Microwave assisted synthesis of 2-amino-6-methoxy-4H-benzo[h]chromene derivatives

A convenient and efficient method using microwave assisted synthesis of 4H-benzo[h]chromenes (7 and 8), by the reaction of 4-methoxy-1-naphthol (1) with a mixture of aromatic aldehydes (2) and malononitrile (3) or ethyl cyanoacetate (5) and also, by the reaction of 4-methoxy-1-naphthol (1) with α-cyanocinnamonitriles (4) or ethyl α-cyanocinnamates (6) in ethanolic piperidine solution was examined. Structures of the newly synthesized compounds were established on the basis of spectral data, IR, 1H NMR, 13C NMR, 13C NMR-DEPT and MS data

2-Amino-4-(4-bromophenyl)-6-methoxy-4H-benzo[h]chromene-3-carbonitrile

In the title compound, C21H15BrN2O2, the 14 non-H atoms of the 4H-benzo[h]chromene fused-ring system are approximately coplanar (r.m.s. deviation = 0.129 Å). Within this system, the 4H-pyran ring adopts a flattened half-chair conformation with the methine C atom lying 0.281 (4) Å above the plane of the remaining atoms (r.m.s. deviation = 0.0446 Å). The bromobenzene ring is almost perpendicular to the fused-ring system [dihedral angle = 85.34 (13)°]. In the crystal, supramolecular layers parallel to (101) are sustained by amine–cyano N—H...N and amine–methoxy N—H...O hydrogen bonds. The layers stack with interactions of the type (bromobenzene)C—H...π(outer-C6 ring of the fused-ring system) connecting them

N′-[3-Cyano-4-(4-fluorophenyl)-6-methoxy-4H-benzo[h]chromen-2-yl]-N,N-dimethylmethanimidamide

In the title compound, C24H20FN3O2, despite the 4H-pyran ring having a flattened half-chair conformation [the methine C atom lies 0.257 (3) Å above the plane of the remaining atoms with an r.m.s. deviation of 0.0295 Å], the 14 non-H atoms of the 4H-benzo[h]chromene residue are approximately coplanar (r.m.s. deviation = 0.081 Å). The benzene ring is nearly perpendicular to this plane [dihedral angle = 76.18 (10)°], but the planar (r.m.s. deviation = 0.033 Å) dimethylmethanimidamide substituent is coplanar [dihedral angle = 1.96 (12)°]. In the crystal, centrosymmetric dimeric aggregates arise from C—H...N interactions, and these are connected into supramolecular layers in the ab plane by C—H...π and π–π [intercentroid (central C6 ring)...(outer C6 ring)i distance = 3.8564 (14) Å] interactions

Design and Synthesis of Novel Heterocyclic-Based 4H-benzo[h]chromene Moieties: Targeting Antitumor Caspase 3/7 Activities and Cell Cycle Analysis

Novel fused chromenes (4,7–11) and pyrimidines (12–16) were designed, synthesized, and evaluated for their mammary gland breast cancer (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2) activities. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR, and mass spectroscopy. The preliminary results of the bioassay disclosed that some of the target compounds were proven to have a significant antiproliferative effect against the three cell lines, as compared to Doxorubicin, Vinblastine, and Colchicine, used as reference drugs. Particularly, compounds 7 and 14 exerted promising anticancer activity towards all cell lines and were chosen for further studies, such as cell cycle analysis, cell apoptosis, caspase 3/7 activity, DNA fragmentation, cell invasion, and migration. We found that these potent cytotoxic compounds induced cell cycle arrest at the S and G2/M phases, prompting apoptosis. Furthermore, these compounds significantly inhibit the invasion and migration of the different tested cancer cells. The structure-activity relationship (SAR) survey highlights that the antitumor activity of the desired compounds was affected by the hydrophobic or hydrophilic nature of the substituent at different positions