicylamides, including 3,5-dibromo-, 5-n-alkyl-, and 5-n-acylsalicyloyl derivatives of various anilines, heterocyclic amines, benzylamines, and alkylamines, was synthesized and evaluated for in vitro antibacterial activity against Actinomyces viscosus, an adherent oral microorganism implicated in periodontal disease. The in vitro minimum inhibitory concentrations of 15 4'-bromosalicylanilides were found to correlate (r = 0.92) with estimated log D values. Several nonhalogenated salicylanilides, such as 5-n-hexyl- (40) and 5-n-decanoyl-4'-nitrosalicylanilide (47), were found to exhibit higher levels of in vitro antibacterial activity against a number of Actinomycetes than did tribromsalan (1) or fluorophene (2).
Actinomyces↗
A simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in plasma by gas liquid chromatography.
A novel method for the simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in biological fluids by gas liquid chromatography is described. The assay has been used to determine the plasma concentration of salicylates in 10 volunteers after oral ingestion of three commercially available aspirin-containing formulations. No difficulty was encountered in determining low concentrations of acetylsalicylic acid in the presence of higher concentrations of salicylic acid. The in vivo plasma half life of acetylsalicylic acid in man was found to be 15.5 min.
Administration, Oral↗
Stability of salicylamide-caffeine complex at different temperatures and its thermodynamic parameters.
The stability constants for formation of complexes of salicylamide with caffeine have been measured between 15 and 45degrees, by means of the solubility method. There was a linear solubility increase at all temperatures but phase diagrams indicated that at 15 and 25degrees an additional phase was formed which was found to be an insoluble 1 : 1 complex. The enthalpies and entropies of interactions were evaluated. They indicate that the interaction is exothermic and enthalpy controlled.
Caffeine↗
The drug salicylamide is an antagonist of the aryl hydrocarbon receptor that inhibits signal transduction induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant, that has been linked with a variety of deleterious effects on human health, including increased cancer rates and reproductive anomalies. The detrimental effects of TCDD are mediated via the aryl hydrocarbon receptor (AhR), a transcription factor that regulates the expression of the carcinogen-activating enzymes cytochromes P-450 (CYP) 1A1, 1A2, and 1B1. In the present study, we examined the ability of synthetic derivatives of salicylic acid to affect TCDD-stimulated AhR-mediated signal transduction in human hepatoma HepG2 cells. Salicylamide (SAL), an analgesic drug, caused a potent and long-lasting inhibition of TCDD-induced CYP enzyme activity. Acetylsalicylic acid (aspirin) and the naturally occurring phytochemical salicylic acid had no effect on CYP activity. SAL inhibited the increase in CYP1A1, -1A2, and -1B1 mRNA levels that occurs on exposure to TCDD. TCDD-induced transcription of these genes was also inhibited by SAL, but not by aspirin or salicylic acid, as demonstrated by luciferase reporter assays. The transcription of the CYP1 family of genes is regulated by the interaction of TCDD-activated AhR with the xenobiotic-responsive element present in the promoter regions of these genes. As shown by electrophoretic mobility shift assay, SAL completely blocked the binding of TCDD-activated AhR to the xenobiotic responsive element. Also, SAL substantially blocked the binding of TCDD to the cytosolic AhR. These results demonstrate that SAL, a commonly used analgesic, is a potent inhibitor of AhR-mediated signal transduction, and may be an effective agent in the prevention of TCDD-associated disease.
Carcinogens↗
Salicylamide-Glucuronide formation in children with favism and in their parents.
Salicylamide-glucuronide formation has been determined in 27 children who underwent a favism crisis, 25 parents, and in 25 normal children who served as controls. A highly significant mean lower glucuronide formation was observed in the favism group in respect to the controls. The difference between fabic children and their parents was significant, and between parents and controls there was no significant difference.
Child↗
Salicylamide glucuronide formation in newborn babies with G-6-PD deficiency.
