CN107890569A - The preparation method for the dual Brain targeting prodrug modified jointly with glucose and ascorbic acid - Google Patents
The preparation method for the dual Brain targeting prodrug modified jointly with glucose and ascorbic acid Download PDFInfo
- Publication number
- CN107890569A CN107890569A CN201711165808.5A CN201711165808A CN107890569A CN 107890569 A CN107890569 A CN 107890569A CN 201711165808 A CN201711165808 A CN 201711165808A CN 107890569 A CN107890569 A CN 107890569A
- Authority
- CN
- China
- Prior art keywords
- glucose
- ascorbic acid
- medicine
- brain targeting
- dual
- 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
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- 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
- A61K31/13—Amines
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
It is formula the invention discloses a kind of dual Brain targeting prodrug modified jointly with glucose and ascorbic acid（I）Shown structure or its pharmaceutically acceptable salt or hydrate：, wherein：X represents (CH2)n‑、‑C(O)‑(CH2)nC (O) or C (O) (CH2)m, (CH2)mC (O), n represent that 0 ~ 6, m represents 1 ~ 4；Y represents (CH2)a‑、‑C(O)‑(CH2)aC (O) or (CH2)b‑O‑、‑(CH2)b‑NH‑、‑C(O)‑(CH2)b‑O‑、‑C(O)‑(CH2)bNH, a represent that 0 ~ 6, b represents 1 ~ 4；Drug represents the medicine that may act on central nervous system.The present invention provides a series of prodrugs, can improve brain targeting, the central concentrations of medicine of medicine, so as to strengthen curative effect of medication, while reduce distribution of the medicine in peripheral organ, reduce the toxic side effect of medicine.
Description
Technical field
The present invention relates to a kind of noval chemical compound, and in particular to before a kind of dual Brain targeting based on glucose and ascorbic acid
The design and preparation method of medicine.Belong to pharmaceutical technology field.
Background technology
According to statistics, the whole world there are about 1/5 central nervous system (CNS) disease of population with variety classes and degree, this
A little diseases include brain tumor, acute or chronic Pain Syndrome, epilepsy, encephalitis, cerebral ischemia and neurodegenerative disease (such as：
Alzheimer's disease, Parkinson's disease etc.).With the aging of world population, this trend will be more serious, and can be right
The health of the mankind causes serious influence.The presence of blood-brain barrier (BBB) serves certain guarantor to mankind's central nervous system
Shield acts on, but also limit many materials simultaneously and enter brain from blood.Nearly all macromolecular and 95% small molecule medicine
Thing can not all be efficiently entering brain and central nervous system, and this to hardly enter CNS lesions positions simultaneously to the effective medicines of CNS
Effective drug concentration is presented so as to reach therapeutic effect.
It is reported that NSAIDs (Non-Steroidal Anti-Inflammatory Drugs, NSAIDs) such as naphthalene
The neuroprotective agents such as general life, brufen have been widely used for treating CNS diseases, it is also possible to make chronic intake type non-steroidal anti-inflammatory
Medicine.For example, naproxen can reduce the risk of CNS diseases, or even the morbidity of CNS diseases can be delayed, so naproxen is being controlled
Treating the disorderly aspects of CNS has broad based growth prospect.But due to the hypotonicity of naproxen, the distribution in CNS is limited, has
The treatment concentration of effect is low, needs to increase the dosage of medicine to reach preferable therapeutic effect, medicine is reached one in vivo
Higher concentration, but at the same time the drug concentration of other organs can also increase, and toxicity is consequently increased, and body is produced
Bigger harm.These long-term use of medicines, will produce different degrees of gastrointestinal discomfort, dizzy, headache, or even renal toxicity
Deng adverse reaction.Distribution of these adverse reactions mainly due to medicine in vivo, when medicine is more in peripheral organ's distribution
When, various toxicities are easily produced, while its distribution proportion in brain tissue is also reduced, so the clinic of naproxen should
With being greatly limited.Therefore, in order to treat CNS diseases, it is necessary to find a kind of effective strategy with improve naproxen
Transport capability in brain.
