IL105264A - History of pyrimidine processes for their preparation and pharmaceutical preparations containing them - Google Patents
History of pyrimidine processes for their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL105264A IL105264A IL10526493A IL10526493A IL105264A IL 105264 A IL105264 A IL 105264A IL 10526493 A IL10526493 A IL 10526493A IL 10526493 A IL10526493 A IL 10526493A IL 105264 A IL105264 A IL 105264A
- Authority
- IL
- Israel
- Prior art keywords
- phenyl
- lower alkyl
- pyridyl
- formula
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 53
- 230000008569 process Effects 0.000 title claims description 22
- 238000002360 preparation method Methods 0.000 title claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 3
- 150000003230 pyrimidines Chemical class 0.000 title description 2
- -1 4-pyrazinyl Chemical group 0.000 claims abstract description 161
- 150000001875 compounds Chemical class 0.000 claims abstract description 138
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 66
- 239000001257 hydrogen Substances 0.000 claims abstract description 64
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 35
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 33
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 24
- 125000003277 amino group Chemical group 0.000 claims abstract description 23
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
- 239000001301 oxygen Substances 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 16
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 10
- 125000002757 morpholinyl group Chemical class 0.000 claims abstract description 10
- 125000003386 piperidinyl group Chemical class 0.000 claims abstract description 10
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 8
- 125000000719 pyrrolidinyl group Chemical class 0.000 claims abstract description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims abstract description 8
- 125000005277 alkyl imino group Chemical group 0.000 claims abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims description 88
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 150000001721 carbon Chemical group 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000006239 protecting group Chemical group 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 15
- 125000000524 functional group Chemical group 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- 239000000460 chlorine Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 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
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 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
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- LLJRXVHJOJRCSM-UHFFFAOYSA-N 3-pyridin-4-yl-1H-indole Chemical group C=1NC2=CC=CC=C2C=1C1=CC=NC=C1 LLJRXVHJOJRCSM-UHFFFAOYSA-N 0.000 claims 1
- 102100035189 GPI ethanolamine phosphate transferase 1 Human genes 0.000 claims 1
- 101710120219 GPI ethanolamine phosphate transferase 1 Proteins 0.000 claims 1
- DTCFXYVLDFXFEA-UHFFFAOYSA-N n-(3-nitrophenyl)-4-pyridin-2-ylpyrimidin-2-amine Chemical compound [O-][N+](=O)C1=CC=CC(NC=2N=C(C=CN=2)C=2N=CC=CC=2)=C1 DTCFXYVLDFXFEA-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 18
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 150000004046 2-(N-anilino)pyrimidines Chemical class 0.000 abstract 1
- 125000002883 imidazolyl group Chemical group 0.000 abstract 1
- 125000001041 indolyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 113
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
- 239000002253 acid Substances 0.000 description 50
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 150000003254 radicals Chemical class 0.000 description 38
- 239000000203 mixture Substances 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000007858 starting material Substances 0.000 description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
- 108090000315 Protein Kinase C Proteins 0.000 description 18
- 102000003923 Protein Kinase C Human genes 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 14
- 150000008064 anhydrides Chemical class 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 10
- 229960004592 isopropanol Drugs 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 9
- 235000011114 ammonium hydroxide Nutrition 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 8
- 108091008606 PDGF receptors Proteins 0.000 description 8
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 229940100445 wheat starch Drugs 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 7
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 7
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 150000001718 carbodiimides Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 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
- 239000000454 talc Substances 0.000 description 6
- 235000012222 talc Nutrition 0.000 description 6
- 229910052623 talc Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- MZLRFUCMBQWLNV-UHFFFAOYSA-N 3-(dimethylamino)-1-pyridin-3-ylprop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=CN=C1 MZLRFUCMBQWLNV-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 125000001931 aliphatic group Chemical group 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
- 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 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000004466 alkoxycarbonylamino group Chemical group 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
- 230000001419 dependent effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- VBYYPCNNGNGURO-UHFFFAOYSA-N nitric acid;2-(3-nitrophenyl)guanidine Chemical compound O[N+]([O-])=O.NC(N)=NC1=CC=CC([N+]([O-])=O)=C1 VBYYPCNNGNGURO-UHFFFAOYSA-N 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000003797 solvolysis reaction Methods 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- ZQTRXPRIWRFHRY-UHFFFAOYSA-N 3-n-(4-pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine Chemical compound NC1=CC=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 ZQTRXPRIWRFHRY-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
