Vesicular monoamine transporter-2 (VMAT2) is a viable target for development of pharmacotherapies for psychostimulant abuse. Lobeline (1) is a potent antagonist at α4β2∗ nicotinic acetylcholine receptors, has moderate affinity (Ki = 5.46 μM) for VMAT2, and is being investigated currently as a...

The formation and further transformation of esters belongs to the fundamentals of organic chemistry. Moreover, some esters have enormous importance; for example triglycerides (1), in the form of fats and oils, are produced in million ton quantities for a number of applications. Other esters, e.g...

A catalyst free procedure for the preparation of amides from inactive esters of N-protected amino acids and various amines is demonstrated under mild reaction conditions. Our effort to recover excess amine and generated alcohol is an approach towards environment friendly and cost effective synth...

The cycloalkeno[1,2-d]furo[2,3-b]pyridine skeleton was conveniently synthesized from fused 4-(2-cyanovinyloxy)butanenitriles in one step through sequential intramolecular Michael addition, β-elimination and intramolecular nucleophilic addition. This sequence thus consists of a novel Truce–Smil...

Ethyl N-(diphenylmethylene)glycinate, 1, undergoes monoalkylations, dialkylations and Michael additions to ethylenic and acetylenic acceptors under appropriate solid-liquid phase transfer catalysis conditions. Further transformations of the α-disubstituted ketimines lead to α-alkylated asparti...

An efficient procedure for preparation of α,β-dehydroamino acids from the reaction of acetylenic ketones with N-(diphenylmethylene)glycinates 2 is described. The reaction of terminal acetylenic ketones with 2 promoted by Et3N at −10 °C gave the dehydroamino acids containing ketone group in go...

Optically active α-amino acid was asymmetrically synthesized under soluble polymer-supported quinine by homogeneous phase catalytic reaction. The precursor of l-phenylalanine, Ph2NCH(CH2Ph)CO2C2H5 (C24H23NO2, Mr=364.38) has been determined by X-ray diffraction analysis. The crystal belongs to m...

The efficient synthesis of N-(diphenylmethylene) glycine alkyl esters was achieved for the first microwave irradiation under solvent-free condition, using PEG or quaternary ammonium salts as phase transfer catalysts (PTCs). Under the optimum conditions, N-(diphenylmethylene) glycine alkyl esters...

A series of non-peptide inhibitors targeting the polo-box domain (PBD) of polo-like kinase 1 (Plk1) was designed based on the potent and selective minimal tripeptide Plk1 PBD inhibitor. Seven compounds were designed, synthesized and evaluated for fluorescence polarization (FP) assay. The most pr...

A series of new hybrid isatin-aminorhodanine molecules was prepared by microwave activation under mild conditions. Unexpected condensation of isatin derivatives at C-5 position of aminorhodanine was highlighted and confirmed by NMR and X-ray analyses. The inhibitory activity of these compounds w...

Aurora kinases are known to be overexpressed in various solid tumors and implicated in oncogenesis and tumor progression. A series of nicotinamide derivatives were synthesized and their biological activities were evaluated, including kinase inhibitory activity against Aur A and Aur B and in vitr...

Receptor-interacting protein kinase 1 (RIPK1), a key component of the cellular necroptosis pathway, has gained recognition as an important therapeutic target. Pharmacologic inhibition or genetic inactivation of RIPK1 has shown promise in animal models of disease ranging from acute ischemic condi...

Protein kinase inhibitors (PKI) are a growing class of anticancer agents. They are prescribed with flat doses, and their oral administration is associated with interindividual variability in exposure. Patients can be over- or underexposed, due to numerous factors. We reviewed key pharmacokinetic...

Because mutations, overexpression, and dysregulation of protein kinases play essential roles in the pathogenesis of many illnesses, this enzyme family has become one of the most important drug targets in the past 20 years. The US FDA has approved 48 small molecule protein kinase inhibitors, near...

BackgroundLiver disease is associated with impaired metabolism of these amino acids phenylalanine and tyrosine. Decreased metabolism of these amino acids leads to abnormal plasma elevations and impaired clearance rates. We have developed a noninvasive breath test that measures hepatic cytosolic ...

Steady state phenylalanine and tyrosine turnover and the rate of conversion of phenylalanine to tyrosine in vivo were determined in 6 healthy postabsorptive adult volunteers. Continuous infusions of tracer amounts of L-[ring-2H5]phenylalanine were administered intravenously for 13–14 hr. After ...

The anti-viral and membrane fusion inhibitor, carbobenzoxy-d-phenylalanine-l-phenylalanine-glycine (ZfFG), was studied in phospholipid bilayers, where earlier studies had indicated this peptide functioned. Multinuclear magnetic resonance (NMR) studies were performed with isotopically labeled pep...

Urine sampling of the free amino acid pool serves to reflect plasma enrichment and is used as a noninvasive means to determine isotope enrichment in studies of amino acid metabolism. We determined the effect of d-[13C]phenylalanine and d-[13C]lysine content of tracers on urinary amino acid enric...

The 13C cross-polarization, magic-angle-spinning (CP-MAS) NMR spectra of poly (l-phenylalanine) and oligopeptides containing a l-phenylalanine or l-tyrosine residue in the solid state have been measured, in order to elucidate the side-chain conformational features of the phenylalanine and tyrosi...

Amino acids labeled with 13C or deuterium are commonly used in studies of amino acid metabolism. Traditionally, amino acid flux has been estimated by measurement of isotopic enrichment in the plasma pool; however, urine sampling as a noninvasive means of determining isotope enrichment has been i...