Camptothecine derivatives and their use
A technology of camptothecin and derivatives, which is applied in the field of new anti-tumor drug compounds, and can solve the problems of anti-tumor activity and low toxicity.
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Embodiment 1
[0142] Example 1: Preparation of N-(3-aminopropyl) morpholine to the ammonolysis ring-opening product (1) XY-8 of CPT
[0143] 105 mg (0.3 mmol) of CPT was dissolved in 15 ml of methanol, and 1.2 equivalents of ammonolysis reagent N-(3-aminopropyl) morpholine (3) a was added. After reacting for 14 hours at 75° C., the system became clear, and the reaction mixture was Poured into diethyl ether, a yellow precipitate was precipitated, which was filtered off and washed with cold diethyl ether. It can be seen from TLC that the product contains unreacted CPT. Dissolve the product in a small amount of CHCl 3 , separated by alumina column chromatography (eluent: ethyl acetate:petroleum ether=1:1→4:1) to obtain 106 mg of pure ring-opened product (1) XY-8, yield 88%.
[0144] IR(KBr)ν: 1620.61cm -1 (-CONH-).
[0145] 1 HNMR (CDCl 3 , 300MHz) δppm: 1.07 (t, J=7.20Hz, 3H, 18-CH 3 ), 1.76 (m, 2H, 19-CH 2 ), 2.25(m, 1H, 22-CH 2 ), 2.43 (m, 1H, 22-CH 2 ), 2.44(m, 6H, 22-CH 2 , and 2...
Embodiment 2
[0146] Example 2, the preparation of the 17-hydroxyacetylation product (1) Bam of the ammonia solution ring-opening product of CPT (1) XY-8
[0147] 126 mg of N-(3-aminopropyl) morpholine CPT ring-opened product (1) XY-8 (0.25 mmol) was dissolved in 2 mL (24.8 mmol) of pyridine, 1 mL (10.6 mmol) of acetic anhydride was added, and the temperature was maintained by heating Stir overnight at around 40°C. The solvent was evaporated under reduced pressure. The residue was washed with a small amount of CHCl 3 Dissolve, pour into 20mL petroleum ether and diethyl ether equal volume mixture, precipitate precipitate, filter, wash with cold diethyl ether. Reuse CHCl 3 Dissolved and purified by silica gel column chromatography (eluent: ethyl acetate:petroleum ether=2:1→pure ethyl acetate) to obtain 112mg of yellow solid powder (1) Bam. Yield 81.9%.
[0148] IR(KBr)ν: 1733.69cm -1 (-CO-CH 3 ), 1620.61cm -1 (-CONH-).
[0149] 1 HNMR (CDCl 3 , 300MHz) δppm: 1.10 (t, J=7.17Hz, 3H, ...
Embodiment 3
[0150] Example 3, Preparation of the 17-hydroxypropionylation product (1) Ban of the ammonia-cleaved ring-opening product (1) XY-8 of CPT
[0151] 150 mg (0.30 mmol) of the CPT ring-opened product (1) XY-8 of N-(3-aminopropyl) morpholine, 1.5 mL of pyridine (18.6 mmol) and 1 mL of propionic anhydride (7.7 mmol) were mixed and heated to 40 ° C, stirred Overnight, the low-boiling solvent was evaporated, and the residue was poured into 50 mL of diethyl ether to precipitate a pale yellow solid, which was further purified by silica gel column chromatography (eluent: ethyl acetate:petroleum ether=1:1→3:1) to obtain (1 ) Bam pure product 111 mg, yield 66.4%.
[0152] IR(KBr)ν: 1729.83cm -1 (-COCH 2 CH 3 ), 1654.52cm -1 (-CONH-)
[0153] 1 HNMR.(CDCl 3 , 300MHz) δppm: 1.11 (t, J=7.23Hz, 3H, 18-CH 3 ), 1.21(t, J=7.05Hz, 3H, -CO-C-CH 3 ), 1.77 (m, 2H, 19-CH 2 ), 2.31(m, 1H, 1 / 2×22-CH 2 ), 2.40~2.15(m, 1H, 1 / 2×22-CH 2 ), 2.55~2.56 (m, 6H, 23-CH 2 and 2×24-CH 2 ), 3.32(m, 1...
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