CN104725307A - PTP1B inhibitor containing nicotinic acid amide structure and preparation method and use thereof - Google Patents
PTP1B inhibitor containing nicotinic acid amide structure and preparation method and use thereof Download PDFInfo
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- CN104725307A CN104725307A CN201510108460.0A CN201510108460A CN104725307A CN 104725307 A CN104725307 A CN 104725307A CN 201510108460 A CN201510108460 A CN 201510108460A CN 104725307 A CN104725307 A CN 104725307A
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- compound
- preparation
- ptp1b inhibitor
- acid amide
- nicotinic acid
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Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000003801 protein tyrosine phosphatase 1B inhibitor Substances 0.000 title abstract description 8
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 title abstract 2
- 239000003814 drug Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 42
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000000967 suction filtration Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 108091005804 Peptidases Proteins 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical group 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 235000001968 nicotinic acid Nutrition 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 230000009514 concussion Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000452 restraining effect Effects 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 108010013043 Acetylesterase Proteins 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N BrCc1ccccc1 Chemical compound BrCc1ccccc1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N C1CCNCC1 Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- DJSLBPHDHOTKMU-UHFFFAOYSA-N COC(c(cncc1)c1SCc1ccccc1)=O Chemical compound COC(c(cncc1)c1SCc1ccccc1)=O DJSLBPHDHOTKMU-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010072039 Histidine kinase Proteins 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- NMQZMCDXMXHXHP-UHFFFAOYSA-N O=C(c(cncc1)c1SCc1ccccc1)N1CCCCC1 Chemical compound O=C(c(cncc1)c1SCc1ccccc1)N1CCCCC1 NMQZMCDXMXHXHP-UHFFFAOYSA-N 0.000 description 1
- QXGWKRJJEODSIZ-UHFFFAOYSA-N OC(c(cncc1)c1S)=O Chemical compound OC(c(cncc1)c1S)=O QXGWKRJJEODSIZ-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- VUOGVQVJJBOXFZ-RGMNGODLSA-N P(O)(O)(O)=O.C(CC)N[C@@H](CCO)C(=O)O Chemical compound P(O)(O)(O)=O.C(CC)N[C@@H](CCO)C(=O)O VUOGVQVJJBOXFZ-RGMNGODLSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004155 insulin signaling pathway Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the field of medicines related to type II diabetes and particularly relates to a PTP1B inhibitor containing a nicotinic acid amide structure, a preparation method thereof and application of the PTP1B inhibitor in preparation of medicines for treating the type II diabetes. The PTP1B inhibitor has a structure represented by a formula shown in descriptions.
Description
Technical field
The present invention relates to the pharmaceutical field of type ii diabetes treatment.More particularly, the present invention relates to type ii diabetes tool medicative a kind of PTP1B inhibitor, its preparation method containing niacin hydroxyacyl amine structure, and the purposes in pharmacy.
Background technology
Type ii diabetes is a kind of common metabolic disturbance diseases, it is characterized in that periphery produces resistant function to film island element, shows as Regular Insulin to be combined signal transduction afterwards with insulin receptor and to lack at molecular level.The phosphorylation level of proteolytic enzyme propylhomoserin is the important regulate factors of intracellular signal transduction, it is by proteolytic enzyme histidine kinase (protein tyrosine kinase, PTK) and proteolytic enzyme propylhomoserin Phosphoric acid esterase (protein tyrosine phosphatase, PTP) jointly regulate and control.Research in recent years finds, proteolytic enzyme propylhomoserin phosphatase 1 B can dephosphorylation proteolytic enzyme propylhomoserin, plays important negative regulation effect in Insulin signaling pathway.Knock out PTPIB gene, or use antisense core former times acid (ASO) to suppress the expression of PTP1B albumen and mRNA in body, not only can significantly improve the susceptibility of test mice to Regular Insulin, and obviously can reduce the ill probability of obesity.These researchs show, PTP1B likely becomes the novel targets for the treatment of type ii diabetes.
The invention discloses a kind of PTP1B inhibitor containing niacin hydroxyacyl amine structure of novel structure, these compounds can be used for the medicine preparing treatment type ii diabetes.
Summary of the invention
An object of the present invention is to provide a kind of PTP1B inhibitor with the excellent activity of formula I.
Another object of the present invention is to provide the method that preparation has the compound of formula I.
The compound that another object of the present invention is to provide containing formula I is treating the application in type ii diabetes as effective constituent.
Now in conjunction with object of the present invention, content of the present invention is specifically described.
The compound that the present invention has formula I has following structural formula:
Formula I of the present invention is synthesized by following route:
Compound II per in the presence of a base with compound III generation substitution reaction, obtain compound IV; There is lower and compound V at DCC (N, N'-dicyclohexyl carbodiimide) and react in compound IV, obtains VI; The oxidation of oxidized dose of compound VI, obtains Compound I.Compound II per can prepare (Leon Katz according to literature method; Et al, Journal of Organic Chemistry, 1954,19,711).
