Category: 328-90-5

Kennedy, Andrew J. published the artcileSynthesis and antimicrobial evaluation of amixicile-based inhibitors of the pyruvate-ferredoxin oxidoreductases of anaerobic bacteria and Epsilonproteobacteria, Quality Control of 328-90-5, the publication is Antimicrobial Agents and Chemotherapy (2016), 60(7), 3980-3987, database is CAplus and MEDLINE.

Synthesis of the amixicile scaffolds I [R = CH₂NH₃, (CH₂)₃NH₃, 4-piperidinyl, etc.; R¹ = H, F; R² = H, Me, F, Cl, CF₃; R³ = H, Me, OMe, F, Cl, CN, CF₃] and study of their direct pyruvate-ferredoxin oxidoreductases (PFOR) inhibition assays, and MIC tests against Clostridium difficile, Campylobacter jejuni, and Helicobacter pylori guided by docking simulations was interrogated. Docking simulations revealed that the nitro group present in nitazoxanide interacts with the protonated N4′-aminopyrimidine of thiamine pyrophosphate. The ortho-propylamine on the benzene ring formed an electrostatic interaction with an aspartic acid moiety (B456) of PFOR that correlated with improved PFOR-inhibitory activity and potency by MIC tests. Aryl substitution with electron-withdrawing groups and substitutions of the propylamine with other alkyl amines or nitrogen-containing heterocycles both improved PFOR inhibition and, in many cases, biol. activity against C. difficile. Docking simulation results correlated well with mechanistic enzymol. and NMR studies that show members of this class of antimicrobials to be specific inhibitors of vitamin B₁ function by proton abstraction, which is both novel and likely to limit mutation-based drug resistance.

Antimicrobial Agents and Chemotherapy published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Quality Control of 328-90-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Molins-Molina, Oscar published the artcileSinglet oxygen production and in vitro phototoxicity studies on fenofibrate, mycophenolate mofetil, trifusal, and their active metabolites, Safety of 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Journal of Physical Organic Chemistry (2017), 30(9), n/a, database is CAplus.

Singlet oxygen photosensitization (studied by time-resolved near-IR emission spectroscopy) and in vitro phototoxicity (by means of the 3T3 neutral red uptake assay) have been investigated for the prodrugs fenofibrate (FFB), mycophenolate mofetil (MMP), and trifusal (TFS) as well as for their active metabolites fenofibric acid (FFA), mycophenolic acid (MPA), and 2-hydroxy-4-(trifluoromethyl)benzoic acid (HTB). The results show that FFB and its active metabolite FFA generate ¹O₂ with a quantum yield in the range 0.30 to 0.40 and show a photo-irritation factor (PIF) higher than 40. By contrast, MMP/MPA and TFS/HTB are not photoactive in the used assays. These results correlate well with the previously reported in vivo phototoxicity in treated patients.

Journal of Physical Organic Chemistry published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Safety of 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Izquierdo, Inaki published the artcileComparative bioavailability study of triflusal oral solution vs. triflusal capsules in healthy subjects: a single, randomized, two-way cross-over, open-label phase I study, Formula: C8H5F3O3, the publication is Arzneimittel Forschung (2010), 60(1), 36-41, database is CAplus and MEDLINE.

Triflusal (CAS 322-79-2) is an antiplatelet agent that irreversibly acetylates cyclooxygenase isoform 1 (COX-1) and therefore inhibits thromboxane biosynthesis. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), possesses also antiaggregant activity. Recently a new oral 600 mg (10 mL) solution form of triflusal has been developed. The purpose of this clin. trial was to study the relative bioavailability of the new oral solution of triflusal vs. the capsules formulation, both administered as a single dose. This was a randomized, two-way, cross-over, open-label, single-site phase I clin. trial, in 24 healthy volunteers who received triflusal as 600 mg oral solution and as two 300 mg capsules in a single administration separated by a washout period of at least 17 days. Blood samples were collected and plasma concentrations of HTB were measured. Pharmacokinetic parameters used for bioequivalence assessment included AUC_0-t, AUC_0-inf and C_max. The formulations were considered bioequivalent if the geometric mean ratios of AUC_0-t, AUC_0-inf and C_max were within the predetermined equivalence range (80% to 125%). Tolerability was based on the recording of adverse events (AEs), phys. examination, ECG and laboratory tests. The parameters for bioequivalence, mean [SD] values were as follows: AUC_0-t (μg/h/mL): 3574.08 [628.17] for triflusal oral solution and 3901.78 [698.43] for triflusal capsules; AUC_{0-âˆ?/sub> (μg/h/mL): 4089.21 [842.54] for triflusal oral solution and 4471.33 [905.93] for triflusal capsules; Cmax (μg/mL): 91.24 [12.88] for triflusal oral solution and 88.61 [13.46] for triflusal capsules; Cmax/AUC0-âˆ?/sub> (h^-1): 0.03 (0.00) for triflusal oral solution and 0.02 (0.00) for triflusal capsules. The 90% confidence intervals for the ratio exptl./control by anal. of variance after log transformed AUC0-âˆ?/sub>, AUC0-t, and Cmax were within 80% to 125%. Similar results were found for the data without log transformation. All adverse events were of mild or moderate intensity and all subjects recovered. Nine and 12 subjects reported at least one adverse event during treatment with triflusal oral solution and with triflusal capsules, resp. The most frequently reported adverse events were headache and dizziness. It was concluded that the 600-mg solution of triflusal appeared to be bioequivalent to the reference formulation capsules. Both formulations were well tolerated.}

