CN110804025B - 一种卤代苯异噁唑衍生物及其制备方法与应用 - Google Patents
一种卤代苯异噁唑衍生物及其制备方法与应用 Download PDFInfo
- Publication number
- CN110804025B CN110804025B CN201911210681.3A CN201911210681A CN110804025B CN 110804025 B CN110804025 B CN 110804025B CN 201911210681 A CN201911210681 A CN 201911210681A CN 110804025 B CN110804025 B CN 110804025B
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- preparation
- halogenated
- pharmaceutical composition
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 150000008316 benzisoxazoles Chemical class 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 229910001923 silver oxide Inorganic materials 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000003801 protein tyrosine phosphatase 1B inhibitor Substances 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 150000007980 azole derivatives Chemical class 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种卤代苯异噁唑衍生物及其制备方法与应用，所述卤代苯异噁唑衍生物具有式I结构：
Description
技术领域
本发明属于药物合成领域，具体涉及一种卤代苯异噁唑衍生物及其制备方法与应用。
背景技术
糖尿病是一种代谢性疾病，患者体内通常会出现高血糖，对人体的眼、心脏、肾脏、神经等组织和器官产生功能性障碍。蛋白酪氨酸磯酸酶1B(PTP1B)通过与蛋白酪氨酸磷酸激酶的共同作用来调节细胞内底物酪氨酸的磷酸化水平，来完成细胞内信号的转导。PTP1B过表达会使胰岛素及其受体过度去磷酸化，进而使胰岛素与胰岛素受体的结合过程受阻，进而使生物体内发生胰岛素抵抗。因此，开发一种新型PTP1B抑制剂有望用于治疗糖尿病。
发明内容
本发明提供一种式I结构的卤代苯异噁唑衍生物或其药学上可接受的盐，其特征在于式I结构如下：
本发明的另一实施方案提供上述式I结构的卤代苯异噁唑衍生物的制备方法，其特征在于包括如下步骤：
(1)有机溶剂中，式II化合物与式III化合物在氧化银作用下反应得到式IV化合物；
(2)式IV化合物于碱性条件下脱除甲基后，调pH至5-6即可得到式I化合物。
步骤(1)中有机溶剂优选乙腈、甲苯、二氧六环中的一种或几种。式II化合物：式III化合物：氧化银＝1:1.5-2.0:3.0-4.0(摩尔比)，反应温度优选为70℃至回流温度；反应中优选加入式III化合物摩尔量5％-6％的AgOTf。
步骤(2)中碱性条件优选NaOH/MeOH或KOH/MeOH，pH为9-10。
本发明的另一实施方案提供一种制备式I化合物的式V中间体，其特征在于式V结构如下：
本发明的另一实施方案提供上述式V中间体(优选式IV)在制备式I化合物中的应用。
本发明的另一实施方案提供一种式IV中间体的制备方法，其特征在于包括如下步骤：
有机溶剂中，式II化合物与式III化合物在氧化银作用下反应得到式IV化合物。
步骤(1)中有机溶剂优选乙腈、甲苯、二氧六环中的一种或几种。式II化合物：式III化合物：氧化银＝1:1.5-2.0:3.0-4.0(摩尔比)，反应温度优选为70℃至回流温度；反应中优选加入式III化合物摩尔量5％-6％的AgOTf。
本发明的另一实施方案提供上述式I结构的卤代苯异噁唑衍生物或其药学上可接受的盐在制备PTP1B抑制剂中的应用。
本发明的另一实施方案提供上述式I结构的卤代苯异噁唑衍生物或其药学上可接受的盐在制备治疗糖尿病的药物中的应用。
本发明的另一实施方案提供一种药物组合物，其特征在于该药物组合物以上述式I结构的卤代苯异噁唑衍生物或其药学上可接受的盐作为有效成分。该药物组合物还可包括其他治疗糖尿病的药物。该药物组合物还可包括药学上可接受的辅料。该药物组合物的剂型选自固体制剂、液体制剂或半固体制剂。优选片剂、胶囊或注射剂。
具体实施方式
为了便于对本发明的进一步理解，下面提供的实施例对其做了更详细的说明。但是这些实施例仅供更好的理解发明而并非用来限定本发明的范围或实施原则，本发明的实施方式不限于以下内容。本发明使用的式II化合物、式III化合物均通过商业购买获得(本领域的技术人员也可根据现有技术自行制备)。
实施例1
取式II化合物(1.0mmol)、式III化合物(2.0mmol)，溶于15mL甲苯中，加入Ag2O(4.0mmol)，升温至回流温度反应10小时后，TLC检测式II化合物消失，停止加热恢复至室温后，过滤、滤液浓缩后经硅胶柱层析(乙酸乙酯/石油醚＝1/10-1/5)得到淡黄色固体36.7mg，即为式IV化合物，收率约为6.9％。结构确证数据：mp：126-128℃，ESI-MS m/z531.2[M+H]+。
取式IV化合物(30mg)溶于NaOH/MeOH溶液(6mL，pH 9-10)，室温下反应2小时后，加入稀盐酸(1mol/L)调pH至5-6，减压浓缩后，用乙酸乙酯萃取、水洗，有机相浓缩后经硅胶柱层析(乙酸乙酯/石油醚＝1/5-1/3)得白色固体25.0mg，即为式I化合物，收率约为85.6％，结构确证数据：mp：140-142℃，ESI-MS m/z 515.2[M-H]-，1H NMR(DMSO-d6,400MHz)δ:7.98(s,1H),7.78(d，1H),7.67-7.58(m，2H),7.57(d，1H),7.49(d,1H),7.38(t,1H),4.21(s,2H),3.78(s,2H),3.08-3.04(m,2H),1.85-1.82(m,2H),1.72-1.69(m,2H),1.33(d,6H),1.08-1.01(m,2H),0.88-0.82(m,4H).
