CN105267191A - Application of propanamide compound - Google Patents
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- CN105267191A CN105267191A CN201510248902.1A CN201510248902A CN105267191A CN 105267191 A CN105267191 A CN 105267191A CN 201510248902 A CN201510248902 A CN 201510248902A CN 105267191 A CN105267191 A CN 105267191A
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- -1 propanamide compound Chemical class 0.000 title claims abstract description 36
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Abstract
The invention provides an application of a propanamide compound in preparation of medicines treating diseases related to insulin resistance. The structural general formula of the propanamide compound is shown in the specification. The propanamide compound can increase glucose consumption of insulin-resistant cells in different degrees, and improve the insulin-resistant state of the cells, and so diseases related to insulin resistance comprising II-type diabetes, abnormal lipid metabolism, hypertension, dyslipidemia, obesity, inflammation and the like can be treated effectively.
Description
Technical field
The present invention relates to medicinal chemistry art, in particular to the application of a class Propionamides compound.
Background technology
Insulin resistant (InsulinResistant, IR) refers to a kind of state of the biological agent of the insulin of unit concentration lower than normal level, i.e. tissue or organ, if liver, fat and skeletal muscle etc. are to the sensitivity of insulin and reactive reduction.Insulin resistant causes body to lower the biological effect of a certain amount of (finite concentration) insulin, mainly refers to that the glucose uptake of body insulin-mediated and metabolic capacity weaken.The cytolipin metabolic capacity being in the nature insulin-mediated of insulin resistant declines.Research shows that insulin resistant can cause fasting glucose and impaired glucose tolerance, blood fat disorder (show as TG, TC and LDL-C significantly raises and HDL-C reduces), and inflammatory reaction.The disease relevant to insulin resistant comprises diabetes, obesity, blood fat disorder, (Zhu Zhiming, the similarities and differences of insulin resistance syndrome and metabolism syndrome and the clinical meaning .JDiagnConceptsPractPract such as inflammation and hypertension, 2009,8 (3): 244-247. Su Lei, repair tinkling of pieces of jades etc., the key character [J] of inflammatory reaction-obesity and insulin resistant. international endocrine metabolism magazine, 2008,6:410-412.).Type ii diabetes patients with insulin resistance sickness rate is more than 80%, and insulin resistant is considered to the initiating agent causing type ii diabetes.Therefore improve IR for improve diabetics blood glucose, impaired glucose tolerance and blood fat disorder have important effect; Improve the insulin resistant of body for improving obesity, blood fat disorder, the disease such as inflammation and hypertension also has positive effect simultaneously.
At present, one of euglycemic agent drug development important target spot is exactly peroxisome proliferator activated receptor (PPAR).PPAR belongs to nuclear hormone receptor superfamily member, is the transcription factors critical regulating Adipocyte Differentiation and energy metabolism.PPAR γ is the one in mankind PPARs tri-kinds of isomeric form.Current PPAR γ is used for the treatment of (the horse Jingjings such as diabetes, obesity, inflammation, bad lipidemia, hypertension and cancer as an important drug screening target, chapter great waves .PPAR γ function and disease relationship progress [J]. Chinese Pharmacological Bulletin .2012,05.).Can regulate after PPAR γ albumen is activated multiple to energy metabolism, cell differentiation, gene expression that inflammation is relevant, comprising: leptin, Insulin receptor INSR, glucose transporter (GLUT4).Increase body target organ if liver, fat and muscle are to the sensitivity of insulin, improve insulin resistant, increase lipogenesis, stimulate Adipocyte Differentiation.