Formula I of the present invention has the restraining effect of PTP1B, can be used as effective constituent for the preparation of type ii diabetes medicine.The activity of formula I of the present invention is verified by receptor binding assays.
Formula I of the present invention is effective in quite wide dosage range.The dosage that such as every day takes, within the scope of 1mg-1000mg/ people, is divided into once or administration for several times.The actual dosage taking formula I can be decided according to relevant situation by doctor.
Embodiment
Below in conjunction with embodiment, the present invention is further illustrated.It should be noted that, following embodiment be only for illustration of, and not for limiting the present invention.The various changes that those skilled in the art's training centre according to the present invention is made all should within the protection domain required by the application's claim.
the synthesis of embodiment 1 Compound I
A. the synthesis of compound IV-1
Compound II per (1.55g, 10mmol), compound III-1 (1.96g, 10mmol) and solid K
2cO
3(5.53g, 40mmol) adds in the DMF of 30mL drying, room temperature for overnight, and TLC follows the tracks of and finds that reaction completes.Reaction mixture pours in 200mL frozen water, stirs, regulates pH=4-5, use CH with concentrated hydrochloric acid
2cl
2(60mL × 3) extract, and merge extraction phase, use salt water washing, anhydrous sodium sulfate drying.Suction filtration removing siccative, filtrate is evaporate to dryness on a rotary evaporator, and the resistates obtained uses column chromatography purification, obtains compound IV-1, white solid.ESI-MS,m/z＝269([M-H]
-)。
B. the synthesis of compound VI-1
Compound IV-1 (1.35g, 5mmol), compound V-1 (0.43g, 5mmol), DCC (1.24g, 6mmol) with DMAP (DMAP, 0.3g) be dissolved in dry 20mL THF, room temperature for overnight, TLC follows the tracks of and finds that reaction completes.Reaction mixture pours in 200mL frozen water, stirs, uses CH
2cl
2(60mL × 3) extract, and merge extraction phase, use 2% dilute hydrochloric acid and salt water washing successively, anhydrous sodium sulfate drying.Suction filtration removing siccative, filtrate is evaporate to dryness on a rotary evaporator, and the resistates obtained uses column chromatography purification, obtains compound VI-1, white solid.ESI-MS,m/z＝338([M+H]
+)。
C. the synthesis of Compound I
Compound VI-1 (0.67g, 2mmol) is dissolved in 10mL CH
2cl
2in, stirred at ambient temperature, add metachloroperbenzoic acid (mCPBA, 1.72g, 10mmol), reaction mixture at room temperature stirs 1 hour, then temperature rising reflux 3 hours, and TLC detection reaction completes.Reaction mixture pours in 200mL frozen water, stirs, uses CH
2cl
2(60mL × 3) extract, and merge extraction phase, use saturated NaHCO successively
3solution and salt water washing, anhydrous sodium sulfate drying.Suction filtration removing siccative, filtrate is evaporate to dryness on a rotary evaporator, and the resistates obtained uses column chromatography purification, obtains Compound I, white solid.ESI-MS，m/z＝386([M+H]
+)。
the synthesis of embodiment 2 reference compound R-1
In order to pharmacological effect more of the present invention further, applicant describes the unknown compound R-1 (not yet open) being all applicant's invention in this application.
A. the synthesis of compound IV-2
Compound II per (1.55g, 10mmol), compound III-2 (1.71g, 10mmol) and solid K
2cO
3(5.53g, 40mmol) adds in the DMF of 30mL drying, room temperature for overnight, and TLC follows the tracks of and finds that reaction completes.Reaction mixture pours in 200mL frozen water, stirs, regulates pH=4-5, use CH with concentrated hydrochloric acid
2cl
2(60mL × 3) extract, and merge extraction phase, use salt water washing, anhydrous sodium sulfate drying.Suction filtration removing siccative, filtrate is evaporate to dryness on a rotary evaporator, and the resistates obtained uses column chromatography purification, obtains compound IV-2, white solid.ESI-MS,m/z＝244([M-H]
-)。
B. the synthesis of compound VI-2
Compound IV-2 (1.23g, 5mmol), compound V-1 (0.43g, 5mmol), DCC (1.24g, 6mmol) with DMAP (DMAP, 0.3g) be dissolved in dry 20mL THF, room temperature for overnight, TLC follows the tracks of and finds that reaction completes.Reaction mixture pours in 200mL frozen water, stirs, uses CH
2cl
2(60mL × 3) extract, and merge extraction phase, use 2% dilute hydrochloric acid and salt water washing successively, anhydrous sodium sulfate drying.Suction filtration removing siccative, filtrate is evaporate to dryness on a rotary evaporator, and the resistates obtained uses column chromatography purification, obtains compound VI-2, white solid.ESI-MS,m/z＝313([M+H]
+)。
C. the synthesis of compound R-1
Compound VI-2 (0.62g, 2mmol) is dissolved in 10mL CH
2cl
2in, stirred at ambient temperature, add metachloroperbenzoic acid (mCPBA, 1.72g, 10mmol), reaction mixture at room temperature stirs 1 hour, then temperature rising reflux 3 hours, and TLC detection reaction completes.Reaction mixture pours in 200mL frozen water, stirs, uses CH
2cl
2(60mL × 3) extract, and merge extraction phase, use saturated NaHCO successively
3solution and salt water washing, anhydrous sodium sulfate drying.Suction filtration removing siccative, filtrate is evaporate to dryness on a rotary evaporator, and the resistates obtained uses column chromatography purification, obtains compound R-1, white solid.ESI-MS，m/z＝361([M+H]
+)。
embodiment 3 Compound ira vitro is to the inhibition test of PTP1B
Be that the compound solution 95%DMSO of 50mM carries out 1/2 gradient dilution by original concentration, dilute 11 concentration gradients altogether.Enzyme reaction system alive amounts to 102 μ L, and wherein compound adds volume is 2 μ L.First, in 96 orifice plates, add 50 μ L PTP1B albumen successively, the testing compound of 2 μ L different concns, concussion 1min, hatches 30min for 30 DEG C, then adds 50 μ L pNPP (para-nitro-pheneye phosphate), concussion 10s.Under mensuration 405nm wavelength, absorbancy is with the change in reaction times, within 6 seconds, survey once, survey 60 points, replicate(determination) three times, and draw out reaction process curve, thus under calculating different concns each compound to the inhibit activities of enzyme, software GraphPad Prism 5 software is utilized to carry out non linear fit analysis, with remaining activity value for ordinate zou, compound concentration logarithmic value is X-coordinate curve plotting, calculates the IC of this compound
50value.