实施例2
取式II化合物(1.0mmol)、式III化合物(1.5mmol)，溶于15mL乙腈中，加入Ag2O(3.0mmol)和AgOTf(0.075mmol,约19.3mg)，升温至70℃反应12小时后，TLC检测式II化合物消失，停止加热恢复至室温后，过滤、滤液浓缩后经硅胶柱层析(乙酸乙酯/石油醚＝1/10-1/5)得到淡黄色固体188.1mg，TLC比对与实施例1制备的式IV化合物相同，收率约为35.4％，ESI-MS m/z 531.2[M+H]+，533.2[M+2+H]+。
实施例3
按照本领域的常规方法测试本发明化合物的酪氨酸磷酸酯酶1B(PTP1B)的抑制活性。反应体系的酶活缓冲液：甘油10％、HEPES 50mM pH7.2、NaCl 10mM、BSA 0.10％；反应在96孔板中进行，总反应体系为100μL，分为三组，实验组，阴性对照组和阳性对照组。实验组每孔依次加入48μL 100nM PTP1B(由人工提纯获得)，2μL 50mM式I化合物(溶于DMSO中)，振荡30s混匀，32℃条件下孵育10min，然后加入50μL 50mM pNPP，振荡30s混匀后，405nm测OD值，计算抑制率，抑制率＝[1-(OD样品-OD空白)/(OD阴性-OD空白)]×100％。利用软件并计算得出IC50，结果见下表。阴性对照组采用2μL DMSO替代实验组中的“2μL 50mM式I化合物(溶于DMSO中)”；阳性对照组采用2μL 50mM的钒酸钠替代实验组中的“2μL 50mM式I化合物(溶于DMSO中)”。
| 组别 | IC<sub>50</sub>(μM) |
| 实验组 | 3.27±0.26 |
| 阳性对照组 | 7.92±0.65 |
Claims (9)
1.一种作为PTP1B抑制剂的式I结构的卤代苯异噁唑衍生物或其药学上可接受的盐，其特征在于式I结构如下：
2.权利要求1所述的式I结构的卤代苯异噁唑衍生物的制备方法，其特征在于包括如下步骤：
(1)有机溶剂中，式II化合物与式III化合物在氧化银作用下反应得到式IV化合物；
(2)式IV化合物于碱性条件下脱除甲基后，调pH至5-6即可得到式I化合物；步骤(1)中有机溶剂选自乙腈、甲苯、二氧六环中的一种或几种；式II化合物：式III化合物：氧化银的摩尔比为1：1.5-2.0：3.0-4.0，反应温度为70℃至回流温度。
3.权利要求2所述的制备方法，其特征在于步骤(1)反应中加入式III化合物摩尔量5％-6％的AgOTf。
4.权利要求2所述的制备方法，其特征在于步骤(2)中碱性条件为KOH/MeOH或NaOH/MeOH，pH为9-10。
5.一种制备式I化合物的式V中间体，其特征在于式V结构如下：
R选自C1-C6烷基、苄基。
6.一种式IV中间体的制备方法，其特征在于包括如下步骤：
有机溶剂中，式II化合物与式III化合物在氧化银作用下反应得到式IV化合物。
7.权利要求1所述的式I结构的卤代苯异噁唑衍生物或其药学上可接受的盐在制备PTP1B抑制剂中的应用。
8.一种药物组合物，其特征在于该药物组合物以权利要求1所述的式I结构的卤代苯异噁唑衍生物或其药学上可接受的盐作为有效成分。
9.权利要求8所述的药物组合物，其特征在于该药物组合物还包括其他治疗糖尿病的药物；该药物组合物还包括药学上可接受的辅料；该药物组合物的剂型选自固体制剂、液体制剂或半固体制剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911210681.3A CN110804025B (zh) | 2019-11-29 | 2019-11-29 | 一种卤代苯异噁唑衍生物及其制备方法与应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911210681.3A CN110804025B (zh) | 2019-11-29 | 2019-11-29 | 一种卤代苯异噁唑衍生物及其制备方法与应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110804025A CN110804025A (zh) | 2020-02-18 |
| CN110804025B true CN110804025B (zh) | 2022-02-08 |
Family
ID=69492042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911210681.3A Active CN110804025B (zh) | 2019-11-29 | 2019-11-29 | 一种卤代苯异噁唑衍生物及其制备方法与应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110804025B (zh) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0812851A2 (pt) * | 2007-07-02 | 2014-09-30 | Glaxosmithkline Llc | Composto, composição farmacêutica, métodos para o tratamento de uma doença e de uma condição em um indivíduo, processo para preparar um composto, e, uso de um composto |
| CN104513213A (zh) * | 2013-09-28 | 2015-04-15 | 山东亨利医药科技有限责任公司 | Fxr激动剂 |
| WO2017201152A1 (en) * | 2016-05-18 | 2017-11-23 | Enanta Pharmaceuticals, Inc. | Isoxazole derivatives as fxr agonists and methods of use thereof |
| CN109906223A (zh) * | 2016-10-04 | 2019-06-18 | 英安塔制药有限公司 | 异噁唑类似物作为fxr激动剂及其使用方法 |