Salicylamide glucuronide formation has been studied in 23 newborn babies with erythrocyte G-6-PD deficiency and in 15 normal newborns on the first day of life. Glucuronide formation was significantly lower (p less than 0.001) in the former in comparison with the controls. In the newborns with G-6-PD deficiency who subsequently became hyperbilirubinemic an even lower mean glucuronide formation was observed (p less than 0.01) in respect to the non-jaundiced G-6-PD-deficient newborns.
Glucosephosphate Dehydrogenase Deficiency↗
Comparison of salicylamide and acetaminophen and their prodrug disposition in dogs.
Comparative studies on the disposition of two pairs of drugs and their prodrugs, i.e., (1) salicylamide (SAM) and ethenzamide (ETB), (2) acetaminophen (NAPA) and phenacetin (PHT), were performed in dogs following intravenous and oral administration of the drugs. ETB and PHT were largely metabolized to SAM and NAPA, respectively, and SAM and NAPA thus formed or those directly administered were conjugated with sulfuric acid and glucuronic acid. It was found that the prodrugs, ETB and PHT, were more susceptible to first-pass metabolism than the corresponding parent drugs, SAM and NAPA, respectively at 30 mg/kg dose of each drug. Free NAPA levels in the blood of dogs receiving PHT were found to be considerably high, whereas free SAM levels in the blood of dogs receiving ETB were very low. These are consistent with results in humans which have been reported earlier, suggesting the similarity between dogs and humans. The ratio of sulfate to the sum of sulfate and glucuronide (S-ratio) as the area under blood concentration-time curve and urine were examined. The prodrugs (ETB and PHT) showed higher S-ratios than the corresponding parent drugs (SAM and NAPA). The S-ratios were greater than 0.6 in ETB and SAM and less than 0.5 in PHT and NAPA, indicating that sulfate formation was predominant in the former pair while glucuronide formation was predominant in the latter pair. No intestinal metabolism was found in the prodrugs. In the parent drugs, however, conjugation with sulfuric acid and glucuronic acid was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetaminophen↗
Effect of oral pretreatment with indomethacin on the intestinal first-pass metabolism of salicylamide in rabbits.
The effect of oral pretreatment with indomethacin on the intestinal first-pass metabolism of salicylamide (SAM) was studied in rabbits using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed rabbit intestine and collecting all venous blood draining from the absorbing region. By oral pretreatment with indomethacin, the total amounts of SAM absorbed in 20 and 120 min were significantly increased compared to the control. These results indicated the alteration of the permeability in the intestinal mucosa. In 20 min, indomethacin pretreatment resulted in increased appearance of SAM and SAM glucuronide in the mesenteric venous blood. In 120 min, increased appearance of SAM and decreased appearance of SAM sulfate were observed, compared to the control. These findings suggested that the change in the intestinal first-pass metabolism of SAM is probably due to the intestinal mucosal damage by oral pretreatment with indomethacin.
Administration, Oral↗
Transport of salicylamide from intestinal lumen to serosal compartment.
This study was aimed to clarify the fate of the perfused drug and the characteristics of the serosal compartment. A portion of rat small intestine immersed in a solution regarded as the serosal compartment was perfused in situ and the permeability of drugs into the mesenteric venous blood and into the serosal solution were determined. The cumulative amounts of salicylamide (SAM) transported to the mesenteric venous blood and the serosal compartment were 19.7 and 45.8% of amount disappeared from the intestinal lumen, respectively and those of benzoic acid (BA) were 47.4 and 12.7%, respectively. The permeability of SAM into the serosal compartment was 2.8 times of that into the mesenteric venous blood, while the permeability of BA into the serosal compartment was only one fourth of that into the mesenteric venous blood.
Animals↗
Significance of 17-hydroxycorticosteroid glucuronide in urine as an index of salicylamide glucuronidation in guinea pigs.