For insulin resistant, people have developed several insulin chemical sensitizers, to increase the sensitivity of histiocyte to insulin, glucose in blood are entered in cell, thus reduce the requirement of insulin., make existing insulin (comprise oneself secretion with injection) effect that performance is larger, and reduce the side effect of hyperinsulinemia.Thiazolidinediones (thiazolidinediones, TZDs) is the medicine of the insulin sensitizer treatment diabetes of last century Mo listing, is the activator of PPAR γ.This kind of medicine comprises a series of compounds such as pioglitazone (pioglitazone), rosiglitazone (Rosiglitazone), ciglitazone (ciglitazone), englitazone (englitazone) and troglitazone (troglitazone).The untoward reaction of TZDs is put on weight, edema and water retention, brings out and increases the weight of cardiac insufficiency and pulmonary edema, and wherein troglitazone is withdrawn from the market because of serious liver toxicity.Therefore insulin sensitivity enhancing agent medicine commercially leaves blank, in the urgent need to the medicine of effective treatment insulin resistant of development of new.
Summary of the invention
In order to solve problems of the prior art, the invention provides the application of Propionamides compound in the medicine preparing the treatment disease relevant to insulin resistant, described Propionamides compound has following general structure:
, wherein, R1 is selected from hydrogen, acetyl group, methyl, ethyl, phenyl, benzyl, phenethyl, benzoyl; R2 is selected from hydrogen, C1-C4 alkyl, benzyl, phenethyl, 4-leptodactyline, 4-methoxyphenethyl, 4-ethoxybenzene ethyl, 3,4-methoxyphenethyl, 4-ethoxycarbonyl phenethyl, furan-2-methyl, picolyl, pyrimidine methyl or 2-(thiophene-2)-ethyl; R3 is selected from hydrogen, C1-C4 alkyl, benzyl, phenethyl, 4-leptodactyline, 4-methoxyphenethyl, 4-ethoxybenzene ethyl, 3,4-methoxyphenethyl, 4-ethoxycarbonyl phenethyl, furan-2-methyl, picolyl, pyrimidine methyl or 2-(thiophene-2)-ethyl.
In above-mentioned application, described acrylamides comprises following compound:
In above-mentioned application, described Propionamides compound, by improving the insulin resistant of cell, improves cell to the absorbability of glucose.
In above-mentioned application, described Propionamides compound reduces the blood glucose of type ii diabetes patient by the insulin resistant improving body, improves the carbohydrate tolerance of patient.
In above-mentioned application, described Propionamides compound can improve the blood fat disorder of type ii diabetes patient by the insulin resistant improving body, comprise and reduce triglyceride (TG), T-CHOL (TC) and low-density lipoprotein cholesterol (LDL-C) level, and improve HDL-C (HDL-C) level.
In above-mentioned application, the pharmaceutical pack of the disease that described treatment is relevant to insulin resistant is containing having the described Propionamides compound of said structure general formula, described Propionamides compound pharmaceutically acceptable salt, ester, hydrate or their combination and adjuvant.
In above-mentioned application, the dosage form of the medicine of the disease that described treatment is relevant to insulin resistant is selected from tablet, capsule, pill, suppository, aerosol, oral liquid, granule, powder, injection, syrup, medicated wine, tincture, distillate medicinal water, membrane or their combination.
In above-mentioned application, the administering mode of the medicine of the disease that described treatment is relevant to insulin resistant comprises oral, injection, implantation, external, spraying, suction or their combination.
In above-mentioned application, the described disease relevant to insulin resistant comprises type ii diabetes, Anomalous lipid metablism, hypertension, blood fat disorder, one or more in obesity, inflammation.
Found through experiments, the Propionamides compound 1401 that the present invention filters out, 1402, 1403, 1404, 1413, 1609, 1609-1, 1609-2, 1635, 1635-1, 1635-2, 1635-3, 1636, 1636-1, 1636-2, 1636-3, 1636-4, 1636-5, 1636-6, 1636-7, 1636-8, 1636-9, 1636-10, 1636-11, 1636-12, 1636-13, 1636-14, 1636-15, 1636-16, 1636-17, 1636-18, 1636-19, 1636-20, 1636-21, 1636-22, 1640, 1701 can the glucose utilization of increase insulin resistant cell in various degree, improve the insulin-resistant states of cell.
