Day: November 29, 2022

Dharuman, Suresh published the artcileSynthesis and Structure-Activity Relationship of Thioacetamide-Triazoles against Escherichia coli, Application In Synthesis of 59032-27-8, the publication is Molecules (2022), 27(5), 1518, database is CAplus and MEDLINE.

Infections due to Gram-neg. bacteria are increasingly dangerous due to the spread of multi-drug resistant strains, emphasizing the urgent need for new antibiotics with alternative modes of action. Authors have previously identified a novel class of antibacterial agents, thioacetamide-triazoles, using an antifolate targeted screen and determined their mode of action which is dependent on activation by cysteine synthase A. Herein, authors report a detailed examination of the anti-E. coli structure-activity relationship of the thioacetamide-triazoles. Analogs of the initial hit compounds were synthesized to study the contribution of the aryl, thioacetamide, and triazole sections. A clear structure-activity relationship was observed generating compounds with excellent inhibition values. Substitutions to the aryl ring were generally best tolerated, including the introduction of thiazole and pyridine heteroaryl systems. Substitutions to the central thioacetamide linker section were more nuanced; the introduction of a Me branch to the thioacetamide linker substantially decreased antibacterial activity, but the isomeric propionamide and N-benzamide systems retained activity. Changes to the triazole portion of the mol. dramatically decreased the antibacterial activity, further indicating that 1,2,3-triazole is critical for potency. From these studies, authors have identified new lead compounds with desirable in-vitro ADME properties and in-vivo pharmacokinetic properties.

Molecules published new progress about 59032-27-8. 59032-27-8 belongs to triazoles, auxiliary class Triazoles, name is Sodium 1,2,3-triazole-5-thiolate, and the molecular formula is C2H2N3NaS, Application In Synthesis of 59032-27-8.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Shevelev, Svyatoslav A. published the artcileInteraction of NH-azoles with O-fluorosulfonyl-N,N-difluorohydroxylamine, Quality Control of 84406-63-3, the publication is Mendeleev Communications (1993), 14-15, database is CAplus.

O-Fluorosulfonyl-N,N-difluorohydroxylamine reacted with NH-azoles, pyrazoles, imidazoles and benzotriazole, in an alk. medium, affording the corresponding N-fluorosulfonylazoles, e.g., I (R = H, Cl, NO₂), and in certain cases also the products of their further reactions, N,N‘-sulfonylbisazoles, II (R = Cl, NO₂).

Mendeleev Communications published new progress about 84406-63-3. 84406-63-3 belongs to triazoles, auxiliary class Triazole,Nitro Compound, name is 4-Nitro-2H-1,2,3-triazole, and the molecular formula is C17H14F3N3O2S, Quality Control of 84406-63-3.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Shevelev, S. A. published the artcileInteraction of NH-azoles with O-fluorosulfonyl-N,N-difluorohydroxylamine. Synthesis of N-fluorosulfonylazoles, Formula: C2H2N4O2, the publication is Izvestiya Akademi Nauk, Seriya Khimicheskaya (1992), 2419-30, database is CAplus.

FSO₂ONF₂ (I) reacts with anions of NH-azoles (imidazoles, pyrazoles, 1,2,3-triazoles) yielding the corresponding N-fluorosulfonylazoles from which sulfonylbisazoles are obtained. N-Fluorosulfonylation occurs at nitrogen atom which is farthest from the most electron-accepting substituent. Anions of nonaromatic NH-acids (imides, primary N-nitramines) can undergo N-fluorosulfonylation, however the yield is low (<5%) and the products are significantly less stable than N-fluorosulfonylazoles. N-Fluorosulfonylation occurs as nucleophilic substitution at the sulfur atom of I.

Izvestiya Akademi Nauk, Seriya Khimicheskaya published new progress about 84406-63-3. 84406-63-3 belongs to triazoles, auxiliary class Triazole,Nitro Compound, name is 4-Nitro-2H-1,2,3-triazole, and the molecular formula is C17H14F3N3O2S, Formula: C2H2N4O2.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Fos, Empar published the artcileMNDO semiempirical and 4-31G ab initio SCF-MO calculations of heteroaromatic compounds, HPLC of Formula: 63598-71-0, the publication is Journal of Organic Chemistry (1985), 50(24), 4894-9, database is CAplus.

The performance of the MNDO method, in terms of the energies of azines and azoles, is evaluated critically after comparing its results with some ab initio calculations at the 4-31G level and with available exptl. data. The lone-pair electronic repulsions between the neighboring pyridine-like N atoms are underestimated systematically by MNDO. Nevertheless, when corrections are introduced, even the relative stabilities of quite complex heterocyclic systems (tetrazolotriazine and -benzotriazine tautomers) are predicted with reasonable accuracy.

