CN101057847A - Polyhydroxy piperidines compound and preparation method and application thereof - Google Patents
Polyhydroxy piperidines compound and preparation method and application thereof Download PDFInfo
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- CN101057847A CN101057847A CN 200610076001 CN200610076001A CN101057847A CN 101057847 A CN101057847 A CN 101057847A CN 200610076001 CN200610076001 CN 200610076001 CN 200610076001 A CN200610076001 A CN 200610076001A CN 101057847 A CN101057847 A CN 101057847A
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- glucosidase
- compounds
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- polyhydroxy
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Abstract
The invention discloses the use of polyhydroxy piperidine compounds having a general formula (I) in preparing hypoglycemic medicaments.
Description
Technical field
The present invention relates to the purposes as hypoglycemic drug of a polyhydroxy piperidines compound.
Technical background
Diabetes are a kind of commonly encountered diseases that are difficult to effect a radical cure, frequently-occurring disease, become the third-largest disease of serious threat human health after cardiovascular and cerebrovascular disease and cancer, the prevalence of diabetes, disability rate and mortality rate and overall health hazard degree have leapt to the 3rd of noninfectious.
The research and the application of treatment diabetes medicament start from the discovery of insulin at the beginning of the twenties, are that the acute complications and the mortality rate of diabetes obviously descends.The appearance of the oral antidiabetic drug fifties (sulfonylurea and biguanides) makes the blood glucose of type ii diabetes controlled, has improved patient's quality of life.But sulfonylurea can cause hypoglycemic reaction, and biguanides exists side effect such as lactic acidosis, often makes therapeutic purposes be difficult to reach or be difficult to and keeps.The approach of treatment diabetes has been expanded in the appearance of oral antidiabetic drug alpha-glucosidase inhibitor-acarbose (Acarbose) that the nineties is novel.The alpha-glucosidase inhibitor that has gone on the market at present only has two kinds of acarbose and miglitols at present, and there is certain side effect in it, and price is more expensive.Therefore, it is reliable to seek drug effect, and the oral hypoglycemic thing that toxic and side effects is little also becomes present international important subject.
Homonojirimycin shown in the formula (I) is a polyhydroxy piperidines compound
The physicochemical property and the spectral data of this chemical compound are as follows:
This chemical compound is a polyhydroxy piperidines compound, white crystals, and mp.206-207 ℃,
[α]
D 25+77.2(c，H
2O)
EIMS：m/z.194.3[M+H
+]162.3[M-CH
2OH]
IR
max KBrcm
-1：3384，3344，1475，1327，1113，1078，1036，987，823，700
1H-NMR(300MHz，D
2O)：δ2.82(1H，ddd，J＝2.7，7.2，9.9Hz，H-2)，3.17(1H，dd，J＝9.3，9.6Hz，H-3)，3.25(1H，ddd，J＝5.3，6.0，9.3Hz，H-6)，3.47(1H，dd，J＝9.6，9.6Hz，H-4)，3.53(1H，dd，J＝7.2，11.4Hz，H-1a)，3.71(1H，dd，J＝6.0，9.9Hz，H-5)，3.76-3.83(2H，m，H-7a，H-7b)，3.86(1H，dd，J＝3.0，11.4Hz，H-1b)。
13C-NMR(75MHz，D
2O)：δ56.3(C-2)，58.6(C-7)，59.2(C-6)，64.4(C-1)，73.9(C-5)，74.4(C-3)，76.6(C-4)。
Summary of the invention
The technical problem to be solved in the present invention provides a kind of new hypoglycemic drug, and suc as formula the polyhydroxy piperidines compound shown in (I).
According to the present invention, this chemical compound has been carried out the pharmacological evaluation relevant with blood sugar lowering.Suppress to demonstrate in the experiment good alpha-glucosidase at external alpha-glucosidase and suppress active.
That the positive control medicine is selected for use is acarbose (Acarbose).
Comparison each dosage group of The compounds of this invention and matched group show the suppression ratio of alpha-glucosidase in external alpha-glucosidase suppresses to test: The compounds of this invention is 4,0.4, and 0.04ug/ml dosage group has significant inhibitory effect to alpha-glucosidase; Its IC
500.009ug/ml.And positive control drug acarbose (Acarbose) is only 4, and 0.4ug/ml demonstrates good inhibitory effect.
Experiment shows suc as formula the polyhydroxy piperidines compound shown in (I) stronger than the similar hypoglycemic drug effect of having gone on the market.
