CN102417487A - 吲唑、苯并异*唑和苯并异噻唑激酶抑制剂 - Google Patents
吲唑、苯并异*唑和苯并异噻唑激酶抑制剂 Download PDFInfo
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- CN102417487A CN102417487A CN2011103041508A CN201110304150A CN102417487A CN 102417487 A CN102417487 A CN 102417487A CN 2011103041508 A CN2011103041508 A CN 2011103041508A CN 201110304150 A CN201110304150 A CN 201110304150A CN 102417487 A CN102417487 A CN 102417487A
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- Prior art keywords
- phenyl
- amino
- urea
- alkyl
- compound
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- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 title abstract description 4
- 229940043355 kinase inhibitor Drugs 0.000 title abstract description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 4
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 title description 4
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 263
- 238000000034 method Methods 0.000 claims abstract description 84
- 239000000203 mixture Substances 0.000 claims abstract description 68
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- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 331
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 330
- 239000001257 hydrogen Substances 0.000 claims description 303
- 229910052739 hydrogen Inorganic materials 0.000 claims description 303
- 125000003545 alkoxy group Chemical group 0.000 claims description 296
- 125000000217 alkyl group Chemical group 0.000 claims description 258
- 239000004202 carbamide Substances 0.000 claims description 186
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 180
- -1 carbonyl thiazolinyl Chemical group 0.000 claims description 131
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims description 120
- 150000002431 hydrogen Chemical class 0.000 claims description 120
- 229910052736 halogen Inorganic materials 0.000 claims description 117
- 150000002367 halogens Chemical class 0.000 claims description 117
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 100
- 125000001188 haloalkyl group Chemical group 0.000 claims description 76
- 125000004104 aryloxy group Chemical group 0.000 claims description 75
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 74
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 57
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 56
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 48
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 47
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 46
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 40
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 26
- 239000001301 oxygen Substances 0.000 claims description 25
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 24
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 21
- 125000004171 alkoxy aryl group Chemical group 0.000 claims description 13
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 12
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 11
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 7
- 102000001253 Protein Kinase Human genes 0.000 claims description 6
- 108060006633 protein kinase Proteins 0.000 claims description 6
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- RTXFGYAFONNKRT-UHFFFAOYSA-N C1=CC(=CC(=C1)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)N(N=C4N)CCO)CN Chemical compound C1=CC(=CC(=C1)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)N(N=C4N)CCO)CN RTXFGYAFONNKRT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 235000013877 carbamide Nutrition 0.000 claims 40
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims 4
- UKUBGLJCBLBBTL-UHFFFAOYSA-N 1-[4-(3-amino-1,2-benzothiazol-4-yl)phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound C=12C(N)=NSC2=CC=CC=1C(C=C1)=CC=C1NC(=O)NC1=CC=CC(C(F)(F)F)=C1 UKUBGLJCBLBBTL-UHFFFAOYSA-N 0.000 claims 1
- XUAVZPFKUWDJJL-UHFFFAOYSA-N 1-[4-(3-amino-1h-indazol-4-yl)phenyl]-3-cyclopentylurea Chemical compound C=12C(N)=NNC2=CC=CC=1C(C=C1)=CC=C1NC(=O)NC1CCCC1 XUAVZPFKUWDJJL-UHFFFAOYSA-N 0.000 claims 1
- OPVYNMNWPXOEJX-UHFFFAOYSA-N 1-[4-(3-amino-1h-indazol-4-yl)phenyl]-3-thiophen-3-ylurea Chemical compound C=12C(N)=NNC2=CC=CC=1C(C=C1)=CC=C1NC(=O)NC=1C=CSC=1 OPVYNMNWPXOEJX-UHFFFAOYSA-N 0.000 claims 1
- KTFDYVNEGTXQCV-UHFFFAOYSA-N 2-Thiophenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CS1 KTFDYVNEGTXQCV-UHFFFAOYSA-N 0.000 claims 1
- PWBSWSJFBGBCDO-UHFFFAOYSA-N C1=CC(=C2C(=C1)SN=C2N)C3=CC=C(C=C3)NC(=O)NC4=C(C=CC(=C4)CN)F Chemical compound C1=CC(=C2C(=C1)SN=C2N)C3=CC=C(C=C3)NC(=O)NC4=C(C=CC(=C4)CN)F PWBSWSJFBGBCDO-UHFFFAOYSA-N 0.000 claims 1
- VRRWCUQNLUCWGW-UHFFFAOYSA-N C1=CC(=CC(=C1)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)SN=C4N)CN Chemical compound C1=CC(=CC(=C1)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)SN=C4N)CN VRRWCUQNLUCWGW-UHFFFAOYSA-N 0.000 claims 1
- UORHQICZWGPJFM-UHFFFAOYSA-N C1=CC=C(C=C1)N2C3=CC=CC(=C3C(=N2)N)C4=CC=C(C=C4)NC(=O)NC5=C(C=CC(=C5)CN)F Chemical compound C1=CC=C(C=C1)N2C3=CC=CC(=C3C(=N2)N)C4=CC=C(C=C4)NC(=O)NC5=C(C=CC(=C5)CN)F UORHQICZWGPJFM-UHFFFAOYSA-N 0.000 claims 1
- APMSTPDRTFILAW-UHFFFAOYSA-N CC(=O)N1C2=CC=CC(=C2C(=N1)N)C3=CC=C(C=C3)NC(=O)NC4=C(C=CC(=C4)CN)F Chemical compound CC(=O)N1C2=CC=CC(=C2C(=N1)N)C3=CC=C(C=C3)NC(=O)NC4=C(C=CC(=C4)CN)F APMSTPDRTFILAW-UHFFFAOYSA-N 0.000 claims 1
- 150000003672 ureas Chemical class 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 22
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 22
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 abstract 1
- 150000002473 indoazoles Chemical class 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 364
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- 239000002585 base Substances 0.000 description 156
- RIKWVZGZRYDACA-UHFFFAOYSA-N 1-fluoro-3-isocyanatobenzene Chemical compound FC1=CC=CC(N=C=O)=C1 RIKWVZGZRYDACA-UHFFFAOYSA-N 0.000 description 121
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 114
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 113
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 99
- 229910052796 boron Inorganic materials 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- 238000002360 preparation method Methods 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
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- CPPGZWWUPFWALU-UHFFFAOYSA-N 1-isocyanato-3-methylbenzene Chemical compound CC1=CC=CC(N=C=O)=C1 CPPGZWWUPFWALU-UHFFFAOYSA-N 0.000 description 44
- 239000000243 solution Substances 0.000 description 39
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 32
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 28
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- 229910052731 fluorine Inorganic materials 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 23
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
- GLSUJZPVKMKUPJ-UHFFFAOYSA-N 1-fluoro-2-isocyanato-4-methylbenzene Chemical compound CC1=CC=C(F)C(N=C=O)=C1 GLSUJZPVKMKUPJ-UHFFFAOYSA-N 0.000 description 21
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Classifications
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- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
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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
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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Landscapes
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- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/443254 | 2003-05-22 | ||
| US10/443,254 US20040235892A1 (en) | 2003-05-22 | 2003-05-22 | Indazole and benzisoxazole kinase inhibitors |
| US10/842,292 US7297709B2 (en) | 2003-05-22 | 2004-05-10 | Indazole, benzisoxazole, and benzisothiazole kinase inhibitors |
| US10/842292 | 2004-05-10 |
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| CN2004800205684A Division CN1826324B (zh) | 2003-05-22 | 2004-05-21 | 吲唑、苯并异*唑和苯并异噻唑激酶抑制剂 |
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| Publication Number | Publication Date |
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| CN102417487A true CN102417487A (zh) | 2012-04-18 |
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| CN2011103041508A Pending CN102417487A (zh) | 2003-05-22 | 2004-05-21 | 吲唑、苯并异*唑和苯并异噻唑激酶抑制剂 |
| CN2004800205684A Expired - Fee Related CN1826324B (zh) | 2003-05-22 | 2004-05-21 | 吲唑、苯并异*唑和苯并异噻唑激酶抑制剂 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2004800205684A Expired - Fee Related CN1826324B (zh) | 2003-05-22 | 2004-05-21 | 吲唑、苯并异*唑和苯并异噻唑激酶抑制剂 |
Country Status (20)
| Country | Link |
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| EP (2) | EP2246333B1 (https=) |
| JP (2) | JP4810427B2 (https=) |
| KR (1) | KR100976076B1 (https=) |
| CN (2) | CN102417487A (https=) |
| AT (1) | ATE469888T1 (https=) |
| AU (2) | AU2004249675B2 (https=) |
| BR (1) | BRPI0410745A (https=) |
| CA (1) | CA2526430C (https=) |
| CY (1) | CY1110742T1 (https=) |
| DE (1) | DE602004027490D1 (https=) |
| DK (1) | DK1638941T3 (https=) |
| ES (2) | ES2398074T3 (https=) |
| IL (1) | IL171976A0 (https=) |
| MX (1) | MXPA05012596A (https=) |
| NZ (1) | NZ543614A (https=) |
| PL (1) | PL1638941T3 (https=) |
| PT (1) | PT1638941E (https=) |
| SI (1) | SI1638941T1 (https=) |
| TW (1) | TWI328579B (https=) |
| WO (1) | WO2004113304A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116535359A (zh) * | 2023-05-12 | 2023-08-04 | 南昌双天使生物科技开发有限公司 | 一种含吲唑基的羟肟酸衍生物及其应用 |
Families Citing this family (125)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0413347A (pt) | 2003-08-06 | 2006-10-10 | Senomyx Inc | novos sabores, modificadores de sabor, agentes de sabor, realçadores de sabor, agentes de sabor e/ou realçadores umami ou doces, e utilização correspondente |
| FR2871158A1 (fr) * | 2004-06-04 | 2005-12-09 | Aventis Pharma Sa | Indazoles substitues, compositions les contenant, procede de fabrication et utilisation |
| DE102004028862A1 (de) * | 2004-06-15 | 2005-12-29 | Merck Patent Gmbh | 3-Aminoindazole |
| US20060045953A1 (en) * | 2004-08-06 | 2006-03-02 | Catherine Tachdjian | Aromatic amides and ureas and their uses as sweet and/or umami flavor modifiers, tastants and taste enhancers |
| US7812166B2 (en) | 2004-10-29 | 2010-10-12 | Abbott Laboratories | Kinase inhibitors |
| PE20061119A1 (es) * | 2005-01-19 | 2006-11-27 | Aventis Pharma Sa | PIRAZOLO PIRIDINAS SUSTITUIDAS COMO INHIBIDORES DE CINASAS FAK, KDR Y Tie |
| US7842809B2 (en) | 2005-01-24 | 2010-11-30 | Bayer Schering Pharma Ag | Pyrazolopyridines and salts thereof, a pharmaceutical composition comprising said compounds, a method of preparing same and use of same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116535359A (zh) * | 2023-05-12 | 2023-08-04 | 南昌双天使生物科技开发有限公司 | 一种含吲唑基的羟肟酸衍生物及其应用 |
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