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However, long-term use of statins will not only cause digestive system symptoms such as upper abdominal discomfort, but also liver function damage, elevated transaminases, muscle pain, and elevated creatine kinase in a considerable number of patients.
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Embodiment 1
[0091] Embodiment 1: the preparation of compound 01
[0092] 2-(4-(2-(4-chlorobenzamido)ethyl)phenoxy)-2-methylpropionic acid 1g, dicyclohexylcarbodiimide 0.57g, 2-amino-1- 0.5 g of (4-hydroxyphenyl) ethyl ketone and 60 ml of dichloromethane were placed in a 100 ml single-necked bottle, reacted at room temperature for 4 hours, the solvent was evaporated to dryness, and 820 mg of the target compound was obtained by silica gel column chromatography. MS(ESI): 495(M+H + ). 1 H-NMR: 7.720-7.698 (2H, d), 7.629 (1H, s), 7.605-7.584 (2H, d), 7.281 (1H, s), 7.232-7.210 (2H, d), 7.158 (1H, s ), 7.011-6.99 (2H, d), 6.810-6.751 (4H, m), 4.559-4.547 (2H, s), 3.484-3.473 (2H, m), 2.764-2.729 (2H, m), 1.381 (6H , s)
Embodiment 2
[0093] Embodiment 2: the preparation of compound 02
[0094] 2-(4-(2-(4-chlorobenzamido)ethyl)phenoxy)-2-methylpropionic acid 2g, dicyclohexylcarbodiimide 1.2g, 2-amino-1- 0.5 g of (4-hydroxyphenyl)ethanone and 60 ml of dichloromethane were placed in a 100 ml single-necked bottle, reacted at room temperature for 4 hours, evaporated to dryness, and 1.3 g of the target compound was obtained by silica gel column chromatography. MS (ESI): 838 (M+H + ).
Embodiment 3
[0095] Embodiment 3: the preparation of compound 03
[0096] 2-methyl-2-(4-(4-chlorobenzoyl)phenoxy)propionic acid 1g, dicyclohexylcarbodiimide 0.57g, 2-amino-1-(4-hydroxyphenyl) 0.5 g of ethyl ketone and 60 ml of dichloromethane were placed in a 100 ml single-necked bottle, reacted at room temperature for 4 hours, the solvent was evaporated to dryness, and 820 mg of the target compound was obtained by silica gel column chromatography. MS(ESI): 452(M+H + ). 1 H-NMR: 7.8-7.85 (2H, d), 7.7-7.8 (4H, m), 7.6 (1H, m), 7.42-7.53 (2H, d), 7.04-7.13 (2H, d), 6.9-7.1 (2H, d), 6.84 (1H, s), 4.7 (2H, d), 1.65 (6H, s)
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Abstract
The invention discloses an amide compound and a preparation method as well as application thereof. The amide compound is specifically a compound shown by a formula I or pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, Q, X and n are defined in the specification. The invention also discloses the preparation method of the compound shown by the formula I, a composition comprising the compound and application of the compound to preparation of medicaments for adjusting blood fat and / or preventing gall stone. The compound shown by the formula I is stable in vitro, has high solubility in pharmaceutically applied organic solvent and has higher bioavailability in animals.
Description
technical field [0001] The present invention relates to a novel amide compound and its preparation method and application. It specifically relates to an amide composed of an amine compound and a carboxylic acid compound, a preparation method and an application thereof. Background technique [0002] Cardiovascular and cerebrovascular diseases are currently the most serious disease that endangers human life and health, and are common and frequently-occurring diseases among middle-aged and elderly people. It ranks first in morbidity and mortality in many countries. Atherosclerosis is the basis of many cardiovascular and cerebrovascular diseases. A large number of experimental and clinical data prove that atherosclerosis is closely related to abnormal blood lipid metabolism. Therefore, lipid-regulating drugs have become an important field of current drug research. [0003] Through prospective, random and controlled clinical studies, it has been proved that some statins can re...
Claims
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