Discovery of a highly specific F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination.

As a member of cyclic nucleotide phosphodiesterase (PDE) enzyme family, PDE10A is in charge of the degradation of cyclic adenosine (cAMP) and guanosine monophosphates (cGMP). While PDE10A is primarily expressed in the medium spiny neurons of the striatum, it has been implicated in a variety of neurological disorders. Indeed, inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system (CNS) pathologies caused by dysfunction of the basal ganglia-of which the striatum constitutes the largest component.

Urinary 8-oxo-7,8-dihydroguanosine levels are elevated in HCV-infected patients.

HCV patients are usually under substantial oxidative stress because of viral infection. A total of 177 patients with HCV infection and 198 age- and sex-matched healthy controls were enrolled in this study. We evaluated the urinary levels of 8-oxo-7, 8-dihydro-2'deoxyguanosine (8-oxodGuo) and 8-oxo-7, 8-dihydroguanosine (8-oxoGuo) in patients with HCV infection and explored the factors affecting the urinary 8-oxodGuo or 8-oxoGuo levels.

Development of a highly-specific F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors.

Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery.

Cyclic nucleotide phosphodiesterases (PDEs) control the intracellular concentrations of cAMP and cGMP in virtually all mammalian cells. Accordingly, the PDE family regulates a myriad of physiological functions, including cell proliferation, differentiation and apoptosis, gene expression, central nervous system function, and muscle contraction. Along this line, dysfunction of PDEs has been implicated in neurodegenerative disorders, coronary artery diseases, chronic obstructive pulmonary disease, and cancer development.

Synthesis and preliminary evaluation of novel C-labeled GluN2B-selective NMDA receptor negative allosteric modulators.

N-methyl-D-aspartate receptors (NMDARs) play critical roles in the physiological function of the mammalian central nervous system (CNS), including learning, memory, and synaptic plasticity, through modulating excitatory neurotransmission. Attributed to etiopathology of various CNS disorders and neurodegenerative diseases, GluN2B is one of the most well-studied subtypes in preclinical and clinical studies on NMDARs. Herein, we report the synthesis and preclinical evaluation of two C-labeled GluN2B-selective negative allosteric modulators (NAMs) containing N,N-dimethyl-2-(1H-pyrrolo[3,2-b]pyridin-1-yl)acetamides for positron emission tomography (PET) imaging.

Synthesis and pharmacokinetic study of a C-labeled cholesterol 24-hydroxylase inhibitor using 'in-loop' [C]CO fixation method.

Cholesterol 24-hydroxylase, also known as CYP46A1 (EC 1.14.13.

Radiosynthesis and preliminary evaluation of C-labeled 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2-benzo[] [1,2,4] thiadiazine 1,1-dioxide for PET imaging AMPA receptors.

The α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) belong to the family of ionotropic transmembrane receptors for glutamate (iGluRs) that are implicated in the pathology of neurological disorders and neurodegenerative diseases. Inspired by a recently developed positive allosteric modulator of AMPARs, 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2-benzo[ ][1,2,4]thiadiazine 1,1-dioxide (; EC = 2.0 nM), we designed a new synthetic route for -protected phenolic precursor and efficiently radiolabeled a PET ligand [C] ([C]) using a modified one-pot two-step strategy in high radiochemical yield and high molar activity.

A new hypervalent iodine(iii/v) oxidant and its application to the synthesis of 2-azirines.

The reaction of -nitroiodobenzene and CPBA in acetic acid was found to afford a novel hypervalent iodine compound, in the structure of which both iodine(iii) and iodine(v) moieties coexist. The nitro groups at the phenyl positions were found to be crucial in stabilizing this uncommon structure. This novel hypervalent iodine(iii/v) oxidant is proved to be effective in realizing the synthesis of 2-unsubstitued 2-azirines intramolecular oxidative azirination, which could not be efficiently achieved by the existing known hypervalent iodine reagents.

Synthesis of trifluoromethylated 2-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination.

The reaction of enamine compounds with the Togni reagent in the presence of CuI afforded β-trifluoromethylated enamine intermediates, which were converted directly to biologically interesting trifluoromethylated 2-azirines by an iodosobenzene (PhIO)-mediated intramolecular azirination in a one-pot process.

Synthesis of chromeno[2,3-b]indol-11(6H)-one via PhI(OAc)2-mediated intramolecular oxidative C(sp(2))–N(H2) bond formation.

Various chromeno[2,3-b]indol-11(6H)-ones were conveniently constructed via phenyliodine(III) diacetate (PIDA)-mediated intramolecular oxidative annulation. This method, while realizing a direct oxidative C–N bond formation between an aromatic ring and a pendent free-NH2 moiety, features a metal-free protocol, mild reaction conditions, simple workup, and the ready availability of the starting substrates.

[Predictive study of HBsAg in different stages of neonatal venous blood on failure of blocking HBV mother to infant transmission].

Objective: In this study, we discuss the predictive value of different content of HBsAg in different stages of neotal venous blood on failure of blocking mother to infant transmission of HBV.

Methods: 150 infants born of chronically HBV infected mothers who were positive of both HBsAg and HBeAg and who also had a HBV DNA virus load above 10(5) copies/ml were enrolled. These infants were given hepatitis B virus immune globin (HBIG) 200 IU immediately after birth and were given hepatitis B vaccine 10 or 20 microg at brith, 1 month and 6 months after birth.