Tag: M.W=300-350

Fullam, Elizabeth published the artcilePhysicochemical properties and Mycobacterium tuberculosis transporters: keys to efficacious antitubercular drugs?, Product Details of C14H17FN4O3, the publication is RSC Medicinal Chemistry (2021), 12(1), 43-56, database is CAplus and MEDLINE.

A review. Securing novel, safe, and effective medicines to treat Mycobacterium tuberculosis remains an elusive goal, particularly influenced by the largely impervious Mtb envelope that limits exposure and thus efficacy of inhibitors at their cellular and periplasmic targets. The impact of physicochem. properties on pharmacokinetic parameters that govern oral absorption and exposure at sites of infection is considered alongside how these properties influence penetration of the Mtb envelope, with the likely influence of transporter proteins. The findings are discussed to benchmark current drugs and the emerging pipeline, while considering tactics for future rational and targeted design strategies, based around emerging data on Mtb transporters and their structures and functions.

RSC Medicinal Chemistry published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Product Details of C14H17FN4O3.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Wu, Yongqi published the artcileIdentification of Novel Tricyclic Benzo[1,3]oxazinyloxazolidinones as Potent Antibacterial Agents with Excellent Pharmacokinetic Profiles against Drug-Resistant Pathogens, SDS of cas: 1219707-39-7, the publication is Journal of Medicinal Chemistry (2021), 64(6), 3234-3248, database is CAplus and MEDLINE.

A series of conformationally constrained novel benzo[1,3]oxazinyloxazolidinones were designed, synthesized, and evaluated on their activities against Mycobacterium tuberculosis, Gram-pos. bacteria, and Gram-neg. bacteria. The studies identified a new compound 20aa that displayed good to excellent antibacterial and antitubercular profiles against drug-resistant TB strains (MIC = 0.48-0.82μg/mL), MRSA (MIC = 0.25-0.5μg/mL), MRSE (MIC = 1μg/mL), VISA (MIC = 0.25μg/mL), and VRE (MIC = 0.25μg/mL) and some linezolid-resistant strains (MIC 1-2μg/mL). Compound 20aa was demonstrated as a promising candidate through ADME/T evaluation including microsomal stability, cytotoxicity, and inhibition of hERG and monoamine oxidase. Notably, 20aa showed excellent mouse PK profile with high plasma exposure (AUC_{0-âˆ?/sub> = 78 669 h·ng/mL), high peak plasma concentration (Cmax = 10 253 ng/mL), appropriate half-life of 3.76 h, and superior oral bioavailability (128%). The present study not only successfully provides a novel benzo[1,3]oxazinyloxazolidinone scaffold with superior druggability but also lays a good foundation for new antibacterial drug development.}

Journal of Medicinal Chemistry published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C8H14O4, SDS of cas: 1219707-39-7.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Messias Monteiro, Alex France published the artcileIn Silico Studies for Bacterystic Evaluation against Staphylococcus aureus of 2-Naphthoic Acid Analogues, Recommanded Product: (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, the publication is Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates) (2020), 20(4), 293-304, database is CAplus and MEDLINE.

Staphylococcus aureus is a gram-pos. spherical bacterium commonly present in nasal fossae and in the skin of healthy people; however, in high quantities, it can lead to complications that compromise health. The pathologies involved include simple infections, such as folliculitis, acne, and delay in the process of wound healing, as well as serious infections in the CNS, meninges, lung, heart, and other areas. This research aims to propose a series of mols. derived from 2-naphthoic acid as a bioactive in the fight against S. aureus bacteria through in silico studies using mol. modeling tools. A virtual screening of analogs was done in consideration of the results that showed activity according to the prediction model performed in the KNIME Analytics Platform 3.6, violations of the Lipinski rule, absorption rate, cytotoxicity risks, energy of binder-receptor interaction through mol. docking, and the stability of the best profile ligands in the active site of the proteins used (PDB ID 4DXD and 4WVG). Seven of the 48 analogs analyzed showed promising results for bactericidal action against S. aureus. It is possible to conclude that ten of the 48 compounds derived from 2-naphthoic acid presented activity based on the prediction model generated, of which seven presented no toxicity and up to one violation to the Lipinski rule.