In addition, Propionamides compound provided by the invention can effectively reduce type ii diabetes rat fasting blood-glucose, improve the carbohydrate tolerance of type ii diabetes rat, reduce glycolated hemoglobin percentage ratio in type ii diabetes rat, reduce triglyceride (TG), T-CHOL (CHOL) and low-density lipoprotein cholesterol (LDL-C) level (P<0.05) in type ii diabetes rat blood serum, and the effect of the level of remarkable high density lipoprotein increasing cholesterol (HDL-C).
Accompanying drawing explanation
Fig. 1 shows the optimal condition that insulin resistant cell model is set up.
Fig. 2 shows the experimental result of positive drug pioglitazone checking insulin resistant cell model.
Fig. 3 illustrates that compound 1636 and pioglitazone are on the impact of rat carbohydrate tolerance.
Fig. 4 illustrates that compound 1636 and pioglitazone are on the impact of rat glycolated hemoglobin, #: compare p<0.05 with Normal group; *: compare p<0.05 with model group, * *: compare p<0.01 with model group, * * *: compare p<0.001 with model group.
Fig. 5 illustrates that compound 1636 and pioglitazone are on the impact of rat fat parameter, #: compare p<0.05 with Normal group, ##: compare p<0.01 with Normal group, ###: compare p<0.001 with Normal group; *: compare p<0.05 with model group, * *: compare p<0.01 with model group, * * *: compare p<0.001 with model group.
Detailed description of the invention
Below in conjunction with the accompanying drawing in the embodiment of the present invention, be clearly and completely described the technical scheme in the embodiment of the present invention, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, the every other embodiment that those of ordinary skill in the art obtain, all belongs to the scope of protection of the invention.
The test material that the present invention uses and source thereof comprise:
HepG2 cell, purchased from Beijing gold amethyst biological medicine technology company limited;
Pioglitazone piogitazone (ACTOS) is sigma Products;
DMEM in high glucose culture medium and hyclone (Gibco), be Invitrogen Products;
People source insulin and dexamethasone are sigma Products;
Tissue Culture Flask and 96 orifice plates are NUNC Products;
Wistar rat, is provided by Academy of Military Medicine, PLA's experimental animal center and Beijing Vital River Experimental Animals Technology Co., Ltd.;
Streptozotocin (STZ), purchased from Dalian Mei Lun company;
Glucose, by Shanghai, Sheng Gong biological engineering company limited provides; And
Compound library, from Tianjin International Joint Academy of Biotechnology & Medicine's high-flux medicaments sifting center.
The foundation of embodiment 1 insulin resistant cell model and drug screening
The foundation of 1.1 insulin resistant cell models
By setting up the cell model of insulin resistant, being convenient to observe intervention factor to the direct impact of insulin resistant, being particularly more convenient for screening the medicine improving insulin resistant.
HepG2 cell comes from the liver embryonic germ of people, be the liver embryonic germ strain very similar to hepatocyte of a kind of phenotype, under high-caliber insulin condition, the number of HepG2 cell surface Insulin receptor INSR declines, and decline degree is with insulin level and stimulate the lasting time to be proportionate.
Concrete steps are as follows:
1) HepG2 cell culture
With the DMEM culture fluid containing 10% deactivation calf serum after HepG2 cell recovery, at 37 DEG C, 5%CO
2cultivate under condition.After cell attachment covers with, culture medium of inclining, with 0.25% trypsinization, goes down to posterity, and the cell of trophophase of taking the logarithm is for experiment.
