Biomimetic and Concise Total Syntheses of Prenylated and Bicyclo[2.2.2]diazaoctane-Containing Indole Alkaloids Including Taichunamide A, Notoamide N and Versicolamide B.

Total syntheses of the title prenylated indole alkaloids together with seven others are reported. Biogenetic considerations have been employed in devising the reaction sequences leading to these targets with, in the opening stages, electrochemically-derived indole-3-carboxaldehyde being subject to an aldol-type condensation reaction involving diketopiperazine derivative . This led, after prototopic shifts, intramolecular Diels-Alder cycloaddition and hydrolysis/deprotection steps, to the racemic forms of the bicyclo[2.

sp. nov. and sp. nov., isolated from the rhizosphere of selenium hyperaccumulator .

Two Gram-stain-negative bacterial strains, R39 and R73, were isolated from the rhizosphere soil of the selenium hyperaccumulator in China. Strain R39 transformed selenite into elemental and volatile selenium, whereas strain R73 transformed both selenate and selenite into elemental selenium. Phylogenetic and phylogenomic analyses indicated that strain R39 belonged to the genus , while strain R73 belonged to the genus .

Amorphous structure and crystal stability determine the bioavailability of selenium nanoparticles.

Microorganisms play a critical role in the biogeochemical cycling of selenium, often reducing selenite/selenate to elemental selenium nanoparticles (SeNPs). These SeNPs typically exist in an amorphous structure but can transform into a trigonal allotrope. However, the crystal structural transition process and its impact on selenium bioavailability have not been well studied.

Safety, tolerability, pharmacokinetics and pharmacodynamics of a novel farnesoid X receptor (FXR) agonist-TQA3526 in healthy Chinese volunteers: a double-blind, randomized, placebo-controlled, dose-escalation, food effect phase I study.

TQA3526 is a novel farnesoid X receptor agonist developed to treat non-alcoholic steatohepatitis (NASH) or primary biliary cholangitis (PBC). This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TQA3526 in healthy Chinese patients. Healthy subjects aged 18-55 years were enrolled in this double-blinded, first-in-human, placebo-controlled single ascending dose (1, 2, 5, and 10 mg) comprising food effect investigation (10 mg) and multiple dose study (2 mg and 0.

Electrochemical Selenylation of Sulfoxonium Ylides for the Synthesis of -Diselenides as Antimicrobials against Fungi.

Organoselenium compounds are important scaffolds in pharmaceutical molecules. Herein, we report metal-free, electrochemical, highly chemo- and regioselective synthesis of -diselenides through the coupling of α-keto sulfoxonium ylides with diselenides. The versatility of the electrochemical manifold enabled the selenylation with ample scope and broad functional group tolerance, as well as setting the stage for modification of complex bioactive molecules.

Disruption of the sensor kinase phoQ gene decreases acid resistance in plant growth-promoting rhizobacterium Rahnella aquatilis HX2.

Aims: Rahnella aquatilis HX2, a promising plant growth-promoting rhizobacterium (PGPR) in the field, contains genes homologous to the PhoP/PhoQ two-component regulatory system. Although this system regulates stress response in numerous pathogens, PhoP/PhoQ characterization in a PGPR has not received in-depth exploration.

Methods And Results: The phoQ gene was mutated in strain HX2 using an in-frame deletion strategy.

Population pharmacokinetic/pharmacodynamic models of JNJ-64794964, a toll-like receptor 7 agonist, in healthy adult participants.

Background: JNJ-4964 is a TLR7 agonist, which, via a type I interferon (IFN)-dependent mechanism, may enhance host immunity suppressed by persistent exposure to hepatitis B antigens in chronic hepatitis B.

Methods: PK and PD data were pooled from 2 studies involving 90 participants ( = 74 JNJ-4964, dose range 0.2-1.

Pharmacokinetics and bioequivalence of two pomalidomide capsules in healthy chinese subjects under fasting and fed conditions.

Objective: Imnovid® is an immunomodulatory drug with antineoplastic activity. The aim of this study was to evaluate the bioequivalence and safety of the generic drug pomalidomide (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and its originator product Imnovid® (Celgene Europe Ltd) in the fasting and fed states, respectively.

One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C.

Background: Entecavir (ETV) is a potent and selective nucleotide analog with significant activity against hepatitis B virus (HBV). ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV (Baraclude) when used in Chinese patients with chronic hepatitis B (CHB) in phase III clinical trials (Clinical Trials.gov number, NCT01926288) at weeks 48, 96, and 144.

240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.

Pharmacokinetics, safety, and tolerability of TQC3564, a novel CRTh2 receptor antagonist: report of the first-in-human single- and multiple-dose escalation trials in healthy Chinese subjects.