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 3
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
- 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 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- 238000006136 alcoholysis reaction Methods 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 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
- 239000000706 filtrate Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- HFAFXVOPGDBAOK-UHFFFAOYSA-M pyridine-2-carboxylate;hydrochloride Chemical compound [Cl-].OC(=O)C1=CC=CC=N1 HFAFXVOPGDBAOK-UHFFFAOYSA-M 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 241000894007 species Species 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
- 229920001567 vinyl ester resin Polymers 0.000 description 3
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CVKKTGQSXNZVKW-UHFFFAOYSA-N 2-(3-methyl-5-nitrophenyl)guanidine;nitric acid Chemical compound O[N+]([O-])=O.CC1=CC(N=C(N)N)=CC([N+]([O-])=O)=C1 CVKKTGQSXNZVKW-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-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
- 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 2
- KNBRFZWWCBSGDU-UHFFFAOYSA-N 4-[(4-methylpiperazin-1-yl)methyl]benzoyl chloride Chemical compound C1CN(C)CCN1CC1=CC=C(C(Cl)=O)C=C1 KNBRFZWWCBSGDU-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
- 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
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 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
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 150000007860 aryl ester derivatives Chemical class 0.000 description 2
- 150000005840 aryl radicals Chemical class 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
- 150000001735 carboxylic acids Chemical class 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
- 239000000470 constituent Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000003950 cyclic amides Chemical class 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000011261 inert gas Substances 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
- 239000011777 magnesium Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- OJITWRFPRCHSMX-UHFFFAOYSA-N n-(2-methyl-5-nitrophenyl)-4-pyridin-3-ylpyrimidin-2-amine Chemical compound CC1=CC=C([N+]([O-])=O)C=C1NC1=NC=CC(C=2C=NC=CC=2)=N1 OJITWRFPRCHSMX-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- BUVZPKSSYOOGFR-UHFFFAOYSA-N nitric acid;2-[3-(trifluoromethoxy)phenyl]guanidine Chemical compound O[N+]([O-])=O.NC(N)=NC1=CC=CC(OC(F)(F)F)=C1 BUVZPKSSYOOGFR-UHFFFAOYSA-N 0.000 description 2
- IDFXVEKMPKNHIC-UHFFFAOYSA-N nitric acid;2-[3-nitro-5-(trifluoromethyl)phenyl]guanidine Chemical compound O[N+]([O-])=O.NC(N)=NC1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 IDFXVEKMPKNHIC-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 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
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- LGRFSURHDFAFJT-UHFFFAOYSA-N phthalic anhydride Chemical compound C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- WTJXVDPDEQKTCV-VQAITOIOSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical group Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O WTJXVDPDEQKTCV-VQAITOIOSA-N 0.000 description 1
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-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
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 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
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-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
- IINMQQJNRFDBMV-UHFFFAOYSA-N 2-(2-methyl-5-nitrophenyl)guanidine;nitric acid Chemical compound O[N+]([O-])=O.CC1=CC=C([N+]([O-])=O)C=C1N=C(N)N IINMQQJNRFDBMV-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-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
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- MPSXGPCFLAGJOM-UHFFFAOYSA-M 2-tert-butyl-5-methyl-1,2-oxazol-2-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC1=CC=[N+](C(C)(C)C)O1 MPSXGPCFLAGJOM-UHFFFAOYSA-M 0.000 description 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 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
- RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 description 1
- LTVWXWWSCLXXAT-UHFFFAOYSA-N 3-nitro-5-(trifluoromethyl)aniline Chemical compound NC1=CC([N+]([O-])=O)=CC(C(F)(F)F)=C1 LTVWXWWSCLXXAT-UHFFFAOYSA-N 0.000 description 1
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-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
- KECCFSZFXLAGJS-UHFFFAOYSA-N 4-methylsulfonylphenol Chemical compound CS(=O)(=O)C1=CC=C(O)C=C1 KECCFSZFXLAGJS-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- QLBMWQJKAHFYHB-UHFFFAOYSA-N 4-pyridin-3-yl-n-[3-(trifluoromethoxy)phenyl]pyrimidin-2-amine Chemical compound FC(F)(F)OC1=CC=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 QLBMWQJKAHFYHB-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
- 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
- 239000005995 Aluminium silicate Substances 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
- 238000011725 BALB/c mouse Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 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
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 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
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-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
- 108010055723 PDGF receptor tyrosine kinase Proteins 0.000 description 1
- 102000009097 Phosphorylases Human genes 0.000 description 1
- 108010073135 Phosphorylases Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000534944 Thia Species 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 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
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 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
- 125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 125000000852 azido group Chemical class *N=[N+]=[N-] 0.000 description 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 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
