Cyclodextrins as pharmaceutical solubilizers.

5-Substituted-1H-tetrazoles as carboxylic acid isosteres: medicinal chemistry and synthetic methods

This work was supported by the Foundation for Science and Technology (FCT), Portugal (projects PTDC/QUI-QUI/113687/2009 and PEst-C/QUI/UI0081/2013). A.G. (SFRH/BD/43531/2008) and M.J.M. (SFRH/BD/61262/2009) thank FCT for grants.

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Chromone: A Valid Scaffold in Medicinal Chemistry

The present invention relates to an electronic device comprising anode, cathode and at least one organic layer which comprises a compound of the formula (I) to (IV). The invention furthermore encompasses the use of compounds of the formula (I) to (IV) in an electronic device and to a compound of the formula (Ic) to (IVc).

Materials for electronic devices

Proliferation of human skin fibroblasts was stimulated significantly by the presence of L-ascorbic acid 2-phosphate (Asc 2-P). The presence of Asc 2-P (0.1-1.0 mM) in the culture medium for 3 weeks enhanced the relative rate of collagen synthesis to total protein synthesis 2-fold as well as cell growth 4-fold. Coexistence of L-azetidine 2-carboxylic acid (AzC), an inhibitor of collagen synthesis, attenuated both effects of Asc 2-P in a dose-dependent manner. Supplementation of the medium with Asc 2-P also accelerated procollagen processing to collagen and deposition of collagen in the cell layer. Among the acidic glycosaminoglycans (GAG), another major component of extracellular matrix (ECM), deposition of sulfated forms was increased by the additive. Electron microscopic observations showed multilayered, rough endoplasmic reticulum-rich cells surrounded by dense ECM. These results indicate that Asc 2-P is useful in culture systems as a long-acting vitamin C derivative and also that it promotes reorganization of a three-dimensional tissuelike substance from skin fibroblasts in culture by stimulating collagen accumulation in the fibroblasts.

L-ascorbic acid 2-phosphate stimulates collagen accumulation, cell proliferation, and formation of a three-dimensional tissuelike substance by skin fibroblasts

5-Oxo-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylic acids 23 and their tetrazole analogues 24 were synthesized from 4-oxo-4H-1-benzopyran-3-carbonitriles 3 or 2-amino-4-oxo-4H-1-benzopyran-3-carboxaldehydes 4. When administered intravenously, they exhibited antiallergic activity in a reaginic PCA test in rats. In the carboxylic acid series, the activity was influenced by the substituents at the 2-position and increased substantially in the following order: Me, OMe less than NH2 less than OH, H less than NHOMe. On the other hand, in the tetrazole series, 2-unsubstituted derivatives showed the highest activity. Regardless of the kinds of substituents at positions 2 and 3, compounds bearing an alkyl group, especially an isopropyl group at the 7-position, were superior in activity to the corresponding unsubstituted compounds. Among these alkyl derivatives, 3-carboxylic acid derivatives, i.e., 23c (7-ethyl), 23g (2-amino-7-isopropyl), 23r [2-(methoxyamino)-7-isopropyl], and a 3-tetrazole derivative 24c (7-isopropyl), were 41-184 times as potent as disodium cromoglycate. They also exhibited remarkable activity when administered orally; clinical studies on 23g (AA-673) are in progress.

Studies on antianaphylactic agents. 7. Synthesis of antiallergic 5-oxo-5H-[1]benzopyrano[2,3-b]pyridines.

The metabolites and degradation products of 2-amino-7-isopropyl-5-oxo-5H-[1] benzopyrano-[2, 3-b] pyridine-3-carboxylic acid (Amoxanox, AA-673, 1), a promising drug for the treatment of bronchial asthma, were synthesized to confirm the proposed structures and to determine their activity in the rat passive cutaneous anaphylaxis test.

Synthesis of the Metabolites and Degradation Products of 2-Amino-7-isopropyl-5-oxo-5H-[1] benzopyrano [2, 3-b] pyridine-3-carboxylic Acid (Amoxanox)

Phosphorylation of 5, 6-isopropylidene-L-ascorbic acid (I) in acetone with phosphoryl chloride gave, in addition to L-ascorbic acid 3-phosphate (II) and 3-pyrophosphate (III), the following two derivatives, i.e., bis (L-ascorbic acid-3, 3') phosphate (IV) and L-ascorbic acid 2-phosphate (V). The structure of these phosphates was determined on the basis of elemental analysis, potentiometric titration, NMR-analysis, supplemented by studies of the hydrolysis. IV was hydrolyzed by acid and alkali most readily among the four isomers. By being passed through a column of Dowex-1-chloride with 1N hydrochloric acid, this compound quantitatively afforded equimolar amount of II and L-ascorbic acid. On the other hand, during the hydrolysis of V in 0.5N hydrochloric acid at 100°, the phosphoryl migration to II was ob served. On the alkali treatment, V was shown to be stable and no migration was detected.

Studies on L-ascorbic acid derivatives. III. Bis(L-ascorbic acid-3,3^+')phosphate and L-ascorbic acid 2-phosphate

6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-cyclodextrin: solubilizing ability and some cellular effects

A composition is disclosed comprising a water-insoluble or slightly water-soluble compound and a branched cyclodextrin-carboxylic acid. The branched cyclodextrin-carboxylic acid significantly increases the water-solubility of the compound. Also disclosed is a method of enhancing water-solubility of the compound.

Toshihiro Ishiguro

Papers

Studies on antianaphylactic agents. 7. Synthesis of antiallergic 5-oxo-5H-[1]benzopyrano[2,3-b]pyridines.

Synthesis of the Metabolites and Degradation Products of 2-Amino-7-isopropyl-5-oxo-5H-[1] benzopyrano [2, 3-b] pyridine-3-carboxylic Acid (Amoxanox)

Studies on L-ascorbic acid derivatives. III. Bis(L-ascorbic acid-3,3^+')phosphate and L-ascorbic acid 2-phosphate

6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-cyclodextrin: solubilizing ability and some cellular effects

Composition containing a water-insoluble or slightly water-soluble compound with enhanced water-solubility