Baclofen (beta-p-chlorophenyl-GABA) is the only selective agonist for the bicuculline-insensitive GABAB receptor. We report the synthesis of new GABA analogues and baclofen analogues. In vitro, two compounds, 4-amino-3-benzo[b]furan-2-ylbutanoic acid (9g) and 4-amino-3-(5-methoxybenzo[b]furan-2-yl)butanoic acid (9h), showed an affinity for the GABAB receptor. The results obtained with racemic compounds of benzofuran structure, new for this series, and the surprising inactivity of compound 3a (4-amino-3-(4-hydroxyphenyl)butanoic acid) permit the proposal of an hypothesis for the structure-activity relationships with regard to GABAB receptor.

Reaction of the phenol (I) with the chlorides (II) and subsequent basic ring cleavage yield the amino acids (III).

Abstract-Cyclin-dependent kinases (CDKs) are regulatory protein kinases which involved in cell cycle control. Many CDK inhibitors have been studied for anticancer potential. Here we conducteda docking studyof 4-(pyrazol-4-yl)-pyrimidine derivatives as CDK1/2 and CDK4/6 inhibitors. Selectivity is an important aspect regarding the anticancer effect. In this computational research, we analyzed the interactionof 4-(pyrazol-4-yl)-pyrimidine derivatives with their receptors, CDK4/6 and CDK2. We compared the docking result of the parent compound, the most selective, and the least selective compound. Docking of the three compounds wasperformed using software Arguslab CDK 4.0.1 to assess the interaction withthereceptors.Three docking parameters were analyzed; Gibbs free energy(∆G), atoms and residue of receptor involved in hydrogen bonding, and the bonding length. All three compounds had value of ΔG <0, indicated that the interaction between the ligand and receptor was spontaneous. However, none of these parameters and descriptors values could explain the selectivity order of the three compounds.Index Terms-Anticancer, CDK inhibitor, computational chemistry, docking, pyrazolo pyrimidine derivatives.

Andrographolide is a bicyclic diterpenoid constituent of Andrographis paniculata which is used extensively in the traditional medicine in Indonesia to treat inflammations. The structure of andrographolide contains an a-alkylidene r-butyrolactone moiety, two olefin bonds at C-8(C-17) and C-12(C-13), and three hydroxyls at C-3, C-19 and C-14. Andrographolide's structure lacks of aromatic ring, hence the iodination reaction of this compound is quite an interesting challenge to be investigated. Iodine atom was incorporated at vinyl position by indirect reaction. The reaction was divided into two steps, which was started by a bromination in non polar medium, then followed by iodination. It is shown that the principal reaction is the addition of bromine atom to an sp2 carbon atom of the vinyl group via electrophilic substitution. Bromination was carried out in chloroform solvent at room temperature to produce bromo-andrographolide. The iodination was applied further by using palladium triphenylphosphine catalyst. Positive charge iodine species was produced in situ with the addition of chloramine-T, an oxidizing agent, at 40 oC. 1H-NMR study shows that iodine attacked the C-12(C-13) vinyl bond which was confirmed by (1) the disappearance of proton chemical shift of C-12 at SH 6.86 ppm and (2) the change of proton chemical shifts of C-11 which shifted downfield at SH 2.74 ppm and 2.63 ppm, due to the deshielding effect of iodine.