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 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
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 150000001912 cyanamides Chemical class 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 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
- 208000035475 disorder Diseases 0.000 description 1
- GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- OKOHFSWRKRCHAD-UHFFFAOYSA-N ethane ethanesulfonic acid Chemical compound CC.CCS(O)(=O)=O OKOHFSWRKRCHAD-UHFFFAOYSA-N 0.000 description 1
- WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical group CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000796 flavoring agent Substances 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
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-O hydron;1,2-oxazole Chemical compound C=1C=[NH+]OC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-O 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 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
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- RJSCZBRDRBIRHP-UHFFFAOYSA-N n,n-diethylprop-1-yn-1-amine Chemical compound CCN(CC)C#CC RJSCZBRDRBIRHP-UHFFFAOYSA-N 0.000 description 1
- CRXFIXDVCCWTEZ-UHFFFAOYSA-N n-(3-methyl-5-nitrophenyl)-4-pyridin-3-ylpyrimidin-2-amine Chemical compound [O-][N+](=O)C1=CC(C)=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 CRXFIXDVCCWTEZ-UHFFFAOYSA-N 0.000 description 1
- HFQHGGZJZTXYKH-UHFFFAOYSA-N n-(3-nitrophenyl)-4-pyridin-3-ylpyrimidin-2-amine Chemical compound [O-][N+](=O)C1=CC=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 HFQHGGZJZTXYKH-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-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
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 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
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 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
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- MYHOHFDYWMPGJY-UHFFFAOYSA-N pentafluorobenzoyl chloride Chemical compound FC1=C(F)C(F)=C(C(Cl)=O)C(F)=C1F MYHOHFDYWMPGJY-UHFFFAOYSA-N 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 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
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000003367 polycyclic group Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002062 proliferating effect 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
- 239000003881 protein kinase C inhibitor Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-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
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 230000021014 regulation of cell growth Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- OLRJXMHANKMLTD-UHFFFAOYSA-N silyl Chemical compound [SiH3] OLRJXMHANKMLTD-UHFFFAOYSA-N 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000005809 transesterification reaction Methods 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
- 230000001173 tumoral effect Effects 0.000 description 1
- 238000010518 undesired secondary reaction Methods 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940001158 ximino Drugs 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)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH108392 | 1992-04-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL105264A0 IL105264A0 (en) | 1993-08-18 |
| IL105264A true IL105264A (en) | 1999-04-11 |
Family
ID=4202064
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10526493A IL105264A (en) | 1992-04-03 | 1993-04-01 | History of pyrimidine processes for their preparation and pharmaceutical preparations containing them |
Country Status (29)
| Country | Link |
|---|---|
| EP (1) | EP0564409B1 (lt) |
| JP (1) | JP2706682B2 (lt) |
| KR (1) | KR100261366B1 (lt) |
| CN (1) | CN1043531C (lt) |
| AT (1) | ATE188964T1 (lt) |
| AU (1) | AU666709B2 (lt) |
| BR (1) | BR1100739A (lt) |
| CA (1) | CA2093203C (lt) |
| CY (2) | CY2229B1 (lt) |
| CZ (1) | CZ283944B6 (lt) |
| DE (2) | DE59309931D1 (lt) |
| DK (1) | DK0564409T3 (lt) |
| ES (1) | ES2142857T3 (lt) |
| FI (1) | FI109534B (lt) |
| GR (1) | GR3032927T3 (lt) |
| HU (2) | HU226488B1 (lt) |
| IL (1) | IL105264A (lt) |
| LU (1) | LU90908I2 (lt) |
| MX (1) | MX9301929A (lt) |
| NL (1) | NL300086I2 (lt) |
| NO (2) | NO302473B1 (lt) |
| NZ (1) | NZ247299A (lt) |
| PT (1) | PT564409E (lt) |
| RU (1) | RU2125992C1 (lt) |
| SA (1) | SA93140441B1 (lt) |
| SG (1) | SG43859A1 (lt) |
| SK (1) | SK280620B6 (lt) |
| TW (1) | TW225528B (lt) |
| ZA (1) | ZA932397B (lt) |
Families Citing this family (350)
| 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 |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| US5612340A (en) * | 1993-10-01 | 1997-03-18 | Ciba-Geigy Corporation | Pyrimidineamine derivatives and processes for the preparation thereof |
| DE69434721T2 (de) * | 1993-10-01 | 2006-11-09 | Novartis Ag | Pharmacologisch wirksame pyrimidinderivate und verfahren zu deren herstellung |
| US5543520A (en) * | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
| NZ273617A (en) * | 1993-10-01 | 1996-11-26 | Ciba Geigy Ag | N-phenyl-2-pyrimidineamine derivatives pharmaceutical compositions |
| GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| GB9326600D0 (en) * | 1993-12-22 | 1994-03-02 | Celltech Ltd | Chemical compounds |
| DE69433594T2 (de) * | 1993-12-22 | 2004-08-05 | Celltech R&D Ltd., Slough | Trisubstituierte phenyl-derivate, verfahren zu deren herstellung und deren verwendung als phosphodiesterase (typ iv) hemmstoffe |
| US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| 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 |
| EP0812830A1 (en) * | 1996-06-14 | 1997-12-17 | Ontogen Corporation | Modulators of multi-drug resistances |
| EP0812829A1 (en) * | 1996-06-14 | 1997-12-17 | Ontogen Corporation | Substituted imidazoles as modulators of multi-drug resistance |
| 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 |