The glucuronidation of 17-hydroxycorticosteroids (17-OHCS) and its effectiveness as an index of salicylamide (SAM) glucuronidation were examined in guinea pigs, the same cortisol type animals as man, treated with carbon tetrachloride (CCl4), D-galactosamine, phenobarbital, D,L-ethionine and alloxan. There was not a statistically significant correlation between the plasma clearance of SAM glucuronidation (CLglu) and the urinary excretion ratio of 17-OHCS glucuronide to total 17-OHCS in the intact, and CCl4, D-galactosamine, alloxan and D,L-ethionine treated guinea pigs (r = 0.158). However, there was a statistically significant correlation between the CLglu and the clearance of 17-OHCS glucuronidation obtained as urinary 17-OHCS glucuronide/plasma cortisol concentration (r = 0.738, p less than 0.1). It was proposed that the clearance of 17-OHCS glucuronide metabolized from endogenous cortisol could be used as an index to assess the drug glucuronidation activity.
17-Hydroxycorticosteroids↗
Some quantitative evaluation of first-pass metabolism of salicylamide in rabbit and rat.
The first-pass metabolism of salicylamide (SAM) was studied in rabbits and rats paying main attention to the amounts of the glucuronide (SAMG) and sulfate (SAMS) formed. The roles of the intestine and liver for SAMG and SAMS formation during the first-pass were also examined quantitatively. Further, an equation was developed to estimate the hepatic first-pass metabolism based on the experiments of intravenous and oral administration and intestinal perfusion experiment. Significant species differences were found in these two animals. The extent of the first-pass metabolism was larger in rabbits (ca95%) than in rats (ca60%). Of the 95% first-pass metabolism in rabbits, about 30% is due to the intestine whereas the remaining 65% is due to the liver. Of the 60% in rats, about 20 and 40% are estimated to be due to the intestinal and hepatic first-pass metabolism, respectively. In rabbits SAMG and SAMS are formed together in nearly equal amounts in the liver and at the ratio 4 : 1 in the intestine. In rats, on the other hand, SAMG is exclusively formed in the intestine and SAMS in the liver. In this context, the equation described here was applied to the data of Gugler et al. (J. Pharmacol. Exp. Ther., 195, 416-423 (1975)) who carried out a study on the first-pass metabolism of SAM in dogs, and consequently, reported that glucuronidation occurs primarily in the liver whereas sulfation occurs primarily in the intestine in dogs.
Animals↗
Comparison of the first-pass metabolism of ethenzamide and salicylamide in rats.
The first-pass metabolism of ethenzamide (ETB), which is considered to be a pro-drug of salicylamide (SAM), was studied in rats in order to compare with that of SAM. The extent of first-pass metabolism after oral ETB estimated by oral and intravenous administration was as much as 82% and remaining 18% ETB entered into systemic circulation. Further, it has been confirmed that the first-pass metabolism of ETB is not due to the intestine but entirely due to the liver in which de-ethylation to SAM occurred at first, followed by exclusive conjugation with sulfuric acid and little SAM enters into systemic circulation. On the other hand, it was previously demonstrated in rats that per se administered SAM is subjected to first-pass metabolism both in the gut and liver as much as about 60% and the remaining 40% entered the systemic circulation. Thus, the behavior of SAM is considerably different depending upon whether it is per se administered or formed from ETB through metabolism. The fact that little SAM appears in the systemic circulation after oral administration of ETB suggests that the pharmacological activity of ETB comes from its own attributes but not from SAM.
Administration, Oral↗
Intestinal absorption of salicylamide and effect of atropine on it.
The effect of atropine (ATR), a parasynpatholytic agent, on the intestinal absorption of salicylamide (SAM) was studied using the absorption kinetic model proposed by Winne et al. The disappearance of SAM from perfusate and the appearance in intestinal blood were determined using perfused intestinal loop of the rat in vivo. The results showed that the absorption of SAM was simulated by the four compartment model consisting of luminal, interstitial, blood and serosal compartments. The model was assumed to have three rate determining factors, namely mucosal membrane permeability, clearance by blood flow and serosal membrane permeability. ATR decreased the absorption of SAM by decreasing the clearance factor relating to intestinal blood flow and increased the fraction of the transported amount of SAM from interstitial space to serosal compartment.