2) optimal condition of HepG2 cell insulin resistant model foundation
By be in exponential phase HepG2 cell dissociation after, suspend by the low sugar DMEM culture medium containing 10%FBS, with 1 × 10
4the density in individual/hole proceeds in 96 porocyte culture plates and continues to cultivate, and is divided into blank group and model group.After cell is completely adherent, after serum-free low sugar DMEM training base washing 2 ~ 3 times, after being replaced by the low sugar DMEM culture fluid synchronization 12h of serum-free, adding the dexamethasone of 0.1 μM, 1 μM, 5 μMs, 10 μMs respectively, be placed in 37 DEG C, 5%CO
2after hatching 24h, 48h and 72h respectively in incubator, abandon the culture supernatant containing dexamethasone, after washing 2 ~ 3 times with the PBS of pH7.4, add with serum-free, contain 1 × 10 without phenol red low sugar DMEM
-9mmol/L insulin collects supernatant after hatching 24h, glucoseoxidase-hydrogen peroxide enzyme process (Glucoseoxidase-peroxidase, GOD-POD) method measures the glucose content in supernatant, and calculates the glucose utilization of each concentration group cell.Measure cell survivaling number with mtt assay, calculate the glucose relative consumption of each group of cell.
By optimizing the concentration of insulin and setting up the HepG2 cell model of insulin-induced hepatoma carcinoma cell insulin resistant action time, for subsequent experimental.Wherein the computing formula of glucose content is:
Glucose content (mmol/L)=(A specimen/A standard) × concentration of standard solution;
Glucose utilization (mmol/L)=culture fluid glucose content-cell conditioned medium liquid glucose content
Comparative survival rate of cells=experimental group A570/ control group A 570
Glucose relative consumption (mmol/L)=grape cell sugar consumption amount/comparative survival rate of cells
3) research of HepG2 insulin resistant cell model persistent period
Adopt 2) after the best modeling method modeling success of setting up, blank group and model group cell are placed in containing 1 × 10 simultaneously
-9the serum-free of mmol/L insulin without continue in phenol red DMEM culture medium cultivation 24,48, after 72h, detect the glucose content in medium supernatant with glucose clinical reagent box.Calculate the glucose relative consumption of blank group and model group, to determine the HepG2 insulin resistant cell model persistent period.
4) positive drug pioglitazone checking
Adopt above-mentioned 2) and 3) after the method modeling of setting up, add positive drug pioglitazone, after 24h, survey glucose content and cell survival rate in supernatant, calculate glucose relative consumption.
1.2 based on the drug screening of insulin resistant cell model
Adopt 2) and 3) method establishment model, blank group is set, insulin resistant model group and insulin resistant dosing group.Each drug screening group arranges 6 multiple holes, calculates the glucose relative consumption often organized.Utilize glucose relative consumption recruitment to react the improvement effect of medicine to insulin resistant, computing formula is as follows:
The glucose relative consumption of the glucose relative consumption-model group of glucose relative consumption recruitment=administration group.
1.3 experimental result
(1) foundation of insulin resistant cell model
1) optimal condition of HepG2 cell insulin resistant model foundation
At different time, under the dexamethasone stimulation of variable concentrations, glucose relative consumption as shown in Figure 1.Abscissa is the concentration of dexamethasone, and vertical coordinate is glucose relative consumption.First group is blank group.Stimulate 24 hours at 0.1 μM of dexamethasone, glucose relative consumption reduces at most, is 26.83%.Determine that 0.1 μM of dexamethasone stimulates the optimal condition that 24 hours is insulin resistant model thus.
2) research of HepG2 insulin resistant cell model persistent period
After insulin resistant model is set up, at 24h, glucose relative amount (table 1) in the culture medium of detection model group and blank group is distinguished during 48h and 72h, to this shows after modeling 24 hours, the insulin resistant of model group is the most obvious, is the best persistent period of insulin resistant.
The research of table 1HepG2 insulin resistant cell model persistent period
| Time after modeling | 24h | 48h | 72h |
| Glucose relative amount in culture medium | 31.25％ | 22.56％ | 11.86％ |
In sum, stimulate 24 hours later cell to produce insulin resistant with 0.1 μM of dexamethasone, and 24 hours insulin resistant effects are best after modeling.Therefore will administration after modeling during drug screening, after administration 24h, detection of drugs is to the improvement effect of insulin resistant.
3) positive drug checking
As shown in Figure 2, abscissa is pioglitazone concentration (μM), and vertical coordinate is glucose relative consumption.Pioglitazone significantly improves the consumption of glucose, improves insulin resistant, proves that this model can be used.