Current Topics in Medicinal Chemistry (Sharjah, United Arab Emirates) published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Recommanded Product: (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Motamen, Sara published the artcileAnalysis of Approaches to Anti-tuberculosis Compounds, Formula: C14H17FN4O3, the publication is ACS Omega (2020), 5(44), 28529-28540, database is CAplus and MEDLINE.

Mycobacterium tuberculosis (Mtb) remains a deadly pathogen two decades after the announcement of tuberculosis (TB) as a global health emergency by the World Health Organization. Medicinal chem. efforts to synthesize potential drugs to shorten TB treatments have not always been successful. Here, we analyze physiochem. properties of 39 TB drugs and 1271 synthetic compounds reported in 40 publications from 2006 to early 2020. We also propose a new TB space of physiochem. properties that may provide more appropriate guidelines for design of anti-TB drugs.

ACS Omega published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Formula: C14H17FN4O3.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Foti, Claudia published the artcileOxazolidinone Antibiotics: Chemical, Biological and Analytical Aspects, Recommanded Product: (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, the publication is Molecules (2021), 26(14), 4280, database is CAplus and MEDLINE.

A review. This review covers the main aspects concerning the chem., the biol. activity and the anal. determination of oxazolidinones, the only new class of synthetic antibiotics advanced in clin. use over the past 50 years. They are characterized by a chem. structure including the oxazolidone ring with the S configuration of substituent at C5, the acylaminomethyl group linked to C5 and the N-aryl substituent. The synthesis of oxazolidinones has gained increasing interest due to their unique mechanism of action that assures high antibiotic efficiency and low susceptibility to resistance mechanisms. Here, the main features of oxazolidinone antibiotics licensed or under development, such as Linezolid, Sutezolid, Eperezolid, Radezolid, Contezolid, Posizolid, Tedizolid, Delpazolid and TBI-223, are discussed. As they are protein synthesis inhibitors active against a wide spectrum of multidrug-resistant Gram-pos. bacteria, their biol. activity is carefully analyzed, together with the drug delivery systems recently developed to overcome the poor oxazolidinone water solubility Finally, the most employed anal. techniques for oxazolidinone determination in different matrixes, such as biol. fluids, tissues, drugs and natural waters, are reviewed. Most are based on HPLC (High Performance Liquid Chromatog.) coupled with UV-Vis or mass spectrometer detectors, but, to a lesser extent are also based on spectrofluorimetry or voltammetry.

Molecules published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Recommanded Product: (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Lee, Hyun-Hee published the artcileResistance mechanism of Enterococcus faecalis to LCB01-0371, a new oxazolidinone, Application of (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, the publication is Yakhak Hoechi (2014), 58(1), 7-11, database is CAplus.

To study the resistance mechanism of E. faecalis to LCB01-0371, several resistant mutants to LCB01-0371 or linezolid were isolated by step-wise selection. The frequency of spontaneous mutations resistant to LCB01-0371 was lower than that of linezolid in E. faecalis. The genetic variations in resistant mutants were analyzed by DNA sequencing of domain V of 23S rRNA in each mutant. The first-step mutant to LCB01-0371 had a G2576T point mutation in V domain of 23S rRNA. However, no resistant mutant to LCB01-0371 was isolated in second-step mutant selection.

Yakhak Hoechi published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Application of (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Cho, Yong-Soon published the artcilePharmacokinetics, pharmacodynamics, and tolerability of single-dose oral LCB01-0371, a novel oxazolidinone with broad-spectrum activity, in healthy volunteers, Safety of (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, the publication is Antimicrobial Agents and Chemotherapy (2018), 62(7), e00451-18/1-e00451-18/11, database is CAplus and MEDLINE.

