CN1043531C - 嘧啶衍生物及其制备方法和用途 - Google Patents
嘧啶衍生物及其制备方法和用途 Download PDFInfo
- Publication number
- CN1043531C CN1043531C CN93103566A CN93103566A CN1043531C CN 1043531 C CN1043531 C CN 1043531C CN 93103566 A CN93103566 A CN 93103566A CN 93103566 A CN93103566 A CN 93103566A CN 1043531 C CN1043531 C CN 1043531C
- Authority
- CN
- China
- Prior art keywords
- pyridyl
- group
- pyrimithamine
- pharmacology
- acceptable salt
- 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
- 238000000034 method Methods 0.000 title claims description 59
- 230000008569 process Effects 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
- 150000003230 pyrimidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 150000003839 salts Chemical class 0.000 claims description 94
- -1 4-methyl-piperazinyl Chemical group 0.000 claims description 90
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 56
- 229910052799 carbon Inorganic materials 0.000 claims description 53
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- 239000001301 oxygen Substances 0.000 claims description 34
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 150000001721 carbon Chemical group 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000001931 aliphatic group Chemical group 0.000 claims description 14
- 230000000903 blocking effect Effects 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 239000011737 fluorine Substances 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000000524 functional group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- JVJQPDTXIALXOG-UHFFFAOYSA-N nitryl fluoride Chemical compound [O-][N+](F)=O JVJQPDTXIALXOG-UHFFFAOYSA-N 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 9
- 150000004046 2-(N-anilino)pyrimidines Chemical class 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- 239000002253 acid Substances 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- 239000002585 base Substances 0.000 description 34
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 29
- 108091000080 Phosphotransferase Proteins 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- 102000020233 phosphotransferase Human genes 0.000 description 29
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- 229960001701 chloroform Drugs 0.000 description 24
- 239000002994 raw material Substances 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000839 emulsion Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 229910021529 ammonia Inorganic materials 0.000 description 13
- 125000003118 aryl group Chemical group 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 238000001035 drying Methods 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 150000008065 acid anhydrides Chemical class 0.000 description 12
- 230000002152 alkylating effect Effects 0.000 description 12
- 230000032050 esterification Effects 0.000 description 12
- 238000005886 esterification reaction Methods 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 150000001335 aliphatic alkanes Chemical class 0.000 description 10
- 125000003282 alkyl amino group Chemical group 0.000 description 10
- 229960004756 ethanol Drugs 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 9
- 125000002252 acyl group Chemical group 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 125000002723 alicyclic group Chemical group 0.000 description 8
- 150000001718 carbodiimides Chemical class 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- 239000005864 Sulphur Chemical group 0.000 description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000000454 talc Substances 0.000 description 7
- 235000012222 talc Nutrition 0.000 description 7
- 229910052623 talc Inorganic materials 0.000 description 7
- 229940100445 wheat starch Drugs 0.000 description 7
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 239000000084 colloidal system Substances 0.000 description 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 6
- 235000012239 silicon dioxide Nutrition 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 102000003916 Arrestin Human genes 0.000 description 5
- 108090000328 Arrestin Proteins 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 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 5
- 241001465754 Metazoa Species 0.000 description 5
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 125000003368 amide group Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000004744 fabric Substances 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 125000002757 morpholinyl group Chemical group 0.000 description 5
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 125000005936 piperidyl group Chemical group 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000000452 restraining effect Effects 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
- GDMOXZZLBLQOGX-UHFFFAOYSA-O carbamimidoyl-(3-nitrophenyl)azanium;nitrate Chemical compound [O-][N+]([O-])=O.NC(N)=[NH+]C1=CC=CC([N+]([O-])=O)=C1 GDMOXZZLBLQOGX-UHFFFAOYSA-O 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
- 150000001727 carbonic acid monoesters Chemical class 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000003797 solvolysis reaction Methods 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- REZQBEBOWJAQKS-UHFFFAOYSA-N triacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO REZQBEBOWJAQKS-UHFFFAOYSA-N 0.000 description 4
- 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 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 238000006136 alcoholysis reaction Methods 0.000 description 3
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- RZNHSEZOLFEFGB-UHFFFAOYSA-N 2-methoxybenzoyl chloride Chemical compound COC1=CC=CC=C1C(Cl)=O RZNHSEZOLFEFGB-UHFFFAOYSA-N 0.000 description 2
- WEGYGNROSJDEIW-UHFFFAOYSA-N 3-Acetylpyridine Chemical compound CC(=O)C1=CC=CN=C1 WEGYGNROSJDEIW-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 238000006418 Brown reaction Methods 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 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 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000007860 aryl ester derivatives Chemical class 0.000 description 2
- KRCSBYPKUJAPSQ-UHFFFAOYSA-N benzene formyl chloride Chemical class C(=O)Cl.C1=CC=CC=C1 KRCSBYPKUJAPSQ-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 150000003950 cyclic amides Chemical class 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- MJFQUUWPZOGYQT-UHFFFAOYSA-O diaminomethylideneazanium;nitrate Chemical compound NC(N)=[NH2+].[O-][N+]([O-])=O MJFQUUWPZOGYQT-UHFFFAOYSA-O 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 238000005502 peroxidation Methods 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 150000007970 thio esters Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 125000005039 triarylmethyl group Chemical group 0.000 description 2
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- KMOUUZVZFBCRAM-OLQVQODUSA-N (3as,7ar)-3a,4,7,7a-tetrahydro-2-benzofuran-1,3-dione Chemical compound C1C=CC[C@@H]2C(=O)OC(=O)[C@@H]21 KMOUUZVZFBCRAM-OLQVQODUSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- LHJGJYXLEPZJPM-UHFFFAOYSA-N 2,4,5-trichlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C=C1Cl LHJGJYXLEPZJPM-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- CXDHJGCWMIOAQP-UHFFFAOYSA-N 2-pyridin-3-yl-1,4,5,6-tetrahydropyrimidine;hydrochloride Chemical compound Cl.C1CCNC(C=2C=NC=CC=2)=N1 CXDHJGCWMIOAQP-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- SADHVOSOZBAAGL-UHFFFAOYSA-N 3-(trifluoromethoxy)aniline Chemical compound NC1=CC=CC(OC(F)(F)F)=C1 SADHVOSOZBAAGL-UHFFFAOYSA-N 0.000 description 1
