A novel method for heteroaromatic N-imines

Tamura, Yasumitsu; Minamikawa, Jun‐ichi; Miki, Yoshio; Matsugashita, Saeko; Ikeda, Masazumi

doi:10.1016/s0040-4039(01)94256-x

Cited by 73 publications

(32 citation statements)

References 12 publications

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“…Synthesis of THIQs has been previously described (16–18) for GM-3-121, with additional information on the synthesis for GM-4-53 as follows General procedure for the synthesis of 2-amino-7-hydroxyisoquinolinium 2,4,6-trimethylbenzenesulfonate: O-mesitylene sulfonyl hydroxylamine (MSH) (3) was used to prepare the N -amino salt as an aminating agent as described (19). An ice cooled solution of 7-hydroxyisoquinoline (2.0 g, 13.78 mmol) in 30 ml of dry methylene chloride, and 15 ml of dry methanol was added drop wise to O -mesitylenesulfonylhydroxylamine (2.97 g, 13.78 mmol) in 10 ml of dry methylene chloride over 5 min with stirring.…”

Section: Methodsmentioning

confidence: 99%

Substituted Tetrahydroisoquinolines as Microtubule-destabilizing Agents in Triple Νegative Human Breast Cancer Cells

Gangapuram

Jean

Mazzio

et al. 2016

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Triple-negative breast cancer (TNBC) occurs in greater frequency amongst African-Americans, and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal receptor 2 (HER2). TNBC is often invasive and typically treated with cytostatic agents such as taxanes in combination with anthracyclines or platinum-based drugs. In this study, we synthesized a number of tetrahydroisoquinoline moieties by N-amination of substituted isoquinolines by O-mesytelene sulfonylhydroxylamine followed by ylide formation and reduction, which yielded the desired, substituted tetrahydroisoquinolines (THIQs) in moderate to good yield. Using a differential scatter plot to identify potential selective ER-modulating drugs in ER-positive control cells (MCF-7) driven by estradiol vs. TNBC (MDA-MB-231) cells, the in vitro data showed an absence of effects on the ER (compared to 4-hydroxy-tamoxifen and raloxifene). In contrast, two lead compounds halted proliferation (cytostatic) in MDA-MB-231 TNBC cells at a potency level below 2.5 µM concomitant with mitotic arrest, attenuated replicative DNA synthesis, halted microtubule nucleation/stunted tubulin polymerization, abnormal expansive cytoskeletal tubulin and actin morphologies with multinucleation of cells. The most effective cytostatic compounds GM-4-53 and GM-3-121 blocked replicative processes at the G2 growth phase. These findings suggest that specific THIQs work independently of the ER, by holding static the microtubule network thereby preventing mitosis. Future work will be required to establish the safety and efficacy of these drugs and their potential adjunct therapeutic gain in the presence of taxanes in TNBC.

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Section: Methodsmentioning

confidence: 99%

Substituted Tetrahydroisoquinolines as Microtubule-destabilizing Agents in Triple Νegative Human Breast Cancer Cells

Gangapuram

Jean

Mazzio

et al. 2016

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“…Salts VIIIa-VIIIc, VIIIe-VIIIi, IX-XII, and XIV were reported previously [21][22][23][24][25][26][27][28][29][30][31]. The structure of salts VIIId, VIIIj, and XIII was confirmed by comparing their 1 H and 13 C NMR spectra with those of structurally related compounds [13,[21][22][23][24]. The relative reactivity of nitrogen-containing heterocycles I-VII was estimated by the competitive reactions method, which was successfully used previously while studying quaternization of nitrogen-containing heterocycles [32].…”

Section: Methodsmentioning

confidence: 99%

Structure-kinetics relations holding in the amination of six-membered nitrogen-containing heterocyclic compounds

2011

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Relative rates of the amination of 3-X-and 4-X-substituted pyridines (X = H, 3-Me, 4-Me, 3-F 3 C, 3-CN, 4-CN, 3-Cl, 3-Br, 4-MeO, 4-Me 2 N), pyrazine, quinoline, isoquinoline, 2,2′-and 4,4′-bipyridines, and 1,10-phenanthroline with O-mesitylenesulfonylhydroxylamine were estimated by NMR spectroscopy. Correlations were found between logarithms of the relative amination rate constants and substituent constants σ or σ I and σ R for X-substituted pyridines. A wide series of nitrogen-containing heterocyclic compounds turned out to fit correlations between logarithms of the relative amination rate constants, on the one hand, and relative stabilities of N-aminoazinium cations, energies of activation of the amination process, and gas-phase proton affinities, calculated by the DFT/PBE/3z and DFT/B3LYP/L2 methods, on the other.

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“…The product was recrystallized form ethyl acetate to afford 1. (12) were synthesized by the method described earlier by Tamura et al [26]. To an ice-cold solution of (12) (5.0 g, 12.71 mmoles) in anhydrous tetrahydrofuran (80 ml) was added 3,4,5-trimethoxy benzenesulfonyl chloride (13a) (5.86 g, 25.42 mmoles) drop wise.…”

Section: Methodsmentioning

confidence: 99%

“…In Scheme 2, O-mesitylene sulfonyl hydroxylamine (MSH) (11) was used to prepare the Namino salt as an aminating agent [26]. Mesitelene sulfonly chloride (9) was added with stirring to a solution of ethylacetohydroxymate (8) and triethylamine in dimethylformamide at 0 °C.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydropyridine‐5‐carboxylic acid diethylamides as potential anti‐inflammatory agents

Gangapuram

Redda

2006

Journal of Heterocyclic Chem

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A novel method for heteroaromatic N-imines

Cited by 73 publications

References 12 publications

Substituted Tetrahydroisoquinolines as Microtubule-destabilizing Agents in Triple Νegative Human Breast Cancer Cells

Substituted Tetrahydroisoquinolines as Microtubule-destabilizing Agents in Triple Νegative Human Breast Cancer Cells

Structure-kinetics relations holding in the amination of six-membered nitrogen-containing heterocyclic compounds

Synthesis of 1‐(substituted phenylcarbonyl/sulfonylamino)‐1,2,3,6‐tetrahydropyridine‐5‐carboxylic acid diethylamides as potential anti‐inflammatory agents

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