DE19816624A1 - Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel - Google Patents
Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als ArzneimittelInfo
- Publication number
- DE19816624A1 DE19816624A1 DE19816624A DE19816624A DE19816624A1 DE 19816624 A1 DE19816624 A1 DE 19816624A1 DE 19816624 A DE19816624 A DE 19816624A DE 19816624 A DE19816624 A DE 19816624A DE 19816624 A1 DE19816624 A1 DE 19816624A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- alkyl
- phenyl
- substituted
- amino
- 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.)
- Withdrawn
Links
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical class C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 8
- -1 nitro, amino Chemical group 0.000 claims description 180
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 53
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 33
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 22
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
- 229910052731 fluorine Inorganic materials 0.000 claims description 21
- 239000011737 fluorine Substances 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 20
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 20
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 12
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 239000007790 solid phase Substances 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 229910052717 sulfur Chemical group 0.000 claims description 7
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 230000010933 acylation Effects 0.000 claims description 5
- 238000005917 acylation reaction Methods 0.000 claims description 5
- 125000006842 cycloalkyleneimino group Chemical group 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 5
- 150000003951 lactams Chemical group 0.000 claims description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
- 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims description 4
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 230000032050 esterification Effects 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 230000001681 protective effect Effects 0.000 claims description 3
- 238000005932 reductive alkylation reaction Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 150000003855 acyl compounds Chemical class 0.000 claims description 2
- 125000005277 alkyl imino group Chemical group 0.000 claims description 2
- 230000009435 amidation Effects 0.000 claims description 2
- 238000007112 amidation reaction Methods 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 230000004663 cell proliferation Effects 0.000 claims description 2
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 5
- 239000003085 diluting agent Substances 0.000 claims 2
- APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 abstract description 6
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 4
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 102000020233 phosphotransferase Human genes 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 230000035755 proliferation Effects 0.000 abstract description 3
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical class C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 255
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 237
- 238000001819 mass spectrum Methods 0.000 description 89
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 69
- 239000000741 silica gel Substances 0.000 description 69
- 229910002027 silica gel Inorganic materials 0.000 description 69
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
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- 239000000203 mixture Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
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- 238000000021 kinase assay Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- CYBPPDZFRDSSME-UHFFFAOYSA-N methyl 2-oxo-1,3-dihydroindole-5-carboxylate Chemical compound COC(=O)C1=CC=C2NC(=O)CC2=C1 CYBPPDZFRDSSME-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- CWLNAJYDRSIKJS-UHFFFAOYSA-N triethoxymethoxyethane Chemical compound CCOC(OCC)(OCC)OCC CWLNAJYDRSIKJS-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/02—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 containing two hetero rings