- DZIJEXQVMORGQX-UHFFFAOYSA-N 3-methyl-5-nitroaniline Chemical compound CC1=CC(N)=CC([N+]([O-])=O)=C1 DZIJEXQVMORGQX-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- USEDMAWWQDFMFY-UHFFFAOYSA-N 4-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(C#N)C=C1 USEDMAWWQDFMFY-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical class OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- DSBIJCMXAIKKKI-UHFFFAOYSA-N 5-nitro-o-toluidine Chemical compound CC1=CC=C([N+]([O-])=O)C=C1N DSBIJCMXAIKKKI-UHFFFAOYSA-N 0.000 description 1
- KMZWFGHTRHOUOQ-UHFFFAOYSA-N 6-diazo-4-phenylcyclohexa-2,4-dien-1-ol Chemical compound [N-]=[N+]=C1C(O)C=CC(C=2C=CC=CC=2)=C1 KMZWFGHTRHOUOQ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229920001817 Agar Polymers 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
- 239000004475 Arginine Substances 0.000 description 1
- 244000186140 Asperula odorata Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- AKYHYWINOSSCIF-UHFFFAOYSA-N Cl(=O)(=O)(=O)O.C(C)(C)(C)N1OC(=CC1)C Chemical compound Cl(=O)(=O)(=O)O.C(C)(C)(C)N1OC(=CC1)C AKYHYWINOSSCIF-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 235000008526 Galium odoratum Nutrition 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 206010048723 Multiple-drug resistance Diseases 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 108010055723 PDGF receptor tyrosine kinase Proteins 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000534944 Thia Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- MFIUDWFSVDFDDY-UHFFFAOYSA-M butyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCC)C1=CC=CC=C1 MFIUDWFSVDFDDY-UHFFFAOYSA-M 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 125000006011 chloroethoxy group Chemical group 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- WQPDQJCBHQPNCZ-UHFFFAOYSA-N cyclohexa-2,4-dien-1-one Chemical compound O=C1CC=CC=C1 WQPDQJCBHQPNCZ-UHFFFAOYSA-N 0.000 description 1
- WVPKAWVFTPWPDB-UHFFFAOYSA-N dichlorophosphinic acid Chemical compound OP(Cl)(Cl)=O WVPKAWVFTPWPDB-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- VKFAUCPBMAGVRG-UHFFFAOYSA-N dipivefrin hydrochloride Chemical compound [Cl-].C[NH2+]CC(O)C1=CC=C(OC(=O)C(C)(C)C)C(OC(=O)C(C)(C)C)=C1 VKFAUCPBMAGVRG-UHFFFAOYSA-N 0.000 description 1
- 235000021186 dishes Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- RMGVZKRVHHSUIM-UHFFFAOYSA-N dithionic acid Chemical compound OS(=O)(=O)S(O)(=O)=O RMGVZKRVHHSUIM-UHFFFAOYSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- ORDFEISUDQEJHY-UHFFFAOYSA-N formyl chloride 1,2,3,4,5-pentafluorobenzene Chemical class C(=O)Cl.FC=1C(=C(C(=C(C1)F)F)F)F ORDFEISUDQEJHY-UHFFFAOYSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- NEXSMEBSBIABKL-UHFFFAOYSA-N hexamethyldisilane Chemical compound C[Si](C)(C)[Si](C)(C)C NEXSMEBSBIABKL-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
- XIFJZJPMHNUGRA-UHFFFAOYSA-N n-methyl-4-nitroaniline Chemical compound CNC1=CC=C([N+]([O-])=O)C=C1 XIFJZJPMHNUGRA-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XNLBCXGRQWUJLU-UHFFFAOYSA-N naphthalene-2-carbonyl chloride Chemical compound C1=CC=CC2=CC(C(=O)Cl)=CC=C21 XNLBCXGRQWUJLU-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- TZMFJUDUGYTVRY-UHFFFAOYSA-N pentane-2,3-dione Chemical compound CCC(=O)C(C)=O TZMFJUDUGYTVRY-UHFFFAOYSA-N 0.000 description 1
- BHTJEPVNHUUIPV-UHFFFAOYSA-N pentanedial;hydrate Chemical compound O.O=CCCCC=O BHTJEPVNHUUIPV-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 150000004992 toluidines Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 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
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D401/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Macromonomer-Based Addition Polymer (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Paints Or Removers (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH108392 | 1992-04-03 | ||
| CH1083/92-1 | 1992-04-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1077713A CN1077713A (zh) | 1993-10-27 |
| CN1043531C true CN1043531C (zh) | 1999-06-02 |
Family
ID=4202064
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93103566A Expired - Lifetime CN1043531C (zh) | 1992-04-03 | 1993-04-02 | 嘧啶衍生物及其制备方法和用途 |
Country Status (29)
| Country | Link |
|---|---|
| EP (1) | EP0564409B1 (enExample) |
| JP (1) | JP2706682B2 (enExample) |
| KR (1) | KR100261366B1 (enExample) |
| CN (1) | CN1043531C (enExample) |
| AT (1) | ATE188964T1 (enExample) |
| AU (1) | AU666709B2 (enExample) |
| BR (1) | BR1100739A (enExample) |
| CA (1) | CA2093203C (enExample) |
| CY (2) | CY2229B1 (enExample) |
| CZ (1) | CZ283944B6 (enExample) |
| DE (2) | DE10299016I2 (enExample) |
| DK (1) | DK0564409T3 (enExample) |
| ES (1) | ES2142857T3 (enExample) |
| FI (1) | FI109534B (enExample) |
| GR (1) | GR3032927T3 (enExample) |
| HU (2) | HU227080B1 (enExample) |
| IL (1) | IL105264A (enExample) |
| LU (1) | LU90908I2 (enExample) |
| MX (1) | MX9301929A (enExample) |
| NL (1) | NL300086I2 (enExample) |
| NO (2) | NO302473B1 (enExample) |
| NZ (1) | NZ247299A (enExample) |
| PT (1) | PT564409E (enExample) |
| RU (1) | RU2125992C1 (enExample) |
| SA (1) | SA93140441B1 (enExample) |
| SG (1) | SG43859A1 (enExample) |
| SK (1) | SK280620B6 (enExample) |
| TW (1) | TW225528B (enExample) |
| ZA (1) | ZA932397B (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006069525A1 (en) * | 2004-12-31 | 2006-07-06 | Piaoyang Sun | Aminopyrimidine compounds and their salts, process for preparation and pharmaceutical use thereof |
| CN100526298C (zh) * | 2003-12-25 | 2009-08-12 | 日本新药株式会社 | 酰胺衍生物及医药品 |
| CN1972917B (zh) * | 2004-12-31 | 2010-08-25 | 孙飘扬 | 氨基嘧啶类化合物及其盐和其制备方法与药物用途 |
| WO2014040549A1 (zh) | 2012-09-17 | 2014-03-20 | 南京圣和药业有限公司 | 炔杂芳环化合物及其应用 |
Families Citing this family (347)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| GB9212673D0 (en) * | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
| US5972598A (en) * | 1992-09-17 | 1999-10-26 | Board Of Trustess Of The University Of Illinois | Methods for preventing multidrug resistance in cancer cells |
| US6171786B1 (en) | 1992-09-17 | 2001-01-09 | Board Of Trustees Of University Of Illinois | Methods for preventing multidrug resistance in cancer cells |
| GB9222253D0 (en) * | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| US5543520A (en) * | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
| PT672042E (pt) * | 1993-10-01 | 2006-08-31 | Novartis Ag | Derivados de pirimidinoamina farmacologicamente activos e processos para a sua preparacao |
| WO1995009847A1 (en) * | 1993-10-01 | 1995-04-13 | Ciba-Geigy Ag | Pyrimidineamine derivatives and processes for the preparation thereof |
| ATE208772T1 (de) * | 1993-10-01 | 2001-11-15 | Novartis Erfind Verwalt Gmbh | Pharmacologisch wirksame pyridinderivate und verfahren zu deren herstellung |
| GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| ATE260911T1 (de) * | 1993-12-22 | 2004-03-15 | Celltech R&D Ltd | Trisubstituierte phenyl-derivate, verfahren zu deren herstellung und deren verwendung als phosphodiesterase (typ iv) hemmstoffe |
| GB9326699D0 (en) * | 1993-12-22 | 1994-03-02 | Celltech Ltd | Chemical compounds |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| GB9412571D0 (en) * | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412573D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412672D0 (en) * | 1994-06-23 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| US5756527A (en) * | 1995-06-07 | 1998-05-26 | Ontogen Corporation | Imidazole derivatives useful as modulators of multi drug resistances |
| GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526246D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526245D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9608435D0 (en) * | 1996-04-24 | 1996-06-26 | Celltech Therapeutics Ltd | Chemical compounds |
| EP0812829A1 (en) * | 1996-06-14 | 1997-12-17 | Ontogen Corporation | Substituted imidazoles as modulators of multi-drug resistance |
| EP0812830A1 (en) * | 1996-06-14 | 1997-12-17 | Ontogen Corporation | Modulators of multi-drug resistances |
| GB9619284D0 (en) * | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9625184D0 (en) * | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2001507349A (ja) * | 1996-12-23 | 2001-06-05 | セルテック セラピューティックス リミテッド | 縮合多環式２−アミノピリミジン誘導体、それらの製造およびたんぱく質チロシンキナーゼ抑制因子としてのそれらの使用 |
| GB9705361D0 (en) | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9713087D0 (en) * | 1997-06-20 | 1997-08-27 | Celltech Therapeutics Ltd | Chemical compounds |
| CO4940418A1 (es) * | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| CA2376957A1 (en) | 1999-06-30 | 2001-01-04 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| JP2003503354A (ja) | 1999-06-30 | 2003-01-28 | メルク エンド カムパニー インコーポレーテッド | Ｓｒｃキナーゼ阻害剤化合物 |
| DE60006541D1 (de) | 1999-06-30 | 2003-12-18 | Merck & Co Inc | Src-kinase hemmende verbindungen |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| HUP0202682A3 (en) | 1999-09-10 | 2003-03-28 | Merck & Co Inc | Tyrosine kinase inhibitors, pharmaceutical compositions containing them and their use |
| GB9924862D0 (en) | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
| WO2001060816A1 (en) * | 2000-02-17 | 2001-08-23 | Amgen Inc. | Kinase inhibitors |
| GB0004890D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004886D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| US7087608B2 (en) | 2000-03-03 | 2006-08-08 | Robert Charles Atkins | Use of PDGF receptor tyrosine kinase inhibitors for the treatment of diabetic nephropathy |
| GB0007371D0 (en) | 2000-03-28 | 2000-05-17 | Astrazeneca Uk Ltd | Chemical compounds |
| US7030219B2 (en) | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
| BR0113356A (pt) | 2000-08-18 | 2004-04-20 | Millennium Pharm Inc | Derivados de quinazolina como inibidores de quinase |
| GB0022438D0 (en) * | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| DK1332137T3 (da) * | 2000-10-27 | 2006-07-17 | Novartis Ag | Behandling af gastrointestinale stromale tumorer |
| AU2002217999A1 (en) | 2000-11-01 | 2002-05-15 | Cor Therapeutics, Inc. | Process for the production of 4-quinazolinylpiperazin-1-carboxylic acid phenylamides |
| GB0103926D0 (en) * | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| LT3143995T (lt) | 2001-02-19 | 2019-01-25 | Novartis Ag | Rapamicino darinys, skirtas plaučių vėžio gydymui |
| SE0100569D0 (sv) * | 2001-02-20 | 2001-02-20 | Astrazeneca Ab | New compounds |
| JP4499359B2 (ja) | 2001-02-27 | 2010-07-07 | ノバルティス アーゲー | シグナル変換阻害剤とエポチロン誘導体とを含有してなる組合せ剤 |
| PT1392313E (pt) | 2001-05-16 | 2007-07-17 | Novartis Ag | Combinação que compreende n - ( 5- [ 4- ( metil-piperazinomrtil ) - benxoilamido ] - 2 -metilfenil ) - 4 -( 3 - piridil ) - 2 - pirimidina-amina e um agente quimioterapêutico |
| US20030176443A1 (en) * | 2001-05-16 | 2003-09-18 | Matthias Stein-Gerlach | Pyridylpyrimidine derivatives as effective compounds against prion diseases |
| EP1466174B1 (en) | 2001-06-14 | 2009-05-13 | The Regents of the University of California | Mutations in the bcr-abl tyrosine kinase associated with resistance to sti-571 |
| AU2002315388A1 (en) | 2001-06-21 | 2003-01-08 | Ariad Pharmaceuticals, Inc. | Novel phenylamino-pyrimidines and uses thereof |
| JP2004535437A (ja) | 2001-06-22 | 2004-11-25 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼ阻害剤 |
| ES2274075T3 (es) | 2001-06-29 | 2007-05-16 | Ab Science | Utilizacion de inhibidores de c-kit para tratar enfermedades inflamatorias intestinales (eii). |
| ES2266553T3 (es) | 2001-06-29 | 2007-03-01 | Ab Science | Utilizacion de derivados de la n-fenil-2-pirimidina-amina para tratar las enfermedades inflamatorias. |
| US7727731B2 (en) | 2001-06-29 | 2010-06-01 | Ab Science | Potent, selective and non toxic c-kit inhibitors |
| WO2003004006A2 (en) * | 2001-06-29 | 2003-01-16 | Ab Science | Use of potent, selective and non toxic c-kit inhibitors for treating tumor angiogenesis |
| US7700610B2 (en) | 2001-06-29 | 2010-04-20 | Ab Science | Use of tyrosine kinase inhibitors for treating allergic diseases |
| WO2003039550A1 (en) * | 2001-09-20 | 2003-05-15 | Ab Science | Use of tyrosine kinase inhibitors for whitening human skin and treating melanocyte dysfunction associated diseases |
| WO2003040141A1 (en) * | 2001-09-28 | 2003-05-15 | Bayer Pharmaceuticals Corporation | Oxazolyl-phenyl-2,4-diamino-pyrimidine compounds and methods for treating hyperproliferative disorders |
| EP2290056A3 (en) | 2001-10-05 | 2011-06-01 | Novartis AG | Mutated Abl kinase domains |
| GB0201508D0 (en) | 2002-01-23 | 2002-03-13 | Novartis Ag | Organic compounds |
| AU2007203463B2 (en) * | 2002-02-07 | 2010-12-23 | Novartis Pharma Ag | N-phenyl-2-pyrimidine-amine derivatives |
| GB0202873D0 (en) | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| GB0202874D0 (en) * | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| DE60305460D1 (de) * | 2002-02-22 | 2006-06-29 | Us Government | Verwendung von 4-(4-methylpiperazin-1-ylmethyl)-n 4-methyl-3-(4-pyridin-3-yl) pyrimidin-2-ylamino) phenyl benzamid zur behandlung von seminomen |
| WO2003072090A2 (en) * | 2002-02-27 | 2003-09-04 | Ab Science | Use of tyrosine kinase inhibitors for treating cns disorders |
| DE60323613D1 (de) * | 2002-02-27 | 2008-10-30 | Ab Science | Verwendung von tyrosinkinase-hemmern zur behandlung von erkrankungen im zusammenhang mit substanzgebrauch |
| PL371466A1 (en) * | 2002-02-28 | 2005-06-13 | Novartis Ag | N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine coated stents |
| GB0206215D0 (en) | 2002-03-15 | 2002-05-01 | Novartis Ag | Organic compounds |
| GB0209265D0 (en) * | 2002-04-23 | 2002-06-05 | Novartis Ag | Organic compounds |
| AU2003231231A1 (en) * | 2002-05-06 | 2003-11-11 | Bayer Pharmaceuticals Corporation | Pyridinyl amino pyrimidine derivatives useful for treating hyper-proliferative disorders |
| PT1505959E (pt) | 2002-05-16 | 2009-02-05 | Novartis Ag | Utilização de agentes de ligação do receptor edg em cancro |
| WO2004000318A2 (en) | 2002-06-21 | 2003-12-31 | Cellular Genomics, Inc. | Certain amino-substituted monocycles as kinase modulators |
| AU2003295320A1 (en) * | 2002-06-26 | 2004-04-08 | The Ohio State University Research Foundation | The method for reducing inflammation using sti-571 or its salt |
| US7494997B2 (en) * | 2002-06-28 | 2009-02-24 | Nippon Shinyaku Co., Ltd. | Amide derivative |
| GB0215676D0 (en) * | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| US6872724B2 (en) | 2002-07-24 | 2005-03-29 | Merck & Co., Inc. | Polymorphs with tyrosine kinase activity |
| MXPA05001277A (es) * | 2002-08-02 | 2005-10-06 | Ab Science | 2-(3-aminoaril)amino-4-aril-tiazoles y su uso como inhibidores del c-kit. |
| GB0222514D0 (en) * | 2002-09-27 | 2002-11-06 | Novartis Ag | Organic compounds |
| AU2003273986A1 (en) * | 2002-10-11 | 2004-05-04 | Novartis Ag | Use of imatinib (glivec, sti-571) to inhibit breast cancer resistance protein (bcrp)-mediated resistance to therapeutic agents |
| GB0224455D0 (en) * | 2002-10-21 | 2002-11-27 | Novartis Ag | Organic compounds |
| US7094785B1 (en) | 2002-12-18 | 2006-08-22 | Cornell Research Foundation, Inc. | Method of treating polycythemia vera |
| US7144911B2 (en) * | 2002-12-31 | 2006-12-05 | Deciphera Pharmaceuticals Llc | Anti-inflammatory medicaments |
| GB2398565A (en) | 2003-02-18 | 2004-08-25 | Cipla Ltd | Imatinib preparation and salts |
| US20070276472A1 (en) * | 2003-04-04 | 2007-11-29 | Gianluca Gazza | Vascular Stent |
| WO2004099186A1 (en) | 2003-05-06 | 2004-11-18 | Il Yang Pharm Co., Ltd. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
| MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
| BRPI0410439A (pt) | 2003-05-19 | 2006-06-06 | Irm Llc | compostos e composições imunossupressoras |
| DK1631291T3 (da) * | 2003-05-27 | 2009-11-02 | Robert P Haegerkvist | Anvendelse af tyrosinkinaseinhibitorer til behandling af diabetes |
| ATE454152T1 (de) * | 2003-06-13 | 2010-01-15 | Novartis Pharma Gmbh | 2-aminopyrimidin-derivate als raf-kinase-hemmer |
| CA2536912C (en) | 2003-08-27 | 2015-03-31 | Eyetech Pharmaceuticals, Inc. | Combination therapy for the treatment of ocular neovascular disorders |
| CN102274230B (zh) | 2003-11-18 | 2015-07-01 | 诺华股份有限公司 | Kit突变形式的抑制剂 |
| WO2005072826A2 (en) * | 2004-01-21 | 2005-08-11 | Emory University | Compositions and use of tyrosine kinase inhibitors to treat pathogenic infection |
| AR047530A1 (es) * | 2004-02-04 | 2006-01-25 | Novartis Ag | Formas de sal de 4-(4-metilpiperazin-1-ilmetil)-n-(4-metil-3-(4-piridin-3-il)pirimidin-2-ilamino)fenil)-benzamida |
| CA2555804C (en) * | 2004-02-11 | 2012-06-26 | Natco Pharma Limited | Polymorphic form of imatinib mesylate and a process for its preparation |
| CN1309719C (zh) * | 2004-02-18 | 2007-04-11 | 陈国庆 | 苯氨基嘧啶衍生物及其用途 |
| EP2253614B1 (en) | 2004-04-07 | 2012-09-19 | Novartis AG | Inhibitors of IAP |
| GB0512324D0 (en) | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| WO2006021458A2 (en) * | 2004-08-27 | 2006-03-02 | Gpc Biotech Ag | Pyrimidine derivatives |
| TR200701870T1 (tr) | 2004-09-02 | 2007-05-21 | Cipla Limited | İmatinib mesilatın kararlı kristal formu ve bu formun hazırlanması için işlem. |
| HRP20070146B1 (hr) | 2004-09-09 | 2015-12-04 | Natco Pharma Limited | Novi derivati fenilaminopiridina kao inhibitori bcr-abl kinaze |
| US8735415B2 (en) | 2004-09-09 | 2014-05-27 | Natco Pharma Limited | Acid addition salts of (3,5-Bis trifluoromethyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide |
| US7939541B2 (en) | 2004-09-09 | 2011-05-10 | Natco Pharma Limited | Intermediates and a process employing the intermediates for the preparation of (3-trifluoromethylsulfonyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide |
| WO2006054314A1 (en) * | 2004-11-17 | 2006-05-26 | Natco Pharma Limited | Polymorphic forms of imatinib mesylate |
| SI1833815T1 (sl) * | 2004-12-30 | 2011-01-31 | Inst Farmaceutyczny | Postopek priprave baze imatiniba |
| WO2006077424A1 (en) | 2005-01-21 | 2006-07-27 | Astex Therapeutics Limited | Pharmaceutical compounds |
| CA2606716C (en) | 2005-05-02 | 2013-07-23 | Novartis Ag | Use of pyrimidylaminobenzamide derivatives for the treatment of systematic mastocytosis |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| UA96139C2 (uk) | 2005-11-08 | 2011-10-10 | Дженентек, Інк. | Антитіло до нейропіліну-1 (nrp1) |
| NZ568182A (en) | 2005-11-21 | 2010-08-27 | Novartis Ag | Neuroendocrine tumor treatment using MTOR inhibitors |
| WO2007059963A1 (en) | 2005-11-25 | 2007-05-31 | Novartis Ag | F,g,h,i and k crystal forms of imatinib mesylate |
| GB0605120D0 (en) | 2006-03-14 | 2006-04-26 | Novartis Ag | Organic Compounds |
| KR20080108517A (ko) | 2006-04-05 | 2008-12-15 | 노파르티스 아게 | 암을 치료하기 위한 치료제의 조합물 |
| BRPI0709749A2 (pt) | 2006-04-05 | 2011-07-26 | Novartis Ag | combinaÇÕes de agentes terapÊuticos para tratamento de cÂncer |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| WO2007128820A1 (en) | 2006-05-09 | 2007-11-15 | Novartis Ag | Combination comprising an iron chelator and an anti-neoplastic agent and use thereof |
| US20060223817A1 (en) * | 2006-05-15 | 2006-10-05 | Chemagis Ltd. | Crystalline imatinib base and production process therefor |
| AU2006345660A1 (en) | 2006-06-01 | 2007-12-06 | Japan As Represented By Director General Of Agency Of National Cancer Center | Tumor suppressor |
| KR20090073121A (ko) | 2006-09-29 | 2009-07-02 | 노파르티스 아게 | Ｐｉ3ｋ 지질 키나제 억제제로서의 피라졸로피리미딘 |
| JP5528807B2 (ja) | 2006-10-12 | 2014-06-25 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
| US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
| US20080207904A1 (en) * | 2006-10-26 | 2008-08-28 | Macdonald Peter | Imatinib base, and imatinib mesylate and processes for preparation thereof |
| RU2480461C2 (ru) * | 2006-11-16 | 2013-04-27 | Ф.И.С. Фаббрика Итальяна Синтетичи С.П.А. | Способ получения иматиниба и его промежуточных соединений |
| CN101245061B (zh) * | 2007-02-13 | 2012-09-19 | 天津天士力集团有限公司 | N-(5-氨基-2-甲基苯基)-4-(3-吡啶基)-2-嘧啶胺类一氧化氮供体型衍生物，制备方法及其用途 |
| CA2677651A1 (en) | 2007-02-15 | 2008-08-21 | Novartis Ag | Combinations of therapeutic agents for treating cancer |
| RU2329260C1 (ru) * | 2007-02-20 | 2008-07-20 | Юрий Иосифович Копырин | Способ получения 2-анилинопиримидинов или их солей (варианты) |
| CN101677955A (zh) * | 2007-03-12 | 2010-03-24 | 雷迪博士实验室有限公司 | 甲磺酸伊马替尼 |
| WO2008117298A1 (en) * | 2007-03-26 | 2008-10-02 | Natco Pharma Limited | A novel method of preparation of imatinib |
| US7550591B2 (en) | 2007-05-02 | 2009-06-23 | Chemagis Ltd. | Imatinib production process |
| WO2008136010A1 (en) * | 2007-05-07 | 2008-11-13 | Natco Pharma Limited | A process for the preparation of highly pure imatinib base |
| EP2166860B1 (en) | 2007-06-07 | 2016-09-21 | Intra-Cellular Therapies, Inc. | Novel heterocycle compounds and uses thereof |
| JP5710251B2 (ja) | 2007-06-07 | 2015-04-30 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 新規ヘテロ環化合物およびその使用 |
| WO2009032861A1 (en) | 2007-09-04 | 2009-03-12 | The Scripps Research Institute | Substituted pyrimidinyl-amines as protein kinase inhibitors |
| WO2009060463A1 (en) * | 2007-11-05 | 2009-05-14 | Natco Pharma Limited | An environmentally friendly process for the preparation of imatinib base |
| EP2062885A1 (en) * | 2007-11-21 | 2009-05-27 | Eczacibasi-Zentiva Kimyasal Ürünler Sanayi ve Ticaret A.S. | Acid addition salts of imatinib and formulations comprising the same |
| US8436171B2 (en) * | 2008-02-01 | 2013-05-07 | Akinion Pharmaceuticals Ab | Amino substituted pyrazines as inhibitors or protein kinases |
| AU2009228765B2 (en) | 2008-03-24 | 2012-05-31 | Novartis Ag | Arylsulfonamide-based matrix metalloprotease inhibitors |
| EA019033B1 (ru) | 2008-03-26 | 2013-12-30 | Новартис Аг | Ингибиторы дезацетилазы в, основанные на гидроксамате |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| CN101584696A (zh) | 2008-05-21 | 2009-11-25 | 上海艾力斯医药科技有限公司 | 包含喹唑啉衍生物的组合物及制备方法、用途 |
| CN102105150B (zh) | 2008-05-21 | 2014-03-12 | 阿里亚德医药股份有限公司 | 用作激酶抑制剂的磷衍生物 |
| PL215042B1 (pl) * | 2008-08-01 | 2013-10-31 | Temapharm Spolka Z Ograniczona Odpowiedzialnoscia | Sposób wytwarzania imatinibu |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| CN102123704B (zh) | 2008-08-15 | 2014-02-12 | 勃林格殷格翰国际有限公司 | 用于治疗fab-相关疾病的嘌呤衍生物 |
| CN102203132A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂的组合物和使用方法 |
| US20110223241A1 (en) | 2008-10-16 | 2011-09-15 | Celator Pharmaceuticals, Inc. | Combination methods and compositions |
| EP2186514B1 (en) | 2008-11-14 | 2016-06-29 | Kinki University | Treatment of Malignant Peripheral Nerve Sheath Tumors |
| CA2747558A1 (en) | 2008-12-18 | 2010-07-15 | Novartis Ag | New salts |
| KR20110112352A (ko) | 2008-12-18 | 2011-10-12 | 노파르티스 아게 | 1-（4-｛ｌ-［（ｅ）-4-시클로헥실-3-트리플루오로메틸-벤질옥시이미노］-에틸｝-2-에틸-벤질）-아제티딘-3-카르복실산의 신규한 다형체 형태 |
| KR20160064245A (ko) | 2008-12-18 | 2016-06-07 | 노파르티스 아게 | 1-［4-［1-(4-시클로헥실-3-트리플루오로메틸-벤질옥시이미노)-에틸］-2-에틸-벤질］-아제티딘-3-카르복실산의 헤미푸마레이트 염 |
| EA022310B1 (ru) | 2008-12-23 | 2015-12-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Солевые формы органического соединения |
| AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
| WO2010083617A1 (en) | 2009-01-21 | 2010-07-29 | Oncalis Ag | Pyrazolopyrimidines as protein kinase inhibitors |
| JP2012516345A (ja) | 2009-01-29 | 2012-07-19 | ノバルティス アーゲー | 星細胞腫治療用置換ベンゾイミダゾール |
| AR075204A1 (es) | 2009-01-29 | 2011-03-16 | Boehringer Ingelheim Int | Inhibidores de dpp-4 y composiciones farmaceuticas que los comprenden, utiles para tratar enfermedades metabolicas en pacientes pediatricos, particularmente diabetes mellitus tipo 2 |
| CN117547538A (zh) | 2009-02-13 | 2024-02-13 | 勃林格殷格翰国际有限公司 | 包含dpp-4抑制剂(利格列汀)任选地组合其它抗糖尿病药的抗糖尿病药物 |
| EP2400985A2 (en) | 2009-02-25 | 2012-01-04 | OSI Pharmaceuticals, LLC | Combination of an either an anti-igf-1r antibody or an igf binding protein and a small molecule igf-1r kinase inhibitor |
| EP2401614A1 (en) | 2009-02-27 | 2012-01-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| US8465912B2 (en) | 2009-02-27 | 2013-06-18 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| UA103918C2 (en) | 2009-03-02 | 2013-12-10 | Айерем Элелси | N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as wnt signaling modulators |
| TW201102068A (en) | 2009-06-02 | 2011-01-16 | Novartis Ag | Treatment of ophthalmologic disorders mediated by alpha-carbonic anhydrase isoforms |
| SG176105A1 (en) | 2009-06-26 | 2011-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
| WO2011014520A2 (en) | 2009-07-29 | 2011-02-03 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| UA111579C2 (uk) | 2009-08-17 | 2016-05-25 | Інтеллікіне Ллк | ГЕТЕРОЦИКЛІЧНІ ПОХІДНІ 2-АМІНОБЕНЗО[d]ОКСАЗОЛУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ НА ЇХ ОСНОВІ ТА ЇХ ЗАСТОСУВАННЯ ДЛЯ ЛІКУВАННЯ ЗАХВОРЮВАННЯ, ПОВ'АНОГО З РІ3-КІНАЗОЮ |
| KR20120089463A (ko) | 2009-08-20 | 2012-08-10 | 노파르티스 아게 | 헤테로시클릭 옥심 화합물 |
| EA201200321A1 (ru) | 2009-08-26 | 2012-09-28 | Новартис Аг | Тетразамещенные гетероарильные соединения и их применение в качестве модуляторов mdm2 и/или mdm4 |
| WO2011029915A1 (en) | 2009-09-10 | 2011-03-17 | Novartis Ag | Ether derivatives of bicyclic heteroaryls |
| JP5662453B2 (ja) | 2009-10-02 | 2015-01-28 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 医薬組成物の治療上の使用 |
| JP2013507366A (ja) | 2009-10-09 | 2013-03-04 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｇｐｒ１１９活性モジュレーターとしての化合物および組成物 |
| PL389357A1 (pl) | 2009-10-22 | 2011-04-26 | Tomasz Koźluk | Sole imatinibu z pochodnymi kwasów winowych i sposób ich wytwarzania |
| MX2012005293A (es) | 2009-11-04 | 2012-06-19 | Novartis Ag | Derivados de sulfonamida heterociclicos utiles como inhibidores de mek. |
| CN102781237A (zh) | 2009-11-23 | 2012-11-14 | 天蓝制药公司 | 用于传递治疗剂的基于环糊精的聚合物 |
| CN102712648A (zh) | 2009-11-25 | 2012-10-03 | 诺瓦提斯公司 | 双环杂芳基的与苯稠合的6元含氧杂环衍生物 |
| BR112012012641A2 (pt) | 2009-11-27 | 2020-08-11 | Boehringer Ingelheim International Gmbh | TRATAMENTO DE PACIENTES DIABÉTICOS GENOTIPADOS COM INIBIDORES DE DPP-lVTAL COMO LINAGLIPTINA |
| US8394858B2 (en) | 2009-12-03 | 2013-03-12 | Novartis Ag | Cyclohexane derivatives and uses thereof |
| EA201200823A1 (ru) | 2009-12-08 | 2013-02-28 | Новартис Аг | Гетероциклические производные сульфонамидов |
| WO2011070588A1 (en) | 2009-12-10 | 2011-06-16 | Arch Pharmalabs Limited | Process for the preparation of imatinib and salts thereof |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| CU24130B1 (es) | 2009-12-22 | 2015-09-29 | Novartis Ag | Isoquinolinonas y quinazolinonas sustituidas |
| US20110178287A1 (en) | 2010-01-19 | 2011-07-21 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
| WO2011099039A1 (en) | 2010-02-15 | 2011-08-18 | Reliance Life Sciences Pvt. Ltd. | Process for the preparation of alpha form of imatinib mesylate |
| PL390611A1 (pl) | 2010-03-04 | 2011-09-12 | Tomasz Koźluk | Sposób otrzymywania polimorficznej formy alfa i nowa forma polimorficzna mesylanu imatinibu |
| WO2011114337A1 (en) | 2010-03-15 | 2011-09-22 | Natco Pharma Limited | Process for the preparation of highly pure crystalline imatinib base |
| US20130109703A1 (en) | 2010-03-18 | 2013-05-02 | Boehringer Ingelheim International Gmbh | Combination of a GPR119 Agonist and the DPP-IV Inhibitor Linagliptin for Use in the Treatment of Diabetes and Related Conditions |
| WO2011119995A2 (en) | 2010-03-26 | 2011-09-29 | Cerulean Pharma Inc. | Formulations and methods of use |
| US8609842B2 (en) * | 2010-04-23 | 2013-12-17 | Fujian South Pharmaceutical Co., Ltd. | Method for synthesizing Imatinib |
| EP2382976A1 (en) | 2010-04-30 | 2011-11-02 | Hiroshima University | Use of pdgf-r inhibitors for the treatment of lymph node metastasis of gastric cancer |
| KR101927068B1 (ko) | 2010-05-05 | 2018-12-10 | 베링거 인겔하임 인터내셔날 게엠베하 | 체중 감소 치료에 후속하는 dpp-4 억제제에 의한 순차적 병용 요법 |
| CN102947275A (zh) | 2010-06-17 | 2013-02-27 | 诺瓦提斯公司 | 哌啶基取代的1,3-二氢-苯并咪唑-2-亚基胺衍生物 |
| JP2013528635A (ja) | 2010-06-17 | 2013-07-11 | ノバルティス アーゲー | ビフェニル置換１，３−ジヒドロ−ベンゾイミダゾール−２−イリデンアミン誘導体 |
| SI2582689T1 (sl) | 2010-06-18 | 2017-05-31 | Krka, D.D., Novo Mesto | Nova polimorfna oblika imatinib baze in priprava njenih soli |
| EP2582362A1 (en) * | 2010-06-21 | 2013-04-24 | Zaklady Farmaceutyczne "Polpharma" S.A. | Pharmaceutical compositions comprising imatinib or pharmaceutically acceptable salt thereof and processes for the manufacture thereof |
| CA2803504C (en) | 2010-06-24 | 2022-08-30 | Boehringer Ingelheim International Gmbh | A combination for diabetes therapy comprising linagliptin and a long-acting insulin |
| UA112517C2 (uk) | 2010-07-06 | 2016-09-26 | Новартіс Аг | Тетрагідропіридопіримідинові похідні |
| RU2571226C2 (ru) | 2010-07-09 | 2015-12-20 | Дженентек, Инк. | Антитела против нейропилина и способы их применения |
| US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
| WO2012019633A1 (en) | 2010-08-11 | 2012-02-16 | Synthon B.V. | Pharmaceutical granulate comprising imatinib mesylate |
| TR201007005A2 (tr) | 2010-08-23 | 2011-09-21 | Mustafa Nevzat İlaç Sanayi̇i̇ A.Ş. | İmatinib baz üretim yöntemi |
| CN103108871B (zh) | 2010-09-16 | 2014-09-10 | 诺华股份有限公司 | 17α-羟化酶/C17,20-裂合酶抑制剂 |
| US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
| TR201010618A2 (tr) | 2010-12-20 | 2012-07-23 | Bi̇lgi̇ç Mahmut | İmatinib içeren bir oral dozaj formu ve bu oral dozaj formunun üretimi |
| AU2011346567A1 (en) | 2010-12-21 | 2013-07-25 | Novartis Ag | Bi-heteroaryl compounds as Vps34 inhibitors |
| WO2012090221A1 (en) | 2010-12-29 | 2012-07-05 | Cadila Healthcare Limited | Novel salts of imatinib |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| EP2678016B1 (en) | 2011-02-23 | 2016-08-10 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
| TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
| CZ305457B6 (cs) | 2011-02-28 | 2015-09-30 | Ústav organické chemie a biochemie, Akademie věd ČR v. v. i. | Pyrimidinové sloučeniny inhibující tvorbu oxidu dusnatého a prostaglandinu E2, způsob výroby a použití |
| EP2683722A1 (en) | 2011-03-08 | 2014-01-15 | Novartis AG | Fluorophenyl bicyclic heteroaryl compounds |
| PL394169A1 (pl) | 2011-03-09 | 2012-09-10 | Adamed Spółka Z Ograniczoną Odpowiedzialnością | Kompozycja farmaceutyczna metanosulfonianu imatinibu do napełniania jednostkowych postaci dawkowania oraz sposób jej wytwarzania |
| EP2508525A1 (en) | 2011-04-05 | 2012-10-10 | Bayer Pharma Aktiengesellschaft | Substituted 2,3-dihydroimidazo[1,2-c]quinazoline salts |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| US9029399B2 (en) | 2011-04-28 | 2015-05-12 | Novartis Ag | 17α-hydroxylase/C17,20-lyase inhibitors |
| KR101884010B1 (ko) | 2011-05-04 | 2018-07-31 | 어리어드 파마슈티칼스, 인코포레이티드 | Egfr-유도된 암의 세포 증식을 억제하는 화합물 |
| CN102796110B (zh) * | 2011-05-23 | 2016-03-30 | 复旦大学 | 苯胺嘧啶化合物及其制备方法和用途 |
| JP2014517004A (ja) | 2011-06-09 | 2014-07-17 | ノバルティス アーゲー | 複素環スルホンアミド誘導体 |
| EP2721008B1 (en) | 2011-06-20 | 2015-04-29 | Novartis AG | Hydroxy substituted isoquinolinone derivatives as p53 (mdm2 or mdm4) inhibitors |
| WO2012175487A1 (en) | 2011-06-20 | 2012-12-27 | Novartis Ag | Cyclohexyl isoquinolinone compounds |
| US9750700B2 (en) | 2011-06-22 | 2017-09-05 | Natco Pharma Limited | Imatinib mesylate oral pharmaceutical composition and process for preparation thereof |
| JP2014518256A (ja) | 2011-06-27 | 2014-07-28 | ノバルティス アーゲー | テトラヒドロ−ピリド−ピリミジン誘導体の固体形態および塩類 |
| ITMI20111309A1 (it) | 2011-07-14 | 2013-01-15 | Italiana Sint Spa | Procedimento di preparazione di imatinib mesilato |
| EP3517539B1 (en) | 2011-07-15 | 2022-12-14 | Boehringer Ingelheim International GmbH | Substituted dimeric quinazoline derivative, its preparation and its use in pharmaceutical compositions for the treatment of type i and ii diabetes |
| WO2013035102A1 (en) | 2011-09-05 | 2013-03-14 | Natco Pharma Limited | Processes for the preparation of imatinib base and intermediates thereof |
| AU2012310168B2 (en) | 2011-09-15 | 2015-07-16 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
| CA2853961C (en) | 2011-11-01 | 2016-09-20 | Modgene, Llc | Compositions and methods for reduction of amyloid-beta load |
| RU2486180C1 (ru) * | 2011-11-02 | 2013-06-27 | Общество с ограниченной ответственностью "ТехноХим" (ООО "ТехноХим") | Способ получения 2-ариламино-4-гетарилпиримидинов |
| EP2785717B1 (en) | 2011-11-29 | 2016-01-13 | Novartis AG | Pyrazolopyrrolidine compounds |
| US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
| CN103159739A (zh) * | 2011-12-09 | 2013-06-19 | 天津市国际生物医药联合研究院有限公司 | 1,4-二取代-1,2,3-三氮唑类化合物及其制备方法 |
| US20150148377A1 (en) | 2011-12-22 | 2015-05-28 | Novartis Ag | Quinoline Derivatives |
| EA025322B1 (ru) | 2011-12-22 | 2016-12-30 | Новартис Аг | Производные дигидробензооксазина и дигидропиридооксазина |
| US20130178520A1 (en) | 2011-12-23 | 2013-07-11 | Duke University | Methods of treatment using arylcyclopropylamine compounds |
| CN104136429A (zh) | 2011-12-23 | 2014-11-05 | 诺华股份有限公司 | 用于抑制bcl2与结合配偶体相互作用的化合物 |
| JP2015503519A (ja) | 2011-12-23 | 2015-02-02 | ノバルティス アーゲー | Ｂｃｌ２と結合相手の相互作用を阻害するための化合物 |
| EP2794589A1 (en) | 2011-12-23 | 2014-10-29 | Novartis AG | Compounds for inhibiting the interaction of bcl2 with binding partners |
| EA201491264A1 (ru) | 2011-12-23 | 2014-11-28 | Новартис Аг | Соединения для ингибирования взаимодействия bcl-2 с партнерами по связыванию |
| JP2015503515A (ja) | 2011-12-23 | 2015-02-02 | ノバルティス アーゲー | Ｂｃｌ２と結合相手の相互作用を阻害するための化合物および組成物 |
| US20130172244A1 (en) | 2011-12-29 | 2013-07-04 | Thomas Klein | Subcutaneous therapeutic use of dpp-4 inhibitor |
| PL226174B1 (pl) | 2011-12-30 | 2017-06-30 | Inst Farm | Polaczenie analogu witaminy D z imatinibem do stosowania w leczeniu skojarzonym niedrobnokomorkowego raka pluc |
| US8815926B2 (en) | 2012-01-26 | 2014-08-26 | Novartis Ag | Substituted pyrrolo[3,4-D]imidazoles for the treatment of MDM2/4 mediated diseases |
| WO2013120852A1 (en) | 2012-02-13 | 2013-08-22 | Grindeks, A Joint Stock Company | Intermediates for a novel process of preparing imatinib and related tyrosine kinase inhibitors |
| IN2012DE00728A (enExample) | 2012-03-13 | 2015-08-21 | Fresenius Kabi Oncology Ltd | |
| KR102115047B1 (ko) | 2012-04-03 | 2020-05-26 | 노파르티스 아게 | 티로신 키나제 억제제들을 갖는 조합 제품 및 그의 용도 |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| SG11201406871UA (en) | 2012-04-24 | 2014-11-27 | Chugai Pharmaceutical Co Ltd | Benzamide derivative |
| WO2013161853A1 (ja) | 2012-04-24 | 2013-10-31 | 中外製薬株式会社 | キナゾリンジオン誘導体 |
| US20150166591A1 (en) | 2012-05-05 | 2015-06-18 | Ariad Pharmaceuticals, Inc. | Methods and compositions for raf kinase mediated diseases |
| JP6224084B2 (ja) | 2012-05-14 | 2017-11-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体 |
| EP4151218A1 (en) | 2012-05-14 | 2023-03-22 | Boehringer Ingelheim International GmbH | Linagliptin, a xanthine derivative as dpp-4 inhibitor, for use in the treatment of sirs and/or sepsis |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| EP2854812A1 (en) | 2012-05-24 | 2015-04-08 | Boehringer Ingelheim International GmbH | A xanthine derivative as dpp -4 inhibitor for use in the treatment of autoimmune diabetes, particularly lada |
| CN104321325B (zh) | 2012-05-24 | 2016-11-16 | 诺华股份有限公司 | 吡咯并吡咯烷酮化合物 |
| EP2861256B1 (en) | 2012-06-15 | 2019-10-23 | The Brigham and Women's Hospital, Inc. | Compositions for treating cancer and methods for making the same |
| WO2014016848A2 (en) | 2012-07-24 | 2014-01-30 | Laurus Labs Private Limited | Solid forms of tyrosine kinase inhibitors, process for the preparation and their pharmaceutical composition thereof |
| EP2879675B1 (en) | 2012-08-06 | 2019-11-13 | Duke University | Compounds and methods for targeting hsp90 |
| WO2014041551A1 (en) | 2012-09-14 | 2014-03-20 | Natco Pharma Limited | Formulation comprising imatinib as oral solution |
| WO2014052619A1 (en) | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
| EP2902028A1 (en) | 2012-09-28 | 2015-08-05 | Hangzhou Bensheng Pharmaceutical Co., Ltd. | Drug composition for treating tumors and application thereof |
| JP6945963B2 (ja) * | 2012-10-04 | 2021-10-06 | インヒビカーセ セラピューティクス，インコーポレーテッド | 新規な化合物、それらの調製及びそれらの使用 |
| WO2014071402A1 (en) | 2012-11-05 | 2014-05-08 | Dana-Farber Cancer Institute, Inc. | Xbp1, cd138, and cs1, pharmaceutical compositions that include the peptides, and methods of using such petides and compositions |
| TW201422625A (zh) | 2012-11-26 | 2014-06-16 | Novartis Ag | 二氫－吡啶并－□衍生物之固體形式 |
| CN103848812B (zh) * | 2012-12-04 | 2016-08-03 | 北大方正集团有限公司 | 精制伊马替尼的方法 |
| CN103044394A (zh) * | 2012-12-20 | 2013-04-17 | 北京理工大学 | 一种苯基氨基嘧啶衍生物及其制备方法和用途 |
| EP2749271A1 (en) | 2012-12-31 | 2014-07-02 | Deva Holding Anonim Sirketi | Optimized manufacturing method and pharmaceutical formulation of imatinib |
| EP2948453B1 (en) | 2013-01-22 | 2017-08-02 | Novartis AG | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the p53/mdm2 interaction |
| US9403827B2 (en) | 2013-01-22 | 2016-08-02 | Novartis Ag | Substituted purinone compounds |
| WO2014124860A1 (en) | 2013-02-14 | 2014-08-21 | Boehringer Ingelheim International Gmbh | Specific pde4b-inhibitors for the treatment of diabetes mellitus |
| DK2958943T3 (da) | 2013-02-20 | 2019-12-09 | Univ Pennsylvania | Behandling af cancer ved anvendelse af humaniseret anti-EGFRvIII kimær antigenreceptor |
| WO2014128612A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Quinazolin-4-one derivatives |
| CN105246482A (zh) | 2013-03-15 | 2016-01-13 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| JP2016510795A (ja) | 2013-03-15 | 2016-04-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 心臓保護及び腎臓保護の抗糖尿病治療におけるリナグリプチンの使用 |
| WO2014155268A2 (en) | 2013-03-25 | 2014-10-02 | Novartis Ag | Fgf-r tyrosine kinase activity inhibitors - use in diseases associated with lack of or reduced snf5 activity |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| EP2803353B1 (en) | 2013-05-14 | 2018-05-23 | Hetero Research Foundation | Compositions of Imatinib |
| US20150018376A1 (en) | 2013-05-17 | 2015-01-15 | Novartis Ag | Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof |
| UY35675A (es) | 2013-07-24 | 2015-02-27 | Novartis Ag | Derivados sustituidos de quinazolin-4-ona |
| US9227969B2 (en) | 2013-08-14 | 2016-01-05 | Novartis Ag | Compounds and compositions as inhibitors of MEK |
| WO2015022664A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
| WO2015022663A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
| US9657007B2 (en) | 2013-09-22 | 2017-05-23 | Calitor Sciences, Llc | Substituted aminopyrimidine compounds and methods of use |
| CA2927708C (en) | 2013-10-17 | 2021-05-25 | Sartar Therapeutics Ltd | Compositions comprising phosphodiesterase inhibitors for use in the treatment of a solid tumor in a human patient |
| CA2927830A1 (en) | 2013-10-23 | 2015-04-30 | Chugai Seiyaku Kabushiki Kaisha | Quinazolinone and isoquinolinone derivative |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| US10000469B2 (en) | 2014-03-25 | 2018-06-19 | Duke University | Heat shock protein 70 (hsp-70) receptor ligands |
| WO2015145388A2 (en) | 2014-03-27 | 2015-10-01 | Novartis Ag | Methods of treating colorectal cancers harboring upstream wnt pathway mutations |
| EP3312164B1 (en) | 2014-03-28 | 2020-12-09 | Calitor Sciences, LLC | Substituted heteroaryl compounds and methods of use |
| JP2017513931A (ja) | 2014-04-03 | 2017-06-01 | インビクタス オンコロジー ピーヴィティー．リミテッド | 超分子コンビナトリアル治療薬 |
| US9630944B2 (en) | 2014-04-04 | 2017-04-25 | F.I.S.—Fabbrica Italiana Sintetici S.p.A. | Process for preparing Imatinib and salts thereof, free of genotoxic impurity F |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
| WO2016016822A1 (en) | 2014-07-31 | 2016-02-04 | Novartis Ag | Combination therapy |
| WO2016059220A1 (en) | 2014-10-16 | 2016-04-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Tcr-activating agents for use in the treatment of t-all |
| CN105585556A (zh) * | 2014-11-13 | 2016-05-18 | 连云港杰瑞药业有限公司 | 一种伊马替尼的合成方法 |
| WO2017044434A1 (en) | 2015-09-11 | 2017-03-16 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
| WO2017129624A1 (en) | 2016-01-25 | 2017-08-03 | Krka, D.D., Novo Mesto | Fast dispersible pharmaceutical composition comprising tyrosine-kinase inhibitor |
| NZ745778A (en) | 2016-03-25 | 2022-07-01 | Ab Science | Use of masitinib for treatment of an amyotrophic lateral sclerosis patient subpopulation |
| WO2017184956A1 (en) | 2016-04-22 | 2017-10-26 | Duke University | Compounds and methods for targeting hsp90 |
| WO2017211979A1 (en) | 2016-06-10 | 2017-12-14 | Boehringer Ingelheim International Gmbh | Combinations of linagliptin and metformin |
| EP3257499A1 (en) | 2016-06-17 | 2017-12-20 | Vipharm S.A. | Process for preparation of imatinib methanesulfonate capsules |
| CN107652269A (zh) * | 2016-07-26 | 2018-02-02 | 江苏豪森药业集团有限公司 | 甲磺酸氟马替尼中间体纯化方法 |
| WO2018039205A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating breast cancer |
| WO2018039203A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating multiple myeloma |
| CN107805240A (zh) * | 2016-09-08 | 2018-03-16 | 中国科学院合肥物质科学研究院 | 一种新型的pdgfr激酶抑制剂及其用途 |
| US20200055917A1 (en) | 2016-09-27 | 2020-02-20 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules |
| US10927083B2 (en) | 2016-09-29 | 2021-02-23 | Duke University | Substituted benzimidazoles as inhibitors of transforming growth factor-β kinase |
| US10207998B2 (en) | 2016-09-29 | 2019-02-19 | Duke University | Substituted benzimidazole and substituted benzothiazole inhibitors of transforming growth factor-β kinase and methods of use thereof |
| EP3333162A1 (en) | 2016-12-12 | 2018-06-13 | Silesian Catalysts sp. z o.o. | Metod for preparing n-(2-methyl-5-nitrophenyl)-4-(pyridin-3-yl)pyrimidin-2-amine |
| CN107089969B (zh) * | 2017-04-26 | 2020-04-24 | 黑龙江鑫创生物科技开发有限公司 | 一种合成伊马替尼中间体的方法 |
| WO2019067328A1 (en) | 2017-09-26 | 2019-04-04 | Cero Therapeutics, Inc. | CHIMERIC ENGINEERING RECEPTOR MOLECULES AND METHODS OF USE |
| WO2019083960A1 (en) | 2017-10-24 | 2019-05-02 | Oncopep, Inc. | PEPTIDE VACCINES AND HDAC INHIBITORS FOR THE TREATMENT OF MULTIPLE MYELOMA |
| WO2019083962A1 (en) | 2017-10-24 | 2019-05-02 | Oncopep, Inc. | PEPTIDE AND PEMBROLIZUMAB VACCINES FOR THE TREATMENT OF BREAST CANCER |
| JP7254076B2 (ja) | 2017-11-19 | 2023-04-07 | サンシャイン・レイク・ファーマ・カンパニー・リミテッド | 置換ヘテロアリール化合物及び使用方法 |
| WO2019119486A1 (zh) | 2017-12-21 | 2019-06-27 | 中国科学院合肥物质科学研究院 | 一类嘧啶类衍生物激酶抑制剂 |
| KR102737185B1 (ko) | 2018-01-20 | 2024-12-05 | 선샤인 레이크 파르마 컴퍼니 리미티드 | 치환된 아미노피리미딘 화합물 및 이의 사용 방법 |
| US12291557B2 (en) | 2018-03-28 | 2025-05-06 | Cero Therapeutics Holdings, Inc. | Chimeric TIM4 receptors and uses thereof |
| MX2020010235A (es) | 2018-03-28 | 2020-10-28 | Cero Therapeutics Inc | Vectores de expresion para receptores de engullimiento quimerico, celulas hospederas geneticamente modificadas y usos de los mismos. |
| JP7444781B2 (ja) | 2018-03-28 | 2024-03-06 | セロ・セラピューティクス・インコーポレイテッド | 細胞免疫療法組成物およびその使用 |
| MX2021000555A (es) | 2018-07-17 | 2021-03-29 | Boehringer Ingelheim Int | Tratamiento antidiabetico cardiovascular seguro. |
| KR20210035227A (ko) | 2018-07-17 | 2021-03-31 | 베링거 인겔하임 인터내셔날 게엠베하 | 심장 안전성 및 신장 안전성 항당뇨 치료법 |
| US12220423B2 (en) | 2018-07-24 | 2025-02-11 | Hygia Pharmaceuticals, Llc | Compounds, derivatives, and analogs for cancer |
| BR112022000571A2 (pt) | 2019-07-15 | 2022-03-15 | Intas Pharmaceuticals Ltd | Composição farmacêutica e processo para preparação de uma composição farmacêutica compreendendo imatinibe ou seu sal farmaceuticamente aceitável e um ou mais excipientes farmaceuticamente aceitáveis em forma de pó |
| WO2021067875A1 (en) | 2019-10-03 | 2021-04-08 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
| EP4058465A1 (en) | 2019-11-14 | 2022-09-21 | Cohbar Inc. | Cxcr4 antagonist peptides |
| WO2021185844A1 (en) | 2020-03-16 | 2021-09-23 | Pvac Medical Technologies Ltd | Use of substance and pharmaceutical composition thereof, and medical treatments or uses thereof |
| WO2021233534A1 (en) | 2020-05-20 | 2021-11-25 | Pvac Medical Technologies Ltd | Use of substance and pharmaceutical composition thereof, and medical treatments or uses thereof |
| EP4136228A4 (en) | 2020-04-15 | 2024-09-11 | California Institute of Technology | THERMAL REGULATION OF T-CELL IMMUNOTHERAPY BY MOLECULAR AND PHYSICAL ACTUATION |
| WO2021228983A1 (en) | 2020-05-13 | 2021-11-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A pharmaceutical composition comprising an arsenic compound, an inductor of type-1 ifn and a protein kinase inhibitor for treating cancer |
| JP2023536346A (ja) | 2020-08-05 | 2023-08-24 | エリプシーズ ファーマ リミテッド | シクロデキストリン含有ポリマートポイソメラーゼ阻害剤コンジュゲートおよびｐａｒｐ阻害剤を用いた癌の処置 |
| WO2022036265A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Chimeric tim receptors and uses thereof |
| WO2022036287A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Anti-cd72 chimeric receptors and uses thereof |
| WO2022036285A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Compositions and methods for treating cancer with chimeric tim receptors in combination with inhibitors of poly (adp-ribose) polymerase |
| US11999964B2 (en) | 2020-08-28 | 2024-06-04 | California Institute Of Technology | Synthetic mammalian signaling circuits for robust cell population control |
| TW202237638A (zh) | 2020-12-09 | 2022-10-01 | 日商武田藥品工業股份有限公司 | 烏苷酸環化酶ｃ（ｇｃｃ）抗原結合劑之組成物及其使用方法 |
| CN117203223A (zh) | 2021-02-26 | 2023-12-08 | 凯洛尼亚疗法有限公司 | 淋巴细胞靶向慢病毒载体 |
| KR20240119868A (ko) | 2021-07-28 | 2024-08-06 | 세로 테라퓨틱스, 인코포레이티드 | 키메라 tim4 수용체 및 이의 용도 |
| CN119816589A (zh) | 2022-08-02 | 2025-04-11 | 国立大学法人北海道大学 | 使用细胞器复合体改善细胞疗法的方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0233461A2 (en) * | 1986-01-13 | 1987-08-26 | American Cyanamid Company | 4,5,6-Substituted-2-pyrimidinamines |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1570555A (en) * | 1977-04-05 | 1980-07-02 | Taiho Pharmaceutical Co Ltd | Anti-cancer composition |
-
1993
- 1993-03-24 TW TW082102196A patent/TW225528B/zh not_active IP Right Cessation
- 1993-03-25 EP EP93810219A patent/EP0564409B1/de not_active Expired - Lifetime
- 1993-03-25 AT AT93810219T patent/ATE188964T1/de active
- 1993-03-25 ES ES93810219T patent/ES2142857T3/es not_active Expired - Lifetime
- 1993-03-25 PT PT93810219T patent/PT564409E/pt unknown
- 1993-03-25 SG SG1996003161A patent/SG43859A1/en unknown
- 1993-03-25 DE DE2002199016 patent/DE10299016I2/de active Active
- 1993-03-25 DK DK93810219T patent/DK0564409T3/da not_active Application Discontinuation
- 1993-03-25 DE DE59309931T patent/DE59309931D1/de not_active Expired - Lifetime
- 1993-03-31 FI FI931458A patent/FI109534B/fi active Protection Beyond IP Right Term
- 1993-03-31 NZ NZ247299A patent/NZ247299A/en not_active IP Right Cessation
- 1993-04-01 RU RU93005357A patent/RU2125992C1/ru active
- 1993-04-01 CZ CZ93560A patent/CZ283944B6/cs not_active IP Right Cessation
- 1993-04-01 IL IL10526493A patent/IL105264A/en active Protection Beyond IP Right Term
- 1993-04-01 CA CA002093203A patent/CA2093203C/en not_active Expired - Lifetime
- 1993-04-01 SK SK280-93A patent/SK280620B6/sk not_active IP Right Cessation
- 1993-04-02 MX MX9301929A patent/MX9301929A/es active IP Right Grant
- 1993-04-02 ZA ZA932397A patent/ZA932397B/xx unknown
- 1993-04-02 HU HU9300982D patent/HU227080B1/hu active Protection Beyond IP Right Term
- 1993-04-02 HU HU9300982A patent/HU226488B1/hu unknown
- 1993-04-02 NO NO931283A patent/NO302473B1/no not_active IP Right Cessation
- 1993-04-02 CN CN93103566A patent/CN1043531C/zh not_active Expired - Lifetime
- 1993-04-02 AU AU35694/93A patent/AU666709B2/en not_active Expired
- 1993-04-03 KR KR1019930005628A patent/KR100261366B1/ko not_active Expired - Lifetime
- 1993-04-05 JP JP5078096A patent/JP2706682B2/ja not_active Expired - Lifetime
- 1993-12-25 SA SA93140441A patent/SA93140441B1/ar unknown
-
1997
- 1997-05-09 BR BR1100739-7A patent/BR1100739A/pt active IP Right Grant
-
2000
- 2000-03-10 GR GR20000400623T patent/GR3032927T3/el unknown
-
2001
- 2001-07-13 CY CY0100019A patent/CY2229B1/xx unknown
-
2002
- 2002-03-01 NL NL300086C patent/NL300086I2/nl unknown
- 2002-03-19 NO NO2002001C patent/NO2002001I2/no unknown
- 2002-04-10 LU LU90908C patent/LU90908I2/fr unknown
-
2003
- 2003-12-04 CY CY2003003C patent/CY2003003I1/el unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0233461A2 (en) * | 1986-01-13 | 1987-08-26 | American Cyanamid Company | 4,5,6-Substituted-2-pyrimidinamines |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100526298C (zh) * | 2003-12-25 | 2009-08-12 | 日本新药株式会社 | 酰胺衍生物及医药品 |
| WO2006069525A1 (en) * | 2004-12-31 | 2006-07-06 | Piaoyang Sun | Aminopyrimidine compounds and their salts, process for preparation and pharmaceutical use thereof |
| CN1972917B (zh) * | 2004-12-31 | 2010-08-25 | 孙飘扬 | 氨基嘧啶类化合物及其盐和其制备方法与药物用途 |
| WO2014040549A1 (zh) | 2012-09-17 | 2014-03-20 | 南京圣和药业有限公司 | 炔杂芳环化合物及其应用 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1043531C (zh) | 嘧啶衍生物及其制备方法和用途 | |
| CN1047776C (zh) | 具有药理学活性的吡啶类衍生物及其制备方法 | |
| CN1148183C (zh) | 具有抗肿瘤作用的吲哚基-3-乙醛酸衍生物 | |
| CN1281606C (zh) | 含氮杂环化合物 | |
| RU2284187C2 (ru) | Производные амида, способы их получения, фармацевтическая композиция, способ лечения | |
| CN1100540C (zh) | 具有选择性抑制her－2自磷酸化性质的蛋白质酪氨酸激酶芳基和杂芳基喹唑啉化合物 | |
| KR101789275B1 (ko) | 에이즈 치료에 유용한 화합물 | |
| CN1219171A (zh) | 苯并呋喃甲酰胺及其治疗用途 | |
| CN1161330A (zh) | 取代的间二氮杂萘衍生物 | |
| CN1671695A (zh) | 用作pde4抑制剂的吡咯烷二酮取代的哌啶－2,3－二氮杂萘酮化合物 | |
| CN1129449A (zh) | 用作神经激肽拮抗剂的杂环类化合物 | |
| CN1100773C (zh) | 苯并呋喃羧酸胺和磺酰胺 | |
| CN1265098A (zh) | 抑制因子xa的杂环衍生物 | |
| JP6694476B2 (ja) | Ａｉｄｓを治療する為に有用な化合物 | |
| CN1133840A (zh) | 吲哚哌啶衍生物 | |
| CN1261887A (zh) | 氮杂环丁基丙基哌啶衍生物、中间体以及作为速激肽拮抗剂的用途 | |
| CN1057649A (zh) | 2，4-和2，5-取代吡啶-n-氧化物，其制备方法和应用 | |
| CN1105360A (zh) | 1-[2h-1-苯并吡喃-2-酮-8-基]-哌嗪衍生物 | |
| CN1216547A (zh) | 质子泵抑制剂 | |
| CN1121389C (zh) | 细胞增生抑制剂氰基胍 | |
| CN1170814C (zh) | 用于强化胆碱能活性的酰胺化合物 | |
| CN1966506A (zh) | 吡唑并嘧啶酮衍生物及其制备方法和用途 | |
| RU2309950C2 (ru) | Производные пиридинамидов и лекарственное средство на их основе | |
| CN1302292A (zh) | 氨基异喹啉衍生物 | |
| CN1097005A (zh) | 2-氰基-3-羟基丙烯酰胺类化合物及其制备和用途 |
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 | ||
| C17 | Cessation of patent right | ||
| CX01 | Expiry of patent term |
Expiration termination date: 20130402 Granted publication date: 19990602 |