| WO1998028281A1 (en) | 1996-12-23 | 1998-07-02 | Celltech Therapeutics Limited | Fused polycyclic 2-aminopyrimidine derivatives, their preparation and their use as protein tyrosine kinase inhibitors |
| 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 |
| CA2376951A1 (en) | 1999-06-30 | 2001-01-04 | Peter J. Sinclair | Src kinase inhibitor compounds |
| JP2003503351A (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キナーゼ阻害化合物 |
| JP2003523942A (ja) | 1999-06-30 | 2003-08-12 | 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 |
| 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 |
| HUP0301117A3 (en) * | 2000-02-17 | 2004-01-28 | Amgen Inc Thousand Oaks | Imidazole derivatives kinase inhibitors, their use, process for their preparation and pharmaceutical compositions containing them |
| 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 |
| 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 |
| 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 |
| ES2311023T3 (es) | 2000-08-18 | 2009-02-01 | Millennium Pharmaceuticals, Inc. | Derivados de quinazolina como inhibidores de cinasa. |
| GB0022438D0 (en) | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| KR100885129B1 (ko) * | 2000-10-27 | 2009-02-23 | 노파르티스 아게 | 위장관의 기질 종양의 치료 |
| WO2002036587A2 (en) | 2000-11-01 | 2002-05-10 | 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 |
| EP2269603B1 (en) | 2001-02-19 | 2015-05-20 | Novartis AG | Treatment of breast tumors with a rapamycin derivative in combination with exemestane |
| SE0100569D0 (sv) * | 2001-02-20 | 2001-02-20 | Astrazeneca Ab | New compounds |
| US7723339B2 (en) * | 2001-02-27 | 2010-05-25 | Novartis Ag | Combination comprising a signal transduction inhibitor and an epothilone derivative |
| DE60212836T2 (de) * | 2001-05-16 | 2007-01-25 | Gpc Biotech Ag | Pyridylpyrimidin-derivate als wirksame verbindungen gegen prionen-krankheiten |
| PL392652A1 (pl) | 2001-05-16 | 2010-12-06 | Novartis Ag | Kombinacja zawierająca N-{5-[4-(4-metylo-piperazyno-metylo)-benzoiloamido]-2-metylofenylo}-4-(3-pirydylo)-2-pirymidyno-aminę oraz środek chemoterapeutyczny, jej zastosowanie, kompozycja farmaceutyczna ją zawierająca oraz zestaw zawierający taką kombinację |
| US7521175B2 (en) | 2001-06-14 | 2009-04-21 | The Regents Of The University Of California | Mutations in the Bcr-Abl tyrosine kinase associated with resistance to STI-571 |
| EP1408978A4 (en) | 2001-06-21 | 2005-07-13 | Ariad Pharma Inc | NOVEL PHENYLAMINO-PYRIMIDINES AND THEIR USE |
| ES2255621T3 (es) | 2001-06-22 | 2006-07-01 | MERCK & CO., INC. | Inhibidores de tirosina quinasa. |
| EP1401412A2 (en) * | 2001-06-29 | 2004-03-31 | AB Science | Use of potent, selective and non toxic c-kit inhibitors for treating tumor angiogenesis |
| ATE330608T1 (de) | 2001-06-29 | 2006-07-15 | Ab Science | Die verwendung von n-phenyl-2-pyrimidine-amine derivaten zur behandlung von entzündlichen erkrankungen |
| CA2452368A1 (en) | 2001-06-29 | 2003-01-09 | Ab Science | New potent, selective and non toxic c-kit inhibitors |
| ATE343415T1 (de) | 2001-06-29 | 2006-11-15 | Ab Science | Die verwendung von c-kit hemmer zur behandlung von entzündlichen darmerkrankungen |
| EP1401413B1 (en) | 2001-06-29 | 2006-11-22 | AB Science | Use of tyrosine kinase inhibitions 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 |
| EP2343367A1 (en) | 2001-10-05 | 2011-07-13 | Novartis AG | Mutated Abl kinase domains |
| GB0201508D0 (en) | 2002-01-23 | 2002-03-13 | Novartis Ag | Organic compounds |
| GB0202873D0 (en) * | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| AU2007203462B2 (en) * | 2002-02-07 | 2011-01-06 | Novartis Pharma Ag | N-phenyl-2-pyrimidine-amine derivatives |
| GB0202874D0 (en) * | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| ATE326970T1 (de) * | 2002-02-22 | 2006-06-15 | Us Gov Veterans Affairs | Verwendung von 4-(4-methylpiperazin-1-ylmethyl)-n 4-methyl-3-(4-pyridin-3-yl) pyrimidin-2-ylamino) phenyl benzamid zur behandlung von seminomen |
| US20050203098A1 (en) * | 2002-02-27 | 2005-09-15 | Alain Moussy | Use of tyrosine kinase inhibitors for treating substance use disorders |
| ATE334693T1 (de) * | 2002-02-27 | 2006-08-15 | Ab Science | Verwendung von tyrosine-kinase inhibitoren zur behandlung von cns krankheiten |
| KR20040093058A (ko) * | 2002-02-28 | 2004-11-04 | 노파르티스 아게 | Ｎ-(5-(4-(4-메틸-피페라지노-메틸)-벤조일아미도-2-메틸페닐)-4-(3-피리딜)-2-피리미딘-아민 코팅된 스텐트 |
| GB0206215D0 (en) | 2002-03-15 | 2002-05-01 | Novartis Ag | Organic compounds |
| GB0209265D0 (en) * | 2002-04-23 | 2002-06-05 | Novartis Ag | Organic compounds |
| WO2003095448A1 (en) * | 2002-05-06 | 2003-11-20 | Bayer Pharmaceuticals Corporation | Pyridinyl amino pyrimidine derivatives useful for treating hyper-proliferative disorders |
| CN1652757B (zh) | 2002-05-16 | 2012-02-08 | 诺瓦提斯公司 | Edg受体结合剂在癌症中的应用 |
| WO2004000318A2 (en) | 2002-06-21 | 2003-12-31 | Cellular Genomics, Inc. | Certain amino-substituted monocycles as kinase modulators |
| WO2004026930A2 (en) * | 2002-06-26 | 2004-04-01 | The Ohio State University Research Foundation | The method for reducing inflammation using sti-571 or its salt |
| ATE447560T1 (de) * | 2002-06-28 | 2009-11-15 | Nippon Shinyaku Co Ltd | Amidderivat |
| 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 |
| PT1525200E (pt) * | 2002-08-02 | 2008-01-10 | Ab Science | 2-(3-aminoaril)amino-4-aril-tiazóis para o tratamento de doenças |
| GB0222514D0 (en) | 2002-09-27 | 2002-11-06 | Novartis Ag | Organic compounds |
| JP2006504721A (ja) * | 2002-10-11 | 2006-02-09 | ノバルティス アクチエンゲゼルシャフト | 治療剤に対する乳癌耐性タンパク質（ｂｃｒｐ）−介在耐性を阻害するためのイマチニブ（グリベック、ｓｔｉ−５７１）の使用 |
| 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 |
| NZ542494A (en) * | 2003-04-04 | 2009-03-31 | Nobil Bio Ricerche Srl | Vascular stent |
| AU2003232650A1 (en) * | 2003-05-06 | 2004-11-26 | 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 |
| PE20050158A1 (es) | 2003-05-19 | 2005-05-12 | Irm Llc | Compuestos inmunosupresores y composiciones |
| DE602004022540D1 (de) * | 2003-05-27 | 2009-09-24 | Robert P Haegerkvist | Verwendung von tyrosin-kinase-hemmern zur behandlung von diabetes |