Description of drawings
Fig. 1. The compounds of this invention to the normal mouse starch-bearing after the amount effect curve of blood sugar increasing reduction effect; With 0 o'clock blood glucose as 100%, n=10
The specific embodiment
The following examples are used for further specifying the present invention, but this and do not mean that any limitation of the invention.
The external alpha-glucosidase of embodiment 1 The compounds of this invention suppresses experiment
Test material (1) is subjected to reagent: The compounds of this invention
(2) positive control drug: acarbose (Acarbose), the Bayer pharmaceutical factory produces
(3) alpha-glucosidase
(4) sucrose
The external alpha-glucosidase of The compounds of this invention suppresses experiment.
It is exactly to observe medicine at external inhibition degree and effectiveness thereof to the sucrose degraded that external alpha-glucosidase suppresses experiment, therefore suppresses experiment.The compounds of this invention and control drug are made into the solution of 1mg/ml respectively.With buffer it is diluted to 4,0.4 respectively, 0.04,0.004,0.0004 5 dosage.Respectively get this liquid 80ul, add 100ul enzyme liquid respectively, in 37 ℃ of jolting 5min, substrate 20ul is at 37 ℃ of jolting 30min, in 83 ℃ of deactivation 3min, the glucose content in the assaying reaction product.
Table 1 The compounds of this invention suppresses experimental result to external alpha-glucosidase
| Suppression ratio | Drug dose (ug/ml) | |||||
| 4 | 0.4 | 0.04 | 0.004 | 0.0004 | IC 50 | |
| The compounds of this invention contrast medicine | 99.5 90.5 | 98.2 51.5 | 78.7 18.4 | 17.8 2.4 | 5.1 0 | 0.009 0.2599 |
Alpha-glucosidase suppresses experiment in the body of embodiment 2 The compounds of this invention.
Behind 50 normal male mice overnight fastings, be divided into 5 groups at random, only irritating stomach starch (4g/kg) for one group organizes in contrast, irritate stomach starch and BAITANGPING (Acarbose for one group, 10mg/kg) as the positive drug group, surplus 3 groups irritate stomach same dose starch and various dose The compounds of this invention (4mg/kg, 2mg/kg respectively, 1mg/kg), before irritating stomach (0min) and irritate stomach after different intervals blood sampling mensuration blood sugar level (glucose oxidase method).Table 2 and Fig. 1 result show, The compounds of this invention to starch-bearing after blood sugar increasing have obvious reduction effect, be tangible dose-effect relationship.
Table 2. invention compound H W-3 to the normal mouse starch-bearing after the reduction effect of blood sugar increasing
| Group | Dosage (mg/kg) | Blood glucose (mg/dl) | |||
| 0min | 30min | 60min | 120min | ||
| Contrast Acarbose | - 10 4 2 1 | 77.6±12.1 70.4±5.5 82.4±11.5 83.1±14.2 75.6±8.2 | 180.4±23.1 108.2±17.0 *** 96.0±10.6 *** 114.5±40.4 *** 117.3±34.2 *** | 153.5±17.9 106.9±14.2 *** 103.4±8.5 *** 120.6±29.6 * 116.3±30.3 ** | 103.8±2.3 92.6±9.1 ** 88.1±9.9 *** 95.9±13.8 100.1±14.0 |
Claims (1)
1, suc as formula the application of the polyhydroxy piperidine compounds shown in (I) in the preparation hypoglycemic drug
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610076001 CN101057847A (en) | 2006-04-21 | 2006-04-21 | Polyhydroxy piperidines compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610076001 CN101057847A (en) | 2006-04-21 | 2006-04-21 | Polyhydroxy piperidines compound and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101057847A true CN101057847A (en) | 2007-10-24 |
Family
ID=38864251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610076001 Pending CN101057847A (en) | 2006-04-21 | 2006-04-21 | Polyhydroxy piperidines compound and preparation method and application thereof |
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| CN (1) | CN101057847A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5769710B2 (en) * | 2010-07-22 | 2015-08-26 | ビオフェルミン製薬株式会社 | Lipid metabolism improving agent, lipid metabolism improving agent, anti-obesity agent and anti-obesity agent |
-
2006
- 2006-04-21 CN CN 200610076001 patent/CN101057847A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5769710B2 (en) * | 2010-07-22 | 2015-08-26 | ビオフェルミン製薬株式会社 | Lipid metabolism improving agent, lipid metabolism improving agent, anti-obesity agent and anti-obesity agent |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20071024 |