(2) based on the drug screening of insulin resistant cell model
After 0.1 μM of dexamethasone stimulates 24 hours, blank group, insulin resistant model group and insulin resistant dosing group (drug level is 50 μMs) are set, positive drug is pioglitazone, drug effect measures glucose content and cell survivaling number in culture medium after 24 hours, obtain glucose relative consumption, and calculate the glucose relative consumption recruitment of administration group.Experimental result is as shown in table 2, and as can be seen from Table 2, the Propionamides compound filtered out can the glucose utilization of increase insulin resistant cell in various degree, improves the insulin-resistant states of cell.
Table 2 medicine is to the improvement result (drug level 50 μMs) of insulin resistant model
Embodiment 2 adopts type ii diabetes animal model to carry out Composition analyzed to compound 1636
(1) experimental procedure:
A. the foundation of Rat Type II diabetes model: utilize high glucose and high fat diet to combine streptozotocin (STZ) and bring out rat generation type Ⅱdiabetes mellitus, negative control group feeding standard feed, after experimental group high lipid food (20% sucrose, 10% Adeps Sus domestica, 10% yolk powder, 1.5% cholesterol, 0.2% cholic acid, 58.3% standard feed) feeds 2 weeks, lumbar injection STZ (40mg/kg, prepare with the aseptic citrate buffer solution pH4.5 of 0.1M, 0.2 μM of filtering with microporous membrane), negative control group only injects citrate buffer solution.Two days later, tail venous blood sampling surveys fasting glucose (fasting overnight before survey blood glucose, carries out blood sugar detection by Roche blood glucose meter) in STZ injection.Fasting glucose is judged to be diabetes higher than 16.89mmol/L.The successful type Ⅱdiabetes mellitus rat of modeling is divided into three groups at random, and often organizing 5, is model group (non-administration), 1636 groups (administration 1636,30mg/kg/ days), pioglitazone group (administration pioglitazone, 30mg/kg/ days).Every day gastric infusion, administration 4 weeks.
B. rat carbohydrate tolerance test experience: administration is after 4 weeks, and fasting 12-16h, tail venous blood sampling survey fasting glucose after administration 1h, and gavage glucose solution (2.5g/kg), continue fasting, respectively at giving sugar rear 0.5h, 1h, 2h tail venous blood sampling survey blood glucose.Blood glucose when being zero with fasting blood sugar, draw blood glucose change curve in time, and calculate Area under the curve of blood glucose variable quantity, computing formula is as follows:
Area under the curve of blood glucose variable quantity (△ sugar area)=(0 hours blood glucose value+2 × 0.5 hours blood glucose value+3 × 1 hours blood glucose value+2 × 2 hours blood glucose value)/4-2 × 0 hours blood glucose value.
C. TC (triglyceride), TG (T-CHOL), HDL-C (high density lipoprotein), LDL-C (low density lipoprotein, LDL) level in rat blood serum, the detection of glycolated hemoglobin percentage ratio in blood: administration put to death rat after 4 weeks, heart extracting blood, add anticoagulant, the difference according to detected parameters adds different anticoagulant.ELISA kit is utilized to detect above-mentioned parameters.
(2) experimental result:
1) compound 1636 is on the impact of type ii diabetes rat fasting blood-glucose:
As shown in table 3, after positive controls rat injection STZ3 week, fasting glucose increases, and comparing with matched group has significant difference.Administration is after 4 weeks, and the blood sugar lowering rate of 1636 groups and pioglitazone group rat is respectively 21.8% and 15.4%.
The change of blood sugar of table 3 normal rat and diabetes rat
(###p<0.001vs Normal group; * p<0.05, * * p<0.01, * * * p<0.001vs model group)
3) compound 1636 is on the impact of type ii diabetes rat carbohydrate tolerance:
As shown in Figure 3, Normal group, model group, 1636 groups, the △ of pioglitazone group sugar area is respectively 4.85h.mmol/L, 15.18h.mmol/L, 14.3h.mmol/L, 8.21h.mmol/L.The significant impaired glucose tolerance of model group rats, after 1636 groups and pioglitazone group rat give sugar, Glucose Tolerance is significantly improved (P<0.01), and 1636 groups embody more effective reduction to the effect (P<0.01) of hyperglycemia after sugar relative to pioglitazone group.
