CN104098513B - A kind of indazole compound derivative and preparation method thereof - Google Patents
A kind of indazole compound derivative and preparation method thereof Download PDFInfo
- Publication number
- CN104098513B CN104098513B CN201410371407.5A CN201410371407A CN104098513B CN 104098513 B CN104098513 B CN 104098513B CN 201410371407 A CN201410371407 A CN 201410371407A CN 104098513 B CN104098513 B CN 104098513B
- Authority
- CN
- China
- Prior art keywords
- compound
- indazole
- preparation
- generates
- derivative
- 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
- -1 indazole compound Chemical class 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 229940126214 compound 3 Drugs 0.000 claims abstract description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims abstract description 8
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229940125782 compound 2 Drugs 0.000 claims abstract description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229940125904 compound 1 Drugs 0.000 claims abstract description 4
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims abstract description 4
- 230000000694 effects Effects 0.000 claims abstract description 3
- LNAHWKUKPHEFST-UHFFFAOYSA-N 1-(6-bromo-1h-indazol-3-yl)ethanone Chemical compound BrC1=CC=C2C(C(=O)C)=NNC2=C1 LNAHWKUKPHEFST-UHFFFAOYSA-N 0.000 claims description 8
- 239000012467 final product Substances 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 abstract description 5
- 230000004054 inflammatory process Effects 0.000 abstract description 5
- 239000007795 chemical reaction product Substances 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- KXTOQWKJKBSECV-UHFFFAOYSA-N formaldehyde 1H-indazole Chemical compound C=O.N1N=CC2=CC=CC=C12 KXTOQWKJKBSECV-UHFFFAOYSA-N 0.000 abstract description 3
- MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 abstract 1
- LTFPRWCVUZBEHX-UHFFFAOYSA-N C(C)(=O)C1=NNC2=CC=CC=C12.[Br] Chemical compound C(C)(=O)C1=NNC2=CC=CC=C12.[Br] LTFPRWCVUZBEHX-UHFFFAOYSA-N 0.000 abstract 1
- 229940125898 compound 5 Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 206010042674 Swelling Diseases 0.000 description 7
- 230000008961 swelling Effects 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 210000005069 ears Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 240000006409 Acacia auriculiformis Species 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- ZPRQXVPYQGBZON-UHFFFAOYSA-N 2-bromo-1h-indole Chemical class C1=CC=C2NC(Br)=CC2=C1 ZPRQXVPYQGBZON-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical group CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 101001031591 Mus musculus Heart- and neural crest derivatives-expressed protein 2 Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 108010014632 NF-kappa B kinase Proteins 0.000 description 1
- 102000019148 NF-kappaB-inducing kinase activity proteins Human genes 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LCWSUVRIRMTCBK-UHFFFAOYSA-N ethanol;1h-indazole Chemical compound CCO.C1=CC=C2C=NNC2=C1 LCWSUVRIRMTCBK-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Group | Left ear (mg) | Auris dextra (mg) | Swelling (mg) | Inhibiting rate (%) |
Blank group | 12.5±1.1 | 24.1±2.7 | 11.7±3.3 | |
Aspirin group | 13.9±1.5 | 18.6±2.6 | 4.7±2.1 | 59.83% |
Test group | 12.9±0.9 | 17.8±1.6 | 4.9±1.8 | 58.12% |
Claims (2)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410371407.5A CN104098513B (en) | 2014-07-30 | 2014-07-30 | A kind of indazole compound derivative and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410371407.5A CN104098513B (en) | 2014-07-30 | 2014-07-30 | A kind of indazole compound derivative and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104098513A CN104098513A (en) | 2014-10-15 |
CN104098513B true CN104098513B (en) | 2016-08-24 |
Family
ID=51667099
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410371407.5A Active CN104098513B (en) | 2014-07-30 | 2014-07-30 | A kind of indazole compound derivative and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104098513B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104324026B (en) * | 2014-11-28 | 2016-08-24 | 温州医科大学 | A kind of pharmaceutical composition antianxity and application thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2465247A1 (en) * | 2001-10-26 | 2003-05-01 | Aventis Pharmaceuticals Inc. | Benzimidazoles and analogues and their use as protein kinases inhibitors |
CN101080408A (en) * | 2004-12-17 | 2007-11-28 | 霍夫曼-拉罗奇有限公司 | Trycyclic heterocycles, their manufacture and use as pharmaceutical agents |
CN101687808A (en) * | 2007-06-21 | 2010-03-31 | 默克专利有限公司 | indazolamide derivatives |
CN103387565A (en) * | 2013-07-29 | 2013-11-13 | 苏州明锐医药科技有限公司 | Preparation method of Axitinib |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2812088A1 (en) * | 2010-09-14 | 2012-03-22 | Exelixis, Inc. | Phtalazine derivatives as jak1 inhibitors |
-
2014
- 2014-07-30 CN CN201410371407.5A patent/CN104098513B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2465247A1 (en) * | 2001-10-26 | 2003-05-01 | Aventis Pharmaceuticals Inc. | Benzimidazoles and analogues and their use as protein kinases inhibitors |
CN101080408A (en) * | 2004-12-17 | 2007-11-28 | 霍夫曼-拉罗奇有限公司 | Trycyclic heterocycles, their manufacture and use as pharmaceutical agents |