The objectives of this study were to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics following single ascending doses. Single oral doses of 600 mg linezolid, a placebo, or LCB01-0371 of between 50 mg and 3,200 mg were tested in 69 healthy male subjects. Blood and urine were sampled, LCB01-0371 concentrations were measured, and the serum inhibitory and bactericidal titers of LCB01-0371 and linezolid were determined LCB01-0371 was well tolerated up to 2,400 mg. The most common drugrelated clin. and laboratory adverse events were nausea with or without vomiting, decreased neutrophil counts, and increased total bilirubin levels. The systemic exposure was approx. dose proportional over the range of 50 mg to 800 mg, which includes the anticipated clin. dose. The mean clearance, renal clearance, and volume of distribution were significantly decreased at higher doses (above 800 mg). LCB01-0371 exhibited early bacteriostatic activity against all tested strains except for Streptococcus pneumoniae strains, and the potency of LCB01-0371 at 800 mg was similar to that of linezolid at the therapeutic dose (600 mg). However, LCB01-0371 had less bactericidal activity than linezolid. Taken together, LCB01-0371 was well tolerated, exhibited approx. dose proportionality within the anticipated clin. relevant dose range, and showed bacteriostatic and bactericidal activity comparable to that of linezolid. These results support the further clin. development of LCB01-0371.

Antimicrobial Agents and Chemotherapy published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Safety of (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Cho, Yong-Soon published the artcileMultiple-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral LCB01-0371 in Healthy Male Volunteers, SDS of cas: 1219707-39-7, the publication is Clinical Therapeutics (2018), 40(12), 2050-2064, database is CAplus and MEDLINE.

LCB01-0371 is a novel oxazolidinone broad-spectrum antibacterial that is more potent than linezolid against systemic infections in animals. The goal of this investigation was to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple-dose LCB01-0371 as well as the pharmacokinetic characteristics of a new 400-mg tablet formulation.: Thirty-two healthy male subjects received BID 400-1600 mg multiple oral dosing of LCB01-0371 (200-mg tablet or 400-mg tablet) for 7 days, and 6 subjects received an 800-mg single oral dose of LCB01-0371 (400-mg tablet). Safety assessments were undertaken at regular intervals. Blood and urine were sampled, and drug concentration and inhibitory and bactericidal titers were measured.LCB01-0371 was generally safe and well tolerated up to 1200 mg BID for 7 days. Adverse events were mild, except for headache, nausea, and dizziness at the dose of 1600 mg, and resolved spontaneously. LCB01-0371 was absorbed rapidly within 2 h after administration, and its accumulation observed on day 7 ranged between 1.10- and 1.46-fold. The elimination t1/2 was 1.64-1.94 h, which remained unchanged across all doses. AUC_0-12 and C_max were not dose proportional across the dose range from 400 to 1200 mg after both single and multiple dosing, indicating a nonlinear pharmacokinetic profile. The percentage of the dose excreted via the urine ranged from 7.84% to 8.95%. The new (400-mg tablet) formulation exhibited less interindividual variability with pharmacokinetic characteristics similar to the original formulation (200-mg tablet). LCB01-0371 exhibited both early serum inhibitory and bactericidal activities against the 4 strains tested in the ex vivo pharmacodynamics study.BID doses of LCB01-0371 up to 1200 mg for 7 days were well tolerated and exhibited rapid serum inhibitory and bactericidal activities against common gram-pos. pathogens. The results warrant further clin. investigation of the antibacterial effect of BID LCB01-0371 administration.

Clinical Therapeutics published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, SDS of cas: 1219707-39-7.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Cho, Yong-Soon published the artcileSingle-dose Intravenous Safety, Tolerability, and Pharmacokinetics and Absolute Bioavailability of LCB01-0371, Related Products of oxazolidine, the publication is Clinical Therapeutics (2019), 41(1), 92-106, database is CAplus and MEDLINE.

