Composition comprising orlistat and glp-1 receptor agonist and use thereof
A receptor agonist, GLP-1 technology, applied in the field of medicine, can solve unspecified problems, achieve the effects of inhibiting weight gain, good weight gain, and inhibiting weight loss
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[0040] 1.1 Preparation of copolymer
[0041] The present invention adopts the synthesis reaction route shown below to prepare the copolymer shown in formula I. For the convenience of description, it is hereinafter referred to as "copolymer 1", and it is numbered according to the x of the R substituents from small to large. Copolymers 1a-1t.
[0042]
[0043] In the above reaction formula, compounds 2a to 2t are cyclopentenyl fatty acids whose structures are shown in the following formula:
[0044]
[0045] Wherein, x is any integer selected from 0-19.
[0046] Compounds 2a~2t exist in nature, or are commercially available, or adopt the method reported by W.M.Stanley et al. (Journal of the American Chemical Society, 1929,51(5):1515~1518) from two carbons less prepared from cyclopentenyl fatty acids.
[0047] Compound 3 and Compound 5 are commonly used chemical raw materials.
[0048] Compound 7 is 2-methacryloyloxyethylphosphorylcholine (MPC), which can be a commercia...
Embodiment 1
[0110] Preparation and structure confirmation of embodiment 1 compound 4k
[0111]
[0112] Preparation: Dissolve 0.252g of compound 2k (1mmol) in 5mL of dichloromethane, stir at -10°C for 5 minutes, then slowly add 0.087mL of oxalyl chloride (1mmol) in 5mL of dichloromethane solution dropwise for 20 minutes After the internal drop is completed, add another drop of N,N-dimethylformamide dropwise, and continue to stir at -10°C for 2 h to obtain solution A; take another 0.063 mL of aminoethanol (1.05 mmol), dissolve it in 5 mL of dichloromethane, and then Add 0.276 mL of triethylamine (2 mmol) dropwise thereto, and stir evenly at -10°C to obtain solution B. Solution A was slowly added dropwise to solution B, and stirring was continued at -10°C for 2h. The reaction solution was washed with 10 mL of 10% sodium carbonate solution, the aqueous layer was extracted with dichloromethane (3×5 mL), and the organic layer was washed with 10 mL of saturated brine. After combining all t...
Embodiment 2
[0116] Preparation and structure confirmation of embodiment 2 compound 6k
[0117]
[0118] Preparation: Take 0.296g of compound 4k (1mmol), 10mL of toluene, 0.125g of p-toluenesulfonic acid and 0.038g of hydroquinone, mix them and put them in a three-necked flask equipped with a water separator, heat and stir until all the solids are dissolved, Further, 0.130 g of methacrylic acid (1.5 mmol) was added to the resulting mixed system. Continue to heat up to the reflux temperature, water and toluene are azeotropic, and are distilled out at the same time. When the amount of water in the water separator is equivalent to the theoretical value (about 0.018g), unreacted methacrylic acid and toluene are removed by distillation under reduced pressure. Cool the crude ester in the flask to room temperature, add an appropriate amount of petroleum ether to dissolve completely, neutralize and wash with lye containing 5% sodium carbonate and 1% sodium hydroxide until slightly alkaline, re...
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