- C07D401/12—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 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Hospice & Palliative Care (AREA)
- AIDS & HIV (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Priority Applications (34)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19816624A DE19816624A1 (de) | 1998-04-15 | 1998-04-15 | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| US09/286,983 US6169106B1 (en) | 1998-04-15 | 1999-04-06 | Indolinones having kinase inhibitory activity |
| NZ507967A NZ507967A (en) | 1998-04-15 | 1999-04-10 | Substituted indolinones having an inhibiting effect on kinases and cycline/CDK complexes |
| CNB998050296A CN100338036C (zh) | 1998-04-15 | 1999-04-10 | 对激酶及细胞周期蛋白复合物具有抑制作用的取代的吲哚满酮 |
| DE59907199T DE59907199D1 (de) | 1998-04-15 | 1999-04-10 | Substituierte indolinone mit inhibierende wirkung auf kinasen und cyclin/cdk-komplexe |
| SI9930481T SI1071665T1 (sl) | 1998-04-15 | 1999-04-10 | Substituirani indolinoni, ki imajo inhibitorni učinek na kinaze in ciklin/CDK komplekse |
| JP2000543432A JP4015365B2 (ja) | 1998-04-15 | 1999-04-10 | 新規な置換インドリノン、それらの調製及び医薬組成物としてのそれらの使用 |
| AT99920635T ATE251138T1 (de) | 1998-04-15 | 1999-04-10 | Substituierte indolinone mit inhibierende wirkung auf kinasen und cyclin/cdk-komplexe |
| EEP200000598A EE04432B1 (et) | 1998-04-15 | 1999-04-10 | Kinaase ja tsükliin/CDK komplekse inhibeerivad asendatud indolinoonid |
| IL13803699A IL138036A0 (en) | 1998-04-15 | 1999-04-10 | Substituted indolines having an inhibiting effect in kinases and cycline/cdk complexes |
| YU59800A YU59800A (sh) | 1998-04-15 | 1999-04-10 | Supstituisani indolinoni sa inhibitorskim dejstom na kinaze i ciklin /cdk komplekse |
| KR1020007011454A KR100588250B1 (ko) | 1998-04-15 | 1999-04-10 | 키나제 및 사이클린/ｃｄｋ 착체에 대한 억제 효과가 있는 치환된 인돌리논, 이의 제조방법 및 이를 함유하는 약제학적 조성물 |
| BR9909688-9A BR9909688A (pt) | 1998-04-15 | 1999-04-10 | Indolinonas substituìdas, a sua preparação e seu uso como composições farmacêuticas |
| IDW20002062A ID26420A (id) | 1998-04-15 | 1999-04-10 | Indolinon-indolinon tersubstitusi baru, pembuatannya dan penggunaannya sebagai komposisi-komposisi farmasi |
| PCT/EP1999/002436 WO1999052869A1 (de) | 1998-04-15 | 1999-04-10 | Substituierte indolinone mit inhibierender wirkung auf kinasen und cyclin/cdk-komplexe |
| SK1513-2000A SK283824B6 (sk) | 1998-04-15 | 1999-04-10 | Substituované indolinóny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie |
| PT99920635T PT1071665E (pt) | 1998-04-15 | 1999-04-10 | Indolinonas substituidas com efeito inibidor sobre cinases e complexos de ciclina/cdk |
| CA002323111A CA2323111C (en) | 1998-04-15 | 1999-04-10 | New substituted indolinones, the preparation thereof and their use as pharmaceutical compositions |
| ES99920635T ES2207209T3 (es) | 1998-04-15 | 1999-04-10 | Indolinonas sustituidas con efecto inhibidor sobre quinasas y complejos de ciclina/cdk. |
| HU0101568A HUP0101568A3 (en) | 1998-04-15 | 1999-04-10 | Substituted indolinones having an inhibiting effect on kinases and cycline/cdk complexes, pharmaceutical compositions containing them and process for producing them |
| PL99343314A PL343314A1 (en) | 1998-04-15 | 1999-04-10 | Substituted indolinones having an inhibiting effect on kinases and cycline/cdk complexes |
| AU38149/99A AU749829B2 (en) | 1998-04-15 | 1999-04-10 | Substituted indolinones having an inhibiting effect on kinases and cycline/CDK complexes |
| TR2000/02980T TR200002980T2 (tr) | 1998-04-15 | 1999-04-10 | İnhibe edici etkiye sahip ikame edilmiş indolinonlar |
| EA200001021A EA003532B1 (ru) | 1998-04-15 | 1999-04-10 | Замещенные индолиноны с ингибирующим действием по отношению к киназам и циклин/cdk-комплексам |
| EP99920635A EP1071665B1 (de) | 1998-04-15 | 1999-04-10 | Substituierte indolinone mit inhibierende wirkung auf kinasen und cyclin/cdk-komplexe |
| DK99920635T DK1071665T3 (da) | 1998-04-15 | 1999-04-10 | Substituerede indolinoner med en inhiberende virkning på kinaser og cyclin/CDK-komplekser |
| MYPI99001427A MY122357A (en) | 1998-04-15 | 1999-04-13 | Indolinones having kinase inhibitory activity |
| CO99022218A CO5011040A1 (es) | 1998-04-15 | 1999-04-14 | Indolinonas sustituidas y procedimiento para su preparacion . |
| TW088105963A TW510897B (en) | 1998-04-15 | 1999-04-14 | New substituted indolinones useful in treating excessive or abnormal cell proliferation, the preparation thereof and their use as pharmaceutical compositions |
| ARP990101700A AR015763A1 (es) | 1998-04-15 | 1999-04-14 | Indolinonas sustituidas y sus sales fisiologicamente compatibles, un procedimiento para su preparacion, su empleo para la preparacion de un medicamento, losmedicamentos que las contienen y un procedimiento para la preparacion de estos medicamentos |
| UA2000116456A UA63009C2 (en) | 1998-04-15 | 1999-10-04 | Substituted indolinones and medicaments based thereon |
| ZA200004623A ZA200004623B (en) | 1998-04-15 | 2000-09-04 | Substituted indolinones having an inhibiting effect on kinases and cycline/CDK complexes. |
| BG104813A BG64443B1 (en) | 1998-04-15 | 2000-09-29 | Substituted indolinones having an inhibiting effect on kinases and cycline/cdk complexes |
| NO20005151A NO317298B1 (no) | 1998-04-15 | 2000-10-13 | Substituerte indoliner med en inhiberende effekt pa kinaser og cyclin/CDK komplekser |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19816624A DE19816624A1 (de) | 1998-04-15 | 1998-04-15 | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19816624A1 true DE19816624A1 (de) | 1999-10-21 |
Family
ID=7864562
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19816624A Withdrawn DE19816624A1 (de) | 1998-04-15 | 1998-04-15 | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| DE59907199T Expired - Lifetime DE59907199D1 (de) | 1998-04-15 | 1999-04-10 | Substituierte indolinone mit inhibierende wirkung auf kinasen und cyclin/cdk-komplexe |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE59907199T Expired - Lifetime DE59907199D1 (de) | 1998-04-15 | 1999-04-10 | Substituierte indolinone mit inhibierende wirkung auf kinasen und cyclin/cdk-komplexe |
Country Status (31)
| Country | Link |
|---|---|
| EP (1) | EP1071665B1 (enExample) |
| JP (1) | JP4015365B2 (enExample) |
| KR (1) | KR100588250B1 (enExample) |
| CN (1) | CN100338036C (enExample) |
| AR (1) | AR015763A1 (enExample) |
| AT (1) | ATE251138T1 (enExample) |
| AU (1) | AU749829B2 (enExample) |
| BG (1) | BG64443B1 (enExample) |
| BR (1) | BR9909688A (enExample) |
| CA (1) | CA2323111C (enExample) |
| CO (1) | CO5011040A1 (enExample) |
| DE (2) | DE19816624A1 (enExample) |
| DK (1) | DK1071665T3 (enExample) |
| EA (1) | EA003532B1 (enExample) |
| EE (1) | EE04432B1 (enExample) |
| ES (1) | ES2207209T3 (enExample) |
| HU (1) | HUP0101568A3 (enExample) |
| ID (1) | ID26420A (enExample) |
| IL (1) | IL138036A0 (enExample) |
| MY (1) | MY122357A (enExample) |
| NO (1) | NO317298B1 (enExample) |
| NZ (1) | NZ507967A (enExample) |
| PL (1) | PL343314A1 (enExample) |
| PT (1) | PT1071665E (enExample) |
| SK (1) | SK283824B6 (enExample) |
| TR (1) | TR200002980T2 (enExample) |
| TW (1) | TW510897B (enExample) |
| UA (1) | UA63009C2 (enExample) |
| WO (1) | WO1999052869A1 (enExample) |
| YU (1) | YU59800A (enExample) |
| ZA (1) | ZA200004623B (enExample) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000073297A1 (de) * | 1999-05-27 | 2000-12-07 | Boehringer Ingelheim Pharma Kg | Substituierte indolinone als tyrosinkinase inhibitoren |
| WO2001016130A1 (de) * | 1999-08-27 | 2001-03-08 | Boehringer Ingelheim Pharma Kg | Substituierte indolinone als tyrosinkinase inhibitoren |
| WO2000055159A3 (en) * | 1999-03-04 | 2001-11-29 | Glaxo Group Ltd | Substituted aza-oxindole derivatives |
| WO2002048114A1 (en) * | 2000-11-27 | 2002-06-20 | Pharmacia Italia S.P.A. | Phenylacetamido- pyrazole derivatives and their use as antitumor agents |
| US6624171B1 (en) | 1999-03-04 | 2003-09-23 | Smithkline Beecham Corporation | Substituted aza-oxindole derivatives |
| CN109293551A (zh) * | 2011-11-14 | 2019-02-01 | 利亘制药公司 | 与粒细胞集落刺激因子受体相关的方法和组合物 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6569868B2 (en) | 1998-04-16 | 2003-05-27 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| GB9904932D0 (en) * | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Composition and method for preventing/reducing the severity of side effects of chemotherapy and/or radiation therapy |
| GB9904933D0 (en) * | 1999-03-04 | 1999-04-28 | Glaxo Group Ltd | Compounds |
| US6762180B1 (en) | 1999-10-13 | 2004-07-13 | Boehringer Ingelheim Pharma Kg | Substituted indolines which inhibit receptor tyrosine kinases |
| UA75054C2 (uk) * | 1999-10-13 | 2006-03-15 | Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг | Заміщені в положенні 6 індолінони, їх одержання та їх застосування як лікарського засобу |
| US6573293B2 (en) | 2000-02-15 | 2003-06-03 | Sugen, Inc. | Pyrrole substituted 2-indolinone protein kinase inhibitors |
| US6620818B1 (en) | 2000-03-01 | 2003-09-16 | Smithkline Beecham Corporation | Method for reducing the severity of side effects of chemotherapy and/or radiation therapy |
| MY128449A (en) | 2000-05-24 | 2007-02-28 | Sugen Inc | Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
| US6706709B2 (en) | 2000-06-02 | 2004-03-16 | Sugen, Inc. | Indolinone derivatives as protein kinase/phosphatase inhibitors |
| AR042586A1 (es) | 2001-02-15 | 2005-06-29 | Sugen Inc | 3-(4-amidopirrol-2-ilmetiliden)-2-indolinona como inhibidores de la protein quinasa; sus composiciones farmaceuticas; un metodo para la modulacion de la actividad catalitica de la proteinquinasa; un metodo para tratar o prevenir una afeccion relacionada con la proteinquinasa |
| DE10117204A1 (de) | 2001-04-06 | 2002-10-10 | Boehringer Ingelheim Pharma | In 6-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| US6599902B2 (en) | 2001-05-30 | 2003-07-29 | Sugen, Inc. | 5-aralkysufonyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors |
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| US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| UY28526A1 (es) | 2003-09-24 | 2005-04-29 | Boehringer Ingelheim Pharma | Miméticos de glucocorticoides, métodos de preparación composiciones farmacéuticas y usos de los mismos |
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| US7795272B2 (en) | 2004-03-13 | 2010-09-14 | Boehringer Ingelheim Pharmaceutical, Inc. | Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| ES2326907T3 (es) | 2004-12-27 | 2009-10-21 | Boehringer Ingelheim Pharmaceuticals Inc. | Mimeticos de glucocorticoides, metodos para su preparacion, composiciones farmaceuticas y su uso. |
| AU2006254758B2 (en) * | 2005-06-10 | 2012-04-05 | Merck Patent Gmbh | Oxindoles as kinase inhibitors |
| WO2007057399A2 (en) * | 2005-11-15 | 2007-05-24 | Boehringer Ingelheim International Gmbh | Treatment of cancer with indole derivatives |
| BRPI0720131A2 (pt) | 2006-12-06 | 2014-02-04 | Boehringer Ingelheim Int | Glicocorticoides miméticos, métodos para fazê-los, composições farmacêuticas e usos dos mesmos. |
| KR20110020902A (ko) | 2008-06-06 | 2011-03-03 | 베링거 인겔하임 인터내셔날 게엠베하 | 글루코코르티코이드 유사체, 이의 제조방법, 약제학적 조성물 및 이의 용도 |
| US20170065529A1 (en) | 2015-09-09 | 2017-03-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical dosage form for immediate release of an indolinone derivative |
| WO2011032320A1 (en) * | 2009-09-21 | 2011-03-24 | F. Hoffmann-La Roche Ag | Novel alkene oxindole derivatives |
| WO2014150252A1 (en) * | 2013-03-15 | 2014-09-25 | Ligand Pharmaceuticals Incorporated | Methods of treatment associated with the granulocyte colony-stimulating factor receptor |
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| CN111285872B (zh) * | 2018-12-06 | 2022-05-17 | 北京志健金瑞生物医药科技有限公司 | 吲哚-2-酮衍生物及其制备方法与用途 |
