(S)-5-Bromo-N-[(1-cyclopropylmethyl-2-pyrrolidinyl)methyl]-2,3-dimethoxybenzamide (4) has pico-molar in vitro binding affinity to D2 receptor (Ki (D2) = 0.003 nM) with lower affinity to D3 receptor (Ki (D3) = 0.22 nM). In this study, we describe radiosynthesis of [11C]4 and evaluation of its bin...

In positron emission tomography (PET) studies, the detailed mapping of neuroreceptor binding is a trade-off between parametric accuracy and spatial precision. Logan's graphical approach is a straightforward way to quickly obtain binding potential values at the voxel level but it has been sh...

To estimate receptor binding of ligand by positron emission tomography (PET) without an arterial input function, several quantitative approaches based on the use of a reference region have been proposed. We compared three approaches for quantifying extrastriatal D2 dopamine receptors using [11C]...

The Computerized Brain Atlas (CBA) transforms PET images of individual subjects into a standard brain anatomy. We have previously applied this to PET images with [11C]raclopride and confirmed that the D2 dopamine receptors in the striatum can be evaluated accurately with a standard brain anatomy...

Both FLB 457 and FLB 463, two substituted benzamides with high affinity for the dopamine D-2 receptors, were labeled with bromine-76 for PET investigations. [76Br]FLB 457 was prepared by electrophilic substitution of the tributyltin precursor. The radiochemical yield was 80%. [76Br]FLB 463 was p...

There is clear evidence that the prefrontal cortex is strongly involved in executive processes and that dopamine can influence performance on working memory tasks. Although, some studies have emphasized the role of striatal dopamine in executive functions, the role played by prefrontal dopamine ...

Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson's disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance ad...

BackgroundReduced dopaminergic function may occur in depressive disorders. In this paper the results of two pilot studies examining different aspects of the dopamine system in depression are presented. First, the binding of [11C]FLB 457 to extrastriatal D2 receptors was measured in a group of de...

Dopamine D2 receptor occupancy by antipsychotic drugs has been measured with positron emission tomography (PET) by comparing the binding potential (BP) values before and after drug administration. This occupancy has been found to be related to clinical effects and side effects. In this study, we...

Purpose[11C]FLB 457, a radioligand with very high affinity and selectivity for dopamine D2/3 receptors, is used to measure receptor binding in extrastriatal regions showing low density of the receptors. The purpose of this study was to estimate the whole-body biodistribution of radioactivity and...

Compounds belonging to the class of 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones were synthesized and evaluated for their TACE inhibitory activity. Most of the compounds showed very good TACE inhibitory activity. Docking study clearly indicates importance of the P1′ group of the inhibi...

The effects of 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone (NZ-107) on immediate type hypersensitivity reactions in rats and guinea-pigs were studied. 1.1. When NZ-107, at a dose of 50 mg/kg (i.p.) or 100 mg/kg (orally), was administered to rats, 48-h homologous passive cutaneou...

The effect of NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) on late-phase airway responses and airway hyperreactivity was investigated in the guinea pig. Challenge with inhaled ovalbumin in conscious guinea pigs actively sensitized with inhaled ovalbumin caused triphasic ...

The synthesis and crystallographic analysis of a bicyclic core related to the esperamicin/calichemicin aglycones is reported. A key reaction involves the skeletal rearrangement of a mesylate derived from a type II Diels-Alder cycloadduct.

Two synthetic approaches to 2,6-dideoxy-4-S-methyl-4-thio-D-ribo pyranose, a component of the oligosaccharide of esperamicins are described. An asymmetric synthesis, starting from the propargylic alcohol dimer, relies on the Sharpless asymmetric epoxidation and the regio-selective opening of epo...

The conversion of keto ester 1, obtained in either enantiomeric form from (−)-quinic acid, to its corresponding enol silyl ether 4 was examined as the first step to construct the allyl trisulfide unit found in esperamicin A1. Under different conditions a very facile dimerization of either 4 or e...

2,6-Diyne-4-cyclodecen-1-ol, a highly simplified and isolable monocyclic analogue of the bicyclic aglycone of esperamicins and calicheamicins, has been obtained by an intramolecular cyclocondensation of 1-iodo-1,5-diyne-3-decen-10-al mediated by chromuim (II)-nickel(II) salts.

Ultraviolet radiation of the enediyne drugs is effective in causing nicks in supercoiled DNA. Of special interest is the fact that the observed nucleotide cleaving specificity for the UV light- and thiol-activated antibiotics was the same with esperamicin A1, but was different with neocarzinosta...

Esperamicin A1 is an enediyne antibiotic possessing antitumor activity associated with its ability to bind and, following activation, affect strand cleavage of DNA. We report on the solution structure of the esperamicin A1-d(C-G-G-A-T-C-C-G) duplex complex based on a combined analysis of NMR and...

The β-D-gluco-hexopyranose configuration has been assigned for the hydroxyamino sugar fragment of esperamicin A1. This determination concluded our study on the absolute configuration of the carbohydrate portion of esperamicins.