1,721,091 research outputs found
Non peptidic alpha(V)beta(3) antagonists: Recent developments
No full textThe alphavbeta3 receptor, which are members of the group of the cellular adhesion
molecules (CAM), are heterodimeric transmembrane glycoprotein receptors involved
in processes such as cell-cell and cell-matrix adhesion, cell migration and
signaling. Integrin alphavbeta3 receptor is expressed on almost all cells
originating from the mesenchyme and seem to mediate several biological processes,
including adhesion of osteoblasts to the bone matrix, migration of vascular
smooth muscle cells, and angiogenesis. Many efforts were done in the last 10
years to individuate inhibitors for alphavbeta3 receptors, due to their
involvement in important pathophysiological functions. In fact, selective
alphavbeta3 antagonists offer new therapeutic opportunities for the treatment of
several human pathologies like osteoporosis, restenosis and diseases involving
neovascularization such as rheumatoid arthritis, tumor induced angiogenesis and
metastasis. Purpose of this account is to summarize the recent developments in
the field of non-peptidic alphavbetav antagonists
2,7-dimethyl-3,8-dinitrodipyrazolo[1,5-a : 1 ',5 '-d]pyrazine-4,9-dione: A new labelling reagent for liquid chromatographic analysis of amino acids
No full textThe use of 2,7-dimethyl-3,8-dinitrodipyrazolo[1,5-a:1’,5’-d]pyrazine-4,9-dione as pre-column reagent for LC analysis of amino acids is proposed. The compound reacts (30 min at 68°C in presence of 0.04 M triethylamine) with primary and secondary amino function and the stable resulting adducts can be chromatographed under reversed-phase conditions and detected at λ=280 nm. The derivatization conditions were optimized by a series of experiments. Application of the method to quality control of commercially available oral polyaminoacid formulations is described
Solid lipid microparticles for the stability enhancement of a dopamine prodrug
No full textDopamine supplementations in the brain alleviates the neurological symptoms associated with the Parkinson’s disease, but several difficulties hamper its oral or peripheral administration for clinical uses: (i) inability to cross the blood brain barrier, (ii) induction of dangerous unwanted effects in peripheral tissues, (iii) extensive hepatic metabolism when orally administered. The enhancement of dopamine stability in physiologic environments and its brain targeting appear therefore useful and a challenging aspect in formulation development. We propose a new study concerning the preparation and characterization of solid lipid microparticles based on tristearin as sustained delivery system for dopamine. The microparticles were produced by the conventional hot emulsion technique. The synthesis of a new valeroyl ester of dopamine (3,4-O-divaleroyl-dopamine, DVD) was necessary to obtain its encapsulation in the microparticles. DVD appeared totally hydrolized to dopamine in human plasma within 40 seconds. The amount of encapsulated DVD in microparticles was 2.67 1.2%. The mean diameter of particles was 14.2 4.8 μm. The DVD release from microparticles was characterized by an initial burst of 20% of incorporated prodrug and a continuous slow release thereafter. The microparticles were found able to stabilize DVD in its solid form. We have finally demonstrated that DVD encapsulated in the microparticles degraded in human plasma with a markedly reduced rate in comparison with free prodrug. The DVD loaded microparticles appear therefore a promising system for dopamine uptake in the brain, following the nasal administration
An efficient procedure for the synthesis of 5H-6-substituted-pyrazolo[1,5-d]-1,2,4-triazine-4,7-diones
No full textA new series of 5,6-dihydropyrazolo[1,5-d]-1,2,4-triazine-4,7-diones substituted in the 6-position with various phenyl substituents has been synthesized and found to have activity, owing to their acylating properties, as inhibitors of the serine protease enzymes
A facile and versatile route to the synthesis of fused 2-pyridones: Useful intermediates for policyclic systems
No full textThe reaction of various heteroarom. amino nitriles with di-Et malonate under basic conditions is reported. This reaction affords a series of different highly functionalized 2-pyridone condensed systems, which can be suitable intermediates in the construction of polyheterocyclic structures
DNA minor groove alkylating agents structurally related to distamycin A
