CN116514719A - Compound SD82-170 for treating cerebrovascular diseases - Google Patents
Compound SD82-170 for treating cerebrovascular diseases Download PDFInfo
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- CN116514719A CN116514719A CN202310344456.9A CN202310344456A CN116514719A CN 116514719 A CN116514719 A CN 116514719A CN 202310344456 A CN202310344456 A CN 202310344456A CN 116514719 A CN116514719 A CN 116514719A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 43
- 208000026106 cerebrovascular disease Diseases 0.000 title claims abstract description 20
- 230000002490 cerebral effect Effects 0.000 claims abstract description 20
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 230000000302 ischemic effect Effects 0.000 claims description 20
- 208000006011 Stroke Diseases 0.000 claims description 14
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 8
- 208000029028 brain injury Diseases 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 claims description 3
- 206010008088 Cerebral artery embolism Diseases 0.000 claims description 3
- 206010008132 Cerebral thrombosis Diseases 0.000 claims description 3
- PDQAZBWRQCGBEV-UHFFFAOYSA-N Ethylenethiourea Chemical compound S=C1NCCN1 PDQAZBWRQCGBEV-UHFFFAOYSA-N 0.000 claims description 3
- 201000001429 Intracranial Thrombosis Diseases 0.000 claims description 3
- 208000004552 Lacunar Stroke Diseases 0.000 claims description 3
- 206010051078 Lacunar infarction Diseases 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
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- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 3
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
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- 238000004519 manufacturing process Methods 0.000 claims 1
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- 230000004224 protection Effects 0.000 abstract description 3
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- 230000034994 death Effects 0.000 description 7
- 210000003414 extremity Anatomy 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
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- 102100033571 Tissue-type plasminogen activator Human genes 0.000 description 4
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- 239000004480 active ingredient Substances 0.000 description 4
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 210000001130 astrocyte Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
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- 241000699666 Mus <mouse, genus> Species 0.000 description 2
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- 238000007911 parenteral administration Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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- 206010067484 Adverse reaction Diseases 0.000 description 1
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- 206010008089 Cerebral artery occlusion Diseases 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 102000010170 Death domains Human genes 0.000 description 1
- 108050001718 Death domains Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
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- -1 SD84-141 Chemical class 0.000 description 1
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- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
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- GKXVJHDEWHKBFH-UHFFFAOYSA-N [2-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=CC=C1CN GKXVJHDEWHKBFH-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
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- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 1
- 229950009041 edaravone Drugs 0.000 description 1
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- 208000035474 group of disease Diseases 0.000 description 1
- 208000037907 haemorrhagic injury Diseases 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
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- 229960000103 thrombolytic agent Drugs 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/30—Oxygen or sulfur atoms
- C07D233/42—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a compound SD82-170 for treating cerebrovascular diseases, the structure of which is shown in a formula I. The compound can obviously reduce the volume of cerebral infarction in the small acute stage of focal cerebral ischemia and obviously improve the neurological symptoms thereof, has a cerebral nerve protection effect, has a better treatment effect on cerebrovascular diseases, particularly on cerebral ischemia diseases, effectively widens the treatment window and has great clinical development value.
Description
Technical Field
The invention relates to the technical field of biological pharmacy, in particular to a compound SD82-170 for treating cerebrovascular diseases.
Background
Cerebral apoplexy is a group of diseases which take ischemia and hemorrhagic injury symptoms of brain tissues as main clinical manifestations, and is also called cerebral apoplexy or cerebrovascular accident. The disease is urgent, has extremely high disability rate and mortality rate, is the second leading cause of death in the world today, and becomes more serious as the population ages. Acute ischemic cerebral apoplexy (acute cerebral infarction) is the most common type of cerebral apoplexy, and accounts for 69.6% -70.8% of cerebral apoplexy in China, the death rate of the patients in China in 1 month after the patients in China are in charge of acute ischemic cerebral apoplexy is about 2.3% -3.2%, the death rate of the patients in 3 months is 9% -9.6%, the death/disability rate of the patients in 3 months is 34.5% -37.1%, the death rate of the patients in 1 year is 14.4% -15.4%, and the death/disability rate of the patients in China is 33.4% -33.8%, and the patients in China become the first cause of death/disability in China.