4) compound 1636 is on the impact of type Ⅱdiabetes mellitus rat glycolated hemoglobin:
As shown in Figure 4, the rat of the glycolated hemoglobin percentage ratio compared with normal of type ii diabetes rat raises (P<0.05), and behind 1636 and pioglitazone treatment, glycolated hemoglobin percentage ratio decreases.
5) compound 1636 is on the impact of TC (triglyceride), TG (T-CHOL), HDL-C (HDL-C), LDL-C (low-density lipoprotein cholesterol) level in type Ⅱdiabetes mellitus rat fat:
As shown in Figure 5, diabetes rat Triglycerides in Serum (TG), T-CHOL (CHOL) and low-density lipoprotein cholesterol (LDL-C) level significantly increase (P<0.05), and the level of HDL-C (HDL-C) significantly reduces (P<0.05).Administration is after 4 weeks, and in rat blood serum, triglyceride (TG), T-CHOL (TC) and low-density lipoprotein cholesterol (LDL-C) level all significantly reduce; The level of HDL-C (HDL-C) significantly raises.In 1636 groups and pioglitazone group, in rat blood serum, triglyceride (TG) level reduces 21.76% and 51.44% respectively relative to model group; In 1636 groups and pioglitazone group, in rat blood serum, T-CHOL (CHOL) level reduces 77.48% and 73.06% respectively relative to model group; In 1636 groups and pioglitazone group, in rat blood serum, low-density lipoprotein cholesterol (LDL-C) level reduces 79.97% and 76.33% respectively relative to model group; In 1636 groups and pioglitazone group, rat blood serum middle-high density lipoprotein cholesterol (HDL-C) level increases 66.88% and 71.25% respectively relative to model group.
Although in example 2, only describe compound 1636 for illustrative purposes and there is effectively reduction type ii diabetes rat fasting blood-glucose, improve the carbohydrate tolerance of type ii diabetes rat, reduce glycolated hemoglobin percentage ratio in type ii diabetes rat, reduce triglyceride (TG), T-CHOL (CHOL) and low-density lipoprotein cholesterol (LDL-C) level (P<0.05) in type ii diabetes rat blood serum, and the effect of the level of remarkable high density lipoprotein increasing cholesterol (HDL-C).But known by table 2 in embodiment 1, Propionamides compound provided by the present invention all can the glucose utilization of increase insulin resistant cell in various degree, improves the insulin-resistant states of cell.And insulin resistant is considered to the initiating agent causing type ii diabetes.Thus, one of ordinary skill in the art will appreciate that, other Propionamides compounds 1401 provided by the present invention, 1402, 1403, 1404, 1413, 1609, 1609-1, 1609-2, 1635, 1635-1, 1635-2, 1635-3, 1636-1, 1636-2, 1636-3, 1636-4, 1636-5, 1636-6, 1636-7, 1636-8, 1636-9, 1636-10, 1636-11, 1636-12, 1636-13, 1636-14, 1636-15, 1636-16, 1636-17, 1636-18, 1636-19, 1636-20, 1636-21, 1636-22, 1640, 1701 equally also have effectively reduction type ii diabetes rat fasting blood-glucose, improve the carbohydrate tolerance of type ii diabetes rat, reduce glycolated hemoglobin percentage ratio in type ii diabetes rat, reduce triglyceride (TG) in type ii diabetes rat blood serum, T-CHOL (CHOL) and low-density lipoprotein cholesterol (LDL-C) level, and the effect of the level of remarkable high density lipoprotein increasing cholesterol (HDL-C).