No full textA review with 39 refs. Analogs of naturally occurring antitumor agents, such us distamycin A, which bind in the minor groove of DNA, represent a new class of antineoplastic compds. currently under investigation. Distamycin A has attracted researchers attention not only for its biol. activity, but also for its non-intercalative binding to the minor groove of double-stranded B-DNA, where it forms a strong reversible complex preferentially at the nucleotide sequences consisting of 4 - 5 adjacent AT base pairs. Distamycin has also been used as a DNA sequence-selective vehicle for the delivery of alkylating functions to DNA targets, leading to a sharp increase in cytotoxicity, in comparison to that of distamycin alone. In the last few years, several hybrid compds., in which known antitumor derivs. or simple active moieties of known antitumor agents have been tethered to distamycin frames, have been designed, synthesized and tested. Several efforts have been made to modify the DNA sequence selectivity and stability of distamycin; structural modifications have been based on replacement of pyrrole by other heterocycles and/or benzoheterocycles resulting in a novel class of minor groove binding mols. called lexitropsins. The role of the amidino moiety has also been studied by substitution with various groups, including ionizable, acid or basic and non-ionizable groups. The synthesis of a hybrid derived from combining distamycin A and a naturally occurring alkylating agent structurally related to pyrrolo [2,1-c][1,4] benzodiazepine group, such as anthramycin and DC-81, has been also reported. Several classes of distamycin derivs. that have been reported in the published literature and in recent patent fillings have been described in this review article
Chemical and biological versatility of pyrazolo[3,4-d]pyrimidines: one scaffold, multiple modes of action
No full textPyrazolo[3,4-d]pyrimidines are chemical compounds possessing remarkable versatility and significance in both biological and chemical contexts. These compounds are composed of specific arrangements of atoms, forming a unique ring structure, which is able to form bonds in a similar way as purines do. In the realm of chemistry, pyrazolo[3,4-d]pyrimidines showcase impressive flexibility due to their ability to easily react with various molecules, opening avenues for the creation of novel compounds with diverse properties for potential applications in medicinal chemistry. In a biological context, pyrazolo[3,4-d]pyrimidines play a crucial role due to their interaction with proteins such as enzymes. In fact, these compounds can impact various biological processes, including cancer cell proliferation, oxidative stress and inflammation. This has led to investigations into their potential as therapeutic agents: by designing pyrazolo[3,4-d]pyrimidines with specific biological targets in mind, new drugs can be developed for the effective treatment of a range of medical conditions. Finally, novel administration tools (e.g., nanomaterials and functionalized liposomes) are being studied as effective ways to overcome the main unwanted characteristics of pyrazolo[3,4-d]pyrimidines (scarce solubility and off-target side effects), thereby increasing their efficacy and specificity toward cell targets. In conclusion, pyrazolo[3,4-d]pyrimidines are fascinating molecules with a dual role in chemistry and biology. Their adaptability in chemical reactions makes them valuable building blocks for designing new compounds with diverse applications. Additionally, their interaction with biological molecules holds promise for the development of innovative medicines. Ongoing research into the properties and behaviors of these compounds could lead to significant advancements in both scientific fields
A(1) and A(3) adenosine receptor agonists: an overview
No full textA review with 51 refs. Adenosine regulates several physiol. functions through specific cell membrane receptors. On the basis of pharmacol. studies and mol. cloning, four distinct adenosine receptors have been identified and classified as A1, A2A, A2B and A3. These adenosine receptors are members of the G-protein coupled receptor family, but while A2A and A2B receptors stimulate adenylyl cyclase with a consequent increase of cAMP levels, A1 and A3 receptor subtypes produce the opposite effect. Intense efforts made over the last 20 yr have led to the synthesis of a variety of selective adenosine agonists. In general, all of the compds. thus far identified are related to the adenosine structure. The A1 receptors are usually found on the working cells of tissues (e.g., neurons and cardiomyocytes) and mediate decreases in oxygen demand; for these reasons A1 agonists could be useful for the treatment of, for example, renal failure, arrhythmias, diabetes Type II, myocardial ischemia and neurodegenerative disorders. The A3 receptor is not yet well known. This receptor subtype seems involved in inflammatory and neurodegenerative diseases, asthma and cardiac ischemia but some paradoxical effects have been obsd. On the basis, the recent developments on structure-activity relationships at A1 and A3 receptors and their possible use as therapeutic agents are reviewed, with particular emphasis on recent patent literature
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