Tomàs Roca

Synthesis of 5-(sulfamoylmethyl)indoles

Abstract The synthesis of 5-(sulfamoylmethyl)indoles bearing a two-carbon chain at C-3 (aminoethyl, acetate, hydroxyethyl, ethyl) either by the Grandberg modification of the Fischer indolization or by intramolecular Heck reaction of suitable o -halotrifluoroacetanilides is reported.

Synthesis and biological evaluation of 1,3,4-triaryl-3-pyrrolin-2-ones, a new class of selective cyclooxygenase-2 inhibitors.

The synthesis and structure activity relationships (SAR) of a series of novel selective COX-2 inhibitors are reported. The results show that some of the 1,3,4-triaryl-3-pyrrolin-2-ones 1 are more potent as COX-2 inhibitors than celecoxib, and that lactam Id has the same selectivity.

Synthesis of 4-functionalized aryl-3,5-diacyl-1,4-dihydropyridines

Abstract The valuable N-unsubstituted 4-aryl-3,5-diacyl-1,4-dihydropyridines 12b–f , bearing an electron-withdrawing substituent at the benzene ring, have been synthesized by the copper-mediated addition of functionalized arylmagnesium reagents 2b–f to N-benzhydrylpyridinium salt 9 , followed by acylation with trichloroacetic anhydride and the subsequent haloform reaction and N-deprotection.

A synthetic entry to 3,5-disubstituted pyridines

Abstract A straightforward entry to 3,5-disubstituted pyridines from 3-substituted pyridines, based on the acylation of N -alkyl-1,4-dihydropyridine derivatives followed by a tandem N -dealkylation–oxidation sequence is reported.

Generation and reactions of 1-(2-indolyl)vinylcopper derivatives with pyridinium salts

Abstract 1-(2-Indolyl)vinylstannane 1b has been transmetallated into both the corresponding HO mixed cyanocuprate and the Cu-catalysed organomagnesium reagent, and the reactivity of these species towards N -alkyl-3-acylpyridinium salts 8 and 17 has been tested.

Synthesis of water-soluble phenytoin prodrugs

The synthesis of novel water-soluble phenytoin derivatives, bearing an ionizable group, and a preliminary study for in vitro blood hydrolysis are reported. The results show that hydrolysis of amino esters 8 is very fast, much more than that of fosphenytoin.

Synthesis and dopaminergic activity of heterocyclic analogues of 5,6-dihydroxy-2-aminotetralins.

The heterocyclic analogues of 5,6-dihydroxy-2-aminotetralins (6) were synthesized and their in vitro dopaminergic activity was compared to that of (-)-DP-5,6-ADTN and the novel potent agonist Z12571. The results show that changing the cathecol ring for a heterocycle decreases the D1-like activity of the target molecules 6. However, the D2-like activity of tetrahydroquinoline (6j) was comparable to that of (-)-DP-5,6-ADTN.

Chapter 1: 2-Indolylacyl radicals in the synthesis of indole compounds

Publisher Summary The indole nucleus is a common substructure of many biologically active compounds and occupies an important position in medicinally relevant heterocyclic systems. This chapter discusses the development of a novel general synthetic entry to indole compounds with the help of 2-indolylacyl radical reactions. 2–Indolylacyl radicals are extremely useful reactive intermediates that participate in intermolecular and intramolecular reactions with alkenes and (hetero)aromatic systems. This radical methodology gives easy access to a wide range of indolic structures, including simple indolyl ketones as well as more complex polycyclic compounds embodying the 2-acylindole moiety. The chapter also discusses the intramolecular reactions with either alkenes or aromatic and heteroaromatic systems, leading to polycyclic structures present in bioactive natural products. Radical reactions are powerful carbon–carbon bond forming processes routinely used as key steps in the synthesis of complex natural products. In particular, functionalized acyl radicals offer a useful means to introduce carbonyl functionality into an organic molecule.

Molecular modeling of (E)-1-alkyl-4(3)-[2-(1H-azolyl)vinyl]-pyridinium salts and evaluation of their behavior towards choline acetyltransferase

A new type of extended pi-system aza-analogue of (E)-4-[2-(1-naphthylvinyl)]-1-substituted pyridinium salts (NVP+) has been designed and its inhibitory activity towards choline acetyltransferase (ChAT) has been evaluated in vitro. Among the several examples of the title quaternary salts synthesized 2 and 3, the indolylvinylpyridinium salt 2e is the only one to show a very low ChAT inhibition. The molecular modeling study is highly illustrative of their behavior towards ChAT and interaction with the recognition site. Thus, several selected cations together with the reference NVP+ compound 1a were studied at the PM3 and AM1 levels respectively. At the global minima, all the compounds are planar, which, from the electron charge distribution, shows a degree of polarization similar to the NVP+ model compound 1a. However, the fitting of all optimized structures indicated that only the indole derivative 2e showed the same aromatic fragment orientation as 1a, which allows us to define a volume that is not accessible to ligands in the enzyme and consequently to a refined model of the choline acetyltransferase recognition site.