Selective non-nucleoside HIV-1 reverse transcriptase inhibitors. New 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds with anti-HIV-1 activity

Abstract

A series of substituted 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds 1-73 were synthesized and evaluated for their ability to inhibit reverse transcriptase (RT) of the human immune deficiency virus 1 (HIV-1) and replication of HIV-1 in MT2 cells. The antiviral activity of these compounds depends on the stereoselective configuration of the substituent in position 9b. Structure-activity studies were done within these series of compounds to determine the optimum substituents for antiviral activity. The most potent inhibitors were found in the class of 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones bearing a phenyl ring system in position 9b optionally substituted with one or two methyl groups or a chlorine atom in position 8. The most active analogues (R)-(+)-1, (R)-(+)-6, (R)-(+)-13, (R)-(+)-26, and (R)-(+)-53 inhibit the HIV-1 RT with an IC50 between 16 and 300 nM and an IC50 between 10 and 392 nM in MT2 cells, respectively.

Social deprivation and outcomes in colorectal cancer

“…This further reaction is clearly due to a tandem process involving Michael addition followed by a cyclization at the amide group. It is worth noting that a similar tricyclic subunit is present in a non‐nucleoside HIV‐1 reverse transcriptase inhibitor3c and can be considered to be an analogue of indolizidine compounds 2g…”

Advanced Methods for the Synthesis of 3-Substituted 1H-Isoindol-1-Ones

“…For the preparation of tetrahydro-5Hpyrrolo-and tetrahydropyrido[2,1-a]isoindol-5-ones 4, lactam 3 was reacted with dihaloalkanes, which resulted in slight yields [12] (Scheme 2). The antiviral activity depends on the configuration of the aryl-or heteroarylsubstituted carbon.…”

“…A great number of compounds with isoindole skeletons have noteworthy pharmacological effects such as antiarrhythmic, antitussive [7], anti-inflammatory, diuretic [8], anxiolytic (non-benzodiazepine type of GABA A /BDZ receptor agonists) [9], anorexic [10,11] and HIV-inhibitory activity [12]. A series of new arylpiperazine derivatives of isoindol-1-ones have been synthetized and tested as 5HT 1A receptor ligands; they display high binding *Address correspondence to this author at the Institute of Pharmaceutical Chemistry, University of Szeged, H-6701 Szeged, POB 121, Hungary; Tel: (36 62) 545563; Fax: (36 62) 545705; E-mail: stajer@pharm.u-szeged.hu affinity in vitro.…”

<strong>Synthesis of 6-triazolylmethyl-pyrrolo[3,4-<em>b</em>]pyridin-5-ones by an efficient MW-assisted (Ugi-3CR / aza Diels-Alder) / Click process</strong>

“…Tetrahydroisoindolo[1,2-a]isoquinoline-amides are tetracyclic lactams with occurrence in nature, for example the (±)-nuevamine, 1 which is an alkaloid isolated from Berberis Darwinii Hook (Figure 1). We reported two methodologies for synthesizing series of novel pyrrolo [3,4-b]pyridine-5-ones using Ugi reactions combined with further condensation processes.…”