| MXPA05013349A (es) * | 2003-06-13 | 2006-03-09 | Novartis Ag | Derivados de 2-amino-pirimidina como inhibidores de quinasa raf. |
| NZ546088A (en) | 2003-08-27 | 2009-10-30 | Ophthotech Corp | Combination therapy for the treatment of ocular neovascular disorders using a PDGF antagonist and a VEGF antagonist |
| KR101153647B1 (ko) | 2003-11-18 | 2012-06-18 | 노파르티스 아게 | Ｋｉｔ 돌연변이형에 대한 저해제 |
| CA2551529C (en) * | 2003-12-25 | 2011-02-01 | Nippon Shinyaku Co., Ltd. | Amide derivative and medicine |
| AU2005209231B8 (en) * | 2004-01-21 | 2011-07-28 | Emory University | Compositions and methods of use for 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 |
| DK1720853T3 (en) | 2004-02-11 | 2016-03-29 | Natco Pharma Ltd | HIS UNKNOWN POLYMORPH FORM OF IMATINIBMYLYLATE AND PROCEDURE FOR PREPARING IT |
| CN1309719C (zh) * | 2004-02-18 | 2007-04-11 | 陈国庆 | 苯氨基嘧啶衍生物及其用途 |
| KR20080083220A (ko) | 2004-04-07 | 2008-09-16 | 노파르티스 아게 | Ｉａｐ 억제제 |
| GB0512324D0 (en) | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| CA2578122A1 (en) * | 2004-08-27 | 2006-03-02 | Gpc Biotech Ag | Pyrimidine derivatives |
| US8269003B2 (en) | 2004-09-02 | 2012-09-18 | Cipla Limited | Stable crystal form of imatinib mesylate and process for the preparation thereof |
| 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 |
| 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 |
| MX2007002819A (es) | 2004-09-09 | 2007-08-14 | Natco Pharma Ltd | Nuevos derivados de fenilaminopirimidina como inhibidores de bcl-abl cinasa. |
| 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 |
| CN1939910A (zh) * | 2004-12-31 | 2007-04-04 | 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 |
| 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 |
| WO2006077424A1 (en) | 2005-01-21 | 2006-07-27 | Astex Therapeutics Limited | Pharmaceutical compounds |
| RU2445960C2 (ru) | 2005-05-02 | 2012-03-27 | Новартис Аг | Применение производных пиримидиламинобензамида для лечения системного мастоцитоза |
| 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) |
| NO20220050A1 (no) | 2005-11-21 | 2008-08-12 | Novartis Ag | Neuroendokrin tumorbehandling |
| BRPI0618993A2 (pt) | 2005-11-25 | 2011-09-20 | Novartis Ag | formas de cristais f, g, h, i e k de mesilato de imatinib |
| GB0605120D0 (en) | 2006-03-14 | 2006-04-26 | Novartis Ag | Organic Compounds |
| KR20080109068A (ko) | 2006-04-05 | 2008-12-16 | 노파르티스 아게 | 암을 치료하기 위한 ｂｃｒ-ａｂｌ/ｃ-ｋｉｔ/ｐｄｇｆ-ｒ ｔｋ 억제제를 포함하는 조합물 |
| EP2591775A1 (en) | 2006-04-05 | 2013-05-15 | Novartis AG | Combinations comprising mtor inhibitors for treating cancer |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| BRPI0711385A2 (pt) | 2006-05-09 | 2011-11-08 | Novartis Ag | combinação compreendendo um quelante de ferro e um agente anti-neoplástico e seu uso |
| 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 |
| ATE502943T1 (de) | 2006-09-29 | 2011-04-15 | Novartis Ag | Pyrazolopyrimidine als pi3k-lipidkinasehemmer |
| US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
| WO2008044045A1 (en) | 2006-10-12 | 2008-04-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
| KR20090061068A (ko) * | 2006-10-26 | 2009-06-15 | 시코르, 인크. | 이매티닙의 제조 방법 |
| JP5265562B2 (ja) * | 2006-11-16 | 2013-08-14 | エッフェ．イー．エッセ． ファブリカ イタリアーナ シンテーティチ エッセ．ペー．アー． | イマチニブおよびその中間体の調製方法 |
| 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 |
| BRPI0807812A2 (pt) | 2007-02-15 | 2020-06-23 | Novartis Ag | Combinações de lbh589 com outros agentes terapêuticos para tratar câncer |
| RU2329260C1 (ru) * | 2007-02-20 | 2008-07-20 | Юрий Иосифович Копырин | Способ получения 2-анилинопиримидинов или их солей (варианты) |
| CA2680249A1 (en) * | 2007-03-12 | 2008-09-18 | Dr. Reddy's Laboratories, Inc. | Imatinib mesylate |
| 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 |
| ES2607794T3 (es) | 2007-06-07 | 2017-04-04 | Intra-Cellular Therapies, Inc. | Compuestos heterocíclicos novedosos y usos de los mismos |
| 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 |
| EP2200436B1 (en) * | 2007-09-04 | 2015-01-21 | 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 |
| RU2493152C2 (ru) * | 2008-02-01 | 2013-09-20 | Акинион Фармасьютикалз Аб | Новые соединения, применение и получение их |
| ES2524259T3 (es) | 2008-03-24 | 2014-12-04 | Novartis Ag | Inhibidores de metaloproteinasa de matriz a base de arilsulfonamida |
| ES2519474T3 (es) | 2008-03-26 | 2014-11-07 | Novartis Ag | Inhibidores de las desacetilasas B basados en hidroxamato |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| HUE035029T2 (en) | 2008-05-21 | 2018-03-28 | Ariad Pharma Inc | Kinase inhibitor phosphorus derivatives |
| 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 |
| 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" |
| BRPI0917675A2 (pt) | 2008-08-15 | 2015-12-01 | Boehringer Ingelheim Int | compostos orgânicos para cura de ferida |
| SI2350129T1 (sl) | 2008-08-25 | 2015-11-30 | Amplimmune, Inc. | Sestavki PD-1 antagonistov in postopek njihove uporabe |
| EP2344161B1 (en) | 2008-10-16 | 2018-12-19 | Celator Pharmaceuticals, Inc. | Combinations of a liposomal water-soluble camptothecin with cetuximab or bevacizumab |
| EP2186514B1 (en) | 2008-11-14 | 2016-06-29 | Kinki University | Treatment of Malignant Peripheral Nerve Sheath Tumors |
| US8486930B2 (en) | 2008-12-18 | 2013-07-16 | Novartis Ag | Salts |
| MX2011006609A (es) | 2008-12-18 | 2011-06-30 | Novartis Ag | Sal de hemi-fumarato del acido 1-[4-[1-(4-ciclohexil-3-trifluoro-m etil-benciloxi-imino)-etil]-2-etil-bencil]-azetidin-3-carboxilico . |
| ES2531831T3 (es) | 2008-12-18 | 2015-03-20 | Novartis Ag | Forma polimórfica del ácido 1-(4-{1-[(E)-4-ciclohexil-3-trifluorometil-benciloxiimino]-etil}-2-etil-bencil)-azetidin-3-carboxilico |
| US8865729B2 (en) | 2008-12-23 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Salt forms of a xanthine compound |
| TW201036975A (en) | 2009-01-07 | 2010-10-16 | Boehringer Ingelheim Int | Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy |
| WO2010083617A1 (en) | 2009-01-21 | 2010-07-29 | Oncalis Ag | Pyrazolopyrimidines as protein kinase inhibitors |
