Synthesis and inverse virtual screening of new bi-cyclic structures towards cancer-relevant cellular targets

Structural Chemistry - We report here synthetic approaches to access new classes of small molecules based on three heterocyclic scaffolds, i.e. 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione,...     

New 3,6‐Disubstituted Pyrazolo[1,5‐a]quinazolines as Ligands to GABAA Receptor Subtype

A new series of 3,6‐disubstituted pyrazolo[1,5‐a]quinazolines (PQs) and their 4,5‐dihydro derivatives as isomer of the potent 3,8‐PQ previously reported by us as high affine GABA_A receptor subtype ligands, have been synthesized and evaluated. These new compounds have been obtained exploiting a different synthetic pathway with respect to the corresponding 3,8‐disubstituted isomers, proposing again the same groups present in the reference 3,8‐PQ. The movement of the substituents from position 8 to position 6 is detrimental for binding recognition, suggesting that the substituents at position 6 are not properly oriented to form adequate interaction with hydrogen bond point and lipophilic area in the receptor protein, as demonstrated in molecular modeling studies.     

Synthesis and structure of symmetrical bicyclic hexapeptides bridged by metathesis reaction

[structure: see text] Bicyclic hexapeptides 1a-c were synthesized via an intramolecular ring-closing metathesis reaction on solid phase followed by an N- to C-terminal cyclization in solution. Structural elucidation showed that these compounds assumed a C2-symmetrical structure with two beta-turns. The trans-ethylene plane was found to occupy two positions in rapid interconversion. One of the bicyclic hexapeptides crystallized with five water molecules, which made an arch above the ethylene group.     

High resolution GC of unsaponifiable matter and sterol fraction in vegetable oils

Summary The analysis of both the total unsaponifiable matter and the sterol fractions in vegetable oils has been performed with a new polar column (TAP, Chrompack). The use of a polar column, which is characterized by high thermal stability, has led to the identification of a greater number of constituents than the use of a nonpolar column (i.e. SE 52, SE 54). The polar column enhances the separation of the main classes of unsaponifiable matter (sterols, 4-methyl sterols and 4,4-dimethyl sterols). When used for the unsaponifiable and sterol fraction analyses, it offers a powerful tool for characterizing the lipid source.