A Convenient Synthesis of Hydroxytyrosol Monosulfate Metabolites.

The growing interest in the bioactivity of natural polyphenols and of their metabolites requires metabolites to be used in bioassays and as standards in research protocols. We report here on the synthesis of several hydroxytyrosol metabolite monosulfates achieved using a simplified protocol with improved yields. A synthetic solution based on avoidance of high temperature conditions during the synthesis and of low pressure conditions during purification has been established.

Patents of bio-active compounds based on computer-aided drug discovery techniques.

In recent times, there has been an increased use of Computer-Aided Drug Discovery (CADD) techniques in Medicinal Chemistry as auxiliary tools in drug discovery. Whilst the ultimate goal of Medicinal Chemistry research is for the discovery of new drug candidates, a secondary yet important outcome that results is in the creation of new computational tools. This process is often accompanied by a lack of understanding of the legal aspects related to software and model use, that is, the copyright protection of new medicinal chemistry software and software-mediated discovered products.

Review of synthesis, assay, and prediction of β and γ-secretase inhibitors.

Alzheimer's disease (AD) is characterize with several pathologies this disease, amyloid plaques, composed of the β-amyloid peptide and β-amyloid peptide are hallmark neuropathological lesions in Alzheimer's disease brain. Indeed, a wealth of evidence suggests that β-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. AD is the most prevalent form of dementia, and current indications show that twenty-nine million people live with AD worldwide, a figure expected rise exponentially over the coming decades.

Synthesis and pharmacological evaluation of novel substituted 9-deazaxanthines as A2B receptor antagonists.

A new series of 9-deazaxanthine derivatives with various substituents at the heterocyclic system were synthesized and evaluated for their binding affinities for the four human recombinant adenosine receptors, A(1)-A(3) subtypes. A number of the 9-deazaxanthines derivatives 3a-m showed moderate-to-high affinity for hA(2B) receptors, with compound 3f showing a 32-fold selectivity for A(2B) over A(1) and a 2750-fold selectivity for A(2B) over A(2A).

Synthesis and pharmacological evaluation of novel 1,3,8- and 1,3,7,8-substituted xanthines as adenosine receptor antagonists.

A number of novel xanthines bearing a variety of substituents at positions 1, 3, 7 and 8 were prepared and evaluated for their binding affinity to the human adenosine receptor A(1), A(2A), A(2B) and A(3) subtypes. Several of the 1,3,8- and 1,3,7,8-substituted xanthines showed moderate-to-high affinity at human A(2B) and A(1) receptors, with the most active compound (14q) having a pK(i) of 7.57 nM for hA(2B) receptors and a selectivity over hA(2A) receptors of 8.

Synthesis and pharmacological evaluation of novel 1- and 8-substituted-3-furfuryl xanthines as adenosine receptor antagonists.

The synthesis of an important set of 3-furfurylxanthine derivatives is described. Binding affinities were determined for rat A(1) and human A(2A), A(2B) and A(3) receptors. Several of the 3-furfuryl-7-methylxanthine derivatives showed moderate-to-high affinity at human A(2B) receptors, the most active compound (10d) having a K(i) of 7.

Synthesis of novel 1-alkyl-8-substituted-3-(3-methoxypropyl) xanthines as putative A(2B) receptor antagonists.

In order to identify a high-affinity, selective antagonist for the A(2B) subtype adenosine receptor, more than 40 1,8-disubstituted-3-(3-methoxypropyl) xanthines were prepared and evaluated for their binding affinity at recombinant human adenosine receptors, mainly of the A(2A) and A(2B) subtypes. Some of the 1-ethyl-3-(3-methoxypropyl)-8-aryl substituted derivatives 15(a-m) showed moderate-to-high affinity at human A(2B) receptors, with compound 15d showing A(2B) selectivity over the other A receptors assayed (A(1), A(2A), A(3)) of 34-fold or over.

Synthesis of novel purinyl-1'-homocarbanucleosides based on a cyclopenta[b]pyrazine system.

cis-2,3-Diphenyl-6,7-dihydro-5H-cyclopenta[b]pyrazine-5,7-dimethanol, prepared by Diels-Alder reaction from cyclopentadiene and appropriately protected 2-imidazolone--followed by dihydroxylation, glycol protection, diamine deprotection, condensation with benzyl, glycol deprotection, oxidative cleavage and reduction--, was used to synthesize (+/-)-cis-([7-(6-chloro-9H-purin-9-yl)methyl]-2,3-diphenyl-6,7-dihydro-5H-cyclopenta[b]pyrazin-5-yl)methanol, a key intermediate for novel 1'-homocarbanucleosides based on a cyclopenta[b]pyrazine scaffold as shown by its conversion into several 6-substituted purinyl derivatives.

Carbocyclic analogues of nucleosides from bis-(Hydroxymethyl)-cyclopentane: synthesis, antiviral and cytostatic activities of adenosine, inosine and uridine analogues.

Six new carbocyclic nucleosides were prepared by constructing a purine base (in compounds 9-11) or pyrimidine base (in 6-8) on the amino groups of (+/-)-(1 beta,2 alpha,4 beta)-4-amino-1,2-cyclopentanedimethanol (4) and (+/-)-(1 beta,3 alpha,4 beta)-4-amino-1,3-cyclopentanedimethanol (5), and their activities against a variety of viruses and tumour cell lines were determined.

Synthesis of series of 1- and 3-differently substituted xanthines from imidazoles.

A new and general method is described for the synthesis, in three steps and in good overall yields, of tetrasubstituted xanthines from an easily prepared imidazole precursor. The method is especially useful for the preparation in standardized conditions of series of xanthines combining a broad variety of primary or secondary alkyl, benzyl or aryl groups at N1 and of alkyl or arylmethyl groups at N3, that are not readily available by other methods.