| 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 |
| SI2391366T1 (sl) | 2009-01-29 | 2013-01-31 | Novartis Ag | Substituirani benzimidazoli za zdravljenje astrocitomov |
| CN106177958A (zh) | 2009-02-13 | 2016-12-07 | 勃林格殷格翰国际有限公司 | 包含dpp‑4抑制剂(利拉列汀)任选地组合其它抗糖尿病药的抗糖尿病药物 |
| US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| 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 |
| 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 |
| 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 |
| JO2892B1 (en) | 2009-06-26 | 2015-09-15 | نوفارتيس ايه جي | CYP inhibitors 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 |
| CA2770873A1 (en) | 2009-08-12 | 2011-02-17 | Novartis Ag | Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation |
| SG178454A1 (en) | 2009-08-17 | 2012-03-29 | Intellikine Inc | Heterocyclic compounds and uses thereof |
| IN2012DN01453A (lt) | 2009-08-20 | 2015-06-05 | Novartis Ag | |
| BR112012008075A2 (pt) | 2009-08-26 | 2016-03-01 | Novartis Ag | compostos de heteroarila tetrassubstituídos e seu uso como moduladores de mdm2 e/ou mdm4 |
| JP2013504543A (ja) | 2009-09-10 | 2013-02-07 | ノバルティス アーゲー | 二環ヘテロアリール類のエーテル誘導体 |
| EP4209210A1 (en) | 2009-10-02 | 2023-07-12 | Boehringer Ingelheim International GmbH | Pharmaceutical compositions comprising bi-1356 and metformin |
| CN102686579A (zh) | 2009-10-09 | 2012-09-19 | Irm责任有限公司 | 作为gpr119活性调节剂的化合物和组合物 |
| PL389357A1 (pl) | 2009-10-22 | 2011-04-26 | Tomasz Koźluk | Sole imatinibu z pochodnymi kwasów winowych i sposób ich wytwarzania |
| PE20121471A1 (es) | 2009-11-04 | 2012-11-01 | Novartis Ag | Derivados de sulfonamida heterociclicos utiles como inhibidores de mek |
| EA201200617A1 (ru) | 2009-11-23 | 2012-11-30 | Серулин Фарма Инк. | Полимеры на основе циклодекстрина для доставки лекарственных средств |
| 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 |
| AU2010323068B2 (en) | 2009-11-27 | 2015-09-03 | Boehringer Ingelheim International Gmbh | Treatment of genotyped diabetic patients with DPP-IV inhibitors such as linagliptin |
| US8394858B2 (en) | 2009-12-03 | 2013-03-12 | Novartis Ag | Cyclohexane derivatives and uses thereof |
| WO2011070030A1 (en) | 2009-12-08 | 2011-06-16 | Novartis Ag | Heterocyclic sulfonamide derivatives |
| EP2509973A1 (en) | 2009-12-10 | 2012-10-17 | Arch Pharmalabs Limited | Process for the preparation of imatinib and salts thereof |
| CU24130B1 (es) | 2009-12-22 | 2015-09-29 | Novartis Ag | Isoquinolinonas y quinazolinonas sustituidas |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| WO2011090940A1 (en) | 2010-01-19 | 2011-07-28 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
| CA2789989A1 (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 |
| KR20130055576A (ko) | 2010-03-15 | 2013-05-28 | 낫코 파마 리미티드 | 고순도의 결정질 이마티닙 염기를 제조하는 방법 |
| WO2011113947A1 (en) | 2010-03-18 | 2011-09-22 | 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 |
| US20110237686A1 (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 |
| WO2011138421A1 (en) | 2010-05-05 | 2011-11-10 | Boehringer Ingelheim International Gmbh | Combination therapy |
| 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 |
| 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 |
| EP2582689B1 (en) | 2010-06-18 | 2017-03-01 | KRKA, D.D., Novo Mesto | New polymorphic form of imatinib base and preparation of salts thereof |
| 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 |
| KR20190050871A (ko) | 2010-06-24 | 2019-05-13 | 베링거 인겔하임 인터내셔날 게엠베하 | 당뇨병 요법 |
| UA112517C2 (uk) | 2010-07-06 | 2016-09-26 | Новартіс Аг | Тетрагідропіридопіримідинові похідні |
| CN103097418A (zh) | 2010-07-09 | 2013-05-08 | 霍夫曼-拉罗奇有限公司 | 抗神经毡蛋白抗体及使用方法 |
| US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
| RU2013110058A (ru) | 2010-08-11 | 2014-09-20 | Синтон Б.В. | Фармацевтический гранулят, содержащий иматиниба мезилат |
| TR201007005A2 (tr) | 2010-08-23 | 2011-09-21 | Mustafa Nevzat İlaç Sanayi̇i̇ A.Ş. | İmatinib baz üretim yöntemi |
| WO2012035078A1 (en) | 2010-09-16 | 2012-03-22 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
| AR083878A1 (es) | 2010-11-15 | 2013-03-27 | Boehringer Ingelheim Int | Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento |
| TR201010618A2 (tr) | 2010-12-20 | 2012-07-23 | Bi̇lgi̇ç Mahmut | İmatinib içeren bir oral dozaj formu ve bu oral dozaj formunun üretimi |
| WO2012085815A1 (en) | 2010-12-21 | 2012-06-28 | 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 |
| US9295673B2 (en) | 2011-02-23 | 2016-03-29 | Intellikine Llc | Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof |
| JP5808826B2 (ja) | 2011-02-23 | 2015-11-10 | インテリカイン， エルエルシー | 複素環化合物およびその使用 |
| 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 |
| JP2014507465A (ja) | 2011-03-08 | 2014-03-27 | ノバルティス アーゲー | フルオロフェニル二環式ヘテロアリール化合物 |
| 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 |
| US9896730B2 (en) | 2011-04-25 | 2018-02-20 | OSI Pharmaceuticals, LLC | Use of EMT gene signatures in cancer drug discovery, diagnostics, and treatment |
| WO2012149413A1 (en) | 2011-04-28 | 2012-11-01 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
| JP5999177B2 (ja) | 2011-05-04 | 2016-09-28 | アリアド・ファーマシューティカルズ・インコーポレイテッド | Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物 |
| 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 |
| EP2718276A1 (en) | 2011-06-09 | 2014-04-16 | Novartis AG | Heterocyclic sulfonamide derivatives |
| US8859586B2 (en) | 2011-06-20 | 2014-10-14 | Novartis Ag | Cyclohexyl isoquinolinone compounds |
| EP2721008B1 (en) | 2011-06-20 | 2015-04-29 | Novartis AG | Hydroxy substituted isoquinolinone derivatives as p53 (mdm2 or mdm4) inhibitors |
| US9750700B2 (en) | 2011-06-22 | 2017-09-05 | Natco Pharma Limited | Imatinib mesylate oral pharmaceutical composition and process for preparation thereof |
| SG195067A1 (en) | 2011-06-27 | 2013-12-30 | Novartis Ag | Solid forms and salts of tetrahydro-pyrido-pyrimidine derivatives |
| ITMI20111309A1 (it) | 2011-07-14 | 2013-01-15 | Italiana Sint Spa | Procedimento di preparazione di imatinib mesilato |
| KR101985384B1 (ko) | 2011-07-15 | 2019-06-03 | 베링거 인겔하임 인터내셔날 게엠베하 | 치환된 퀴나졸린, 이의 제조 및 약제학적 조성물에서의 이의 용도 |