| AU2018360577A1 (en) * | 2017-11-01 | 2020-06-18 | Bristol-Myers Squibb Company | Bridged bicyclic compounds as farnesoid X receptor modulators |
-
2019
- 2019-11-29 CN CN201911210681.3A patent/CN110804025B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110804025A (zh) | 2020-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109963844B (zh) | 一类抑制并降解酪氨酸蛋白激酶alk的化合物 | |
| KR100708783B1 (ko) | Ｎｏｓ 억제제로서의 ｎ-헤테로시클릭 유도체 | |
| CN110997669B (zh) | 取代五元并六元杂环类化合物、其制备方法、药物组合及其用途 | |
| EP0366061A1 (de) | Die Verwendung von 4H-1-Benzopyran-4-on-Derivaten, neue 4H-1-Benzopyran-4-on-Derivate und diese enthaltende Arzneimittel | |
| JPH03173867A (ja) | 環状アミン化合物 | |
| CA2694724C (en) | Cyclic inhibitors of carnitine palmitoyltransferase and treating cancer | |
| JP7439018B2 (ja) | 置換アリールエーテル系化合物、その調製方法、医薬組成物およびその応用 | |
| CA2627477A1 (en) | Novel beta-agonists, process for their preparation and their use as medicaments | |
| AU2005240733A1 (en) | Novel beta agonists, method for producing the same and their use as drugs | |
| JP5404607B2 (ja) | 抗ｒｎａウイルス作用を有するアニリン誘導体 | |
| JPH0428269B2 (zh) | ||
| JP4564713B2 (ja) | 窒素性複素環式化合物、ならびに窒素性複素環式化合物およびその中間体を作製するための方法 | |
| KR20190096949A (ko) | 소분자 ampk 활성화제 | |
| CN110804025B (zh) | 一种卤代苯异噁唑衍生物及其制备方法与应用 | |
| WO2017204319A1 (ja) | グルコシルセラミド合成酵素阻害剤 | |
| CN110776504B (zh) | 一种苯异噁唑乙氧基环丁胺衍生物及其制备方法与应用 | |
| CN110922368B (zh) | 一种氯代苯异噁唑氨基苯甲酸衍生物及其制备方法与应用 | |
| EP0485583B1 (fr) | Utilisation de derives de la tetrahydro isoquinoleine pour la preparation de medicaments anti-tumoraux | |
| EP0039989B1 (en) | Pyrimidone derivatives, processes for their preparation and pharmaceutical compositions containing them | |
| SK2722002A3 (en) | Use of bis-sulfonamides for producing medicaments used for preventing or treating hyperlipidaemia | |
| HU179361B (en) | Process for preparing indoly-methyl-piperidine derivatives | |
| EP0531228A1 (en) | Thiourea derivatives, antimicrobial agent and antiulcer agent containing the same | |
| DE3710469A1 (de) | Neue benzofuranderivate und diese enthaltende therapeutische mittel | |
| KR20210059663A (ko) | 신규한 벤즈이미다졸 유도체 및 이의 용도 | |
| CN107652275B (zh) | 喹唑啉衍生物及其制备方法和用途 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20240329 Address after: 730300 No. 1699 Daxiahe Street, Qinchuan Chemical Industry Park, Lanzhou New Area, Lanzhou City, Gansu Province Patentee after: Gansu Lanwo Technology Co.,Ltd. Country or region after: China Address before: 225127 No. 199, Yang Hua Xi Road, Yangzhou, Jiangsu Patentee before: YANGZHOU POLYTECHNIC INSTITUTE Country or region before: China |
|
| TR01 | Transfer of patent right |