Background: This is the first-in-human study to evaluate the pharmacokinetics, safety, and tolerability of TQC3564 (a novel CRTh2 receptor antagonist) in healthy Chinese subjects.

Research Design And Methods: This project was a phase Ia clinical study of TQC3564 as a single-ascending dose (SAD) (25 to 1200 mg) and a multiple-ascending dose (MAD) (100 or 500 mg, QD) as well as a two-period crossover food-effect study (300 mg).

Results:     In the SAD and MAD study, TQC3564 were found to be safe and well tolerated, without dose-dependent adverse events (AEs), and all AEs were mild or moderate in severity.

Electrochemical regioselective C-H selenylation of 2-indazole derivatives.

Selenium-substituted heteroarenes are biologically active compounds and useful building blocks. In this study, we have developed a metal- and oxidant-free, environmentally friendly protocol for the regioselective selenylation of 2-indazole derivatives by an electrochemical strategy. A number of selenylated 2-indazoles with a wide range of functional groups have been synthesized in moderate to good yields under mild and environment-friendly reaction conditions.

First-in-Human, Double-Blind, Randomized, Placebo-Controlled Trial of TQ-F3083, a New Dipeptidyl Peptidase-4 Inhibitor, in Healthy Chinese Adults.

As a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, TQ-F3083 represents a promising new drug for type 2 diabetes mellitus (T2DM). This phase I, first-in-human study evaluated the tolerability, pharmacokinetics, and pharmacodynamics of TQ-F3083 in healthy Chinese adults. Sixty healthy participants total were enrolled in the single-ascending dose, multiple-dose, and food-effect studies.

Direct Electrochemical Selenylation/Cyclization of Alkenes: Access to Functionalized Benzheterocycles.

A catalyst-free, environmentally friendly, and efficient electrochemical selenylation/cyclization of alkenes has been developed with moderate to excellent yields. This selenylated transformation proceeds smoothly and tolerates a wide range of synthetically useful groups to deliver diverse functionalized benzheterocycles, including iminoisobenzofuran, lactones, oxindoles, and quinolinones. Moreover, the present synthetic route could also be readily scaled up to gram quantity with convenient operation in an undivided cell.

Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients: Results of a multicenter, double-blind, double-dummy, clinical trial at 96 weeks.

Background: Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). Qingzhong, a brand name of TDF, commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd.

Comparison of the Pharmacokinetics of Generic Versus Branded Obeticholic Acid in a Chinese Population: Effects of Food and Sex.

The present study assessed the pharmacokinetics and bioequivalence of a single 10-mg dose of a generic and the branded formulation (Ocaliva) of obeticholic acid (OCA) in healthy Chinese subjects under fasting and fed conditions. The possible effects of food and sex on the pharmacokinetics of OCA and its 2 active metabolites (glyco-OCA and tauro-OCA) were evaluated. Plasma concentrations of OCA and its 2 active metabolites were measured by liquid chromatography-tandem mass spectrometry.

Electrochemical Oxidative Phosphorylation of Aldehyde Hydrazones.

The electrochemical phosphorylation of aldehyde hydrazones has been developed under exogenous oxidant-free conditions. The strategy provides expedient access to highly functionalized α-iminophosphine oxides with ample scope and broad functional group tolerance by means of mild, user-friendly electrolysis, in an undivided cell.

A randomized, double-blind, double-dummy, controlled, multicenter study of Qingzhong (tenofovir disoproxil fumarate) versus Viread for the treatment of chronic hepatitis B: First-stage results at week 48.

Background: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB.

Catalyst-Free, Direct Electrochemical Tri- and Difluoroalkylation/Cyclization: Access to Functionalized Oxindoles and Quinolinones.

The catalyst-free electrochemical di- and trifluoromethylation/cyclization of N-substituted acrylamides was realized under external oxidant-free conditions. The strategy provides expedient access to fluoroalkylated oxindoles and 3,4-dihydroquinolin-2(1 H)-ones with ample scope and broad functional group tolerance by mild, direct electrolysis of sodium sulfinates in an undivided cell. Detailed mechanistic studies provided strong support for a SET-based reaction manifold.

First-Principles Investigation of the Epitaxial Stabilization of Oxide Polymorphs: TiO on (Sr,Ba)TiO.

Metastable polymorphs, many of which have never been fabricated, have been predicted to exhibit interesting and technologically relevant properties. Epitaxial synthesis is a powerful structure-directing method that can produce metastable polymorphs but is typically done in a trial and error fashion. Unfortunately, the relevant thermodynamic terms governing epitaxial synthesis of new materials are unknown.