Blood brain barrier (blood-brain barrier, BBB) is to be present in blood-brain, blood-brain spinal fluid (BCB) and brain-brain
Between spinal fluid selectively control into cerebrospinal fluid and brain material, as the adjustment interface between blood and central nervous system,
To maintaining the environment in central nervous system is constant to have vital effect.This to hardly enter the effective medicines of CNS
Simultaneously effective drug concentration is presented so as to reach therapeutic effect in CNS lesions positions.Therefore to across BBB administering modes research
As the key for the treatment of CNS diseases.Research shows that these specific transporters have higher selectivity, generally specific
Carrier protein can only transport specific substrate.
Glucose is one of main energy sources source of mammalian cell, and brain but occupies although only the 2% of body weight
About the 30% of human consumption glucose total amount.GLUT (GLUT on studies have shown that blood-brain barrier1) quantity is a lot,
About each cerebrovascular endothelial cell contains 6 × 106Individual GLUT1Molecule, it is that quantity is most in all transport proteins on BBB.
GLUT1Primary structure shows that it has 12 transmembrane helix structures, forms the hydrophilic passage through bilayer lipid membrane, permits
Perhaps D-Glucose and other hexoses pass through.The GLUT that altimeter reaches on BBB1Transport efficacy is very high, its transhipment per minute
Glucose quality is ten times of sole mass, therefore turns into the target spot often considered during current Brain targeting drug modification.Research hair
It is existing, when glucose 6 is connected with medicine, itself and GLUT1Affinity it is most strong, illustrating that medicine is connected with 6 hydroxyls can be most
The reservation glucose and GLUT of big degree1Affine activity.CNS classes medicine after glucose modified also shows to compare parent drug
Preferably activity, as anticonvulsive drug 7-Cl-Kyn, NSAIDs brufen, parkinsonism medicine dopamine with
It is all significantly improved in the distribution of intracerebral after glucose coupling, and these results all show using glucose as carrier, GLUT1For target spot
Prodrug be Brain targeting drug design effective means.
In addition to glucose, ascorbic acid derivates equally have good brain targeting.Ascorbic acid (Ascorbic
Acid), also known as vitamin C, there are many biological functions, including：Participate in amino acid metabolism；Neurotransmitter, collagen and
The synthesis of histocyte interstitial；Increase the resistivity to infection；The permeability of capillary is reduced, accelerates blood clotting；And
There is antihistamine and prevent carcinogen generation etc..Ascorbic acid in more than 10 times that the concentration of intracerebral is other organs,
This comes from GLUT in brain1、SVCT2With a small amount of SVCT1Transfer body of the ascorbic acid by blood-brain barrier can be served as, so as to
Ascorbic acid is set to maintain an of a relatively high level in intracerebral.Therefore, can be using ascorbic acid as medicine brain target
To the carrier of administration.C2-OH, C3-OH that Christopher P.Corpe et al. mention ascorbic acid turn for ascorbic acid
Transport most important, it is necessary that the hydroxyl in C2 and C3 on enediol is that ascorbic acid plays reducing power institute in oxidation-reduction process
Important reaction site, and effect very little of the hydroxyl in ascorbic acid on C5 and C6 played in transport process, therefore
The modification of Ascorbic Acid is concentrated mainly on the two positions.
Based on the studies above and it is assumed that object of this investigation is to propose a kind of new spread out based on glucose and ascorbic acid
The preparation method for the pharmaceutical carrier with dual Brain targeting function that biology is modified jointly, to improve the brain targeting of medicine, increase
The central concentrations of dosing thing, so as to strengthen curative effect of medication, while distribution of the medicine in peripheral organ is reduced, reduce medicine
Toxic side effect.Therefore, we are devised as led to a kind of prodrug shown in formula (I).
The content of the invention
The present invention provides the compound or its pharmaceutically acceptable salt or hydrate of structure shown in a kind of logical formula (I)：
Wherein：
X representative-(CH2)n-、-C(O)-(CH2)n- C (O)-or-C (O)-(CH2)m- ,-(CH2)m- C (O)-, n represents 0~6, m
Represent 1~4；
Y representative-(CH2)a-、-C(O)-(CH2)a- C (O)-or-(CH2)b-O-、-(CH2)b-NH-、-C(O)-(CH2)b-O-、-C
(O)-(CH2)b- NH-, a represent that 0~6, b represents 1~4；
Drug represents the medicine that may act on central nervous system.