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| GB9501567D0 (en) * | 1995-01-26 | 1995-03-15 | Pharmacia Spa | Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors |
| US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| GB9718913D0 (en) * | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
| DE19824922A1 (de) * | 1998-06-04 | 1999-12-09 | Boehringer Ingelheim Pharma | Neue substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| UA75054C2 (uk) * | 1999-10-13 | 2006-03-15 | Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг | Заміщені в положенні 6 індолінони, їх одержання та їх застосування як лікарського засобу |
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1998
- 1998-04-15 DE DE19816624A patent/DE19816624A1/de not_active Withdrawn
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- 1999-04-10 NZ NZ507967A patent/NZ507967A/xx unknown
- 1999-04-10 TR TR2000/02980T patent/TR200002980T2/xx unknown
- 1999-04-10 HU HU0101568A patent/HUP0101568A3/hu unknown
- 1999-04-10 PT PT99920635T patent/PT1071665E/pt unknown
- 1999-04-10 BR BR9909688-9A patent/BR9909688A/pt not_active Application Discontinuation
- 1999-04-10 WO PCT/EP1999/002436 patent/WO1999052869A1/de not_active Ceased
- 1999-04-10 DK DK99920635T patent/DK1071665T3/da active
- 1999-04-10 ES ES99920635T patent/ES2207209T3/es not_active Expired - Lifetime
- 1999-04-10 SK SK1513-2000A patent/SK283824B6/sk unknown
- 1999-04-10 CN CNB998050296A patent/CN100338036C/zh not_active Expired - Fee Related
- 1999-04-10 CA CA002323111A patent/CA2323111C/en not_active Expired - Fee Related
- 1999-04-10 EA EA200001021A patent/EA003532B1/ru not_active IP Right Cessation
- 1999-04-10 AT AT99920635T patent/ATE251138T1/de active
- 1999-04-10 YU YU59800A patent/YU59800A/sh unknown
- 1999-04-10 JP JP2000543432A patent/JP4015365B2/ja not_active Expired - Lifetime
- 1999-04-10 EP EP99920635A patent/EP1071665B1/de not_active Expired - Lifetime
- 1999-04-10 AU AU38149/99A patent/AU749829B2/en not_active Ceased
- 1999-04-10 PL PL99343314A patent/PL343314A1/xx not_active Application Discontinuation
- 1999-04-10 IL IL13803699A patent/IL138036A0/xx not_active IP Right Cessation
- 1999-04-10 DE DE59907199T patent/DE59907199D1/de not_active Expired - Lifetime
- 1999-04-10 EE EEP200000598A patent/EE04432B1/xx not_active IP Right Cessation
- 1999-04-10 KR KR1020007011454A patent/KR100588250B1/ko not_active Expired - Fee Related
- 1999-04-13 MY MYPI99001427A patent/MY122357A/en unknown
- 1999-04-14 TW TW088105963A patent/TW510897B/zh active
- 1999-04-14 AR ARP990101700A patent/AR015763A1/es active IP Right Grant
- 1999-04-14 CO CO99022218A patent/CO5011040A1/es unknown
- 1999-10-04 UA UA2000116456A patent/UA63009C2/uk unknown
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2000
- 2000-09-04 ZA ZA200004623A patent/ZA200004623B/xx unknown
- 2000-09-29 BG BG104813A patent/BG64443B1/bg unknown
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000055159A3 (en) * | 1999-03-04 | 2001-11-29 | Glaxo Group Ltd | Substituted aza-oxindole derivatives |
| US6624171B1 (en) | 1999-03-04 | 2003-09-23 | Smithkline Beecham Corporation | Substituted aza-oxindole derivatives |
| US6815439B2 (en) | 1999-03-04 | 2004-11-09 | Smithkline Beecham Corporation | Substituted aza-oxindole derivatives |
| WO2000073297A1 (de) * | 1999-05-27 | 2000-12-07 | Boehringer Ingelheim Pharma Kg | Substituierte indolinone als tyrosinkinase inhibitoren |
| WO2001016130A1 (de) * | 1999-08-27 | 2001-03-08 | Boehringer Ingelheim Pharma Kg | Substituierte indolinone als tyrosinkinase inhibitoren |
| US6794395B1 (en) | 1999-08-27 | 2004-09-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Substituted indolinones, their manufacture and their use as medicaments |
| WO2002048114A1 (en) * | 2000-11-27 | 2002-06-20 | Pharmacia Italia S.P.A. | Phenylacetamido- pyrazole derivatives and their use as antitumor agents |
| CN109293551A (zh) * | 2011-11-14 | 2019-02-01 | 利亘制药公司 | 与粒细胞集落刺激因子受体相关的方法和组合物 |
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