Journal of Organic Chemistry published new progress about 63598-71-0. 63598-71-0 belongs to triazoles, auxiliary class Triazole, name is 4H-1,2,4-Triazole, and the molecular formula is C2H3N3, HPLC of Formula: 63598-71-0.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Vereshchagin, L. I. published the artcileSynthesis of polynuclear heterocyclic polynitrogen systems based on cyanuric chloride and its derivatives, Formula: C2H2N4O2, the publication is Chemistry of Heterocyclic Compounds (New York, NY, United States) (2010), 46(2), 206-211, database is CAplus.

Polynuclear structures containing several heterocycles of various types were synthesized by the reaction of cyanuric chloride and its mono- and dichloro derivatives with triazoles and tetrazoles in the presence of bases.

Chemistry of Heterocyclic Compounds (New York, NY, United States) published new progress about 84406-63-3. 84406-63-3 belongs to triazoles, auxiliary class Triazole,Nitro Compound, name is 4-Nitro-2H-1,2,3-triazole, and the molecular formula is C15H14Cl2S2, Formula: C2H2N4O2.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Semenov, V. V. published the artcileNitroazole alkylation with α-haloketones – carbon-13, nitrogen-15, nitrogen-14 NMR study, Quality Control of 14544-45-7, the publication is Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya (1990), 1827-37, database is CAplus.

A general method for alkylation of nitroazoles (35 compounds) by BrCH₂COMe, N₂CHCOMe, and BrCOPh in homogeneous media and under phase-transfer catalyzed conditions to give acetonyl or phenacyl derivatives is described. Thus, treating imidazole with KOH in H₂O or solvent with BrCH₂COMe 20 h at 20° gave 80% 1-acetonylimidazole whose structure was confirmed by spectral data.

Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya published new progress about 14544-45-7. 14544-45-7 belongs to triazoles, auxiliary class Triazoles, name is 5-Nitro-1H-1,2,3-triazole, and the molecular formula is C8H15BN2O2, Quality Control of 14544-45-7.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Hsu, Fang-Chi published the artcileEn Route to the Formation of High-Efficiency, Osmium(II)-Based Phosphorescent Materials, HPLC of Formula: 219508-27-7, the publication is Inorganic Chemistry (2006), 45(25), 10188-10196, database is CAplus and MEDLINE.

Triosmium cluster complexes [Os₃(CO)₈(fppz)₂] (2a) and [Os₃(CO)₈(fptz)₂] (2b) bearing two 2-pyridyl azolate ligands were synthesized in an attempt to establish the reaction mechanism that gives rise to the blue-emitting phosphorescent complexes [Os(CO)₂(fppz)₂] (1a) and [Os(CO)₂(fptz)₂] (1b) [(fppz)H = 3-(trifluoromethyl)-5-(2-pyridyl)pyrazole; (fptz)H = 3-(trifluoromethyl)-5-(2-pyridyl)triazole]. X-ray structural anal. of 2b showed an open triangular metal framework incorporating multisite-coordinated 2-pyridyltriazolate ligands. Treatment of 2 with the resp. 2-pyridylazolate ligand gave blue-emitting complex 1b, confirming their intermediacy, while the reaction of 2b with phosphine ligand PPh₂Me afforded two hitherto novel isomeric hydride complexes 3 and 4 [Os(CO)(fptz)(PPh₂Me)₂(H)], for which the reversible interconversion was clearly established at higher temperatures (>180°). The single-crystal x-ray diffraction analyses of 3 and 4 confirmed their monometallic and isomeric nature, together with the coordination of two phosphine ligands located in the trans-disposition and one CO and one hydride located opposite to the pyridyl triazolate chelate. Subtle differences in photophys. properties were examined for isomers 3 and 4 from steady state absorption and emission, the relaxation dynamics, and temperature-dependent luminescent studies. The results, in combination with time-dependent d. function theory (TDDFT) calculations, provide fundamental insights into the future design and preparation of highly efficient phosphorescent emitters.

Inorganic Chemistry published new progress about 219508-27-7. 219508-27-7 belongs to triazoles, auxiliary class Trifluoromethylated Building Blocks, name is 2-[5-(Trifluoromethyl)-1H-1,2,4-triazol-3-yl]pyridine, and the molecular formula is C8H5F3N4, HPLC of Formula: 219508-27-7.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Cutler, David L. published the artcileEvaluation of the effects of a high-fat meal on the oral bioavailability of a single dose of preladenant in healthy subjects, Name: 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, the publication is Journal of Clinical Pharmacology (2012), 52(11), 1698-1703, database is CAplus and MEDLINE.