The specific preparation method of compound is as follows shown in logical formula (I)：
Specific implementation method
But following examples are intended to illustrate invention rather than limitation of the invention further.
Embodiment 1
The preparation of compound 2
D-Glucose (30g, 0.167mol) is dissolved in the pyridine of 230ml dryings, trim,ethylchlorosilane is slowly added dropwise under ice bath
(128ml, 1mol) and hexamethyldisilane amine (105ml, 0.5mol) mixed solution, after being stirred overnight at room temperature, are removed under reduced pressure
Solvent, residue are dissolved in water, and ether is extracted twice, and merge organic layer, successively with the respectively washing three of 1N hydrochloric acid and saturated aqueous common salt
It is secondary, anhydrous sodium sulfate drying, filtering, the give light yellow oil that is concentrated under reduced pressure 87.3g, yield 96.6%.Product can not be purified
Directly carry out next step reaction.MS(m/z):491.5[M+Na]+。
Embodiment 2
The preparation of compound 3
Under ice bath, acetic acid is slowly added dropwise into compound 2 (20g, 37mmol) acetone-methanol (50ml-80mll) solution
Acetone-methanol (5ml-8ml) solution of (4.2ml, 74mmol).Drop finishes, and after reaction is moved into room temperature reaction 2h, is removed under reduced pressure molten
Agent obtains crude product.Column chromatography purifies, and obtains white solid 13.04g, yield 75.2%.1H-NMR(400MHz,CDCl3):δ0.14-
0.19(s,36H,-(SiCH3)3× 4), 3.34 (dd, 1H, J=2.8Hz, 9.2Hz), 3.66 (t, 1H, J=9.2Hz), 3.68
(dd, 1H, J=4.8Hz, 12Hz), 3.73-3.76 (m, 2H), 3.80 (t, 1H, J=8.8Hz), 5.16 (d, 1H, J=
3.2Hz)。
Embodiment 3
The preparation of compound 4
Dicyclohexylcarbodiimide is added into dichloromethane (25ml) solution of succinic acid list benzyl ester (660mg, 3.18mmol)
(DCC, 660mg, 3.18mmol), DMAP (DMAP, 16mg, 0.127mmol), is stirred at room temperature, and activates 30min
Afterwards, compound 3 (600mg, 1.27mmol) is added.After reacting at room temperature 6h, filtering, filtrate concentration, purify, obtain pale yellow through column chromatography
Color grease 400mg, yield 47.8%.1H-NMR(400MHz,CDCl3):δ0.13-0.18(s,36H,-(SiCH3)3×4),
3.36 (dd, 1H, J=3.2Hz, 9.2Hz ,-4C-H),2.68(s,4H,-OOC(CH2)2), COO- 3.42 (t, 1H, J=
8.8Hz,-3C-H), 3.78 (t, 1H, J=8.8Hz ,-2C-H),3.91(m,1H,-6C-H), 4.05 (dd, 1H, J=5.2Hz,
12Hz,-6C-H), 4.36 (dd, 1H, J=2.4Hz, 12.4Hz ,-5C-H), 5.00 (d, 1H, J=3.2Hz ,-1C-H),5.13
(s,2H,PhCH2-),7.35(m,5H,aromatic-H)。
Embodiment 4
The preparation of compound 5
Pd/C (10%, 40mg) is added into compound 4 (400mg, 0.61mmol) ethanol (10ml) solution, in atmosphere of hydrogen
Under, react at room temperature 2h.Pd/C is filtered to remove, filtrate is concentrated to give colorless oil 300mg, and yield 86.9%, product is without purifying
Next step reaction can directly be carried out.1H-NMR(400MHz,CDCl3):δ0.13-0.28(s,36H,-(SiCH3)3×4),2.68
(s,4H,-(CH2)2COOH), 3.37 (dd, 1H, J=3.2Hz, 9.2Hz ,-4C-H), 3.43 (t, 1H, J=8.8Hz ,-3C-H),
3.78 (t, 1H, J=8.4Hz, -2C-H), 3.92 (m, 1H, -6C-H), 4.07 (dd, 1H, J=4.8Hz, 12Hz ,-6C-H),
4.36 (dd, 1H, J=2.4Hz, 11.6Hz ,-5C-H), 5.01 (d, 1H, J=3.2Hz ,-1C-H)。
Embodiment 5
The preparation of compound 7
Ascorbic acid (Ascorbic acid) (24g, 0.135mol) is taken in 500ml two-neck bottles, argon gas protection, adds drying
Acetone (150ml), chloroacetic chloride (0.6ml, 7.5mmol).24h is stirred at room temperature, TLC detection reactions are complete, stop reaction.Filtering
Reaction solution, acetone washing filter cake, dries, obtains white solid 7, yield 85.3%, mp::202-204℃.