Animals↗
Conjugation of salicylamide in the intestinal wall of dogs and rabbits.
The intestinal conjugation of salicylamide (SAM) the formation of SAM sulfate (SAMS) and SAM glucuronide (SAMG) were investigated in dogs and rabbits by using in situ intestinal sac preparation with mesenteric vein cannulation. SAM, SAMS and SAMG in the mesenteric venous blood, sampled at successive intervals after injection of SAM solutions into the sac, were determined. Total recoveries in 1 h were not significantly different in dogs (71%) and rabbits (64%). Both animals, however, showed a quantitative difference in intestinal conjugation. Sulfation predominated over glucuronidation in dog intestine while the formation of the glucuronide was exclusively high in rabbit intestine. Furthermore, the dose-dependent conjugation of SAM was investigated in dog intestine at four doses, 2, 3, 6 and 10 mg/one animal. Upon increasing the doses from 2 to 10 mg, the amounts of SAMS appearing in the blood remained unchanged, those of SAMG increased about two times and those of free SAM increased about six times, while the total recoveries increased parallel to the doses, suggesting saturation kinetics in the formation step of the two conjugates. Simultaneous computer-fitting of the experimental data for 2 and 10 mg doses to a simplified model, containing Michaelis-Menten kinetics in the formation of the conjugates, was examined and good agreement between the observed data and the theoretical values was obtained.
Animals↗
An assessment of mucosal damage in vivo: effect of oral pretreatment with 5-fluorouracil on the intestinal first-pass metabolism of salicylamide in rabbits.
An assessment of 5-fluorouracil (5-FU)-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The mucosal damage in the intestine 48 h after oral administration of 5-FU (30 mg/kg) was examined using a scanning electron microscope. By the oral pretreatment with 5-FU, the morphological changes of jejunal and ileal mucosa were recognized compared with the control. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with 5-FU, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with 5-FU orally. However, the blood concentration of SAMG after intravenous administration of SAM was not increased compared with the control. These findings suggest that the change in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage by oral pretreatment with 5-FU. The alteration of intestinal first-pass metabolism of a marker compound may be utilized for the assessment of intestinal mucosal damage in vivo.
Administration, Oral↗
An assessment of indomethacin-induced mucosal damage in vivo by measuring the metabolism of salicylamide in rabbit intestine.
Indomethacin-induced mucosal damage was assessed in vivo by measuring salicylamide (SAM) metabolism in rabbit intestine. Intestinal mucosal damage 48 h after oral indomethacin (500 mg/kg) administration was examined using a scanning electron microscope. Duodenal, jejunal and ileal mucosal toxicity was compared with that in controls. Intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with intact mesenteric venous blood collection. The appearance of both SAM and its metabolites in the mesenteric venous blood was measured following cannulation of the mesenteric vein of the exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with indomethacin, the appearance of SAM and SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The concentrations of SAM and SAMG in the blood increased following intraduodenal administration of SAM in vivo in rabbits orally pretreated with indomethacin compared with controls. However, after intravenous administration of SAM, the blood concentration of SAM and SAMG was not increased compared with controls. These findings suggest that the differences in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral indomethacin pretreatment. The results indicate that the alteration of intestinal first-pass metabolism of a marker compound may be utilized to assess intestinal mucosal damage in vivo.
Animals↗
An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide in rabbit intestine.
An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with salicylic acid, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased compared with the control. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with salicylic acid orally. The blood concentration of SAMG after the intravenous administration of SAM was not increased compared with the control. We suggest that the change in the intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral pretreatment with salicylic acid. The measurement of SAM metabolites may be of value in the assessment of intestinal mucosal damage in vivo.
Animals↗