Synthesis, crystal structure and docking studies of tetracyclic 10-iodo-1,2-dihydroisoquinolino[2,1-b][1,2,4]benzothiadiazine 12,12-dioxide and its precursors

Abstract

The title compound, 10-iodo-1,2-dihydroisoquinolino[2,1-b][1,2,4]benzothiadiazine 12,12-dioxide, C15H11IN2O2S (8), was synthesized via the metal-free intramolecular N-iodosuccinimide (NIS)-mediated radical oxidative sp 3-C—H aminative cyclization of 2-(2′-aminobenzenesulfonyl)-1,3,4-trihydroisoquinoline, C15H16N2O2S (7). The amino adduct 7 was prepared via a two-step reaction, starting from the condensation of 2-nitrobenzenesulfonyl chloride (4) with 1,2,3,4-tetrahydroisoquinoline (5), to afford 2-(2′-nitrobenzenesulfonyl)-1,3,4-trihydroisoquinoline, C15H14N2O4S (6), in 82% yield. The catalytic hydrogenation of 6 with hydrogen gas, in the presence of 10% palladium-on-charcoal catalyst, furnished 7. Products 6–8 were characterized by their melting points, IR and NMR (1H and 13C) spectroscopy, and single-crystal X-ray diffraction. The three compounds crystallized in the monoclinic space group, with 7 exhibiting classical intramolecular hydrogen bonds of 2.16 and 2.26 Å. All three crystal structures exhibit centrosymmetric pairs of intermolecular C—H...π(ring) and/or π–π stacking interactions. The docking studies of molecules 6, 7 and 8 with deoxyribonucleic acid (PDB id: 1ZEW) revealed minor-groove binding behaviours without intercalation, with 7 presenting the most favourable global energy of the three molecules. Nonetheless, molecule 8 interacted strongly with the DNA macromolecule, with an attractive van der Waals energy of −15.53 kcal mol−1.

Synthesis and molecular docking studies of novel tricyclic and angular tetracyclic benzothiadiazines via sp3‐C‐Hactivation as potential colon cancer inhibitors

“…Their crystal structures were determined by singlecrystal X-ray diffraction (SC-XRD). The data from the spectroscopic and X-ray diffraction analyses are in agreement with and confirmed the assigned chemical structures of the compounds that have not been previously assigned shown in Figure 3A, while Figure 3B has been previously assigned [29].…”

“…FT-IR, MS, 1 H-and 13 C-NMR spectra of the synthesized compounds (18)(19)(20)(21)(22) are presented in the Data S1. 5.2.7 | Synthesis of N-cycloamino-4-substituted-2-sulfanilamides (27)(28)(29)(30)(31) An evacuated, nitrogen gas-filled round-bottomed flask was charged with N-cycloamino-o-nitrobenzenesulfonamides (18-22) (15.63 mmol) dissolved in ethanol (30 mL) at ambient temperature, and 10% palladium-on-charcoal catalyst (3.35 mol%) was added with stirring. Hydrogen gas was then introduced via a balloon, and stirring continued at ambient temperature for 12 h. The reaction mixture was filtered, and the solvent was evaporated in vacuo.…”

“…S C H E M E 1 Synthesis of N-cycloamino-4-substituted-2-nitrobenzenesulfonamides (14)(15)(16)(17)(18)(19)(20)(21)(22) and their sulfanilamide analogs (23)(24)(25)(26)(27)(28)(29)(30)(31).…”

“…The synthesis of the tricyclic and angular tetracyclic benzothiadiazines started with the formation of nitro sulfonamides under basic conditions as previously reported by us [14, 29] and amino sulfonamide under reduction with palladium/charcoal in good to high yield [30] Scheme 1. The result of the reduction of the nitro adduct is as shown in Table 1, five of the amides are reported for the first time (entry 5 to 9).…”

“…SCXRD of 10‐iodo‐1,2‐dihydrobenzo[ e ]isoquinolino[1,2‐ b ][1,2,4]thiadiazine 12,12‐dioxide 34 (crystal 34 has been published in Kolade et al) [29]. …”