Embodiment 6
The preparation of compound 8
By compound 7 (20g, 0.108mol), K2CO3Powder (37.3g, 0.27mol) is dissolved in dry acetone (150ml) room temperature
20min is stirred, BrBn (30ml, 0.25mol), temperature rising reflux 4h are added in upward suspension.Removal of solvent under reduced pressure, sequentially add
A small amount of water, ether, white solid is separated out, filtering, ice ether washing filter cake, dries, obtains white solid 8, yield 44.1%, mp:
200-202℃。
Embodiment 7
The preparation of compound 9
Compound 8 (10g, 25.23mmol) is dissolved in acetonitrile (500ml), HCl (2mol/L, 75ml) is added dropwise, room temperature is stirred
Mix 3h.Removal of solvent under reduced pressure, ethyl acetate (30ml) dissolving is added, three times, organic layer is washed twice with saturated common salt, nothing for washing
Water Na2SO4Dry, be concentrated to give yellow oil sterling, be slowly cured as white solid 9, yield 99%, mp afterwards:67-69℃.1H-NMR(400MHz,CDCl3,ppm):δ2.09(s,2H),3.77(m,2H),3.91(m,1H),4.72(m,1H),5.15
(ABq, 4H, J=11.4Hz), 7.22-7.38 (m, 10H)
Embodiment 8
The preparation of compound 10
Naproxen (587mg, 2.55mmol) is dissolved in 20ml dichloromethane, is placed at -5 DEG C, addition DCC (1.16g,
5.61mmol) and after DMAP (171mg, 1.40mmol), stirring 30min, compound 9 (1.0g, 2.81mmol) is added, moves to room
Temperature is stirred overnight.Filtering, white solid is removed, filtrate concentration, purifies to obtain white solid 0.8g, yield through column chromatography
55.2%.1H-NMR(400MHz,CDCl3):δ 1.57 (d, 3H, J=6..8Hz), 3.45-3.47 (m, 1H), 3.90 (s, 3H),
3.97-3.99(m,1H),4.14-4.21(m,1H),4.28-4.34(m,1H),4.48-4.50(m,1H),5.02-5.16(m,
4H),7.08-7.69(m,16H)。
Embodiment 9
The preparation of compound 11
Compound 5 (481mg, 0.845mmol) is dissolved in 10ml dichloromethane, is placed at -5 DEG C, addition DCC (232mg,
1.12mmol) and after DMAP (14mg, 0.112mmol), stirring 30min, compound 10 (320mg, 0.563mmol) is added, is moved
To being stirred overnight at room temperature.Filtering, white solid is removed, filtrate concentration, purifies to obtain white solid 0.25g, yield through column chromatography
39.7%.1H-NMR(400MHz,CDCl3):δ0.07-0.18(s,36H,-(SiCH3)3× 4), 1.55 (d, 3H, J=
7.2Hz),2.31-2.54(m,4H),3.34-3.41(m,2H),3.75-3.98(m,4H),3.90(s,3H),4.26-4.35
(m, 3H), 4.58-4.62 (m, 1H), 4.99 (d, 1H, J=2.8Hz), 5.05-5.19 (m, 4H), 5.33-5.38 (m, 1H),
7.07-7.70(m,16H)。
Embodiment 10
The preparation of compound 12
Under ice bath, TFA is added into compound 11 (238mg, 0.212mmol) dichloromethane (10ml) solution
