Design, synthesis and evaluation of 1,3,6-trisubstituted-4-oxo-1,4-dihydroquinoline-2-carboxylic acid derivatives as ET A receptor selective antagonists using FRET assay

Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity

“…Scheme represents the synthesis of substituted benzaldehydes. For the synthesis of 4-phenyl or 4-thiazol-2-yl benzaldehydes 2 and 3 , reported Suzuki coupling conditions were utilized. , The [2 + 3] cycloaddition reaction of 4-cyanobenzaldehyde with sodium azide in the presence of triethylamine produced tetrazolyl derivative 4 . An alternate procedure (sodium azide/diethylamine hydrochloride/toluene) was used for conversion of 4-cyano-3-fluorobenzaldehyde and 4-cyano-2-methoxybenzaldehyde to corresponding tetrazolyl-substituted benzaldehydes 5 and 6 because the conditions used for the synthesis of 4 proved unsuccessful.…”

“…38,39 The [2 + 3] cycloaddition reaction of 4cyanobenzaldehyde with sodium azide in the presence of triethylamine produced tetrazolyl derivative 4. 40 An alternate procedure (sodium azide/diethylamine hydrochloride/toluene) 41 was used for conversion of 4-cyano-3-fluorobenzaldehyde and 4-cyano-2-methoxybenzaldehyde to corresponding tetrazolyl-substituted benzaldehydes 5 and 6 because the conditions used for the synthesis of 4 proved unsuccessful. N-Methyl derivative 7 was prepared from benzaldehyde 4 using iodomethane.…”

“…Intermediate 39 was synthesized by reaction of 4formylbenzoic acid (190 mg, 1.27 mmol) with 2-(5-fluoro-1Hbenzo[d]imidazol-2-yl)ethan-1-amine (249 mg, 1.39 mmol) using general procedure C, where the ethyl acetate extract was subjected to evaporation and the crude residue was washed further with ethyl acetate to obtain 39 as an off-white solid (271 mg, 69% yield); 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.44 (bs, 1H), 10.08 (s, 1H), 8.91 (d, J = 7.6 Hz, 1H), 8.06−7.97 (m, 4H), 7.57−7.39 (m, 1H), 7.30 (ddd, J = 36.5, 9.6, 2.6 Hz, 1H), 7.05−6.91 (m, 1H), 3.73 (q, J = 6.8 Hz, 2H), 3.10 (td, J = 7.3, 3.6 Hz, 2H). (40). Aldehyde 40 was synthesized by reaction of 3-formylbenzoic acid (212 mg, 1.41 mmol) with 2-(1H-benzo[d]imidazol-2-yl)ethan-1amine (250 mg, 1.55 mmol) using general procedure C, where the ethyl acetate extract was subjected to evaporation and the crude residue was washed further with ethyl acetate to obtain 40 as a brown solid (209 mg, 51% yield); 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.31 (bs, 1H), 10.08 (s, 1H), 8.95 (t, J = 5.6 Hz, 1H), 8.39 (t, J = 1.8 Hz, 1H), 8.16 (dt, J = 7.8, 1.5 Hz, 1H), 8.07 (dt, J = 7.7, 1.3 Hz, 1H), 7.71 (t, J = 7.7 Hz, 1H), 7.61−7.36 (m, 2H), 7.13 (dd, J = 6.2, 3.0 Hz, 2H), 3.75 (q, J = 6.8 Hz, 2H), 3.12 (t, J = 7.3 Hz, 2H).…”