Ischemic cerebral apoplexy has complex pathogenesis, and relates to various mechanisms such as peroxidation, energy metabolism disorder, calcium overload, excitatory amino acid toxicity, etc. The only drug currently approved by the U.S. FDA for ischemic stroke treatment is tissue-type plasminogen activator (tissue plasminogen activator, t-PA, intravenous injection), which can dissolve thrombus and recanalize blood vessels, thereby restoring blood flow. However, because t-PA has a narrow therapeutic window (effective 4.5 hours after stroke), and t-PA is also known as a plasminogen activator, which is a physiological agonist of the fibrinolytic system in vivo, bleeding is easily caused, and only a small proportion of patients are treated by thrombolysis. Therefore, searching for new targets for treating ischemic cerebral apoplexy, and medicines with new action mechanisms and less adverse reactions are an urgent problem to be solved.
Disclosure of Invention
In order to solve the technical problems, the invention provides a novel compound SD82-170, the structure of which is shown as a formula I, the compound SD82-170 has remarkable cerebral neuroprotection, the acute cerebral infarction volume of a focal cerebral ischemia mouse can be remarkably reduced, the neurological symptoms of the focal cerebral ischemia mouse can be remarkably improved, the compound can treat cerebrovascular diseases by inhibiting TRADD, the action mechanism of the compound is different from t-PA, and the compound is a non-thrombolytic agent and does not have bleeding risks.
A first object of the present invention is to provide a compound of formula I:
further, the pharmaceutically acceptable salt has the structure shown in formula II:
wherein X is halogen.
Further, the compound shown in the formula I is prepared by the following steps:
s1, reacting benzhydryl amine with a compound shown in a formula III to obtain a compound shown in a formula IV;
s2, reacting a compound shown in a formula IV with ethylene thiourea to obtain a compound shown in a formula I;
wherein,,
x is halogen.
A second object of the present invention is to provide the use of the above-mentioned compound or a pharmaceutically acceptable salt thereof for the preparation of a medicament for preventing or treating cerebrovascular diseases.
Further, the cerebrovascular disease is ischemic brain injury disease.
Further, the ischemic brain injury disease is cerebral apoplexy, cerebral thrombosis, cerebral embolism, cerebral infarction, transient cerebral ischemia, lacunar infarction, cerebral arteriosclerosis or diabetic cerebrovascular complications.
Further, the therapeutic window of the drug is within 6 hours of onset, which is prolonged compared with the existing therapeutic window (within 4.5 hours of onset).
Further, the medicine consists of 0.1-100% of a compound shown in a formula I or pharmaceutically acceptable salt thereof and 99.9-0% of a medicinal carrier and/or auxiliary materials.
In the present invention, the type of formulation of the pharmaceutical composition is not particularly limited, and may be a formulation including those suitable for oral, parenteral (including subcutaneous, intradermal, intramuscular, intravenous and articular), rectal and topical (including skin, buccal, sublingual and intraocular) administration. In the present invention, the pharmaceutical composition is a solvent or diluent.
In the present invention, preferably, the pharmaceutical composition is a formulation suitable for oral, rectal, topical, buccal, sublingual, subcutaneous, intramuscular, intravenous. The most suitable route may depend on the condition and disorder of the recipient. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy.
The formulations suitable for oral administration may be presented in discrete unit form, for example as capsules or tablets, powders or granules, solutions or suspensions with or without an aqueous liquid, or oil-in-water or water-in-oil emulsions containing a predetermined amount of the active ingredient. The active ingredient may also be presented in the form of a pill or cream. In the present invention, preferably, the pharmaceutical composition is a tablet, capsule, dispersible powder or granule.
The tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable apparatus the active ingredient in a free-flowing form, optionally mixed with a binder, lubricant, inert diluent, surfactant or dispersing agent. Molded tablets may be made by molding in a suitable apparatus a powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated to provide sustained, delayed or controlled release of the active ingredient.
Formulations for parenteral administration as described above include aqueous and non-aqueous sterile injectable solutions containing antioxidants, buffers, bacteriostats and solutes. Formulations for parenteral administration also include aqueous and non-aqueous sterile suspensions which may contain suspending agents and thickening agents.
In the present invention, preferably, the pharmaceutical composition is in the form of an injectable preparation.
The various dosage forms for the pharmaceutical compositions of the present invention described above may be prepared according to methods well known in the pharmaceutical arts.
By means of the scheme, the invention has at least the following advantages:
the invention provides a novel compound for treating cerebrovascular diseases, which can obviously reduce the volume of cerebral infarction in focal cerebral ischemia acute stage and obviously improve the neurological symptoms thereof, has a cerebral neuroprotection effect, and particularly has a better effect on cerebral ischemic diseases. The medicine prepared based on the compound is expected to be used for treating ischemic brain injury, cerebral thrombosis, cerebral embolism, cerebral infarction, cerebral apoplexy, lacunar infarction, transient cerebral ischemia, cerebral arteriosclerosis, diabetic cerebrovascular complications and other diseases.
The foregoing description is only an overview of the present invention, and is presented in terms of preferred embodiments of the present invention and the following detailed description of the invention in conjunction with the accompanying drawings.
Drawings
In order that the contents of the present invention may be more clearly understood, the present invention will be further described in detail with reference to specific embodiments thereof with reference to the accompanying drawings.
FIG. 1 is a hydrogen spectrum of compound SD 82-170;
FIG. 2 is a schematic representation of the effect of compound SD82-170 on improving neurological symptoms in brain ischemic mice;
FIG. 3 is a graph showing the effect of compounds SD82-170 on improving right limb utilization in brain ischemic mice;
FIG. 4 is a graph showing the effect of compounds SD82-170 on the reduction of cerebral infarct volume in the acute phase of cerebral ischemic mice;
FIG. 5 is the protective activity of SD84-141, SD84-139, SD82-163 against OGD-induced astrocytes; wherein "#" represents that the OGD-induced group has a significant difference in p < 0.01 compared to the OGD-free induced group, and "×" represents that the OGD-induced + edaravone-treated group has a significant difference in p < 0.01 compared to the OGD-induced group.
Detailed Description
The present invention will be further described with reference to the accompanying drawings and specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the invention and practice it.
Tumor necrosis factor receptor type 1 related death domain protein (TRADD) is a unique adaptor protein which plays a central role in various downstream signal events in different cellular environments, including cell survival and apoptosis, and is related to various human diseases such as autoimmune diseases, neurodegenerative diseases and the like, so that the TRADD becomes a potential drug target for treatment and has important research significance. The inventors of the present invention studied and found that: after cerebral ischemia occurs, the level of RIP1K in brain tissue and ischemic astrocytes increases and autophagic flow is blocked. While SD82-170 is capable of activating autophagy and reducing RIP1K levels by inhibiting TRADD, SD82-170 was further found to treat ischemic stroke.
Example 1
SD82-170 synthetic route:
82-170-1 synthesis:
xylylenediamine (500 mg,2.7 mmol), triethylamine (334 mg,3.3 mmol) were dissolved in dichloromethane, and a dichloromethane solution of chloroacetyl chloride (306 mg,2.7 mmol) was slowly added to the mixture at 0℃and the reaction was continued at room temperature for 4 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was washed with 1N diluted hydrochloric acid and dried in dichloromethane: recrystallization from petroleum ether gave 518mg (yield: 74%) of white solid.
82-170:
82-170-1 (518 mg,2 mmol), ethylene thiourea (204 mg,2 mmol), potassium carbonate (276 mg,2 mmol) were placed in acetone (10 mL) and refluxed at 65℃for 10h. At the end of the reaction, the solvent was removed by rotary evaporation, the residue was purified by column chromatography on silica gel and purified with diethyl ether: ethyl acetate (5:1) was slurried to give 180mg (yield: 28%) of a white solid.
82-170 are shown in figure 1.
Example 2
Protection of focal ischemic cerebral apoplexy in mice by SD82-170 prepared in example 1.
Male C57 mice were randomized into control (sham) group, model group, SD82-170 dosing group (3 nmol), 10 per group. A transient middle cerebral artery occlusion model (tMCAO) was obtained from mice by the wire-plug method. Reperfusion was performed 60min after ischemia, and lateral ventricle injection at 6 hours of reperfusion was SD82-170. Mice were decapitated and sectioned to observe the effect of SD82-170 on cerebral ischemic acute phase cerebral infarction volume. Mice post-reperfusion (I/R) were scored for neurological symptoms in the acute phase of cerebral ischemia using Longa method prior to sacrifice, with higher scores indicating more pronounced neurological deficit. And the right limb usage of the mice was observed through a barrel experiment to evaluate the improvement of the neurological symptoms of the mice. The neurological symptom scoring criteria are shown in table 1.
TABLE 1 neurological symptom score table
| Scoring of | Neurological symptoms |
| 0 | Normal, no damage to nerve function |
| 1 | Incomplete extension of left forelimb and slight injury of nerve function |
| 2 | The mice turn around to paralysis side when walking, and the nerve function is moderately damaged |
| 3 | The mice topple to paralysis side when walking, and the nerve function is severely damaged |
| 4 | The mice can not walk at all, and consciousness is impaired |
FIG. 2 is a graph showing the effect of the compound SD82-170 in example 1 of the present invention on improving neurological symptoms in mice with cerebral ischemia; mean±sd, n=10; in comparison with the set of models, ** p<0.01. as can be seen from fig. 2: compound SD82-170 was able to reduce the neurological symptom score in brain ischemic mice.
Barrel experiment: the mice were placed in a barrel and the use of their forelimbs touching the barrel wall was observed. After the forelimbs of the mice are put down from the barrel wall, the conditions of the left and right limbs attached to the barrel wall are recorded. Each rat was tested 10 times in this manner. The final statistical formula is (number of non-damaged forelimb movements-number of damaged forelimb movements)/(number of non-damaged forelimb movements + number of forelimb co-movements).
The right limb usage of mice was observed by a barrel experiment to evaluate the improvement of neurological symptoms of mice.
FIG. 3 is a graph showing the effect of the compounds SD82-170 in example 1 of the present invention on improving right limb utilization in mice with cerebral ischemia; mean±sd, n=10; in comparison with the set of models, ** p<0.01. as can be seen from fig. 4: compound SD82-170 was able to improve right limb utilization in brain ischemic mice.
FIGS. 4a and 4b are graphs showing the effect of the compounds SD82-170 in example 1 of the present invention on the reduction of cerebral infarct volume in the acute phase of cerebral ischemic mice; mean±sd, n=10; in comparison with the set of models, * p<0.05， ** p<0.01. as can be seen from fig. 4a and 4 b: compound SD82-170 was able to reduce cerebral infarct volume in the acute phase of cerebral ischemic mice.
The above results indicate that: SD82-170 has certain protection effect on ischemic brain injury, and can be used for preventing and treating diseases.
Comparative example 1
Other engineered compounds, such as SD84-141, SD84-139, and SD82-163, were not protective against OGD-induced astrocytes (FIG. 5), and the compound structures of SD84-141, SD84-139, and SD82-163 were as follows:
it is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations and modifications of the present invention will be apparent to those of ordinary skill in the art in light of the foregoing description. It is not necessary here nor is it exhaustive of all embodiments. And obvious variations or modifications thereof are contemplated as falling within the scope of the present invention.
Claims (10)
1. A compound of formula I or a pharmaceutically acceptable salt thereof, characterized in that:
2. the compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt has the structure shown in formula II:
wherein X is halogen.
3. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein: the compound shown in the formula I is prepared by the following steps:
s1, reacting benzhydryl amine with a compound shown in a formula III to obtain a compound shown in a formula IV;
s2, reacting a compound shown in a formula IV with ethylene thiourea to obtain a compound shown in a formula I;
wherein,,
x is halogen.
4. Use of a compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention or treatment of cerebrovascular disease.
5. The use according to claim 4, characterized in that: the cerebrovascular disease is ischemic brain injury disease.
6. The use according to claim 5, characterized in that: the ischemic brain injury disease is cerebral apoplexy, cerebral thrombosis, cerebral embolism, cerebral infarction, transient cerebral ischemia, lacunar infarction, cerebral arteriosclerosis or diabetic cerebrovascular complications.
7. The use according to claim 4, characterized in that: the therapeutic window of the medicine is within 6 hours of onset.
8. The use according to claim 4, characterized in that: the medicine consists of 0.1-100% of a compound shown in a formula I or pharmaceutically acceptable salt thereof and 99.9-0% of a medicinal carrier and/or auxiliary materials.
9. The use according to claim 4, characterized in that: the medicament is a formulation suitable for oral, rectal, topical, buccal, sublingual, subcutaneous, intramuscular or intravenous.
10. The use according to claim 4, characterized in that: the medicine is tablet, capsule, dispersible powder, granule or injection.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109966290A (en) * | 2019-04-16 | 2019-07-05 | 苏州大学 | Application and its pharmaceutical composition of the CID1067700 in the drug of preparation prevention and/or treatment cranial vascular disease |
| CN110974828A (en) * | 2019-12-24 | 2020-04-10 | 苏州大学 | Application of compound Axitinib in preparation of medicine for treating cerebrovascular diseases and pharmaceutical composition of compound Axitinib |
| WO2021257697A1 (en) * | 2020-06-16 | 2021-12-23 | President And Fellows Of Harvard College | Compounds and methods for blocking apoptosis and inducing autophagy |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109966290A (en) * | 2019-04-16 | 2019-07-05 | 苏州大学 | Application and its pharmaceutical composition of the CID1067700 in the drug of preparation prevention and/or treatment cranial vascular disease |
| CN110974828A (en) * | 2019-12-24 | 2020-04-10 | 苏州大学 | Application of compound Axitinib in preparation of medicine for treating cerebrovascular diseases and pharmaceutical composition of compound Axitinib |
| WO2021257697A1 (en) * | 2020-06-16 | 2021-12-23 | President And Fellows Of Harvard College | Compounds and methods for blocking apoptosis and inducing autophagy |
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