(0.32ml.4.25mmol), reaction solution is moved into room temperature after 5min, react 3h.Removal of solvent under reduced pressure, nothing is purified to obtain through column chromatography
Color grease 121mg, yield 68.5%.1H-NMR(400MHz,CDCl3):δ 1.53 (d, 3H, J=5.6Hz), 2.25-2.37
(m,4H),3.26-3.56(m,8H),3.80-3.98(m,3H),3.87(s,3H),4.24-4.34(m,3H),4.52-4.57
(m,1H),4.99-5.12(m,4H),5.26(br,1H),7.06-7.68(m,16H)。
Embodiment 11
Prodrug G-A-Nap preparation
Pd/C (10%, 10mg) is added to compound 12 (115mg) methanol (10ml) solution, in 0.4MPa H2Lower room temperature is anti-
Answer 2h.Pd/C is filtered off, concentrated solvent obtains white solid 80mg, yield 88.9%.1H-NMR(400MHz,CD3OD):δ1.54(d,
3H, J=7.2Hz), 2.28-2.41 (m, 4H), 3.11-5.40 (m, 18H), 3.88 (s, 3H), 7.10 (d, 1H, J=8.8Hz),
7.19 (s, 1H), 7.37 (d, 1H, J=8.8Hz), 7.65 (s, 1H), 7.70-7.73 (m, 2H).
Claims (6)
1. a kind of dual Brain targeting prodrug modified jointly with glucose and ascorbic acid, is formula（I）Shown structure or its medicine
Acceptable salt or hydrate on：
Wherein：
X representative-(CH2)n-、-C(O)-(CH2)n- C (O)-or-C (O)-(CH2)m- ,-(CH2)m- C (O)-, n represents that 0 ~ 6, m is represented
1~4；
Y representative-(CH2)a-、-C(O)-(CH2)a- C (O)-or-(CH2)b-O-、-(CH2)b-NH-、-C(O)-(CH2)b-O-、-C
(O)-(CH2)b- NH-, a represent that 0 ~ 6, b represents 1 ~ 4；
Drug represents the medicine that may act on central nervous system.
2. the dual Brain targeting prodrug according to claim 1 modified jointly with glucose and ascorbic acid, its feature exist
Identical group or different groups can be made in X and Y, it is specifically described as：X both ends are respectively with ester bond or ether
Key is connected with the C6-O of glucose with vitamin C 5-O, and Y one end is connected with ester bond or ehter bond with vitamin C 6-O, another
End is connected with ester bond or ehter bond or amido link with medicine.
3. the dual Brain targeting prodrug according to claim 1 modified jointly with glucose and ascorbic acid, its feature exist
Combine in by the Brain targeting characteristic of glucose and ascorbic acid, form dual Brain targeting prodrug.
4. the dual Brain targeting prodrug according to claim 1 modified jointly with glucose and ascorbic acid, its feature exist
The medicine that naproxen, brufen, Venlafaxine, Memantine hydrochloride etc. may act on central nervous system can be but not limited in medicine
Thing.
5. the dual Brain targeting prodrug according to claim 1 modified jointly with glucose and ascorbic acid, its feature exist
When as n=0, the C6-OH of glucose directly can be connected with the C5-OH of ascorbic acid with ehter bond.