LCB01-0371 is a novel broad-spectrum oxazolidinone antibacterial agent under investigation for the treatment of infection by gram-pos. pathogens, including methicillin-resistant Staphylococcus aureus. This study evaluated the safety, tolerability, and pharmacokinetics of LCB01-0371 after a single i.v. (IV) infusion and determined its absolute oral bioavailability at a therapeutic dose of 800 mg.: This study was conducted in 2 parts. The first part was a single-blind, placebo-controlled, escalating single IV dose study (200, 400, 800, and 1200 mg) of LCB01-0371 via 2 different infusion regimens (250 mL over 60 min or 150 mL over 30 min) in 36 healthy male volunteers. The second part was an open-label, 2-way crossover design study in which 8 subjects were randomly assigned to 1 of 2 sequences of a single oral (800 mg) or IV (400 mg) administration of LCB01-0371. Safety assessments were conducted at regular intervals. Blood and urine were serially sampled, and drug concentrations were measured for up to 24 h to calculate pharmacokinetic parameters. LCB01-0371 after IV administration was generally safe and well tolerated up to 800 mg regardless of the infusion regimen. Adverse events were mild, excluding nausea at the highest dose, and resolved spontaneously. After a single IV administration, LCB01-0371 exhibited linear pharmacokinetic properties over the range of 200-800 mg. The elimination t_1/2, volume of distribution, and clearance ranged from 1.48 to 1.68 h, 57.74-76.72 L, and 33.17-43.31 L/h, resp., and they remained unchanged over the corresponding dose range. C_max, AUC_0-last, and AUC_{0-�/sub> increased in a dose-dependent manner. The dose-normalized total exposure after single PO and IV dosing were equivalent, with 90% CIs of the geometric least squares mean ratio of 86.6%-110% for AUC0-last and 86.6%-111% for AUC0-�/sub>. The dose-normalized Cmax was not equivalent between oral and IV dosing, with a 90% CI of the geometric least squares mean ratio of 50.0%-105%. The absolute oral bioavailability of LCB01-0371 after a single 800-mg dose was 99.75%. After a single IV administration, LCB01-0371 was well tolerated in healthy volunteers at doses up to 800 mg, and it exhibited linear pharmacokinetic properties. The comparable total systemic exposure between IV and oral administration supports the ability to switch administration routes without a need for dose adjustment. ClinicalTrials.gov identifier: NCT02882789.}

Clinical Therapeutics published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Related Products of oxazolidine.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem

Choi, Yewon published the artcileSafety, tolerability and pharmacokinetics of 21 day multiple oral administration of a new oxazolidinone antibiotic, LCB01-0371, in healthy male subjects, Related Products of oxazolidine, the publication is Journal of Antimicrobial Chemotherapy (2018), 73(1), 183-190, database is CAplus and MEDLINE.

Background: LCB01-0371 is a new oxazolidinone antibiotic, which targets most Gram-pos. organisms. High rates of adverse reactions including myelosuppression have been reported for existing oxazolidinones, limiting their long-term use. Objectives: The safety, tolerability and pharmacokinetics (PK) of 21 day multiple oral administrations of LCB01-0371 in healthy male subjects (clinicaltrials.gov: NCT02540460) were investigated. Methods: In this randomized, double-blind, placebo-controlled study, subjects received 800mg of LCB01-0371 once or twice daily or 1200mg of LCB01-0371 twice-daily for 21 days in a fasting state. Safety and tolerability profiles including laboratory tests were evaluated during the study and on a post-study visit and the results were analyzed using repeated-measures anal. of variance (RM-ANOVA). Serial blood samples for PK anal. were collected up to 12 h after dosing on day 21. Results: A total of 40 subjects were enrolled and 34 subjects completed the study. Two subjects dropped out according to stopping rules. In the 1200mg twice-daily dose group, the absolute value of red blood cell count, haematocrit and Hb decreased by 500×10⁶/L (6.5%), 4.5% (6.8%) and 1.6 g/dL (6.9%), resp., after 21 day administrations of LCB01-0371. However, mean relative changes from baseline of all haematol. values were not significantly different among doses, including placebo (all, P<0.05). PK profiles of LCB01-0371 in the dose range of 800mg once daily to 1200mg twice daily were consistent with previous studies. Conclusions: LCB01-0371 is well tolerated in healthy male subjects with comparable haematol. profiles to placebo, after multiple doses of up to 1200mg twice daily for 21 days.

Journal of Antimicrobial Chemotherapy published new progress about 1219707-39-7. 1219707-39-7 belongs to oxazolidine, auxiliary class Other Aliphatic Heterocyclic,Oxazolidine,Chiral,Fluoride,Benzene,Amide,Alcohol,Anti-infection, name is (R)-3-(3-Fluoro-4-(1-methyl-5,6-dihydro-1,2,4-triazin-4(1H)-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one, and the molecular formula is C14H17FN4O3, Related Products of oxazolidine.

Referemce:
https://en.wikipedia.org/wiki/Oxazolidine,
Oxazolidine | C3H7NO – PubChem