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (9)
1. Propionamides compound treats the application in the medicine of the disease relevant to insulin resistant in preparation, and it is characterized in that, described Propionamides compound has following general structure:
, wherein, R1 is selected from hydrogen, acetyl group, methyl, ethyl, phenyl, benzyl, phenethyl, benzoyl; R2 is selected from hydrogen, C1-C4 alkyl, benzyl, phenethyl, 4-leptodactyline, 4-methoxyphenethyl, 4-ethoxybenzene ethyl, 3,4-methoxyphenethyl, 4-ethoxycarbonyl phenethyl, furan-2-methyl, picolyl, pyrimidine methyl or 2-(thiophene-2)-ethyl; R3 is selected from hydrogen, C1-C4 alkyl, benzyl, phenethyl, 4-leptodactyline, 4-methoxyphenethyl, 4-ethoxybenzene ethyl, 3,4-methoxyphenethyl, 4-ethoxycarbonyl phenethyl, furan-2-methyl, picolyl, pyrimidine methyl or 2-(thiophene-2)-ethyl.
2. application according to claim 1, is characterized in that, described acrylamides comprises following compound:
3. application according to claim 1, is characterized in that, described Propionamides compound, by improving the insulin resistant of cell, improves cell to the absorbability of glucose.
4. application according to claim 1, is characterized in that, described Propionamides compound reduces the blood glucose of type ii diabetes patient by the insulin resistant improving cell and improves carbohydrate tolerance.
5. application according to claim 1, it is characterized in that, described Propionamides compound improves the blood fat disorder state of type ii diabetes patient by the insulin resistant improving cell, comprise and reduce triglyceride (TG), T-CHOL (TC) and low-density lipoprotein cholesterol (LDL-C) level, and improve HDL-C (HDL-C) level.
6. application according to claim 1, it is characterized in that, the pharmaceutical pack of the disease that described treatment is relevant to insulin resistant is containing having the described Propionamides compound of described general structure, described Propionamides compound pharmaceutically acceptable salt, ester, hydrate or their combination and adjuvant.
7. application according to claim 6, it is characterized in that, the dosage form of the medicine of the disease that described treatment is relevant to insulin resistant is selected from tablet, capsule, pill, suppository, aerosol, oral liquid, granule, powder, injection, syrup, medicated wine, tincture, distillate medicinal water, membrane or their combination.
8. application according to claim 6, is characterized in that, the administering mode of the medicine of the disease that described treatment is relevant to insulin resistant comprises oral, injection, implantation, external, spraying, suction or their combination.
9. the application according to any one of claim 1-8, is characterized in that, the described disease relevant to insulin resistant comprise in type ii diabetes, Anomalous lipid metablism, hypertension, blood fat disorder, obesity and inflammation one or more.
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| CN108272784A (en) * | 2018-03-09 | 2018-07-13 | 天津国际生物医药联合研究院 | Application of the Propionamides compound in treating enteric flora disturbance relevant disease |
| TWI688386B (en) * | 2018-03-16 | 2020-03-21 | 輔英科技大學 | Use of propanamide |
| US10888536B1 (en) | 2019-08-28 | 2021-01-12 | Fooyin University | Method of improvement of insulin sensitivity in obese patients |
-
2015
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| ALEXEY A. LAGUNIN ET AL.: "Computer-Aided Selection of Potential Antihypertensive Compounds with Dual Mechanism of Action", 《J. MED. CHEM.》 * |
| HUI-JUAN LIU ET AL.: "A Novel Partial Agonist of Peroxisome Proliferator-Activated Receptor γ with Excellent Effect on Insulin Resistance and Type 2 Diabetes", 《 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108272784A (en) * | 2018-03-09 | 2018-07-13 | 天津国际生物医药联合研究院 | Application of the Propionamides compound in treating enteric flora disturbance relevant disease |
| TWI688386B (en) * | 2018-03-16 | 2020-03-21 | 輔英科技大學 | Use of propanamide |
| US10888536B1 (en) | 2019-08-28 | 2021-01-12 | Fooyin University | Method of improvement of insulin sensitivity in obese patients |
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