6. the dual Brain targeting prodrug according to claim 1 modified jointly with glucose and ascorbic acid, its feature exist
When as a=0, medicine can directly using its contained free carboxy, hydroxyl etc. as open end with vitamin C 6-O with ester bond or
Ehter bond etc. is connected.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711165808.5A CN107890569A (en) | 2017-11-21 | 2017-11-21 | The preparation method for the dual Brain targeting prodrug modified jointly with glucose and ascorbic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711165808.5A CN107890569A (en) | 2017-11-21 | 2017-11-21 | The preparation method for the dual Brain targeting prodrug modified jointly with glucose and ascorbic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107890569A true CN107890569A (en) | 2018-04-10 |
Family
ID=61805726
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711165808.5A Pending CN107890569A (en) | 2017-11-21 | 2017-11-21 | The preparation method for the dual Brain targeting prodrug modified jointly with glucose and ascorbic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107890569A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110917139A (en) * | 2019-12-02 | 2020-03-27 | 四川大学 | Preparation and application of multi-branch biotin modified breast cancer targeted liposome |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102989004A (en) * | 2012-10-31 | 2013-03-27 | 四川大学 | Brain-targeting prodrug with vitamin C as carrier |
| CN105641711A (en) * | 2016-01-25 | 2016-06-08 | 四川大学 | Dual brain-targeted prodrug with organic-amine-modified vitamin C being carrier |
| CN105732733A (en) * | 2016-01-22 | 2016-07-06 | 四川大学 | Novel glucose-based brain-targeting prodrug with locking function |
-
2017
- 2017-11-21 CN CN201711165808.5A patent/CN107890569A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102989004A (en) * | 2012-10-31 | 2013-03-27 | 四川大学 | Brain-targeting prodrug with vitamin C as carrier |
| CN105732733A (en) * | 2016-01-22 | 2016-07-06 | 四川大学 | Novel glucose-based brain-targeting prodrug with locking function |
| CN105641711A (en) * | 2016-01-25 | 2016-06-08 | 四川大学 | Dual brain-targeted prodrug with organic-amine-modified vitamin C being carrier |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110917139A (en) * | 2019-12-02 | 2020-03-27 | 四川大学 | Preparation and application of multi-branch biotin modified breast cancer targeted liposome |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108743953B (en) | Dual brain tumor targeting lipid material and application thereof | |
| CN108395443B (en) | Cyclic compounds inhibiting programmed death receptor ligand 1 and uses thereof | |
| CN103140227A (en) | Processes for preparing tubulysins | |
| CN108517033A (en) | A kind of novel dual Brain targeting matrix material and its application in drug delivery system | |
| CN101362702B (en) | Emodin derivates and application thereof in anti-cancer medicine preparation | |
| CN108349880B (en) | CYP eicosanoid metabolism robust analogs for treatment of cardiac disorders | |
| CN107890569A (en) | The preparation method for the dual Brain targeting prodrug modified jointly with glucose and ascorbic acid | |
| CN105641711A (en) | Dual brain-targeted prodrug with organic-amine-modified vitamin C being carrier | |
| CN101633684A (en) | Novel tetraterpene derivatives and pharmaceutical use thereof | |
| CN107266404A (en) | A kind of neuraminidase inhibitor zanamivir derivative and preparation method thereof | |
| CN105732733A (en) | Novel glucose-based brain-targeting prodrug with locking function | |
| CN103145636A (en) | 1,4-diacyl-3,6-diphenyl-1,4-dihydrotetrazine compound as well as preparation method and application thereof | |
| CN112898381A (en) | Dioxahexacyclic modified tetrahydrocarboline-3-formyl-The-EDG, preparation, anti-inflammatory and antithrombotic activity and application thereof | |
| EP3431478B1 (en) | Micromolecular lung-targeting drug | |
| TWI794994B (en) | Pyrimidinamide compounds and their applications | |
| CN107899016A (en) | The dual Brain targeting prodrug modified jointly with glucose and vitamin C | |
| CN112175014B (en) | Nitric oxide donor type tetravalent platinum derivative, preparation method and medical application thereof | |
| CN112979751B (en) | Dioxane-modified tetrahydrocarboline-3-formyl-The-HGK, preparation thereof, anti-inflammatory activity thereof and application thereof | |
| WO2014068506A2 (en) | Compositions and methods for the treatment of autoimmune diseases | |
| CN113185447A (en) | Phthaloyl cysteamine compound, preparation method and use thereof | |
| CN116157133A (en) | 2',3' -diacetyluridine substituted with acetoacetyl group at 5' position | |
| EP3525795B1 (en) | Phenothiazine derivatives and methods of use thereof | |
| CN112830884A (en) | Salvianic acid A derivative, preparation method and medical application thereof | |
| CN106279086B (en) | Ganoderma lucidum furans A and its pharmaceutical composition and its application in pharmacy and food | |
| JP2022528237A (en) | Glucoside derivatives and their use as SGLT1 inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180410 |