| WO2013035102A1 (en) | 2011-09-05 | 2013-03-14 | Natco Pharma Limited | Processes for the preparation of imatinib base and intermediates thereof |
| CA2848809A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6-substituted 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyradines as c-met tyrosine kinase |
| AU2012332416B2 (en) | 2011-11-01 | 2017-06-15 | 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 |
| WO2013080141A1 (en) | 2011-11-29 | 2013-06-06 | 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 |
| IN2014CN04174A (lt) | 2011-12-22 | 2015-09-04 | Novartis Ag | |
| US20150148377A1 (en) | 2011-12-22 | 2015-05-28 | Novartis Ag | Quinoline Derivatives |
| MX2014007725A (es) | 2011-12-23 | 2015-01-12 | Novartis Ag | Compuestos para inhibir la interaccion de bcl2 con los componentes de enlace. |
| BR112014015308A8 (pt) | 2011-12-23 | 2017-06-13 | Novartis Ag | compostos para inibição da interação de bcl2 com contrapartes de ligação |
| KR20140107573A (ko) | 2011-12-23 | 2014-09-04 | 노파르티스 아게 | Bcl2와 결합 파트너의 상호작용을 억제하기 위한 화합물 |
| BR112014015322A8 (pt) | 2011-12-23 | 2017-06-13 | Novartis Ag | compostos e composições para inibir a interação de bcl2 com parceiros de ligação |
| US20140357633A1 (en) | 2011-12-23 | 2014-12-04 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
| US20130178520A1 (en) | 2011-12-23 | 2013-07-11 | Duke University | Methods of treatment using arylcyclopropylamine compounds |
| 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 |
| UY34591A (es) | 2012-01-26 | 2013-09-02 | Novartis Ag | Compuestos de imidazopirrolidinona |
| 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 |
| WO2013136141A1 (en) | 2012-03-13 | 2013-09-19 | Fresenius Kabi Oncology Ltd. | An improved process for the preparation of alpha form of imatinib mesylate |
| EP3964513A1 (en) | 2012-04-03 | 2022-03-09 | Novartis AG | Combination products with tyrosine kinase inhibitors and their use |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| BR112014026266A2 (pt) | 2012-04-24 | 2017-06-27 | Chugai Pharmaceutical Co Ltd | derivado de quinazolidinadiona |
| SG11201406860SA (en) | 2012-04-24 | 2014-11-27 | Chugai Pharmaceutical Co Ltd | Quinazolinedione derivative |
| AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| WO2013171166A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis |
| EP2849755A1 (en) | 2012-05-14 | 2015-03-25 | Boehringer Ingelheim International GmbH | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
| JP6374862B2 (ja) | 2012-05-24 | 2018-08-15 | 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 | 自己免疫性糖尿病、特に、ｌａｄａの治療に使用するためのｄｐｐ−４阻害剤としてのキサンチン誘導体 |
| 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 |
| JP6171003B2 (ja) | 2012-05-24 | 2017-07-26 | ノバルティス アーゲー | ピロロピロリジノン化合物 |
| CN104582732A (zh) | 2012-06-15 | 2015-04-29 | 布里格姆及妇女医院股份有限公司 | 治疗癌症的组合物及其制造方法 |
| 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 |
| WO2014025395A1 (en) | 2012-08-06 | 2014-02-13 | 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 |
| CN103664787B (zh) | 2012-09-17 | 2015-09-09 | 南京圣和药业股份有限公司 | 炔杂芳环化合物及其应用 |
| WO2014052619A1 (en) | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
| JP2015531355A (ja) | 2012-09-28 | 2015-11-02 | ハンジョウ ベンシェン ファーマシューティカル シーオー．， エルティーディー．Ｈａｎｇｚｈｏｕ Ｂｅｎｓｈｅｎｇ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｃｏ．， Ｌｔｄ． | 腫瘍治療のための薬剤組成物及びその適用 |
| US9487500B2 (en) * | 2012-10-04 | 2016-11-08 | Inhibikase Therapeutics, Inc. | Compounds and compositions thereof |
| US9950047B2 (en) | 2012-11-05 | 2018-04-24 | Dana-Farber Cancer Institute, Inc. | XBP1, CD138, and CS1 peptides, pharmaceutical compositions that include the peptides, and methods of using such peptides 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 |
| EP2948451B1 (en) | 2013-01-22 | 2017-07-12 | Novartis AG | Substituted purinone compounds |
| EP2948453B1 (en) | 2013-01-22 | 2017-08-02 | Novartis AG | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the p53/mdm2 interaction |
| WO2014124860A1 (en) | 2013-02-14 | 2014-08-21 | Boehringer Ingelheim International Gmbh | Specific pde4b-inhibitors for the treatment of diabetes mellitus |
| RU2708032C2 (ru) | 2013-02-20 | 2019-12-03 | Новартис Аг | ЛЕЧЕНИЕ РАКА С ИСПОЛЬЗОВАНИЕМ ХИМЕРНОГО АНТИГЕНСПЕЦИФИЧЕСКОГО РЕЦЕПТОРА НА ОСНОВЕ ГУМАНИЗИРОВАННОГО АНТИТЕЛА ПРОТИВ EGFRvIII |
| WO2014128612A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Quinazolin-4-one derivatives |
| WO2014151147A1 (en) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
| EP3744327A1 (en) | 2013-03-15 | 2020-12-02 | Boehringer Ingelheim International GmbH | Use of linagliptin in cardio- and renoprotective antidiabetic therapy |
| 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 |
| WO2015022663A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
| 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 |
| KR20160060100A (ko) | 2013-09-22 | 2016-05-27 | 칼리토르 사이언시즈, 엘엘씨 | 치환된 아미노피리미딘 화합물 및 이용 방법 |
| JP6445573B2 (ja) | 2013-10-17 | 2018-12-26 | サルタル セラピューティクス エルティーディＳａｒｔａｒ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｔｄ | ヒト患者の固形腫瘍の治療に用いるためのホスホジエステラーゼ阻害剤含有組成物 |
| 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 |
| WO2015148714A1 (en) | 2014-03-25 | 2015-10-01 | 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 |
| US9399637B2 (en) | 2014-03-28 | 2016-07-26 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
| CA2944401A1 (en) | 2014-04-03 | 2015-10-08 | Invictus Oncology Pvt. Ltd. | Supramolecular combinatorial therapeutics |
| 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 |
| AU2015294889B2 (en) | 2014-07-31 | 2018-03-15 | 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 |
| JP2018527362A (ja) | 2015-09-11 | 2018-09-20 | サンシャイン・レイク・ファーマ・カンパニー・リミテッドＳｕｎｓｈｉｎｅ Ｌａｋｅ Ｐｈａｒｍａ Ｃｏ．，Ｌｔｄ． | 置換されたヘテロアリール化合物および使用方法 |
| EA035891B1 (ru) | 2016-01-25 | 2020-08-27 | КРКА, д.д., НОВО МЕСТО | Быстродиспергируемая фармацевтическая композиция, включающая ингибитор тирозинкиназы |
| ES2899929T3 (es) | 2016-03-25 | 2022-03-15 | Ab Science | Uso de masitinib para el tratamiento de una subpoblación de pacientes con esclerosis lateral amiotrófica |