Test result sees the following form.
| Compound | IC 50(nM) |
| Reference compound R-1 | 18.6 |
| The compounds of this invention I | 9.5 |
As can be seen from upper table result, compound of the present invention has very strong restraining effect to PTP1B, can as preparation treatment type ii diabetes medicine.
Claims (2)
1. a compound for formula I structure,
2. the application of the described formula I of one of claim 1 in preparation treatment diabetes B medicine.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710074729.7A CN106831559A (en) | 2015-03-12 | 2015-03-12 | A kind of PTP1B inhibitor, preparation method and its usage containing niacin hydroxyacyl amine structure |
| CN201510108460.0A CN104725307A (en) | 2015-03-12 | 2015-03-12 | PTP1B inhibitor containing nicotinic acid amide structure and preparation method and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510108460.0A CN104725307A (en) | 2015-03-12 | 2015-03-12 | PTP1B inhibitor containing nicotinic acid amide structure and preparation method and use thereof |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710074729.7A Division CN106831559A (en) | 2015-03-12 | 2015-03-12 | A kind of PTP1B inhibitor, preparation method and its usage containing niacin hydroxyacyl amine structure |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104725307A true CN104725307A (en) | 2015-06-24 |
Family
ID=53449788
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|---|---|---|---|
| CN201710074729.7A Pending CN106831559A (en) | 2015-03-12 | 2015-03-12 | A kind of PTP1B inhibitor, preparation method and its usage containing niacin hydroxyacyl amine structure |
| CN201510108460.0A Pending CN104725307A (en) | 2015-03-12 | 2015-03-12 | PTP1B inhibitor containing nicotinic acid amide structure and preparation method and use thereof |
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Country Status (1)
| Country | Link |
|---|---|
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6262044B1 (en) * | 1998-03-12 | 2001-07-17 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (PTPASES) |
| WO2002018321A2 (en) * | 2000-08-29 | 2002-03-07 | Abbott Laboratories | Amino(oxo)acetic acid protein tyrosine phosphatase inhibitors |
| CN101123964A (en) * | 2004-12-24 | 2008-02-13 | 普罗西迪恩有限公司 | G protein-coupled receptor (GPR116) agonists and their use for the treatment of obesity and diabetes |
| CN101484440A (en) * | 2006-07-06 | 2009-07-15 | 艾尼纳制药公司 | Modulators of metabolism and the treatment of disorders related thereto |
-
2015
- 2015-03-12 CN CN201710074729.7A patent/CN106831559A/en active Pending
- 2015-03-12 CN CN201510108460.0A patent/CN104725307A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6262044B1 (en) * | 1998-03-12 | 2001-07-17 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (PTPASES) |
| WO2002018321A2 (en) * | 2000-08-29 | 2002-03-07 | Abbott Laboratories | Amino(oxo)acetic acid protein tyrosine phosphatase inhibitors |
| CN101123964A (en) * | 2004-12-24 | 2008-02-13 | 普罗西迪恩有限公司 | G protein-coupled receptor (GPR116) agonists and their use for the treatment of obesity and diabetes |
| CN101484440A (en) * | 2006-07-06 | 2009-07-15 | 艾尼纳制药公司 | Modulators of metabolism and the treatment of disorders related thereto |
Non-Patent Citations (1)
| Title |
|---|
| 李升康等: "蛋白酪氨酸磷酸酶1B (PTP-1B)在2 型糖尿病治疗中的研究进展", 《衡阳师范学院学报》 * |
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| Publication number | Publication date |
|---|---|
| CN106831559A (en) | 2017-06-13 |
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