Bioactive conjugate, preparation method therefor and use thereof
a bioactive molecule and conjugate technology, applied in the field of medical technology, can solve the problems of serious toxic and side effects, smdc available, serious side effects, etc., and achieve the effects of improving the coupling way of drugs and targeting moieties, coupling efficiency, and high coupling efficiency
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Examples
example 1
of (2S)—N-((3R,4S,5S)-1-((2S)-2-((1R,2R)-3-((1-((4-aminobenzyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-propionyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-heptanoyl-4-yl)-2-((S)-2-(dimethylamino)-3-methylbutyrylamino)-N,3-dimethylbutyramide (T001)
[0296]
Step 1: Synthesis of Tert-Butyl (4-((2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((S)-2-(dimethylamino)-3-methylbutyrylamino)-N,3-dimethylbutyrylamino)-3-methoxy-5 methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropionamido)-3-phenylpropionamido)methyl)phenyl) carbamate
[0297]At room temperature, 1-hydroxybenzotriazole (2.0 mg, 14.74 μmol) was dissolved in N,N-dimethylformamide (4 mL), cooled to 0° C., and then tert-butyl 4-methylaminobenzyl carbamate (4.0 mg, 16.1 μmol), N,N-diisopropylethylamine (8.5 mg, 66.8 μmol), ((2R, 3R)-3-((S)-1-((3R,4S,5S)-4-((S)-2-((S)-2-(dimethylamino)-3-methylbutyrylamino)-N,3-dimethylbutyrylamino)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropionyl)-L-phenylalanine (1...
example 2
of (S)—N-((3R,4S,5S)-1-((S)-2-((1R,2R)-3-((S)-1-((4-aminobenzyl)amino)1-oxo-3-phenylprop-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl) pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptyl-4-yl)-2-((S)-2-(dimethylamino)-3-methylbutyrylamino)-N,3-dimethylbutyramide (T011)
[0299]
Step 1: Synthesis of Tert-Buty (S)-(4-((2-(((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-phenylpropionamido) methyl)phenyl) 1 Carbamate
[0300]At 0° C., 4-aminobenzylamine (222 mg, 1.0 mmol) and N-methylmorpholine (306 mg, 1.5 mmol) were added to a solution of (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-phenylpropionicacid (387 mg, 1.0 mmol) in N,N-dimethylformamide (5 mL), then 1-hydroxybenzotriazole (203 mg, 1.5 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (288 mg, 1.5 mmol) were successively added. The resulting mixture was reacted overnight at 0° C. The reaction solution was poured into water (50 mL), and a white solid was precipitated. The solid was filtered, the filter cake was wash...
example 3
of (S)—N-(2-(4-ethyl-4-hydroxyl-3,14-dione-3,4,12,14-tetrahydro-1H-pyrano[3′,4′,6,7]indolizino[1,2-b]quinolin-11-yl)ethyl)-N-isopropylacetamide
[0305]
[0306]Belotecan hydrochloride (1.0 g, 2.13 mmol) and triethylamine (0.65 g, 0.9 mL) were dissolved in dichloromethane (50 mL) at room temperature, and acetic anhydride (0.22 g, 2.13 mmol) was slowly added dropwise. The resulting mixture was reacted at room temperature for 1 h. The organic phase was washed with water (10 mL×2) and dried over anhydrous sodium sulfate. Insoluble substances were removed by filtration, the solvent was evaporated, and the residue was purified by silica gel column chromatography (dichloromethane / methanol=50 / 1) to obtain the title compound (1g). ESI-MS (m / z): 476.2 [M+H]+.
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Abstract
Description
Claims
Application Information
- IPC
- C07D491/22; C07D403/12; C07D403/14; C07D401/14; A61P35/00; A61K47/68; C07K16/32; C07K16/30
- CPC
- C07D491/22; C07D403/12; C07D403/14; C07D401/14; A61K45/06; A61K47/6803; A61K47/6851; C07K16/32
- Inventors
- CAI, JIAQIANG; SONG, SHUAI