| US11261187B2 (en) | 2016-04-22 | 2022-03-01 | Duke University | Compounds and methods for targeting HSP90 |
| US10155000B2 (en) | 2016-06-10 | 2018-12-18 | Boehringer Ingelheim International Gmbh | Medical use of pharmaceutical combination or composition |
| 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 |
| WO2018039203A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating multiple myeloma |
| CA3034666A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating breast cancer |
| 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 |
| JP2019536471A (ja) | 2016-09-27 | 2019-12-19 | セロ・セラピューティクス・インコーポレイテッドＣＥＲＯ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | キメラエンガルフメント受容体分子 |
| 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 |
| US10927083B2 (en) | 2016-09-29 | 2021-02-23 | Duke University | Substituted benzimidazoles as inhibitors of transforming growth factor-β kinase |
| 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 |
| AU2018341244A1 (en) | 2017-09-26 | 2020-03-05 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules and methods of use |
| AU2018353984A1 (en) | 2017-10-24 | 2020-05-07 | Oncopep, Inc. | Peptide vaccines and pembrolizumab for treating breast cancer |
| WO2019083960A1 (en) | 2017-10-24 | 2019-05-02 | Oncopep, Inc. | PEPTIDE VACCINES AND HDAC INHIBITORS FOR THE TREATMENT OF MULTIPLE MYELOMA |
| US10683297B2 (en) | 2017-11-19 | 2020-06-16 | Calitor Sciences, Llc | Substituted heteroaryl compounds and methods of use |
| JP7021356B2 (ja) | 2017-12-21 | 2022-02-16 | ヘフェイ インスティテューツ オブ フィジカル サイエンス， チャイニーズ アカデミー オブ サイエンシーズ | ピリミジン誘導体系キナーゼ阻害剤類 |
| US10751339B2 (en) | 2018-01-20 | 2020-08-25 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
| CN112218887A (zh) | 2018-03-28 | 2021-01-12 | 森罗治疗公司 | 细胞免疫疗法组合物及其用途 |
| EP3774906A1 (en) | 2018-03-28 | 2021-02-17 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
| CN112218886A (zh) | 2018-03-28 | 2021-01-12 | 森罗治疗公司 | 嵌合吞噬受体的表达载体、基因修饰的宿主细胞及其用途 |
| BR112020026164A2 (pt) | 2018-07-17 | 2021-03-23 | Boehringer Ingelheim International Gmbh | terapia antidiabética cardioprotetora e nefroprotetora |
| KR20210032468A (ko) | 2018-07-17 | 2021-03-24 | 베링거 인겔하임 인터내셔날 게엠베하 | 심장에 안전한 항당뇨병 요법 |
| EP3826988A4 (en) | 2018-07-24 | 2023-03-22 | Hygia Pharmaceuticals, LLC | COMPOUNDS, DERIVATIVES AND ANALOGS AGAINST CANCER |
| WO2021009686A1 (en) | 2019-07-15 | 2021-01-21 | Intas Pharmaceuticals Ltd. | Pharmaceutical composition of imatinib |
| WO2021067875A1 (en) | 2019-10-03 | 2021-04-08 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
| WO2021097256A1 (en) | 2019-11-14 | 2021-05-20 | Cohbar, Inc. | Cxcr4 antagonist peptides |
| 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 |
| 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 |
| 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 |
| WO2022029220A1 (en) | 2020-08-05 | 2022-02-10 | Ellipses Pharma Ltd | Treatment of cancer using a cyclodextrin-containing polymer-topoisomerase inhibitor conjugate and a parp inhibitor |
| 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 |
| WO2022036265A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Chimeric tim receptors and uses thereof |
| 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 |
| EP4376874A1 (en) | 2021-07-28 | 2024-06-05 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
| WO2024030441A1 (en) | 2022-08-02 | 2024-02-08 | National University Corporation Hokkaido University | Methods of improving cellular therapy with organelle complexes |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3751742T3 (de) * | 1986-01-13 | 2002-11-21 | American Cyanamid Co., Wayne | 4,5,6-Substituierte 2-Pyrimidinamine |
-
1993
- 1993-03-24 TW TW082102196A patent/TW225528B/zh not_active IP Right Cessation
- 1993-03-25 DE DE59309931T patent/DE59309931D1/de not_active Expired - Lifetime
- 1993-03-25 DE DE2002199016 patent/DE10299016I2/de active 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 EP EP93810219A patent/EP0564409B1/de not_active Expired - Lifetime
- 1993-03-25 DK DK93810219T patent/DK0564409T3/da not_active Application Discontinuation
- 1993-03-25 AT AT93810219T patent/ATE188964T1/de active
- 1993-03-25 SG SG1996003161A patent/SG43859A1/en unknown
- 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 CA CA002093203A patent/CA2093203C/en not_active Expired - Lifetime
- 1993-04-01 RU RU93005357A patent/RU2125992C1/ru active
- 1993-04-01 SK SK280-93A patent/SK280620B6/sk not_active IP Right Cessation
- 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
- 1993-04-02 HU HU9300982A patent/HU226488B1/hu unknown
- 1993-04-02 AU AU35694/93A patent/AU666709B2/en not_active Expired
- 1993-04-02 ZA ZA932397A patent/ZA932397B/xx unknown
- 1993-04-02 NO NO931283A patent/NO302473B1/no not_active IP Right Cessation
- 1993-04-02 HU HU9300982D patent/HU227080B1/hu active Protection Beyond IP Right Term
- 1993-04-02 CN CN93103566A patent/CN1043531C/zh not_active Expired - Lifetime
- 1993-04-02 MX MX9301929A patent/MX9301929A/es active IP Right Grant
- 1993-04-03 KR KR1019930005628A patent/KR100261366B1/ko not_active IP Right Cessation
- 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
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2093203C (en) | Pyrimidine derivatives and processes for the preparation thereof | |
| US5521184A (en) | Pyrimidine derivatives and processes for the preparation thereof | |
| EP0672042B1 (en) | Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof | |
| KR100330553B1 (ko) | 약물학적활성피리딘유도체및그의제조방법 | |
| AU693475B2 (en) | Pyrimidineamine derivatives and processes for the preparation thereof | |
| CA2149147C (en) | Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| PEL | Intention of commissioner to extend period of protection | ||
| EXTG | Extension of patent term granted | ||
| KB | Patent renewed | ||
| EXTG | Extension of patent term granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| EXTN | Extension order renewed | ||
| EXTN | Extension order renewed | ||
| EXTN | Extension order renewed |