Arzneimittel Forschung published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Formula: C8H5F3O3.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Nemeth, Ansley M. published the artcileStructure-Function Studies on IMD-0354 Identifies Highly Active Colistin Adjuvants, Synthetic Route of 328-90-5, the publication is ChemMedChem (2020), 15(2), 210-218, database is CAplus and MEDLINE.

Infections caused by multidrug-resistant (MDR) bacteria, particularly Gram-neg. bacteria, are an escalating global health threat. Often clinicians are forced to administer the last-resort antibiotic colistin; however, colistin resistance is becoming increasingly prevalent, giving rise to the potential for a situation in which there are no treatment options for MDR Gram-neg. infections. The development of adjuvants that circumvent bacterial resistance mechanisms is a promising orthogonal approach to the development of new antibiotics. We recently disclosed that the known IKK-β inhibitor IMD-0354 potently suppresses colistin resistance in several Gram-neg. strains. In this study, we explore the structure-activity relationship (SAR) between the IMD-0354 scaffold and colistin resistance suppression, and identify several compounds with more potent activity than the parent against highly colistin-resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae.

ChemMedChem published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Synthetic Route of 328-90-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Valle, M. published the artcileAccess of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is European Journal of Clinical Pharmacology (2005), 61(2), 103-111, database is CAplus and MEDLINE.

Triflusal has been shown to exert neuroprotective effects by downregulating mols. considered responsible for the development of Alzheimer’s disease (AD). The aim of this study was to develop a population pharmacokinetic model to characterize plasma and cerebrospinal fluid (CSF) pharmacokinetics of the main active metabolite of triflusal-HTB (2-hydroxy-4-trifluoro-methylbenzoic acid)-in healthy volunteers. Data from two studies were combined. Study A: subjects received single oral doses of triflusal 900 mg. Triflusal and HTB plasma concentrations were extensively measured. Study B: triflusal 600 mg once daily was administered orally for 14 days. HTB plasma and CSF concentrations were determined in healthy volunteers. Population pharmacokinetic modeling was performed using NONMEM. A one-compartmental model with rapid first-order absorption for triflusal and first-order formation of HTB best described plasma concentrations Triflusal elimination rate constant was 50 times faster than that estimated for the metabolite. CSF concentrations of HTB ranged between 0.011 μg/mL and 0.341 μg/mL. A CSF-plasma partition coefficient of 0.002 and a k_e0 value of 0.059 h^-1 were estimated by means of population modeling. In the present study in healthy volunteers, HTB penetrated into the CSF in a range of concentrations exptl. proven to have protective effects in AD. These concentrations suggest that triflusal could be used in the treatment of central nervous system diseases in doses similar to those used in cardiovascular diseases. Access to the CSF compartment was characterized by a slow equilibrium rate constant and a low CSF-plasma partition coefficient

European Journal of Clinical Pharmacology published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C10H14BNO4S, Application of 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Gonzalez-Correa, J. A. published the artcileProtective effect of triflusal and its main metabolite HTB in an in vitro model of anoxia-reoxygenation in rat brain slices: comparison with acetylsalicylic and salicylic acids, Recommanded Product: 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Naunyn-Schmiedeberg’s Archives of Pharmacology (2005), 371(1), 81-88, database is CAplus and MEDLINE.

