Synthesis and Antiviral Activity of Some 1H-Pyrrolo[3,2-b]pyridin-6-yl)acetic Acid Derivatives

Abstract

Pyrrolopyridine derivatives for the treatment of HIV1-infection were synthesized by 10 step reactions. Methyl 2-(3-bromo-7-(4chlorophenyl)-1,5-dimethyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-2-(tert-butoxy)acetate converted efficiently into the corresponding 1Hpyrrolo[3,2-b]pyridin-6-yl)acetic acid derivatives by Suzuki coupling reaction. Present procedure provides short reaction times and good to excellent yields for a wide range of compounds, including pyrrolopyridine scaffolds. 7-Halogenated 1H-pyrrolo[3,2,b]pyridine acetic acid derivatives of final products showed good activity inthe HIV-1 IN inhibition test, while the other derivatives showed relatively low activity. gel (Merck, 60A pore size, 230-400 mesh). 1 H NMR spectra were recorded on a Bruker 300 MHz or 500 MHz spectrometer (Bruker Corporation Ltd., Germany) using CDCl3 or methanol-d4 as solvent with TMS as the internal standard. Chemical shift values are given in ppm. Both EI-MS spectra and high resolution mass spectra (HR-MS) were recorded on a JEOL JMS-700 double-focusing type mass spectrometer. LC-MS data were obtained on Waters Acquity UPLC H-Class/SQD2 system (ESI, 70 ev). Elementary analysis was performed on a Thermo Scientific FLASH EA-2000 organic elemental analyzer. Following products were obtained from various reactions:Ethyl 3-amino-1H-pyrrole-2-carboxylate (1): To a solution of isoxazole (30 g, 0.43 mol) in anhydrous ethanol (120 mL) was added drop-wise sodium ethoxide (21 %, in ethanol) (0.45 mol) at 0-5 °C. After stirring for 30 min, acetic acid (0.43 mol), diethyl amino malonate hydrochloride (0.30 mol), anhydrous sodium acetate (0.33 mol) were added. After stirring at room temperature for 18 h, the reaction mixture was concentrated under reduced pressure. The residue was diluted with chloroform (1.5 L) and water (500 mL), the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in anhydrous ethanol (450 mL), sodium ethoxide (21 %, in ethanol) (0.45 mol) was added drop-wise at 0-5 °C. The reaction mixture was warmed to room temperature slowly, stirred for 18 h, was quenched with acetic acid (0.45 mol) and basified with aq.

Pyrroles as Privileged Scaffolds in the Search for New Potential HIV Inhibitors

“…The docking analysis carried out with crystal structures of RT of HIV-1 and HIV-2 suggested that compound 38 was a potent HIV-1 NNRTI agent [83]. In an attempt to obtain active compounds in cells infected by HIV-1, Yonn et al [82] synthesized new scaffolds of pyrrolo-pyridine derivatives (Figure 16). The N-substituted pyrroles 35-37 (Figure 16) showed moderate activity against HIV-1 (EC50 values ranging from 5.02 to 5.07 µ M) when compared with the control drugs (AZT, EC50 0.0063 µ M; raltegravir, EC50 0.0063 µ M) (Table 3).…”