A new synthetic methodology for 3-aminotropones is described. Tropones and 3-aminotroponic building blocks, present in a number of active natural products, could be prepared by a two step synthetic pathway: a first step consisting in a [4+3] cycloaddition reaction between a conveniently substitu...

The antioxidant capacity of 9 pure lipophilic compounds was examined by microplate-ABTS and HPLC-ABTS, using similar experimental conditions. Results obtained showed that HPLC-ABTS method can be used for a rapid determination of individual antioxidant capacity of compounds in standard solutions ...

Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monotherapy of renal cell carcinoma (RCC) are inconsistent across studies. ABT-737, an BH3 mimetic inhibitor, is also a promising antitumor drug. Cancer cells including those from RCC, that have high levels...

SummaryDrug-tolerant “persister” tumor cells underlie emergence of drug-resistant clones and contribute to relapse and disease progression. Here we report that resistance to the BCL-2 targeting drug ABT-199 in models of mantle cell lymphoma and double-hit lymphoma evolves from outgrowth of per...

BackgroundPrevious “high-stakes” examinations by the American Board of Thoracic Surgery (ABTS) required remote testing, were non-educational and not tailored to individual practices. Given the ABTS mission of public safety and diplomate education, the ABTS-MOC examination was revised in 2015 t...

ABT-450 (8), a potent hepatitis C (HCV) NS3/4A protease inhibitor, was approved as part of AbbVie's first generation HCV treatment for the United States in December 2014. A series of process optimizations were developed over six years to support the program starting with recycling of a prev...

The degradation of lignin has attracted much attention since it represents approximately 30% of all non-fossil carbon sources and constitutes a sustainable bio-resource for fuels and aromatic derivatives. Here we investigated the degradation of lignin by laccase-catalysed reactions using 2,2′-A...

A spectrophotometric method using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) as the indicator was proposed for measuring persulfates, i.e., peroxymonosulfate (PMS) and peroxydisulfate (PDS). This method was based on the direct oxidation of the colorless ABTS by PMS/PDS to generat...

ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax) are under intensive preclinical and clinical investigation as treatments for hematologic and other malignancies. These small molecules mimic pro-death B-cell lymphoma-2 (Bcl-2) Homology 3 (BH3) domain-only proteins. They also bear a structur...

With the aim to discover a gastric antisecretory agent more potent than the existing proton pump inhibitors, novel 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-one derivatives, which could occupy two important lipophilic pockets (described as LP-1 and LP-2) of H+,K+-ATPase and can strongl...

Benidipine hydrochloride, used as an antihypertensive agent and long-acting calcium antagonist, is synthesized for commercial use as a drug substance in highly pure form. During the synthetic process development studies of benidipine, process related impurities were detected. These impurities we...

In the process of drug development, preclinical safety studies are to be performed that require the analysis of the compound at very low concentrations with high demands on the performance of the analytical methods. In the current study, a UPLC–MS/MS method was developed and validated to quanti...

We searched for a strong and selective nonprostanoid IP agonist bearing piperidine and benzanilide moieties. Through optimization of substituents on the benzanilide moiety, the crucial part of the agonist, 43 (2-((1-(2-(N-(4-tolyl)benzo[d][1,3]dioxole-5-carboxamido)ethyl)piperidin-4-yl)oxy)aceti...

A new general synthetic route towards three key Maillard flavour compounds, namely 2-acetyl-1-pyrroline, 6-acetyl-1,2,3,4-tetrahydropyridine and 5-acetyl-2,3-dihydro-4H-1,4-thiazine, was developed. The key step in the process is the methylenation reaction of azaheterocyclic carboxylic esters by ...

Based on the ligand 1,3-bis[2-(4-pyridyl)ethenyl] benzene (1,3-BPEB), three coordination polymers [Zn(1,3-BPEB)(1,4-BDC)]n (1), [Zn2(1,3-BPEB)(4,4′- BPDC)2·DMF]n (2), [Zn(1,3-BPEB)(4,4′-STDC)]n (3) have been obtained respectively by the hydrothermal synthesis of 1,4-benzenedicarboxylic acid (...

Studies of the binding of [3H]-SKF10047 to rat brain membrane preparations revealed a binding site which possessed high affinity for κ and agonist/antagonist analgesics. However, this site was distinguished from κ sites labelled with [3H]-ethylketazocine by its high affinity for Met5-enkephali...

Specific binding of one of the most potent analogs of phencyclidine (PCP), [3H]PCP-3-OH, in rat brain membranes revealed the labeling of high (Kd = 0.5 nM) and low (Kd = 16 nM) affinity binding sites. (+)SKF 10047 potently inhibited high, but not low, affinity [3H]PCP-3-OH binding. (+)[3H]SKF 10...

Interaction of σ receptors with intracellular Ca2+ channel blocker and modulators was examined. Ryanodine and inositol 1,4,5-trisphosphate (IP3) did not inhibit [3H](+)-N-allylnormetazocine ([3H](+)-SKF-10047) binding to σ receptors from either brain microsomal fractions or liver membrane extr...

The repeated administration of phencyclidine (PCP, 72 mg/kg/day) to rats led to physical dependence, as evidenced by a withdrawal syndrome exhibited approx. 24–48 h following suspension of drug. All components of the withdrawal syndrome were suppressed by s.c. injections of PCP (16 mg/kg), (±)...

The serotonin transporter (SERT) is functionally regulated via membrane trafficking. Our previous studies have demonstrated that the SERT C-terminal deletion mutant (SERTΔCT) showed a robust decrease in its membrane trafficking and was retained in the endoplasmic reticulum (ER), suggesting that...