CN108478556A - The new pharmaceutical uses of dihydroartemisinine - Google Patents
The new pharmaceutical uses of dihydroartemisinine Download PDFInfo
- Publication number
- CN108478556A CN108478556A CN201810269018.XA CN201810269018A CN108478556A CN 108478556 A CN108478556 A CN 108478556A CN 201810269018 A CN201810269018 A CN 201810269018A CN 108478556 A CN108478556 A CN 108478556A
- Authority
- CN
- China
- Prior art keywords
- dpp
- dihydroartemisinine
- new pharmaceutical
- pharmaceutical uses
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Abstract
The title of the present invention is the new pharmaceutical uses of dihydroartemisinine.Affiliated technical field is medical science.The technical problems to be solved by the invention are to be related to dihydroartemisinine or its pharmaceutically acceptable solvate and its purposes as therapeutic agent especially as inhibitors of dipeptidyl IV.The main points of the technical solution of the technical problems to be solved by the invention are test of the compound to DPP IV enzyme inhibition activities.
Description
Technical field
The present invention relates to pharmaceutical technology fields, specifically, the present invention relates to compound dihydroartemisinines to be used as two peptidyls
The new pharmaceutical uses of peptase IV (DPP-IV) inhibitor.
Background technology
DPP IV (IUBMB enzyme nomenclature EC.3.4.14.5) is a kind of II types memebrane protein, in the literature with a variety of
Title refers to, including DPP4, DP4, DAP-IV, FAP β, adenosine deaminase complex protein 2, adenosine deaminase binding protein
(ADAbp), bis- peptidyls of Dipeptidylaminopeptidase IV, Xaa-Pro--aminopeptidase, Gly-Pro naphthalenes amidase, rear proline
(postproline) Dipeptidylaminopeptidase IV, lymphocyte antigen CD26, glycoprotein GP110, DPP IV, sweet ammonia
Acyl Prolyl iminopeptidase, glycyl Prolyl iminopeptidase, X- prolyl pipeptidyl bases aminopeptidase, pepX, leukocyte antigen
CD26, glycylprolyl Dipeptidylaminopeptidase, two peptidyl-peptide hydrolases, glycylprolyl aminopeptidase, two peptidyls-
Aminopeptidase IV, DPPIV/CD26, aminoacyl-prolyl pipeptidyl base aminopeptidase, T cell triggering molecule Tp103, X-
PDAP.DPP IV is referred to herein as " DPP-IV ".
DPP-IV is a kind of non-classical serine aminopeptidase, is removed from the amino terminal (ends N-) of peptide and protein
Remove Xaa-Pro dipeptides.Some naturally occurring peptides are also it has been reported that the DPP-IV dependences of X-Gly or X-Ser type dipeptides are slow
Release.
The present invention relates to can inhibit dipeptidyl peptidase-IV (DipeptidylpeptidaseIV, DPP-IV) active chemical combination
Object and/or pharmaceutically acceptable solvate, this kind of compound can be used for treating diabetes, as diabetes B, hyperglycemia,
Metabolic syndrome, hyperinsulinemia, obesity, angiocardiopathy and abnormal such as atherosclerosis, cranial vascular disease, maincenter god
Include schizophrenia, anxiety disorder, Bipolar depression, depression, insomnia, cognitive disorder, stomach and intestine through systemic disease or exception
Disease and exception, cancer, inflammation and inflammatory disease, respiratory disease and exception, skeletal muscle is abnormal, osteoporosis, climacteric
Symptom or exception, periodontal disease such as gingivitis and various immunoregulatory disorders.
DPP-IV belongs to serine peptide enzyme family, belong to together the family also have DPP2, DPP8, DPP9, FAP and
POP etc..Animal model experiment is the results show that inhibit DPP8/9 that can cause such as anaemia, alopecia, decrease of platelet and splenomegaly
Equal toxic reactions [Lankas GR, Leiting B, et al.Dipeptidyl peptidase IV inhibition for
the treatment of type2diabetes:potential importance of selectivity over
dipeptidyl peptidases8and9.Diabetes,2005,54:2988-2994].Therefore, for the single targets of DPP-IV
The design and exploitation for the selective depressant selected are of great significance [Bhumika DP, ManJunath DG.Recent
approaches to medicinal chemistry and therapeutic potential of dipeptidyl
peptidase-4(DPP-4)inhibitors.European Journal of Medicinal Chemistry,2014,74:
574-605], this is also the difficult point and key point of new selective DPP-IV inhibitor research and development.
Therefore, there is still a need for the strong selective DPP-IV inhibitors of structure novel, activity to meet clinical treatment for this field
Demand.
Invention content
DPP IV (Dipeptidyl peptidase IV, DPP-IV, CD26, EC 3.4.14.5) is a kind of energy
The serine protease of specific for hydrolysis polypeptide or protein N-terminal Xaa-Pro or Xaa-Ala dipeptides.DPP-IV is atypia
Serine protease, the Ser-Asp-His catalytic triads in C-terminal region are different from typical serine protease, are backward
Arrangement.DPP-IV is II type integral membrane proteins, is distributed widely in mammal and respectively organizes.DPP-IV is small in intestines, liver, kidney proximal end
Pipe, prostate, the differentiation surface epithelial cell of corpus luteum and leukocyte sub-type such as lymphocyte and Expression of Macrophages.It is deposited in serum
In the soluble protein form of DPP-IV, structure and function is identical as embrane-associated protein form but lacks hydrophobic transmembrane structure
Domain.
Inhibit DPP-IV that can become diabetes B and fat attractive therapy.Although DPP-IV inhibitor energy
It is effectively improved the sugar tolerance of diabetes B patient, but the half-life period of many inhibitor is shorter, or is more toxic.Therefore, it is necessary to open
Hair has more the DPP-IV of advantage in pharmaceutical activity, stability, selectivity, toxicity, pharmacokinetics or medicine at least one aspect of characteristic
Inhibitor is treated for diabetes B.Therefore, the present invention provides a kind of novel DPP-IV inhibitors.
Specific implementation mode
Test example below is for illustrating the present invention.
Compound dihydroartemisinine (CAS used in the present invention:It is 71939-50-9) obtained by mm Suppliers.
Biological assessment
Test example 1
The compounds of this invention tests DPP-IV enzyme inhibition activities：
Instrument:
Microplate reader, Envision (PerkinElmer, USA)
Material:
People source DPP-IV is obtained to be expressed in insect cell using baculovirus expression system.
Substrate, Ala-Pro-AMC.
Process:
DPP-IV can the ultraviolet excitation production of the la-Pro-AMC generations of specific for hydrolysis substrate A product AMC, AMC through 355nm
The transmitting light of raw 460nm, fluorescent value linear change at 460nm wavelength, is calculated DPP4 activity in dynamic cooling water of units of measurement time.
Experiment uses MERK-0431 compounds as a contrast.
Sample is dissolved with DMSO, Cord blood, DMSO in final system concentration control do not influence to detect it is active
Within the scope of.
It is 17.57 that compound MERK-0431, which is IC50 [nM] to the inhibiting effect of DPP-IV,.
Compound dihydroartemisinine is 87.6% to the inhibiting effect of DPP-IV in a concentration of 20 μ g/mL.
Conclusion：Compound dihydroartemisinine in the present invention has good inhibiting effect to DPP-IV enzymes.
The present invention can be summarized with others without prejudice to the concrete form of the spirit or essential characteristics of the present invention.Therefore, nothing
By from the point of view of which point, the embodiment above of the invention can only all be considered the description of the invention and cannot limit this hair
It is bright.
Claims (2)
1. application of the compound dihydroartemisinine in preparing DPP IV (DPP-IV) inhibitor medicaments.
2. compound dihydroartemisinine is not more than 87.6% in a concentration of 20 μ g/mL to the inhibiting effect of DPP-IV.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810269018.XA CN108478556A (en) | 2018-03-29 | 2018-03-29 | The new pharmaceutical uses of dihydroartemisinine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810269018.XA CN108478556A (en) | 2018-03-29 | 2018-03-29 | The new pharmaceutical uses of dihydroartemisinine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108478556A true CN108478556A (en) | 2018-09-04 |
Family
ID=63316718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810269018.XA Pending CN108478556A (en) | 2018-03-29 | 2018-03-29 | The new pharmaceutical uses of dihydroartemisinine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108478556A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111632048A (en) * | 2019-06-11 | 2020-09-08 | 中国农业大学 | Application of dihydroartemisinin in preparation of medicine for preventing and treating hyperammonemia |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101879158A (en) * | 2010-07-01 | 2010-11-10 | 中国科学院广州生物医药与健康研究院 | New application of artemisinin derivant |
| CN107349198A (en) * | 2016-05-10 | 2017-11-17 | 复旦大学 | Artemether is preparing the purposes in promoting lipolysis and improving glycometabolism preparation |
-
2018
- 2018-03-29 CN CN201810269018.XA patent/CN108478556A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101879158A (en) * | 2010-07-01 | 2010-11-10 | 中国科学院广州生物医药与健康研究院 | New application of artemisinin derivant |
| CN107349198A (en) * | 2016-05-10 | 2017-11-17 | 复旦大学 | Artemether is preparing the purposes in promoting lipolysis and improving glycometabolism preparation |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111632048A (en) * | 2019-06-11 | 2020-09-08 | 中国农业大学 | Application of dihydroartemisinin in preparation of medicine for preventing and treating hyperammonemia |
| CN111632048B (en) * | 2019-06-11 | 2021-09-21 | 中国农业大学 | Application of dihydroartemisinin in preparation of medicine for preventing and treating hyperammonemia |
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| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180904 |
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| WD01 | Invention patent application deemed withdrawn after publication |