阅读说明：本技术 新型磺胺类化合物及其在治疗高血脂中的用途 (Novel sulfonamides compound and its purposes in treatment hyperlipidemia ) 是由 王广忠 于 2019-09-23 设计创作，主要内容包括：本发明公开了如化合物1所示的磺胺类化合物或其药学上可接受的盐,<Image he="583" wi="563" file="DDA0002211460040000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>通过对模型鼠体内血清、肝脏血脂水平的检测,以及对泡沫细胞内胆固醇含量的影响,发现化合物1能够明显降低血清及肝脏TG、TC水平,使细胞内聚集的胆固醇酯明显减少,显著抑制泡沫化细胞的形成,具有抗高血脂及抗动脉粥样形成的能力。通过对PPARα、PPARγ活性测定发现,化合物1通过双重激动PPARα、PPARγ的作用来改善脂质代谢紊乱,具有同时调节脂代谢和糖代谢的双重作用。(The invention discloses the sulfonamides compound as shown in compound 1 or its pharmaceutically acceptable salt, Pass through the detection to serum, liver blood lipid level in model mouse body, and the influence to foam cells inner cholesterol content, it was found that compound 1 can be substantially reduced serum and liver TG, TC are horizontal, significantly reduce the cholesteryl ester of intracellular accumulation, the formation of foamed cell is significantly inhibited, the ability formed with lipidemia and anti-atherogenic.By the way that PPAR α, the measurement discovery of PPAR gamma activity, compound 1 improves disorders of lipid metabolism by the effect of double excitations PPAR α, PPAR γ, has while adjusting the double action of lipid metaboli and glycometabolism.)

1. novel sulfonamides compound or its pharmaceutically acceptable salt, chemical structural formula are

2. novel sulfonamides compound as described in claim 1 or its pharmaceutically acceptable salt are as treatment hyperlipidemia medicine The application of object, especially TG, TC are horizontal high, and merge the treatment of the hyperlipemia of carbohydrate metabolism disturbance.

Technical field

The present invention relates to field of medicaments, and in particular to sulfonamides compound and its purposes in treatment hyperlipidemia.

Background technique

Blood lipid is the general name of contained lipid in human plasma, including cholesterol, triglyceride, cholesterol ester, β-rouge Albumen, phosphatide, not esterified resin acid etc..It is just being frequently referred to when fat metabolism or operating exception are higher than the one or more lipids of blood plasma Hyperlipemia.Total cholesterol is more than 5.72mmol/L in general adult's Diagnostic Value of Fasting Serum, and triglycerides is more than 1.70mmol/L, can It is diagnosed as hyperlipidemia.Hyperlipidemia is the Main Etiological Factors of atherosclerosis, is often caused because invading vitals tight The consequence of weight.Epidemiology shows that there are dyslipidemias by least 200,000,000 Chinese.The national survey carried out according to 2002, in State adult blood lipid abnormality prevalence rate is 18.6%, wherein 2.9% is that (total cholesterol is greater than or equal to hypercholesterolemia 5.72mmol/L), 11.9% is highly dense for hypertriglyceridemia (triglycerides is greater than or equal to 1.70mmol/L), 7.4% It is relatively low (being less than 1.04mmol/L) to spend lipoprotein.

Clinical treatment hyperlipidemia chemicals are divided into four seed types: (1) HMG-CoA reductase inhibitor.HMG-CoA is also Speed limit enzymatic activity during the internal cholesterol biosynthesis of the inhibition of reductase inhibitor contestable, so that the generation of cholesterol is blocked, Then low-density lipoprotein (LDL) receptor for raising cell surface, accelerates the catabolism of blood plasma LDL, represents that drug is for example pungent to be cut down Statin；(2) fibrate blood lipid-lowering medicine.Fibrate blood lipid-lowering medicine can peroxide activator enzyme body vegetation swash Receptor (PPAR) α living, induction lipoprotein lipase expression, promotes very low density lipoprotein (VLDL), chylomicron etc. to be rich in glycerol three The hydrolysis of triglycerides (TG) ingredient in the hdl particle of ester；It can also make blood by raising the expression of Apolipoprotein A1 and A2 The content for starching middle-high density lipoprotein (HDL) increases, and represents drug such as Bezafibrate；(3) cholic acid chelating agent.Bile acid sequestrant Cholic acid or cholesterol can be prevented from intestinal absorption, cholic acid or cholesterol is promoted to be discharged with excrement；And it being capable of feedback up-regulation liver Cell surface LDL receptors expression, and then accelerate blood plasma LDL catabolism, total plasma cholesterol (TC) and LDL concentration are reduced, Represent drug such as cholestyramine acid；(4) niacin class blood lipid-lowering medicine.Niacin class blood lipid-lowering medicine two core of nicotinamide adenine in vivo Lipid-loweringing effect is played after being changed into NAD in thuja acid (NAD) coenzyme system, represents drug such as acipimox.

PPAR α, PPAR gamma agonist difference regulating lipid metabolism and glycometabolism, double excitations PPAR α and PPAR γ can be used Merge metabolic function exception person in treatment cardiovascular disease, and adverse reaction can be offset.

Sulfonamides compound provided by the invention has the new skeleton entirely different with the above types of drug, and dual can swash The activity of dynamic PPAR α, PPAR γ, the effect for reducing TC, TG, LDL is found to have by pharmacological evaluation, to treat hyperlipidemia, The treatment for especially merging abnormal carbohydrate metabolism provides new research direction.

Summary of the invention

The present invention provides a kind of novel sulfonamides compound, specially compound 1, compound 2, shown in compound 3 Compound or its pharmaceutically acceptable salt,

Above compound 1, compound 2, the structured data of compound 3 and its synthetic method are referring to embodiment part.

The present invention also provides the experiments of the pharmacological activity of the compound 1-3, including serum, liver blood lipid in model mouse body Horizontal detection, the influence to foam cells inner cholesterol content, and test is influenced on PPAR α, PPAR gamma activity.

Specific embodiment