Pharmacophore modeling, 3D-QSAR, synthesis, and anti-lung cancer evaluation of novel thieno[2,3-d][1,2,3]triazines targeting EGFR was written by Elrayess, Ranza;Abdel Aziz, Yasmine M.;Elgawish, Mohamed S.;Elewa, Marwa;Elshihawy, Hosam A.;Said, Mohamed M.. And the article was included in Archiv der Pharmazie (Weinheim, Germany) in 2020.Safety of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile This article mentions the following:
Two series of thieno[2,3-d][1,2,3]triazine derivatives were designed, synthesized, and biol. evaluated as potential epidermal growth factor receptor (EGFR) inhibitors targeting the non-small-cell lung cancer cell line H1299. Most of the synthesized compounds displayed IC50 values ranging from 25 to 58 nM against H1299, which are superior to that of gefitinib (40μM). 3-(5,6,7,8-Tetrahydro-7H-cyclohexa[4:5]thieno[2,3-d]-1,2,3-triazin-4-ylamino)benzene-1,3-diamine (6b) achieved the highest cytotoxic activity against H1299 with an IC50 value of 25 nM; it had the ability to decrease the EGFR concentration in H1299 cells from 7.22 to 2.67 pg/mL. In vitro, the IC50 value of compound 6b was 0.33 nM against EGFR, which is superior to that of gefitinib at 1.9 nM and erlotinib at 4 nM. The three-dimensional quant. structure-activity relationships and mol. modeling studies revealed comparable binding modes of compound 6b, gefitinib, and erlotinib in the EGFR active site. The in silico ADME (absorption, distribution, metabolism, and excretion) prediction parameters of this compound revealed promising pharmacokinetic and physicochem. properties. Moreover, DFT (d. functional theory) calculations showed the high reactivity of compound 6b toward the EGFR compared with other compounds The designed compound 6b might serve as an encouraging lead compound for the discovery of promising anti-lung cancer agents targeting EGFR. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Safety of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile).
2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2) belongs to nitriles. Trimerization of aromatic nitriles requires harsh reaction conditions, high temperatures, long reaction times, and pressure. Nitriles are susceptible to hydrogenation over diverse metal catalysts. The reaction can afford either the primary amine (RCH2NH2) or the tertiary amine ((RCH2)3N), depending on conditions.Safety of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts