CN1051074C - 异噁唑－4－羧酰胺及羟基亚烷基氰基乙酰胺用于制备药物的用途 - Google Patents
异噁唑－4－羧酰胺及羟基亚烷基氰基乙酰胺用于制备药物的用途 Download PDFInfo
- Publication number
- CN1051074C CN1051074C CN91103182A CN91103182A CN1051074C CN 1051074 C CN1051074 C CN 1051074C CN 91103182 A CN91103182 A CN 91103182A CN 91103182 A CN91103182 A CN 91103182A CN 1051074 C CN1051074 C CN 1051074C
- Authority
- CN
- China
- Prior art keywords
- carbon atoms
- group
- alkyl
- hydrogen
- fluorine
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 46
- 239000003814 drug Substances 0.000 title claims description 11
- QBPXGTUBZXXKJO-UHFFFAOYSA-N 1,2-oxazole-4-carboxamide Chemical class NC(=O)C=1C=NOC=1 QBPXGTUBZXXKJO-UHFFFAOYSA-N 0.000 title abstract description 4
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- 208000025747 Rheumatic disease Diseases 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims description 94
- 125000004432 carbon atom Chemical group C* 0.000 claims description 85
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 57
- 229910052731 fluorine Inorganic materials 0.000 claims description 57
- 239000011737 fluorine Substances 0.000 claims description 57
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 56
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 56
- 229910052794 bromium Inorganic materials 0.000 claims description 56
- 239000000460 chlorine Substances 0.000 claims description 56
- 229910052801 chlorine Inorganic materials 0.000 claims description 56
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 55
- 229910052736 halogen Inorganic materials 0.000 claims description 55
- 150000002367 halogens Chemical class 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- -1 oxygen radical Chemical class 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims description 49
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 239000011630 iodine Substances 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 238000006467 substitution reaction Methods 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000002915 carbonyl group Chemical class [*:2]C([*:1])=O 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- JJJXXHCDSQSIFQ-YFHOEESVSA-N (z)-2-cyano-3-hydroxy-n-[4-(trifluoromethoxy)phenyl]but-2-enamide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(OC(F)(F)F)C=C1 JJJXXHCDSQSIFQ-YFHOEESVSA-N 0.000 claims description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- RXSNFDWFKNKMKV-UHFFFAOYSA-N n-(1h-indazol-5-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=C3C=NNC3=CC=2)=C1C RXSNFDWFKNKMKV-UHFFFAOYSA-N 0.000 claims description 3
- NWOVTJSCRMZLMM-UHFFFAOYSA-N n-(1h-indazol-6-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=C3NN=CC3=CC=2)=C1C NWOVTJSCRMZLMM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- VKXYORVLYJXLSK-UHFFFAOYSA-N 5-methyl-n-(4-methylsulfonylphenyl)-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)S(C)(=O)=O)=C1C VKXYORVLYJXLSK-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- NCJHFNRNOOGXMN-UHFFFAOYSA-N n-(1h-indol-5-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=C3C=CNC3=CC=2)=C1C NCJHFNRNOOGXMN-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- CIAYWDIOMYFBGQ-YFHOEESVSA-N (z)-2-cyano-3-hydroxy-n-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]but-2-enamide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(OC(F)(F)C(F)F)C=C1 CIAYWDIOMYFBGQ-YFHOEESVSA-N 0.000 claims 1
- MCQBBMWGWZVCPF-WJDWOHSUSA-N (z)-2-cyano-n-[4-(4-fluorobenzoyl)phenyl]-3-hydroxybut-2-enamide Chemical compound C1=CC(NC(=O)C(/C#N)=C(O)/C)=CC=C1C(=O)C1=CC=C(F)C=C1 MCQBBMWGWZVCPF-WJDWOHSUSA-N 0.000 claims 1
- XLWOZNBEEQLMKL-KTKRTIGZSA-N (z)-n-(1,3-benzodioxol-5-yl)-2-cyano-3-hydroxypent-2-enamide Chemical compound CC\C(O)=C(/C#N)C(=O)NC1=CC=C2OCOC2=C1 XLWOZNBEEQLMKL-KTKRTIGZSA-N 0.000 claims 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims 1
- BPOJESSTIKFRED-UHFFFAOYSA-N 5-ethyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound C1(=CC=CC=C1)C1=NOC(=C1C(=O)N)CC BPOJESSTIKFRED-UHFFFAOYSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- AFIFBOMOIFYWFT-UHFFFAOYSA-N n-(4,6-dimethylpyridin-2-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2N=C(C)C=C(C)C=2)=C1C AFIFBOMOIFYWFT-UHFFFAOYSA-N 0.000 claims 1
- RLGIIWFUFLEEEX-UHFFFAOYSA-N n-(4,6-dimethylpyrimidin-2-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2N=C(C)C=C(C)N=2)=C1C RLGIIWFUFLEEEX-UHFFFAOYSA-N 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 201000011510 cancer Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 83
- 230000008018 melting Effects 0.000 description 83
- 238000000354 decomposition reaction Methods 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 18
- ZKAQPVQEYCFRTK-UHFFFAOYSA-N 5-methyl-1,2-oxazole-4-carbonyl chloride Chemical compound CC=1ON=CC=1C(Cl)=O ZKAQPVQEYCFRTK-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- RFXIFHIHWYTKIG-UHFFFAOYSA-N 5-ethyl-1,2-oxazole-4-carbonyl chloride Chemical compound CCC=1ON=CC=1C(Cl)=O RFXIFHIHWYTKIG-UHFFFAOYSA-N 0.000 description 12
- 239000002609 medium Substances 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- MNANGXNDRCOVLE-UHFFFAOYSA-N 1,2-oxazole-4-carbonyl chloride Chemical compound ClC(=O)C=1C=NOC=1 MNANGXNDRCOVLE-UHFFFAOYSA-N 0.000 description 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000003226 mitogen Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 229940125904 compound 1 Drugs 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 108700031361 Brachyury Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000011785 NMRI mouse Methods 0.000 description 6
- 231100000403 acute toxicity Toxicity 0.000 description 6
- 230000007059 acute toxicity Effects 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- RBKHNGHPZZZJCI-UHFFFAOYSA-N (4-aminophenyl)-phenylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)C1=CC=CC=C1 RBKHNGHPZZZJCI-UHFFFAOYSA-N 0.000 description 4
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 4
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 4
- JKKHPBPDSLVAHU-UHFFFAOYSA-N 5-(trifluoromethyl)-1,2-oxazole-4-carbonyl chloride Chemical compound FC(F)(F)C=1ON=CC=1C(Cl)=O JKKHPBPDSLVAHU-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 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 3
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 3
- MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 description 3
- GRCVQCCYLUGKPI-UHFFFAOYSA-N 5-phenyl-1,2-oxazole-4-carbonyl chloride Chemical compound C1=NOC(C=2C=CC=CC=2)=C1C(=O)Cl GRCVQCCYLUGKPI-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 210000004988 splenocyte Anatomy 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 2
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 2
- MFWVUXQQNCGGPX-UHFFFAOYSA-N 5-butyl-1,2-oxazole-4-carbonyl chloride Chemical compound CCCCC=1ON=CC=1C(Cl)=O MFWVUXQQNCGGPX-UHFFFAOYSA-N 0.000 description 2
- XABBLBODRYLNHT-UHFFFAOYSA-N 5-ethyl-n-(4-nitrophenyl)-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)[N+]([O-])=O)=C1CC XABBLBODRYLNHT-UHFFFAOYSA-N 0.000 description 2
- VQBXUKGMJCPBMF-UHFFFAOYSA-N 5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC=1ON=CC=1C(O)=O VQBXUKGMJCPBMF-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- MLZFCSTWZWPZMB-UHFFFAOYSA-N n-(4-benzoylphenyl)-5-butyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(=O)C=2C=CC=CC=2)=C1CCCC MLZFCSTWZWPZMB-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- UTNUDOFZCWSZMS-YFHOEESVSA-N teriflunomide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 UTNUDOFZCWSZMS-YFHOEESVSA-N 0.000 description 2
- XAEOHUZBLQYPMT-UHFFFAOYSA-N (4-hydroxypiperidin-1-yl)-(5-methyl-1,2-oxazol-4-yl)methanone Chemical compound O1N=CC(C(=O)N2CCC(O)CC2)=C1C XAEOHUZBLQYPMT-UHFFFAOYSA-N 0.000 description 1
- ZWNGSOLJLMBZFZ-UHFFFAOYSA-N (5-methyl-1,2-oxazol-4-yl)-piperidin-1-ylmethanone Chemical compound O1N=CC(C(=O)N2CCCCC2)=C1C ZWNGSOLJLMBZFZ-UHFFFAOYSA-N 0.000 description 1
- QWWHMGZLXAPVGL-YFHOEESVSA-N (z)-2-cyano-3-hydroxy-n-(1h-indazol-5-yl)but-2-enamide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C2NN=CC2=C1 QWWHMGZLXAPVGL-YFHOEESVSA-N 0.000 description 1
- QCWWKRYKJMPFEI-YFHOEESVSA-N (z)-2-cyano-3-hydroxy-n-(1h-indazol-6-yl)but-2-enamide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C2C=NNC2=C1 QCWWKRYKJMPFEI-YFHOEESVSA-N 0.000 description 1
- QDIGJWPZWCJJSJ-YFHOEESVSA-N (z)-2-cyano-3-hydroxy-n-(4-hydroxyphenyl)but-2-enamide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(O)C=C1 QDIGJWPZWCJJSJ-YFHOEESVSA-N 0.000 description 1
- BSZKTGBAWRIJJB-CLFYSBASSA-N (z)-2-cyano-3-hydroxy-n-pyridin-3-ylbut-2-enamide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=CN=C1 BSZKTGBAWRIJJB-CLFYSBASSA-N 0.000 description 1
- HKJVRASVBMJFBG-FPLPWBNLSA-N (z)-n-(1h-benzimidazol-2-yl)-2-cyano-3-hydroxybut-2-enamide Chemical compound C1=CC=C2NC(NC(=O)C(/C#N)=C(O)/C)=NC2=C1 HKJVRASVBMJFBG-FPLPWBNLSA-N 0.000 description 1
- WLOUBVPSLGWZPE-VBKFSLOCSA-N (z)-n-(4-benzoylphenyl)-2-cyano-3-hydroxybut-2-enamide Chemical compound C1=CC(NC(=O)C(/C#N)=C(O)/C)=CC=C1C(=O)C1=CC=CC=C1 WLOUBVPSLGWZPE-VBKFSLOCSA-N 0.000 description 1
- XGNXYCFREOZBOL-UHFFFAOYSA-N 1,3-benzodioxol-5-amine Chemical compound NC1=CC=C2OCOC2=C1 XGNXYCFREOZBOL-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-OFKYTIFKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(tritiooxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO[3H])O[C@H]1N1C(=O)NC(=O)C(C)=C1 IQFYYKKMVGJFEH-OFKYTIFKSA-N 0.000 description 1
- KEJFADGISRFLFO-UHFFFAOYSA-N 1H-indazol-6-amine Chemical compound NC1=CC=C2C=NNC2=C1 KEJFADGISRFLFO-UHFFFAOYSA-N 0.000 description 1
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 1
- XBTOSRUBOXQWBO-UHFFFAOYSA-N 1h-indazol-5-amine Chemical compound NC1=CC=C2NN=CC2=C1 XBTOSRUBOXQWBO-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- YKFROQCFVXOUPW-UHFFFAOYSA-N 4-(methylthio) aniline Chemical compound CSC1=CC=C(N)C=C1 YKFROQCFVXOUPW-UHFFFAOYSA-N 0.000 description 1
- QDTUQGSYECRXDO-UHFFFAOYSA-N 4-[chloro(difluoro)methoxy]aniline Chemical compound NC1=CC=C(OC(F)(F)Cl)C=C1 QDTUQGSYECRXDO-UHFFFAOYSA-N 0.000 description 1
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 1
- VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 1
- MECSKRLTNBOYDC-UHFFFAOYSA-N 5-(chloromethyl)-1,2-oxazole-4-carbonyl chloride Chemical compound ClCC=1ON=CC=1C(Cl)=O MECSKRLTNBOYDC-UHFFFAOYSA-N 0.000 description 1
- FZOKYEOAVXBMDA-UHFFFAOYSA-N 5-[(5-methyl-1,2-oxazole-4-carbonyl)amino]pentanoic acid Chemical compound CC=1ON=CC=1C(=O)NCCCCC(O)=O FZOKYEOAVXBMDA-UHFFFAOYSA-N 0.000 description 1
- JDMCMSRWRLIABB-FPLPWBNLSA-N 5-[[(z)-2-cyano-3-hydroxybut-2-enoyl]amino]pentanoic acid Chemical compound C\C(O)=C(/C#N)C(=O)NCCCCC(O)=O JDMCMSRWRLIABB-FPLPWBNLSA-N 0.000 description 1
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 1
- HVCBMEHPQXPQEC-UHFFFAOYSA-N 5-butyl-n-(4-chlorophenyl)-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(Cl)=CC=2)=C1CCCC HVCBMEHPQXPQEC-UHFFFAOYSA-N 0.000 description 1
- OUAWEPPBGSVAAD-UHFFFAOYSA-N 5-ethyl-1,2-oxazole-4-carboxamide Chemical compound CCC=1ON=CC=1C(N)=O OUAWEPPBGSVAAD-UHFFFAOYSA-N 0.000 description 1
- XNDQEJUJIKRGBT-UHFFFAOYSA-N 5-ethyl-n-(4-fluorophenyl)-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(F)=CC=2)=C1CC XNDQEJUJIKRGBT-UHFFFAOYSA-N 0.000 description 1
- BFTQSCLPVHMLRP-UHFFFAOYSA-N 5-ethyl-n-[4-(trifluoromethoxy)phenyl]-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(OC(F)(F)F)=CC=2)=C1CC BFTQSCLPVHMLRP-UHFFFAOYSA-N 0.000 description 1
- AGQOIYCTCOEHGR-UHFFFAOYSA-N 5-methyl-1,2-oxazole Chemical compound CC1=CC=NO1 AGQOIYCTCOEHGR-UHFFFAOYSA-N 0.000 description 1
- RDOUKTHVTCVUAV-UHFFFAOYSA-N 5-methyl-n-(4-methylsulfanylphenyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC(SC)=CC=C1NC(=O)C1=C(C)ON=C1 RDOUKTHVTCVUAV-UHFFFAOYSA-N 0.000 description 1
- VKEUQSSLRITZMR-UHFFFAOYSA-N 5-methyl-n-[4-(trifluoromethoxy)phenyl]-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(OC(F)(F)F)=CC=2)=C1C VKEUQSSLRITZMR-UHFFFAOYSA-N 0.000 description 1
- QHTOGQWHZBOPMU-UHFFFAOYSA-N 5-methyl-n-pyridin-3-yl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=NC=CC=2)=C1C QHTOGQWHZBOPMU-UHFFFAOYSA-N 0.000 description 1
- XJTZLNPOBIBOJD-UHFFFAOYSA-N 5-phenyl-n-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1NC(=O)C1=C(C=2C=CC=CC=2)ON=C1 XJTZLNPOBIBOJD-UHFFFAOYSA-N 0.000 description 1
- PVOAUAGSWWTCGQ-UHFFFAOYSA-N 5-propyl-1,2-oxazole-4-carbonyl chloride Chemical compound CCCC=1ON=CC=1C(Cl)=O PVOAUAGSWWTCGQ-UHFFFAOYSA-N 0.000 description 1
- OWPHGJKKEPRCGQ-KTKRTIGZSA-N 7-[[(z)-2-cyano-3-hydroxybut-2-enoyl]amino]heptanoic acid Chemical compound C\C(O)=C(/C#N)C(=O)NCCCCCCC(O)=O OWPHGJKKEPRCGQ-KTKRTIGZSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- YAGSTKPHGAGQSD-UHFFFAOYSA-N CCC1=CCN(C(C=C2)=CC=C2C(C(C=C2)=CC=C2Br)=O)O1 Chemical compound CCC1=CCN(C(C=C2)=CC=C2C(C(C=C2)=CC=C2Br)=O)O1 YAGSTKPHGAGQSD-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108010047620 Phytohemagglutinins Proteins 0.000 description 1
- 108010033737 Pokeweed Mitogens Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 229960002684 aminocaproic acid Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- NBVXINZPFWISLK-UHFFFAOYSA-N ethyl 5-[(5-methyl-1,2-oxazole-4-carbonyl)amino]pentanoate Chemical compound CCOC(=O)CCCCNC(=O)C=1C=NOC=1C NBVXINZPFWISLK-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- CZGDYZDUMJDQSD-UHFFFAOYSA-N hydron;4-(trifluoromethyl)aniline;chloride Chemical compound Cl.NC1=CC=C(C(F)(F)F)C=C1 CZGDYZDUMJDQSD-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 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
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000010453 lymph node cancer Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- WYOZYSVLVQHLTO-UHFFFAOYSA-N n-(1,3-benzodioxol-5-yl)-1,2-oxazole-4-carboxamide Chemical compound C=1C=C2OCOC2=CC=1NC(=O)C=1C=NOC=1 WYOZYSVLVQHLTO-UHFFFAOYSA-N 0.000 description 1
- SKBLHSYVAVBLOL-UHFFFAOYSA-N n-(1h-benzimidazol-2-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2NC3=CC=CC=C3N=2)=C1C SKBLHSYVAVBLOL-UHFFFAOYSA-N 0.000 description 1
- CWHKJJSMEOYBOQ-UHFFFAOYSA-N n-(2-chloropyridin-3-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C(=NC=CC=2)Cl)=C1C CWHKJJSMEOYBOQ-UHFFFAOYSA-N 0.000 description 1
- GJQOBIGDCYTRPW-UHFFFAOYSA-N n-(4-benzoylphenyl)-1,2-oxazole-4-carboxamide Chemical compound C1=NOC=C1C(=O)NC(C=C1)=CC=C1C(=O)C1=CC=CC=C1 GJQOBIGDCYTRPW-UHFFFAOYSA-N 0.000 description 1
- SBZKBZWIIXWTKM-UHFFFAOYSA-N n-(4-benzoylphenyl)-5-ethyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(=O)C=2C=CC=CC=2)=C1CC SBZKBZWIIXWTKM-UHFFFAOYSA-N 0.000 description 1
- VRRKESFVUKKBDG-UHFFFAOYSA-N n-(4-benzoylphenyl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(=O)C=2C=CC=CC=2)=C1C VRRKESFVUKKBDG-UHFFFAOYSA-N 0.000 description 1
- RQTPQAGOGNQBBN-UHFFFAOYSA-N n-(4-benzoylphenyl)-5-propyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(=O)C=2C=CC=CC=2)=C1CCC RQTPQAGOGNQBBN-UHFFFAOYSA-N 0.000 description 1
- BVDHPPMRWQWFAJ-UHFFFAOYSA-N n-(4-bromophenyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC(Br)=CC=C1NC(=O)C1=CON=C1 BVDHPPMRWQWFAJ-UHFFFAOYSA-N 0.000 description 1
- UBKRMWFVYAYNLO-UHFFFAOYSA-N n-(4-bromophenyl)-5-ethyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(Br)=CC=2)=C1CC UBKRMWFVYAYNLO-UHFFFAOYSA-N 0.000 description 1
- KGAYATWZCBFEPV-UHFFFAOYSA-N n-(4-chlorophenyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)C1=CON=C1 KGAYATWZCBFEPV-UHFFFAOYSA-N 0.000 description 1
- UBNPYFRCAXBBPC-UHFFFAOYSA-N n-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(Cl)=CC=2)=C1C(F)(F)F UBNPYFRCAXBBPC-UHFFFAOYSA-N 0.000 description 1
- FPIDHLWKJGZVOY-UHFFFAOYSA-N n-(4-chlorophenyl)-5-ethyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(Cl)=CC=2)=C1CC FPIDHLWKJGZVOY-UHFFFAOYSA-N 0.000 description 1
- LAXQCXCWUSHHBG-UHFFFAOYSA-N n-(4-cyanophenyl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C#N)=C1C LAXQCXCWUSHHBG-UHFFFAOYSA-N 0.000 description 1
- RJWBPHKBPNRKGX-UHFFFAOYSA-N n-(4-fluorophenyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=CON=C1 RJWBPHKBPNRKGX-UHFFFAOYSA-N 0.000 description 1
- USIYWETWTBELJU-UHFFFAOYSA-N n-(4-fluorophenyl)-5-(trifluoromethyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=C(C(F)(F)F)ON=C1 USIYWETWTBELJU-UHFFFAOYSA-N 0.000 description 1
- YEPVJMPNKJNKBR-UHFFFAOYSA-N n-(4-fluorophenyl)-5-phenyl-1,2-oxazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=C(C=2C=CC=CC=2)ON=C1 YEPVJMPNKJNKBR-UHFFFAOYSA-N 0.000 description 1
- UINQKGBHZHDNAC-UHFFFAOYSA-N n-(4-hydroxyphenyl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2C=CC(O)=CC=2)=C1C UINQKGBHZHDNAC-UHFFFAOYSA-N 0.000 description 1
- DUHGKVDOEFNLBG-UHFFFAOYSA-N n-(4-iodophenyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC(I)=CC=C1NC(=O)C1=CON=C1 DUHGKVDOEFNLBG-UHFFFAOYSA-N 0.000 description 1
- MMDRBVZPFRNXLJ-UHFFFAOYSA-N n-(4-nitrophenyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC(=O)C1=CON=C1 MMDRBVZPFRNXLJ-UHFFFAOYSA-N 0.000 description 1
- PBQHUPBIASHLLY-UHFFFAOYSA-N n-(4-nitrophenyl)-5-(trifluoromethyl)-1,2-oxazole-4-carboxamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC(=O)C1=C(C(F)(F)F)ON=C1 PBQHUPBIASHLLY-UHFFFAOYSA-N 0.000 description 1
- YPWARVICKUQNMF-UHFFFAOYSA-N n-(5-bromopyridin-2-yl)-5-ethyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2N=CC(Br)=CC=2)=C1CC YPWARVICKUQNMF-UHFFFAOYSA-N 0.000 description 1
- KVRLDKHFSVWVID-UHFFFAOYSA-N n-(5-chloropyridin-2-yl)-1,2-oxazole-4-carboxamide Chemical compound N1=CC(Cl)=CC=C1NC(=O)C1=CON=C1 KVRLDKHFSVWVID-UHFFFAOYSA-N 0.000 description 1
- XLSBWASZNIGSIT-UHFFFAOYSA-N n-(5-chloropyridin-2-yl)-5-ethyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2N=CC(Cl)=CC=2)=C1CC XLSBWASZNIGSIT-UHFFFAOYSA-N 0.000 description 1
- QHDXHVAUPGUMRX-UHFFFAOYSA-N n-(5-chloropyridin-2-yl)-5-methyl-1,2-oxazole-4-carboxamide Chemical compound O1N=CC(C(=O)NC=2N=CC(Cl)=CC=2)=C1C QHDXHVAUPGUMRX-UHFFFAOYSA-N 0.000 description 1
- KBLQZNWSRDESEY-UHFFFAOYSA-N n-(5-chloropyridin-2-yl)-5-phenyl-1,2-oxazole-4-carboxamide Chemical compound N1=CC(Cl)=CC=C1NC(=O)C1=C(C=2C=CC=CC=2)ON=C1 KBLQZNWSRDESEY-UHFFFAOYSA-N 0.000 description 1
- LQFLWKPCQITJIH-UHFFFAOYSA-N n-allyl-aniline Chemical compound C=CCNC1=CC=CC=C1 LQFLWKPCQITJIH-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960003552 other antineoplastic agent in atc Drugs 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 1
- 230000001885 phytohemagglutinin Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000000849 skin cancer 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
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/23—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same unsaturated acyclic carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
- C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
- C07C317/40—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Indole Compounds (AREA)
- Medicinal Preparation (AREA)
- Photoreceptors In Electrophotography (AREA)
- Air Conditioning Control Device (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4016178.1 | 1990-05-18 | ||
| DE4016178 | 1990-05-18 | ||
| DE4017020 | 1990-05-26 | ||
| DEP4017020.9 | 1990-05-26 | ||
| DE4017043 | 1990-05-26 | ||
| DEP4017043.8 | 1990-05-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1056684A CN1056684A (zh) | 1991-12-04 |
| CN1051074C true CN1051074C (zh) | 2000-04-05 |
Family
ID=27201216
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN91103182A Expired - Lifetime CN1051074C (zh) | 1990-05-18 | 1991-05-16 | 异噁唑－4－羧酰胺及羟基亚烷基氰基乙酰胺用于制备药物的用途 |
Country Status (28)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105272882A (zh) * | 2014-07-23 | 2016-01-27 | 欣凯医药化工中间体（上海）有限公司 | 一种环保简便制备泰瑞米特的方法 |
Families Citing this family (78)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ235563A (en) * | 1989-10-13 | 1993-04-28 | Merck & Co Inc | Fibrinogen receptor antagonist and pharmaceutical composition |
| GB9200275D0 (en) * | 1992-01-08 | 1992-02-26 | Roussel Lab Ltd | Chemical compounds |
| GB9300083D0 (en) | 1993-01-05 | 1993-03-03 | Roussel Lab Ltd | Chemical compounds |
| DK0607777T3 (da) * | 1993-01-08 | 1999-08-16 | Hoechst Ag | Anvendelse af leflunomid til inhibering af interleukin 8 |
| ES2124800T3 (es) * | 1993-01-08 | 1999-02-16 | Hoechst Ag | Empleo de leflunomida para la inhibicion de interleuquina 1 beta. |
| ES2124801T3 (es) * | 1993-01-08 | 1999-02-16 | Hoechst Ag | Empleo de leflunomida para la inhibicion del factor de necrosis de tumores alfa. |
| DE59407412D1 (de) * | 1993-01-08 | 1999-01-21 | Hoechst Ag | Verwendung von Leflunomid zur Hemmung von Interleukin 1 alpha |
| TW314467B (cg-RX-API-DMAC7.html) * | 1993-03-31 | 1997-09-01 | Hoechst Ag | |
| GB9313365D0 (en) * | 1993-06-29 | 1993-08-11 | Roussel Lab Ltd | Chemical compounds |
| DE4323636A1 (de) * | 1993-07-15 | 1995-01-19 | Hoechst Ag | Arzneistoffzubereitungen aus umhüllten, schwerstwasserlöslichen Arzneistoffen für Inhalationsarzneiformen und Verfahren zu ihrer Herstellung |
| GB9322781D0 (en) * | 1993-11-04 | 1993-12-22 | Roussel Lab Ltd | Aromatic amides |
| US6335356B1 (en) | 1994-01-07 | 2002-01-01 | Sugen, Inc. | Method of treating a patient by parenteral administration of a lipophilic compound |
| US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| US5610173A (en) * | 1994-01-07 | 1997-03-11 | Sugen, Inc. | Formulations for lipophilic compounds |
| US5721277A (en) * | 1995-04-21 | 1998-02-24 | Sugen, Inc. | Compounds and methods for inhibiting hyper-proliferative cell growth |
| US6331555B1 (en) | 1995-06-01 | 2001-12-18 | University Of California | Treatment of platelet derived growth factor related disorders such as cancers |
| GB9520092D0 (en) * | 1995-10-02 | 1995-12-06 | Hoechst Roussel Ltd | Chemical compounds |
| DE19539638A1 (de) * | 1995-10-25 | 1997-04-30 | Hoechst Ag | Die Verwendung von Isoxazol- und Crotonsäureamidderivaten zur Behandlung von Krebserkrankungen |
| DE19547648A1 (de) * | 1995-12-20 | 1997-06-26 | Hoechst Ag | Zubereitung, enthaltend High Density Lipoproteine und Crotonsäureamidderivate |
| EP0795334B1 (de) * | 1996-03-12 | 2006-02-01 | Sanofi-Aventis Deutschland GmbH | Neuartige Prodrugs für die Therapie von Tumoren und entzündlichen Erkrankungen |
| DE19610955A1 (de) * | 1996-03-20 | 1997-09-25 | Hoechst Ag | Kombinationspräparat, enthaltend 5-Methylisoxazol-4-carbonsäure-(4-trifluormethyl)- anilid und N-(4-Trifluormethylphenyl)-2-cyan-3- hydroxycrotonsäureamid |
| US6011051A (en) * | 1996-07-31 | 2000-01-04 | Hoechst Aktiengesellschaft | Use of isoxazole and crotonamide derivatives for the modulation of apoptosis |
| EA002113B1 (ru) | 1996-09-04 | 2001-12-24 | Пфайзер Инк. | Производные индазола и их использование в качестве ингибиторов фосфодиэстеразы (фдэ) типа iv и продуцирования фактора некроза опухоли (фно) |
| DE19702988A1 (de) | 1997-01-28 | 1998-07-30 | Hoechst Ag | Isoxazol- und Crotonsäureamidderivate und deren Verwendung als Arzneimittel und Diagnostika |
| EP1012150A4 (en) * | 1997-05-19 | 2002-05-29 | Sugen Inc | HETEROARYLCARBOXAMIDE COMPOUNDS THAT ARE EFFECTIVE OF DISEASES CAUSED BY PROTEIN-TYROSIN-KINASE |
| US6316479B1 (en) | 1997-05-19 | 2001-11-13 | Sugen, Inc. | Isoxazole-4-carboxamide compounds active against protein tryosine kinase related disorders |
| EP0903345B1 (de) * | 1997-08-08 | 2000-10-04 | Aventis Pharma Deutschland GmbH | Kristallform von 5-Methylisoxazol-4-carbonsäure-(4-trifluormethyl)-anilid |
| IL135714A0 (en) * | 1997-11-04 | 2001-05-20 | Pfizer Prod Inc | Therapeutically active compounds based on indazole bioisostere replacement of catechol in pde4 inhibitors |
| ATE269295T1 (de) * | 1998-04-17 | 2004-07-15 | Parker Hughes Inst | Btk inhibitoren und verfahren zur identifizierung und verwendung |
| US6303652B1 (en) | 1998-08-21 | 2001-10-16 | Hughes Institute | BTK inhibitors and methods for their identification and use |
| US6355678B1 (en) * | 1998-06-29 | 2002-03-12 | Parker Hughes Institute | Inhibitors of the EGF-receptor tyrosine kinase and methods for their use |
| DE19908527C2 (de) * | 1999-02-26 | 2001-08-30 | Aventis Pharma Gmbh | Verfahren zur Kristallisation von N-(4-Trifluormethylphenyl)-5-methyl-isoxazol-4-carboxamid |
| CN1411373A (zh) * | 1999-12-16 | 2003-04-16 | 特瓦制药工业有限公司 | 制备来氟米特的新方法和新晶形的来氟米特 |
| US7217722B2 (en) * | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| ES2237553T3 (es) * | 2000-02-15 | 2005-08-01 | Teva Pharmaceutical Industries Ltd. | Procedimiento para la sintesis de leflunomida. |
| DE10133665A1 (de) * | 2001-07-11 | 2003-01-30 | Boehringer Ingelheim Pharma | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Herstellung |
| US20030055263A1 (en) * | 2001-07-11 | 2003-03-20 | Boehringer Ingelheim Pharma Kg | Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production |
| EP1487796A4 (en) * | 2002-03-28 | 2005-11-16 | Neurogen Corp | SUBSTITUTED BIARYLAMIDES AS MODULATORS OF THE C5A RECEPTOR |
| US6858637B2 (en) | 2002-03-28 | 2005-02-22 | Neurogen Corporation | Substituted biaryl amides as C5a receptor modulators |
| WO2004035571A1 (en) * | 2002-10-15 | 2004-04-29 | Rigel Pharmaceuticals, Inc. | Substituted indoles and their use as hcv inhibitors |
| RU2280464C2 (ru) * | 2004-03-22 | 2006-07-27 | Александр Иванович Петенко | Способ получения сухого пробиотического препарата "бацелл" |
| US7842815B2 (en) | 2004-06-17 | 2010-11-30 | Infinity Pharmaceuticals, Inc. | Compounds and methods for inhibiting the interaction of BCL proteins with binding partners |
| MXPA06014754A (es) | 2004-06-17 | 2007-06-22 | Infinity Pharmaceuticals Inc | Compuestos y metodos para inhibir la interaccion de las proteinas bcl con los componentes de enlace. |
| WO2006115509A2 (en) | 2004-06-24 | 2006-11-02 | Novartis Vaccines And Diagnostics Inc. | Small molecule immunopotentiators and assays for their detection |
| DE102006014165A1 (de) * | 2006-03-24 | 2007-09-27 | Schebo Biotech Ag | Neue Isooxazol-Derivate und deren Verwendungen |
| AU2007275301A1 (en) * | 2006-07-20 | 2008-01-24 | Amgen Inc. | Substituted azole aromatic heterocycles as inhibitors of 11-beta-HSD-1 |
| TWI389895B (zh) | 2006-08-21 | 2013-03-21 | Infinity Discovery Inc | 抑制ｂｃｌ蛋白質與結合夥伴間之交互作用的化合物及方法 |
| CA2684105C (en) * | 2007-05-03 | 2011-09-06 | Pfizer Limited | Pyridine derivatives |
| US20090076275A1 (en) * | 2007-09-19 | 2009-03-19 | David Robert Bolin | Diacylglycerol acyltransferase inhibitors |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| NZ593649A (en) | 2008-12-23 | 2013-11-29 | Gilead Pharmasset Llc | Nucleoside analogs |
| AU2009329872B2 (en) | 2008-12-23 | 2016-07-07 | Gilead Pharmasset Llc | Synthesis of purine nucleosides |
| PA8855601A1 (es) | 2008-12-23 | 2010-07-27 | Forformidatos de nucleósidos | |
| MY159575A (en) | 2009-04-02 | 2017-01-13 | Merck Serono Sa | Dihydroorotate dehydrogenase inhibitors |
| EP2236505A1 (de) * | 2009-04-03 | 2010-10-06 | Bayer CropScience AG | Acylierte Aminopyridine und - pyridazine als Insektizide |
| WO2011004282A2 (en) | 2009-07-09 | 2011-01-13 | Alembic Limited | Novel polymorphic form of teriflunomide salts |
| SG184324A1 (en) | 2010-03-31 | 2012-11-29 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
| JP5820476B2 (ja) | 2010-08-24 | 2015-11-24 | アルギアックス ファルマコウティカルス ゲーエムベーハーＡＬＧＩＡＸ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ ＧｍｂＨ | レフルノミドおよびマロノニトリラマイドの新規の使用 |
| PT2632451T (pt) | 2010-10-29 | 2017-12-14 | Algiax Pharmaceuticals Gmbh | Utilização de malononitrilamidas na dor neuropática |
| WO2012110911A1 (en) | 2011-02-18 | 2012-08-23 | Alembic Pharmaceuticals Limited | Novel polymorphic form of teriflunomide |
| US20140057978A1 (en) | 2011-03-17 | 2014-02-27 | Algiax Pharmaceuticals Gmbh | Novel use of benzofuranylsulfonates |
| EP2685983B1 (en) | 2011-03-17 | 2016-05-18 | Algiax Pharmaceuticals GmbH | Novel use of imidazotriazinones |
| RS57962B1 (sr) | 2013-02-25 | 2019-01-31 | Aurigene Discovery Tech Ltd | Derivati trisupstituisanog benzotriazola kao inhibitori dihidroorotat oksigenaze |
| WO2015029063A2 (en) * | 2013-08-30 | 2015-03-05 | Msn Laboratories Private Limited | Novel polymorph of (z)-2-cyano-3-hydroxy-but-2-enoic acid-(4-trifluoromethyl phenyl)-amide and process for the preparation thereof |
| EP3071199A2 (en) | 2013-11-22 | 2016-09-28 | Genzyme Corporation | Novel methods for treating neurodegenerative diseases |
| LT3466955T (lt) | 2014-01-13 | 2021-02-25 | Aurigene Discovery Technologies Limited | Oksazol[4,5-b]piridino ir tiazol[4,5-b]piridino darinių, kaip irak4 inhibitorių, skirtų vėžio gydymui, gamybos būdas |
| AU2015275730A1 (en) * | 2014-06-20 | 2016-12-15 | Aurigene Discovery Technologies Limited | Substituted indazole compounds as IRAK4 inhibitors |
| US10526279B2 (en) | 2015-06-17 | 2020-01-07 | Biocon Limited | Process for the preparation of teriflunomide |
| BR112019017567A2 (pt) | 2017-02-24 | 2020-03-24 | Merck Patent Gmbh | Derivados de 1,4,6-trissubstituído-2-alquil-1h-benzo[d]imidazol como inibidores da di-hidro-orotato oxigenase |
| EP3600270B1 (en) | 2017-03-31 | 2023-06-14 | Aurigene Oncology Limited | Compounds and compositions for treating hematological disorders |
| HRP20211462T1 (hr) | 2017-04-24 | 2021-12-24 | Aurigene Discovery Technologies Limited | Postupci uporabe za trisupstituirane derivate benzotriazola kao inhibitora dihidroorotatne oksigenaze |
| US20180369206A1 (en) | 2017-04-24 | 2018-12-27 | Aurigene Discovery Technologies Limited | Methods of Use for Trisubstituted Benzotriazole Derivatives as Dihydroorotate Oxygenase Inhibitors |
| HUE067356T2 (hu) | 2017-10-31 | 2024-10-28 | Curis Inc | IRAK4 inhibitor és BCL-2 inhibitor kombinációban, rák kezelésére való felhasználásra |
| TR202022336A2 (tr) | 2020-12-30 | 2022-07-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A film coated tablet comprising teriflunomide |
| EP4319750A4 (en) | 2021-04-08 | 2025-02-26 | Curis, Inc. | COMBINATION THERAPIES FOR THE TREATMENT OF CANCER |
| EP4162933A1 (en) | 2021-10-08 | 2023-04-12 | Algiax Pharmaceuticals GmbH | Compound for treating non-alcoholic fatty liver disease and related diseases |
| CN117126078B (zh) * | 2022-05-19 | 2025-11-25 | 四川大学 | 一类化合物及在治疗hDHODH介导的疾病中的用途 |
| EP4382097A1 (en) | 2022-11-25 | 2024-06-12 | Sanovel Ilac Sanayi Ve Ticaret A.S. | A tablet comprising teriflunomide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4087535A (en) * | 1975-06-05 | 1978-05-02 | Hoechst Aktiengesellschaft | 5-Methyl-isoxazole-4-carboxylic acid anilides |
| EP0257882A1 (en) * | 1986-08-08 | 1988-03-02 | Lilly Industries Limited | N-Phenyl butenamides with pharmaceutical properties |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL186239B (nl) * | 1975-06-05 | Hoechst Ag | Werkwijze voor de bereiding van een geneesmiddel met antiflogistische en/of analgetische werking, alsmede werkwijze voor de bereiding van een 2-hydroxyethylideencyaanazijnzuuranilide geschikt voor toepassing bij deze werkwijze. | |
| DE2524959C2 (de) * | 1975-06-05 | 1983-02-10 | Hoechst Ag, 6000 Frankfurt | 5-Methyl-isoxazol-4-carbonsäureanilide, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Mittel |
| DE2557003A1 (de) * | 1975-12-18 | 1977-06-23 | Hoechst Ag | Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
| DE2555789A1 (de) * | 1975-12-11 | 1977-07-07 | Hoechst Ag | Neue cyanessigsaeureanilid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
| DE2655009A1 (de) * | 1976-12-04 | 1978-06-15 | Hoechst Ag | Isoxazolderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende mittel |
| DE2854439A1 (de) * | 1978-12-16 | 1980-07-03 | Hoechst Ag | Ein isoxazolderivat, verfahren zu seiner herstellung, diese verbindung enthaltende mittel und verwendung |
| DE3405727A1 (de) * | 1984-02-17 | 1985-08-22 | Hoechst Ag, 6230 Frankfurt | Isoxazol-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3534440A1 (de) * | 1985-09-27 | 1987-04-02 | Hoechst Ag | Arzneimittel gegen chronische graft-versus-host-krankheiten sowie gegen autoimmunerkrankungen, insbesondere systemischen lupus erythematodes |
| GB8619433D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
| US4816467A (en) * | 1987-01-09 | 1989-03-28 | Farmitalia Carlo Erba S.R.L | Heteroaryl 3-oxo-propanenitrile derivatives, pharmaceutical compositions and use |
-
1990
- 1990-10-24 ES ES90915462T patent/ES2102367T3/es not_active Expired - Lifetime
- 1990-10-24 RU RU94033835A patent/RU2142937C1/ru active
- 1990-10-24 DE DE59010701T patent/DE59010701D1/de not_active Expired - Lifetime
- 1990-10-24 KR KR1019920702895A patent/KR100188801B1/ko not_active Expired - Lifetime
- 1990-10-24 AT AT90915462T patent/ATE151633T1/de not_active IP Right Cessation
- 1990-10-24 EP EP90915462A patent/EP0527736B1/de not_active Expired - Lifetime
- 1990-10-24 AU AU65468/90A patent/AU649421B2/en not_active Expired
- 1990-10-24 US US07/938,048 patent/US5494911A/en not_active Expired - Lifetime
- 1990-10-24 WO PCT/EP1990/001800 patent/WO1991017748A1/de not_active Ceased
- 1990-10-24 CA CA002083179A patent/CA2083179C/en not_active Expired - Lifetime
- 1990-10-24 DK DK90915462.7T patent/DK0527736T3/da active
- 1990-10-24 HU HU9203619A patent/HU222234B1/hu active IP Right Grant
- 1990-10-24 RU RU9092016445A patent/RU2084223C1/ru active
- 1990-10-24 JP JP2514415A patent/JP2995086B2/ja not_active Expired - Lifetime
- 1990-10-24 BR BR909008022A patent/BR9008022A/pt not_active Application Discontinuation
- 1990-10-27 TW TW079109110A patent/TW205004B/zh active
- 1990-10-27 TW TW081101406A patent/TW211558B/zh active
-
1991
- 1991-05-16 SK SK1376-98A patent/SK281317B6/sk not_active IP Right Cessation
- 1991-05-16 IL IL9816391A patent/IL98163A/en not_active IP Right Cessation
- 1991-05-16 CZ CS19911450A patent/CZ290474B6/cs not_active IP Right Cessation
- 1991-05-16 CN CN91103182A patent/CN1051074C/zh not_active Expired - Lifetime
- 1991-05-16 SK SK1450-91A patent/SK281316B6/sk not_active IP Right Cessation
- 1991-05-16 SK SK542-99A patent/SK281318B6/sk not_active IP Right Cessation
- 1991-05-16 NZ NZ238165A patent/NZ238165A/en not_active IP Right Cessation
- 1991-05-16 PT PT97689A patent/PT97689B/pt not_active IP Right Cessation
- 1991-05-17 IE IE169491A patent/IE911694A1/en not_active IP Right Cessation
- 1991-05-20 YU YU88491A patent/YU48765B/sr unknown
-
1992
- 1992-11-17 FI FI925211A patent/FI105683B/fi active
- 1992-11-17 NO NO924433A patent/NO180118C/no not_active IP Right Cessation
-
1993
- 1993-05-07 LV LVP-93-310A patent/LV10575B/en unknown
-
1994
- 1994-03-23 AU AU57992/94A patent/AU662465B2/en not_active Expired
-
1995
- 1995-06-07 US US08/476,278 patent/US5532259A/en not_active Expired - Lifetime
- 1995-08-24 CZ CZ19952176A patent/CZ290717B6/cs not_active IP Right Cessation
- 1995-11-23 CZ CZ19953091A patent/CZ290736B6/cs not_active IP Right Cessation
- 1995-11-23 CZ CZ19953092A patent/CZ290737B6/cs not_active IP Right Cessation
-
1997
- 1997-05-30 GR GR970401284T patent/GR3023638T3/el unknown
-
1998
- 1998-09-29 CY CY9800032A patent/CY2123B1/xx unknown
-
1999
- 1999-03-01 JP JP05210899A patent/JP3233610B2/ja not_active Expired - Lifetime
- 1999-03-01 JP JP05210799A patent/JP3201747B2/ja not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4087535A (en) * | 1975-06-05 | 1978-05-02 | Hoechst Aktiengesellschaft | 5-Methyl-isoxazole-4-carboxylic acid anilides |
| EP0257882A1 (en) * | 1986-08-08 | 1988-03-02 | Lilly Industries Limited | N-Phenyl butenamides with pharmaceutical properties |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105272882A (zh) * | 2014-07-23 | 2016-01-27 | 欣凯医药化工中间体（上海）有限公司 | 一种环保简便制备泰瑞米特的方法 |
| CN105272882B (zh) * | 2014-07-23 | 2019-05-31 | 欣凯医药化工中间体（上海）有限公司 | 一种环保简便制备泰瑞米特的方法 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1051074C (zh) | 异噁唑－4－羧酰胺及羟基亚烷基氰基乙酰胺用于制备药物的用途 | |
| CN1213022C (zh) | 用对称和不对称的取代二苯脲抑制raf激酶 | |
| CN1036920C (zh) | 含杂环碳酸衍生物 | |
| CN1219764C (zh) | 用ω－羧基芳基取代的二苯脲作为raf激酶抑制剂 | |
| CN1176651C (zh) | N-(3-苯并呋喃基)脲衍生物 | |
| CN1025999C (zh) | 咪唑并[4，5-b]喹啉氧烷酰胺的制备方法 | |
| CN1149085C (zh) | 用取代杂环脲抑制raf激酶 | |
| CN1049651C (zh) | 金属蛋白酶抑制剂 | |
| CN1130363C (zh) | 嘌呤衍生物以及含有其作为有效成分的药物 | |
| CN1263755C (zh) | 作为选择性cox－2抑制剂的吡唑并吡啶衍生物 | |
| CN1109022C (zh) | 芳基链烷酰基哒嗪衍生物、其制备方法和含有它们的药物以及应用 | |
| CN1198807C (zh) | 作为环加氧酶－2抑制剂的5－芳基－1h－1,2,4－三唑化合物及含有它们的药物组合物 | |
| CN1294577A (zh) | 钾通道抑制剂 | |
| CN1044811A (zh) | 杂环化合物 | |
| CN1168720C (zh) | 芳基链烷酰基哒嗪化合物 | |
| CN1056836C (zh) | 3,5－二取代的和3,4,5－三取代的2－异唑啉和异唑,其制备方法及其作为药物的用途 | |
| CN1281441A (zh) | 以在pde4抑制剂中的儿茶酚的吲唑生物等排物置换为基础的治疗活性化合物 | |
| CN85104893A (zh) | 有关苯磺酰胺衍生物的改进 | |
| CN1271353A (zh) | 呋喃磺酸衍生物及包含它们的药物组合物 | |
| CN86102761A (zh) | N-吲哚基乙基-磺酰胺类其制备方法及用途 | |
| CN1882571A (zh) | 吡咯衍生物 | |
| CN1732147A (zh) | 作为抗炎、免疫调节和抗增殖试剂的环烯二羧酸化合物 | |
| CN1407975A (zh) | 氧亚氨基链烷酸衍生物的结晶及它们作为抗糖尿病药的用途 | |
| CN1665506A (zh) | 作为ccr－3受体拮抗剂ⅸ的2,5－取代的嘧啶衍生物 | |
| CN1023479C (zh) | 乙二胺的单酰胺衍生物的制备方法 |
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 | ||
| C53 | Correction of patent of invention or patent application | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: PATENTEE; FROM: HOECHST AKTIENGESELLSCHAFT (DE) TO: AVENTIS PHARMACY (GERMANY)INTERNATIONAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Patentee after: Awentis Medicines Deutschland GmbH Patentee before: Hechester JSC |
|
| C15 | Extension of patent right duration from 15 to 20 years for appl. with date before 31.12.1992 and still valid on 11.12.2001 (patent law change 1993) | ||
| OR01 | Other related matters | ||
| C56 | Change in the name or address of the patentee |
Owner name: SANOFI- AVENTIS GERMAN CO., LTD. Free format text: FORMER NAME OR ADDRESS: AVENTIS PHARMACY (GERMANY)INTERNATIONAL CO., LTD. |
|
| CP03 | Change of name, title or address |
Address after: Frankfurt, Germany Patentee after: Hoechst Marion Roussel de GmbH Address before: Frankfurt, Federal Republic of Germany Patentee before: Awentis Medicines Deutschland GmbH |
|
| C17 | Cessation of patent right | ||
| CX01 | Expiry of patent term |
Expiration termination date: 20110516 Granted publication date: 20000405 |