Triflusal is a fluorinated derivative of acetylsalicylic acid (ASA) with demonstrated antithrombotic activity. Recently, evidence for a neuroprotective effect was obtained. The aim of this study was to compare the neuroprotective effects of the main metabolite of triflusal (2-hydroxy-4-trifluoromethylbenzoic acid, HTB) and the ASA metabolite salicylic acid (SA) in an in vitro model of anoxia-reoxygenation in rat brain slices. Rat brain slices (n=10 per group) were subjected to a period of anoxia followed by 180 min reoxygenation. The authors measured oxidative stress parameters (lipid peroxidation, glutathione system), prostaglandins (PGE₂), nitric oxide pathway activity (NO) (nitrites+nitrates, constitutive and inducible NO synthase activity) and LDH efflux, a biochem. marker of cell death. Various concentrations (10, 100, and 1000 μM) of triflusal, HTB, ASA, or SA were tested. Triflusal at 10, 100, and 1000 μM decreased LDH efflux in rat brain slices after anoxia/reoxygenation by 24, 35, and 49% resp. This effect was proportionately greater than that of ASA (0, 13, and 32%). The results with HTB were similar to those with triflusal, whereas SA showed a greater protective effect than ASA (13, 33, and 35%). The antioxidant effects of HTB and SA on the biochem. mechanisms of cell damage studied here were also greater than the effects of triflusal and ASA, a finding attributable mainly to the decrease in lipid peroxidation and to the ability of HTB to also increase glutathione levels. The triflusal metabolite reduced inducible NO synthase activity by 18, 21, and 30%, whereas SA inhibited this activity by 9, 17, and 23%. Triflusal and HTB led to greater increases in NO synthase than ASA or AS. In conclusion, the metabolite HTB plays an important role in the neuroprotective effect of triflusal, at least in the exptl. model of anoxia-reoxygenation tested here.

Naunyn-Schmiedeberg’s Archives of Pharmacology published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Recommanded Product: 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Lopez-Periago, A. published the artcileImpregnation of a biocompatible polymer aided by supercritical CO₂: Evaluation of drug stability and drug-matrix interactions, Safety of 2-Hydroxy-4-(trifluoromethyl)benzoic acid, the publication is Journal of Supercritical Fluids (2009), 48(1), 56-63, database is CAplus.

Poly(Me methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by a supercritical carbon dioxide (scCO₂) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chem. and H-bonding interactions between the matrix and the infused drug were evaluated together with the impregnated drug stability. The composition of the obtained systems was characterized by ¹H magnetic nuclear resonance and liquid chromatog. The microstructure of the impregnated matrix was studied using thermal anal. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatog. was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 weight% of active agent in PMMA were obtained, while the drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the drug over a long period of time.

Journal of Supercritical Fluids published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Safety of 2-Hydroxy-4-(trifluoromethyl)benzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Serratore, Nicholas A. published the artcileIntegrating Metal-Catalyzed C-H and C-O Functionalization To Achieve Sterically Controlled Regioselectivity in Arene Acylation, HPLC of Formula: 328-90-5, the publication is Journal of the American Chemical Society (2018), 140(31), 10025-10033, database is CAplus and MEDLINE.

One major goal of organometallic chemists is the direct functionalization of the bonds most recurrent in organic mols.: C-H, C-C, C-O, and C-N. An even grander challenge is C-C bond formation when both precursors are of this category. Parallel to this is the synthetic goal of achieving reaction selectivity that contrasts with conventional methods. Electrophilic aromatic substitution (EAS) via Friedel-Crafts acylation is the most renowned method for the synthesis of aryl ketones, a common structural motif of many pharmaceuticals, agrochems., fragrances, dyes, and other commodity chems. However, an EAS synthetic strategy is only effective if the desired site for acylation is in accordance with the electronic-controlled regioselectivity of the reaction. Herein we report steric-controlled regioselective arene acylation with salicylate esters via iridium catalysis to access distinctly substituted benzophenones. Exptl. and computational data indicate a unique reaction mechanism that integrates C-O activation and C-H activation with a single iridium catalyst without an exogenous oxidant or base. We disclose an extensive exploration of the synthetic scope of both the arene and the ester components, culminating in the concise synthesis of the potent anticancer agent hydroxyphenstatin.

