Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors

Synthesis and antiviral activity of 4-(7,7-dimethyl-4-[4-{N-aroyl/benzyl}1-piperazinyl]-5,6,7,8-tetrahydroquinazolin-2-yl)morpholine derivatives

“…Similarly Nbenzyl-substituted piperizine 3a-f derivatives of 1 were synthesized via reductive amination of 1 by respective aryl aldehydes using sodium triacetoxyborohydride (STAB). The structures of these compounds 2a-g and 3a-f were confirmed by 1 H and 13 C NMR and LCMS spectra. The results provided in the Table 1 indicated that the test compounds 2a and 2c-g showed antiviral activity by inhibiting the plaque formation by 22, 6, 25, 12, 28 and 17%, respectively at the minimum test dose when compared to infected untreated controls, while the compounds 2b and 3a-f did not show any antiviral activity at the tested concentrations.…”

“…Melting points were determined using a melting point apparatus (B-540 Buchi, Germany) without corrections. All 1 H and 13 C NMR spectra were recorded on a Bruker 300 or 400 MHz instrument. Molecular masses of unknown compounds were checked by LCMS 6200 series Agilent Technology instrument.…”

“…Organic layer was washed with 10% of citric acid solution followed by brine solution. Organic layer was concentrated under reduce pressure and purified using column chromatography using ethyl acetate-hexanes to afford pure compounds 2a-g. 4-{7,7-Dimethyl-2-morpholino-5,6,7,8-tetrahydroquinazolin-4-yl}piperazin-1-yl) (4-{7,7-Dimethyl-2-morpholino-5,6,7,8-tetrahydroquinazolin-4-yl}piperazin-1-yl) 4-{7,7-Dimethyl-2-morpholino-5,6,7,8-tetrahydroquinazolin-4-yl}piperazin-1-yl)[1H-imidazol-1 63 (s, 4H), 3.72-3.75 (m, 8H), 6.39 (bs, NH), 7-7.39 (m,5H); 13 C NMR (75 MHz, DMSOd6) δ: 22.2, 28.4, 29.3, 44.4, 46.0, 46.5, 47.6, 66.5, 106.3, 119.1, 129.3, 137.6, 150.8, 159.4, 165.3 To the resultant mixture, sodium triacetoxy borohydride (0.0025 mol) was added in several lots and contents were stirred for 4 h to go for completion. After reaction completion by TLC, reaction was quenched with 10% sodium bicarbonate solution and product was extracted using ethyl acetate.…”

Design, Synthesis, and Biological Evaluation of Novel PARP-1 Inhibitors Based on a 1H-Thieno[3,4-d] Imidazole-4-Carboxamide Scaffold

“…According to previous literatures [23,24], despite the large variety in chemical structures of current PARP-1 inhibitors, the common structural features are aromatic ring and carboxamide moiety, which are responsible for the formation of hydrogen bonds and pi-stacking interaction with PARP-1, respectively. On this basis, we have previously reported a series of potent phthalazinone-containing PARP-1 inhibitors with fairly good potency [25], such as XM-17 ( Figure 1). In this study, we report a series of compounds containing a novel thieno-imidazole scaffold that can form a six-membered 'pseudo-cycle' through an intramolecular hydrogen bond ( Figure 2).…”

A New Approach in Cancer Treatment: Poly(ADP-Ribose) Polymerase-1 Inhibitors

“…Aşağıda formülü gözlenen bileşiğin, R gruplarına bağlı olarak aktiviteleri için bulunan IC50 değerleri Tablo 5'de verilmiştir (31).…”