The aim of this study was to evaluate the effect of food on the oral bioavailability of preladenant, a novel adenosine A_2A receptor antagonist. This open-label, randomized, single-dose, 2-way crossover study evaluated the effects of a high-fat, high-calorie meal on the pharmacokinetics of preladenant and its metabolite (SCH434748) following oral administration of a single 25-mg preladenant capsule to 24 healthy subjects. When administered with food, the time of maximum concentration (T_max) of preladenant was prolonged compared with administration in the fasting state. Whereas T_max was increased from 0.9 h to 2.6 h and maximum concentration (C_max) was decreased (from 212 ng/mL to 128 ng/mL), the extent of absorption (area under the plasma concentration-time curve from time 0 to time of final quantifiable sample, or AUC_[tf]) was unaffected by the meal. Similarly, SCH434748 T_max was prolonged in the fed state, and C_max decreased from 43.7 ng/mL to 28.6 ng/mL. The assessment of AUC_[tf] and area under the plasma concentration-time curve from time 0 to infinity [AUC_[I]] together suggests that the AUC for the metabolite remained unchanged. No serious, significant, or unexpected adverse events occurred. In summary, food delays absorption and reduces peak exposure (C_max) but does not alter the extent of preladenant exposure (AUC). These small changes are unlikely to be of clin. importance. A single 25-mg dose of preladenant is safe and well tolerated in healthy subjects under both fed and fasting conditions.

Journal of Clinical Pharmacology published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C25H29N9O3, Name: 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Cutler, D. L. published the artcileSafety, tolerability and pharmacokinetics after single and multiple doses of preladenant (SCH420814) administered in healthy subjects, Application of 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, the publication is Journal of Clinical Pharmacy and Therapeutics (2012), 37(5), 578-587, database is CAplus and MEDLINE.

Summary : What is known and Objective: Preladenant (SCH420814, MK-3814) is a highly selective orally bioavailable non-methylxanthine adenosine 2A (A₂A) receptor antagonist under investigation for the treatment for Parkinson’s disease. This study evaluated the safety, tolerability and pharmacokinetics of preladenant at single and multiple doses for the first time in humans. Methods: These were two randomized, double-blind, placebo-controlled, ascending-dose studies, one evaluating single rising preladenant doses (5-200 mg) compared with placebo and the other evaluating multiple rising preladenant doses (10-200 mg once daily over 10 days) compared with placebo. Safety was the primary end point of both studies. Safety evaluations, phys. examinations, electrocardiograms, vital signs determinations and routine laboratory tests were performed before and at intervals throughout the studies. Blood samples were collected immediately before study drug administration and at various time points after dosing. Pharmacokinetic assessments of plasma preladenant and metabolites SCH434748 and SCH446637 were performed. Results and Discussion: One hundred and eight healthy adult men were randomly assigned in a 3 : 1 ratio to receive oral preladenant or matching placebo capsules under fasting conditions. Preladenant reached peak plasma concentrations in ∼1 h and then declined rapidly. Dose-related increases in exposure were observed up to 100 mg/day; accumulation was negligible at all doses. Transient mild increases in blood pressure occurred within a few hours after preladenant administration; blood pressure changes were neither cumulative nor dose-related nor associated with clin. sequelae. What is new and Conclusion: Preladenant was generally well tolerated up to the maximum dose tested (200 mg/day).

Journal of Clinical Pharmacy and Therapeutics published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C25H29N9O3, Application of 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics

Bennett, Kirstie A. published the artcilePharmacology and structure of isolated conformations of the adenosine A_2A receptor define ligand efficacy, Application of 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, the publication is Molecular Pharmacology (2013), 83(5), 949-958, database is CAplus and MEDLINE.

Using isolated receptor conformations crystal structures of the adenosine A_2A receptor have been solved in active and inactive states. Studying the change in affinity of ligands at these conformations allowed qual. prediction of compound efficacy in vitro in a system-independent manner. Agonist 5′-N-ethylcarboxamidoadenosine displayed a clear preference to bind to the active state receptor; inverse agonists (xanthine amine congener, ZM 241385, SCH 58261, and preladenant) bound preferentially to the inactive state, whereas neutral antagonists (theophylline, caffeine, and istradefylline) demonstrated equal affinity for active and inactive states. Ligand docking into the known crystal structures of the A_2A receptor rationalized the pharmacol. observed; inverse agonists, unlike neutral antagonists, cannot be accommodated within the agonist-binding site of the receptor. The availability of isolated receptor conformations opens the door to the concept of “reverse pharmacol.” whereby the functional pharmacol. of ligands can be characterized in a system-independent manner by their affinity for a pair (or set) of G protein-coupled receptor conformations.

Molecular Pharmacology published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C25H29N9O3, Application of 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics