CN112876485A - Compound for treating uterine smooth muscle high-frequency tonic contraction related diseases - Google Patents
Compound for treating uterine smooth muscle high-frequency tonic contraction related diseases Download PDFInfo
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- CN112876485A CN112876485A CN202110099675.6A CN202110099675A CN112876485A CN 112876485 A CN112876485 A CN 112876485A CN 202110099675 A CN202110099675 A CN 202110099675A CN 112876485 A CN112876485 A CN 112876485A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 42
- 201000010099 disease Diseases 0.000 title claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 13
- 210000002460 smooth muscle Anatomy 0.000 title claims description 21
- 230000036977 tonic contraction Effects 0.000 title claims description 8
- 239000003814 drug Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 12
- 230000002265 prevention Effects 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 13
- 230000008602 contraction Effects 0.000 abstract description 11
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- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 abstract description 5
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 abstract description 5
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- 238000002474 experimental method Methods 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
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- 239000000050 smooth muscle relaxant Substances 0.000 description 2
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- 238000005303 weighing Methods 0.000 description 2
- IOVGROKTTNBUGK-SJKOYZFVSA-N (1S,2R)-ritodrine Chemical compound N([C@H](C)[C@@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJKOYZFVSA-N 0.000 description 1
- MOQVHOPVBREXLY-UHFFFAOYSA-N 3h-dioxol-4-ylmethanol Chemical compound OCC1=COOC1 MOQVHOPVBREXLY-UHFFFAOYSA-N 0.000 description 1
- UYIFTLBWAOGQBI-BZDYCCQFSA-N Benzhormovarine Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3OC(=O)C1=CC=CC=C1 UYIFTLBWAOGQBI-BZDYCCQFSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 206010046809 Uterine pain Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229950002007 estradiol benzoate Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
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- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
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- 238000010438 heat treatment Methods 0.000 description 1
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- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 239000002840 nitric oxide donor Substances 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 229960000720 ritodrine hydrochloride Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Inorganic Chemistry (AREA)
- Pregnancy & Childbirth (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a compound for treating uterine smooth high-frequency myotonic contraction diseases, which has obvious inhibiting effect on frequency, amplitude and activity of uterine smooth myotonic contraction caused by oxytocin.
Description
Technical Field
The invention belongs to the field of medicinal chemistry, and particularly relates to a compound for inducing contraction of uterine smooth muscle and a medicinal preparation thereof.
Background
The excessive contraction of the uterine smooth muscle can cause the phenomena of dysmenorrheal of adolescent girls, married and married uninitiated women, premature birth of pregnant women and the like, is a common disease of women, and seriously affects the health and the working efficiency of the women. At present, the uterine smooth muscle relaxants commonly used in clinic mainly comprise an cyclooxygenase inhibitor (such as indometacin), a nitric oxide donor (such as nitroglycerin), a beta 2 receptor agonist (such as ritodrine hydrochloride), a calcium channel blocker (such as nifedipine) and the like, and the drugs can relieve the uterine pain symptoms at different degrees, but have obvious adverse reactions of digestive tract, heart, liver, kidney and the like, have non-lasting curative effect, are not suitable for long-term administration, and have obvious limitation in clinical use.
Therefore, the development of a novel uterine smooth muscle relaxant with definite curative effect and small adverse reaction is necessary.
Disclosure of Invention
In one aspect of the inventionA compound G and pharmaceutically acceptable salts thereof are provided, having the structure:
wherein R is halogen.
In some embodiments, the R is optionally F, Cl or Br; preferably Cl.
In some preferred embodiments, the present invention provides a compound G-1, and pharmaceutically acceptable salts thereof, having the structure:
in another aspect, the present invention provides a compound of formula G, or a pharmaceutically acceptable salt thereof, for use in the prevention and/or treatment of a disease or condition caused by high frequency tonic contractility of uterine smooth muscle.
In another aspect, the present invention provides a compound of formula G-01 or a pharmaceutically acceptable salt thereof for use in the prevention and/or treatment of a disease or condition caused by high frequency tonic contractility of uterine smooth muscle.
In another aspect, the present invention provides the use of a compound of formula G, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention or treatment of a disease or condition caused by high frequency tonic contractility of uterine smooth muscle.
In another aspect, the invention provides the use of a compound of formula G-01 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a disease or condition caused by high frequency tonic contractility in uterine smooth muscle.
In another aspect, the invention provides a suppository consisting of Pluronic F-108, Pluronic L31, glycerin and Compound G.
In some preferred embodiments, the suppository contains 100 parts Pluronic F-108, 1-3 parts Pluronic L31, 5 parts glycerin and 1 part Compound G.
In some preferred embodiments, the suppository contains 100 parts Pluronic F-108, 1 part Pluronic L31, 5 parts glycerin and 1 part Compound G.
In some preferred embodiments, the compound G is preferably compound G-01.
In another aspect, the present invention provides a suppository for use in the preparation of a medicament for the prevention or treatment of a disease or condition caused by high frequency of uterine smooth muscle tonic contraction, wherein said suppository consists of Pluronic F-108, Pluronic L31, glycerol and compound G.
In some preferred embodiments, the suppository is prepared by the following method: melting 100 parts of Pluronic F-108, weighing 1 part of compound G-01, dissolving in 5 parts of glycerol, pouring into the molten Pluronic F-108, adding 1-3 parts of Pluronic L31 while hot, stirring for 2h, defoaming, and pouring into a plug mold coated with liquid paraffin in advance. Curing at 4 deg.C for 1 hr, taking out, removing excessive part, sucking surface lubricating oil, and packaging.
The compound has obvious inhibiting effect on the frequency, amplitude and activity of uterus smooth muscle tonic contraction caused by oxytocin, and the prepared suppository can obviously enhance the drug release, has obvious long-acting slow release effect, can reduce the administration times and increase the compliance of patients. At the same time, the suppository can be administered via vagina, and has reduced side effects.
Detailed Description
Drawings
Fig. 1 is a graph of cumulative release for examples 3, 4, and 5.
Correlation definition
Unless specifically stated otherwise, the following terms used in the specification and claims have the following meanings:
the term "compound" as used herein includes all stereoisomers and tautomers.
The compounds of the invention may be asymmetric, e.g., having one or more stereoisomers. Unless otherwise indicated, all stereoisomers include, for example, enantiomers and diastereomers. The compounds of the invention containing asymmetric carbon atoms can be isolated in optically active pure form or in racemic form. The optically active pure form can be resolved from a racemic mixture or synthesized by using chiral starting materials or chiral reagents. Racemates, diastereomers, enantiomers are included within the scope of the present invention.
The term "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.
Example 1
Compound G-01
Preparation of
According to the preparation scheme of example 1 of patent application CN1195353A, isoamyl nitrite is added to a solution of [3aR- (3a α, 4 α,6 α,6a α) ] -6- [ 5-amino-6-chloro-2- (propylsulfanyl) -4-pyrimidinylamino ] -tetrahydro-2, 2-dimethyl-4H-cyclopentyl-1, 3-dioxacyclopentene-4-methanol in acetonitrile and heated at 70 ℃ for 1H. After cooling, the reaction mixture is concentrated and purified (SiO2, eluent, dichloromethane: ethyl acetate, 4:1) to give the compound of formula G-01.
Example 2
According to the literature method, preparing the isolated uterine smooth muscle strips of the rats, taking the non-pregnant female rats, and injecting 2mg/kg of estradiol benzoate for molding 5 days before the experiment every day. After 5 days, the rats are killed, the uteruses are dissected rapidly, 2 lining uterus sections are respectively taken from two uterine horns, the two uterine horns are longitudinally dissected along muscle textures respectively to obtain 4 uterine muscle strips with the length of 2 cm, the uterine muscle strips are hung in De-Jalon liquid, one sections of the uterine smooth muscle strips are fixed on a T-shaped hook in a bath, the other sections of the uterine smooth muscle strips are connected with a muscle tension transducer, the pre-drug load is 1.0g, the temperature is constant at 37 ℃, and the incubation is carried out by saturated oxygen. The muscle tension transducer records the contraction condition of the muscle through the Med lab biological signal acquisition and processing system.
The uterus smooth muscle strips are balanced in De-Jalon liquid for 15min, the motion waveform curve of the contraction activity of normal uterus smooth muscle is traced, then different medicines are added according to the following table for treatment, the contraction frequency and the contraction amplitude of the uterus are recorded, and the uterus activity is calculated, namely the uterus activity is the contraction frequency multiplied by the contraction amplitude, and each group of experiments are carried out in parallel for 6 times. The results of the experiments are shown in the following table.
The experimental result shows that compared with a blank control group, the oxytocin can obviously enhance the uterine smooth muscle movement waveform of a rat and has obvious excitation effect on the contraction frequency, amplitude and uterine activity of the uterine smooth muscle (P is less than 0.01); the compound G-01 with different concentrations has inhibition effect (P is less than 0.01) on oxytocin-induced uterine smooth muscle contraction, and the inhibition effect on oxytocin-induced uterine smooth muscle contraction is stronger along with the increase of the concentration of the compound G-01.
Example 3
Melting 1000G Pluronic F-108, dissolving 10G Compound G-01 in 50G glycerol, pouring into the molten Pluronic F-108, and adding 10G
L31, magnetically stirring for 2h, defoaming, and pouring into a plug mold coated with liquid paraffin in advance. Curing at 4 deg.C for 1 hr, taking out, removing excessive part, sucking surface lubricating oil, and packaging. The average suppository weight was 1G, and each suppository contained 10mg of compound G-01. (the in vitro adhesion time is 164.62s, and the cumulative release rate of the drug is about 86.2 percent after 24 h)
Example 4
1010G of Pluronic F-108 was melted, 10G of Compound G-01 was additionally weighed and dissolved in 50G of glycerol, poured into the melted Pluronic F-108, magnetically stirred for 2h, defoamed, and poured into a plug mold previously coated with liquid paraffin. Curing at 4 deg.C for 1 hr, taking out, removing excessive part, sucking surface lubricating oil, and packaging. The average suppository weight was 1G, and each suppository contained 10mg of compound G-01. (the in vitro adhesion time is 87.83s, and the cumulative release rate of the drug is about 45.1 percent after 24 h)
Example 5
Weighing 10G of polyoxyethylene monostearate, adding 4001000G of PEG, heating in a water bath to melt, adding G-0110G of compound, fully stirring until the medicine is dissolved uniformly, defoaming, and pouring the mixture into an acid model coated with liquid paraffin in advance. Curing at 4 deg.C for 1 hr, taking out, removing excessive part, sucking surface lubricating oil, and packaging. The average suppository weight was 1G, and each suppository contained 10mg of compound G-01. (the in vitro adhesion time is 29.21s, and the cumulative release rate of the drug is about 26.3 percent after 24 h)
Example 6
Melting 1000G Pluronic F-108, dissolving 10G Compound G-01 in 50G glycerol, pouring into the molten Pluronic F-108, and adding 20G
L31, magnetically stirring for 2h, defoaming, and pouring into a plug mold coated with liquid paraffin in advance. Curing at 4 deg.C for 1 hr, taking out, removing excessive part, sucking surface lubricating oil, and packaging. The average suppository weight was 1G, and each suppository contained 10mg of compound G-01. (153.19 s in vitro adhesion time, and the cumulative release rate of the drug is about 84.9% in 24 h)
Example 7
Melting 1000G Pluronic F-108, dissolving 10G Compound G-01 in 50G glycerol, pouring into the molten Pluronic F-108, and adding 30G
L31, magnetically stirring for 2h, defoaming, and pouring into a plug mold coated with liquid paraffin in advance. Curing at 4 deg.C for 1 hr, taking out, removing excessive part, sucking surface lubricating oil, and packaging. The average suppository weight was 1G, and the amount of compound G-01 contained in each suppository was 10 mg. (the in vitro adhesion time is 142.90s, and the cumulative release rate of the drug is about 82.3 percent after 24 h).
Claims (7)
1. A compound G, and pharmaceutically acceptable salts thereof, having the structure:
wherein R is halogen.
2. The compound of claim 1, R is optionally F, Cl or Br; preferably Cl.
3. A compound G-1, and pharmaceutically acceptable salts thereof, having the structure:
4. a compound of formula G or a pharmaceutically acceptable salt thereof, for use in the prevention and/or treatment of a disease or condition caused by uterine high frequency smooth muscle tonic contraction.
5. A compound of formula G-01 or a pharmaceutically acceptable salt thereof for use in the prevention and/or treatment of a disease or condition caused by uterine high frequency smooth muscle tonic contraction.
6. Use of a compound of formula G or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a disease or condition caused by high frequency smooth muscle tonic contraction.
7. Use of a compound of formula G-01 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a disease or condition caused by high frequency smooth muscle tonic contraction.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1195353A (en) * | 1995-07-11 | 1998-10-07 | 英国阿斯特拉药品有限公司 | Novel platelet aggregation inhibitors |
| AU2650099A (en) * | 1998-02-17 | 1999-08-30 | Astrazeneca Uk Limited | Novel triazolo(4,5-(d))pyrimidine compounds |
| AU2016500A (en) * | 1998-12-04 | 2000-06-26 | Astrazeneca Ab | Novel triazolo(4,5-d)pyrimidine compounds |
| CN102924457A (en) * | 2011-08-12 | 2013-02-13 | 上海恒瑞医药有限公司 | Triazolopyrimidine derivatives, preparation method and uses thereof |
| CN111116592A (en) * | 2019-11-27 | 2020-05-08 | 杭州沧海帆医药科技有限公司 | Pyrimidotriazole compounds and medical application thereof |
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2021
- 2021-01-25 CN CN202110099675.6A patent/CN112876485A/en active Pending
Patent Citations (5)
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| CN1195353A (en) * | 1995-07-11 | 1998-10-07 | 英国阿斯特拉药品有限公司 | Novel platelet aggregation inhibitors |
| AU2650099A (en) * | 1998-02-17 | 1999-08-30 | Astrazeneca Uk Limited | Novel triazolo(4,5-(d))pyrimidine compounds |
| AU2016500A (en) * | 1998-12-04 | 2000-06-26 | Astrazeneca Ab | Novel triazolo(4,5-d)pyrimidine compounds |
| CN102924457A (en) * | 2011-08-12 | 2013-02-13 | 上海恒瑞医药有限公司 | Triazolopyrimidine derivatives, preparation method and uses thereof |
| CN111116592A (en) * | 2019-11-27 | 2020-05-08 | 杭州沧海帆医药科技有限公司 | Pyrimidotriazole compounds and medical application thereof |
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