CN101687808A (en) * | 2007-06-21 | 2010-03-31 | 默克专利有限公司 | indazolamide derivatives |
CN103387565A (en) * | 2013-07-29 | 2013-11-13 | 苏州明锐医药科技有限公司 | Preparation method of Axitinib |
Also Published As
Publication number | Publication date |
---|---|
CN104098513A (en) | 2014-10-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Usui et al. | HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats | |
Hui et al. | MicroRNA-34a and microRNA-21 play roles in the chemopreventive effects of 3, 6-dihydroxyflavone on 1-methyl-1-nitrosourea-induced breast carcinogenesis | |
Yang et al. | Synthesis and pharmacological evaluation of novel limonin derivatives as anti-inflammatory and analgesic agents with high water solubility | |
Liu et al. | Synthesis and biological evaluation of curcumin derivatives containing NSAIDs for their anti-inflammatory activity | |
CN104098513B (en) | A kind of indazole compound derivative and preparation method thereof | |
EP2751084B1 (en) | Pyrimidine carboxamide derivatives | |
Ahn et al. | Discovery of indane propanamides as potent and selective TRPV1 antagonists | |
Liu et al. | Inhibitory effect of 4, 4′-dihydroxy-α-truxillic acid derivatives on NO production in lipopolysaccharide-induced RAW 264.7 macrophages and exploration of structure–activity relationships | |
CN104095860B (en) | O-(nafoxidine base) ethyl derivative of Cleistanthus sumafranus (Miq) Muell-Arg-C. Saichikii Merr wood ketone Cleistanone is preparing the application in anti-inflammatory drug | |
CN105254699A (en) | 4-(4 minute-trifluoromethyl) phenyl-2-dehydroepiandrosterone-17 minute-hydrazone thiazole as well as preparation method and application thereof | |
CN104045533A (en) | Indanone compound and medicinal application | |
CN102558058B (en) | 1-aryl-3-substituent-5-substituted amino-4-pyrazole formamide compound and application thereof | |
CN104546843A (en) | Application of pyrazole hydrazone derivative in preparation of anti-breast cancer drug | |
CN102964414A (en) | Synthesis method of 17-position steroid carboxylic ester | |
CN104130191B (en) | A kind of indazole compound and preparation method thereof | |
CN102503857B (en) | Bexarotene hydroximic acid as well as preparation method and application thereof | |
Song et al. | Synthesis and biological evaluation of novel hydrogen sulfide releasing glycyrrhetic acid derivatives | |
Martín-Escura et al. | β-Lactam TRPM8 Antagonists Derived from Phe-Phenylalaninol Conjugates: Structure–Activity Relationships and Antiallodynic Activity | |
CN102532024B (en) | Sinomenine derivate | |
CN101891730B (en) | Synthesizing method of 7-alkoxy methyl hesperetin and pharmaceutical use thereof | |
CN105315282A (en) | Preparation method of ticagrelor amorphous form | |
CN105287509A (en) | MEK kinase inhibitor | |
Chen et al. | Design and synthesis of pterostilbene derivatives bearing triazole moiety that might treat DSS-induced colitis in mice through modulation of NF-κB/MAPK signaling pathways | |
CN102617474A (en) | Preparation method for celecoxib isomer | |
CN104098564A (en) | Pyrazol pyridine compound and preparation method thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee | ||
CP03 | Change of name, title or address |
Address after: The 300000 Tianjin economic and Technological Development Zone Haiyun Street No. 80 plant No. 17 A6-8 Patentee after: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Address before: 300000 Tianjin Binhai New Area Haiyun Street No. 80 No. 17 building A6-8 Patentee before: SPHINX SCIENTIFIC LABORATORY Corp. |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Indazole compound derivative and preparation method Effective date of registration: 20190926 Granted publication date: 20160824 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2019120000007 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20200910 Granted publication date: 20160824 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) Co.,Ltd. Registration number: Y2019120000007 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: The invention relates to an indazole compound derivative and a preparation method thereof Effective date of registration: 20210526 Granted publication date: 20160824 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) Co.,Ltd. Registration number: Y2021120000020 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20220519 Granted publication date: 20160824 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2021120000020 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: An indazole compound derivative and its preparation method Effective date of registration: 20220525 Granted publication date: 20160824 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2022120000023 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230612 Granted publication date: 20160824 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2022120000023 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: An indole compound derivative and its preparation method Effective date of registration: 20230703 Granted publication date: 20160824 Pledgee: Tianjin Binhai rural commercial bank Limited by Share Ltd. Pledgor: SPHINX SCIENTIFIC LABORATORY (TIANJIN) CO.,LTD. Registration number: Y2023120000052 |