Carbazole and carboline derivatives, and preparation and therapeutic applications thereof
A compound and alkylene technology, applied in the prevention or treatment of various proliferative diseases and disorders, prevention or treatment of proliferative diseases such as cancer, β-carboline derivatives, can solve problems such as toxicity, side effects, and danger
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[0258] The present invention is described in more detail by referring to the following examples.
[0259] compound synthesis
[0260]
[0261] Option I
[0262] Compounds according to the invention are abbreviated "E" and comparative compounds are abbreviated "C" in the tables.
[0263] The structures of the compounds according to the present invention (E1-E60) and the structures of the comparative compounds (C1-C14) are shown in Table 1. Compounds (E1-E60) according to the invention were prepared by analogous methods using appropriate starting materials as shown in Scheme I.
[0264] Table 1.
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[0267]
[0268]
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[0270]
[0271]
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[0274]
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[0277] It will be appreciated by those skilled in the art that the above synthetic schemes are for illustrative purposes only and can be modified using conventional synthetic methods to produce any compound of general formula (I). Depen...
Embodiment E1
[0288] Example E1: 6-Phenyl-1-methyl-9H-pyrido[3,4-b]indole
[0289] Phenylboronic acid (0.459mmol; 56mg), 6-bromo-1-methyl-9H-pyrido[3,4-b]indole (0.383mmol; 100mg), K 2 CO 3 (0.766mmol; 106mg) and tetrakis(triphenylphosphine)palladium (0.00191mmol; 22mg) were placed in vials. A degassed solvent mixture of dioxane:water (3:1; 2 mL) was added. After heating the sealed vial (10 min; 150°C), the reaction mixture was filtered through celite and evaporated to dryness. The crude product was purified first by flash chromatography on silica gel eluting with n-hexane / acetone, then by adsorption on a strong cation exchange column eluting with methanol / aqueous ammonia (20%). A final purification step was performed using preparative reverse phase HPLC with a gradient from 0.1% ammonia / acetonitrile (50:50) to 0.1% ammonia / acetonitrile (5:95) to yield 12 mg of El.
Embodiment E2
[0290] Example E2: 6-(3-Chlorophenyl)-1-methyl-9H-pyrido[3,4-b]indole
[0291] 3-Chlorophenylboronic acid (0.459mmol; 71.8mg), 6-bromo-1-methyl-9H-pyrido[3,4-b]indole (0.383mmol; 100mg), K 2 CO 3 (0.766mmol; 106mg) and tetrakis(triphenylphosphine)palladium (0.00191mmol; 22mg) were placed in vials. A degassed solvent mixture of dioxane:water (3:1; 2 mL) was added. After heating the sealed vial (10 min; 120 °C), the reaction mixture was filtered through celite and the filtrate was absorbed onto a cation exchange column (SCX), which was then washed with methanol and eluted with methanol / ammonia (20%) . A final purification step was performed using preparative reverse phase HPLC with a gradient from 0.1% ammonia / acetonitrile (50:50) to 0.1% ammonia / acetonitrile (5:95) to afford 23.6 mg of E2.
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