Journal of the American Chemical Society published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C18H15N3O3, HPLC of Formula: 328-90-5.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Velasco, C published the artcileEffects of the nuclear factor-kappaB inhibitors 2-hydroxy-4-trifluoromethylbenzoic acid and aspirin on micturition in rats with normal and inflamed bladder., Category: alcohols-buliding-blocks, the publication is The Journal of urology (2001), 166(5), 1962-8, database is MEDLINE.

PURPOSE: We examined the effects of intravenous administration of the 2 nuclear factor-kappaB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) on bladder filling and voiding in anesthetized and conscious rats. MATERIALS AND METHODS: Disappearance of isovolumic bladder contractions after intravenous administration of different doses of aspirin and HTB in anesthetized, transurethrally catheterized rats was evaluated. Cystometry was performed in conscious rats during bladder infusion with saline or diluted acetic acid as well as in those with cyclophosphamide induced cystitis. Changes in bladder capacity and voiding pressure were evaluated after intravenous administration of test compounds. RESULTS: Aspirin induced a dose dependent disappearance of isovolumic bladder contractions in anesthetized rats with an extrapolated dose of 2.1 mg./kg. inducing 10 minutes of bladder quiescence. HTB was practically inactive, inducing a dose independent block of 3 to 4 minutes after intravenous administration of 1 to 10 mg./kg. In conscious rats with a bladder infused with saline aspirin was poorly active on bladder capacity, inducing a 20% increase 60 minutes after intravenous administration of 30 and 100 mg./kg. In rats with a bladder infused with acetic acid aspirin was much more active when injected at the initiation of inflammation and after 1 hour of irritant infusion. In this latter situation aspirin increased bladder capacity up to 60% after intravenous administration of 30 and 100 mg./kg. Similar results were obtained in rats with cyclophosphamide induced cystitis in which the bladder was infused with saline. In these cystometrography models 30 mg./kg. HTB intravenously was completely inactive. CONCLUSIONS: The results show that HTB is devoid of significant effects on the micturition reflex in the absence or presence of bladder inflammation, suggesting that acute inhibition of nuclear factor-kappaB does not influence bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygenase and nuclear factor-kappaB inhibitor, was always effective, indicating the important role of cyclooxygenase enzymes.

The Journal of urology published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C12H20O6, Category: alcohols-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts

Velasco, C. published the artcileEffects of the nuclear factor-κB inhibitors 2-hydroxy-4-trifluoromethylbenzoic acid and aspirin on micturition in rats with normal and inflamed bladder, Formula: C8H5F3O3, the publication is Journal of Urology (Hagerstown, MD, United States) (2001), 166(5), 1962-1968, database is CAplus.

We examined the effects of i.v. administration of the 2 nuclear factor-κB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) on bladder filling and voiding in anesthetized and conscious rats. Disappearance of isovolumic bladder contractions after i.v. administration of different doses of aspirin and HTB in anesthetized, transurethrally catheterized rats was evaluated. Cystometry was performed in conscious rats during bladder infusion with saline or diluted acetic acid as well as in those with cyclophosphamide induced cystitis. Changes in bladder capacity and voiding pressure were evaluated after i.v. administration of test compounds Aspirin induced a dose dependent disappearance of isovolumic bladder contractions in anesthetized rats with an extrapolated dose of 2.1 mg./kg. inducing 10 min of bladder quiescence. HTB was practically inactive, inducing a dose independent block of 3 to 4 min after i.v. administration of 1 to 10 mg./kg. In conscious rats with a bladder infused with saline aspirin was poorly active on bladder capacity, inducing a 20% increase 60 min after i.v. administration of 30 and 100 mg./kg. In rats with a bladder infused with acetic acid aspirin was much more active when injected at the initiation of inflammation and after 1 h of irritant infusion. In this latter situation aspirin increased bladder capacity up to 60% after i.v. administration of 30 and 100 mg./kg. Similar results were obtained in rats with cyclophosphamide induced cystitis in which the bladder was infused with saline. In these cystometrog. models 30 mg./kg. HTB i.v. was completely inactive. The results show that HTB is devoid of significant effects on the micturition reflex in the absence or presence of bladder inflammation, suggesting that acute inhibition of nuclear factor-κB does not influence bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygenase and nuclear factor-κB inhibitor, was always effective, indicating the important role of cyclooxygenase enzymes.

Journal of Urology (Hagerstown, MD, United States) published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C14H10O4, Formula: C8H5F3O3.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts