CN108186635A - The new pharmaceutical uses of dictamine - Google Patents
The new pharmaceutical uses of dictamine Download PDFInfo
- Publication number
- CN108186635A CN108186635A CN201810269501.8A CN201810269501A CN108186635A CN 108186635 A CN108186635 A CN 108186635A CN 201810269501 A CN201810269501 A CN 201810269501A CN 108186635 A CN108186635 A CN 108186635A
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- China
- Prior art keywords
- dpp
- dictamine
- pharmaceutical uses
- new pharmaceutical
- compound
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Classifications
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- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The title of the present invention is the new pharmaceutical uses of dictamine.Affiliated technical field is medical science.The technical problems to be solved by the invention are to be related to dictamine 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 field, specifically, the present invention relates to compound dictamines to be used as dipeptidyl peptidase
The new pharmaceutical uses of 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 (N- ends) 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 the chemical combination that can inhibit dipeptidyl peptidase-IV (DipeptidylpeptidaseIV, DPP-IV) activity
Object and/or pharmaceutically acceptable solvate, this kind of compound can be used for treat 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
Wait 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, this field still needs the strong selective DPP-IV inhibitors of structure novel, activity to meet clinical treatment
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 with 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 toxicity is larger.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 embodiment
Following test example is for illustrating the present invention.
Compound dictamine (CAS used in the present invention:484-29-7) 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 specific for hydrolysis substrate A la-Pro-AMC generations 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 is using MERK-0431 as control compound.
Sample is dissolved with DMSO, Cord blood, and concentration controls of the DMSO in final system is not influencing detection activity
Within the scope of.
Compound MERK-0431 is that IC50 [nM] is 17.57 to the inhibiting effect of DPP-IV.
Compound dictamine is 63.1% to the inhibiting effect of DPP-IV in a concentration of 20 μ g/mL.
Conclusion：Compound dictamine 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 dictamine in DPP IV (DPP-IV) inhibitor medicaments are prepared.
2. compound dictamine is not more than 63.1% 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 |
|---|---|---|---|
| CN201810269501.8A CN108186635A (en) | 2018-03-29 | 2018-03-29 | The new pharmaceutical uses of dictamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810269501.8A CN108186635A (en) | 2018-03-29 | 2018-03-29 | The new pharmaceutical uses of dictamine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108186635A true CN108186635A (en) | 2018-06-22 |
Family
ID=62596304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810269501.8A Pending CN108186635A (en) | 2018-03-29 | 2018-03-29 | The new pharmaceutical uses of dictamine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108186635A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111317734A (en) * | 2020-03-27 | 2020-06-23 | 广州医科大学附属第二医院 | Wnt signal pathway inhibitor and application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101543546A (en) * | 2008-03-28 | 2009-09-30 | 上海安普生物科技有限公司 | Antioxidative substance and composition and use thereof |
-
2018
- 2018-03-29 CN CN201810269501.8A patent/CN108186635A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101543546A (en) * | 2008-03-28 | 2009-09-30 | 上海安普生物科技有限公司 | Antioxidative substance and composition and use thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111317734A (en) * | 2020-03-27 | 2020-06-23 | 广州医科大学附属第二医院 | Wnt signal pathway inhibitor and application |
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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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180622 |