Andrea Santagati

Thienopyrimidine derivatives prevent cartilage destruction in articular disease.

The effects of a series of thienopyrimidine derivatives on the prevention of cartilage destruction in articular disease were investigated. Anti-degenerative activity was assayed on culture of nasal pig cartilage in the presence or in the absence of interleukin 1beta (IL-1beta). The amount of glycosaminoglycans (GAGs) and the production of nitric oxide (NO) in the culture medium were determined. Some thienopyrimidine derivatives, in the presence of IL-beta, blocked the cartilage breakdown by inhibiting both the NO production and GAGs release in a dose-dependent manner.

Synthesis and NK-2 antagonist effect of 1,6-diphenyl-pyrazolo [3,4-d]-thiazolo[3,2-a]4H-pyrimidin-4-one

Abstract 1,6-Diphenyl-pyrazolo[3,4-d]thiazolo[3,2-a]4H-pyrimidin-4-one caused parallel displacement of the dose-response curve to the NK-2 receptor agonist in the guinea pig trachea suggesting it acts as a competitive antagonist. It is not active in the NK-1 and NK-3 receptor binding assays. A Ca ++ channel blocking action at the voltage-operated channels (L-type) was observed.

Building a model of interaction at the NK-2 receptors: Polycondensed heterocycles containing the pyrimidoindole skeleton†

Summary The pyrazolopyrimidothiazole ring system (compound N, table II) has been previously reported by us as a new competitive antagonist (apparent pA 2 = 7.3 equiv to 55 nM) at NK2-receptors. As part of our investigation on polycondensed heterocycles containing the pyrimidine ring as antagonists of G-protein coupled receptors, pyrimidoindole derivatives were prepared and tested in order to probe the topography of the NK2-receptors and ascertain the pattern of frameworks that result in optimum affinity and specificity. The title indole derivatives 5, 11a-d, 12c, 13a,b and 14b were ‘de novo’ designed or selected from our chemical archives and prepared by up-to-date synthetic routes, thus exploring new synthetic methodologies. According to the established graphic computer model, none of the tested substances exhibited activity as a consequence of the violation of an excluded volume area due the unfavourable position of the aromatic substituents.

Synthesis of 2,3,5,6,7,8-hexahydro-3-amino-2-thioxo[1]benzothieno-[2,3-d]pyrimidin-4(1H)-one and derivatives of the new heterocyclic system 7,8,9,10-tetrahydro-3H,11H-[1]benzothieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazin-11-one

A versatile compound, 2,3,5,6,7,8-hexahydro-3-amino-2-thioxo[1]benzothienol[2,3-d]pyrimidin-4(1H)-one (4), was synthesized from ethyl 4,5,6,7-tetrahydro-2-isothiocyanato-1-benzothiophene-3-carboxylate(1). Derivatives of a heterocyclic linear system having the 1,3,4- thiadiazine ring were obtained from the key intermediate (4)

Studies on annelated thiazolopyrimidines IV. Synthesis and pharmacological properties of thiazolothienopyrimidine derivatives

Abstract During our research on analgesic and anti-inflammatory active condensed heterocyclic compounds containing the pyrimidine ring, a number of thiazolothienopyrimidines was synthesized and tested. The results of pharmacological assays are reported and discussed.

High Potent and Selective Arylpiperazine Derivatives as Ligands for the 5-HT 1A Receptor

This paper reports the synthesis and affinities on the 5-HT1A versus the alpha1A receptors of new arylpiperazinylalkylthiothienopyrimidine and thiadiazole derivatives 16-24. Arylpiperazines 16-23 show affinities values in the nanomolar range for the 5-HT1A receptor. The compound 16 is highly potent (Ki 0.26 nM, selectivity 28), the derivatives 20 and 21 are less potent, but highly selective (Ki 9.40 and 5.06 nM, selectivity 207 and 73, respectively).

Synthesis and biological evaluation of new benzo-thieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives as potential selective cyclooxygenase-2 inhibitors

The aim of this work was to evaluate the potential anti-inflammatory activity of eleven (5–15) new synthesized derivatives of benzo-thieno[3,2-d]pyrimidine on two cell models, namely human keratinocytes NCTC 2544 and mouse monocyte-macrophages J774. For the synthesis of test compounds an efficient approach was developed: the key isothiocyanate was prepared through a simple and ecological method using di-2-pyridyl thionocarbonate (DPT) in substitution of thiophosgene, a highly toxic agent, and the cyclization reaction of benzo-thiosemicarbazide derivates was performed through Wamhoff methods. This procedure can be a new alternative method economically and environmentally advantageous by the simplicity of procedure, reduction of isolation and purification steps, time, costs, and waste production. The potential anti-inflammatory activity of 5–15 was evaluated by determining the expression of cyclooxygenase (COX)-2, inducible NO synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1), and the release of prostaglandins (PG)E

Synthesis and biological evaluation of sulfonilamidothienopyrimidinone derivatives as novel anti-inflammatory agents.

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