NZ586642A - Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents - Google Patents
Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agentsInfo
- Publication number
- NZ586642A NZ586642A NZ586642A NZ58664209A NZ586642A NZ 586642 A NZ586642 A NZ 586642A NZ 586642 A NZ586642 A NZ 586642A NZ 58664209 A NZ58664209 A NZ 58664209A NZ 586642 A NZ586642 A NZ 586642A
- Authority
- NZ
- New Zealand
- Prior art keywords
- pyrazolo
- phenyl
- pyrimidine
- amine
- formula
- Prior art date
Links
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical class C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 title claims description 17
- 239000002246 antineoplastic agent Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 218
- -1 pyrimidine-4yl Chemical group 0.000 claims abstract description 124
- 238000000034 method Methods 0.000 claims abstract description 42
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 37
- 238000002360 preparation method Methods 0.000 claims abstract description 29
- 201000011510 cancer Diseases 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims abstract description 7
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims abstract description 7
- 201000002528 pancreatic cancer Diseases 0.000 claims abstract description 7
- 208000008443 pancreatic carcinoma Diseases 0.000 claims abstract description 7
- 206010005003 Bladder cancer Diseases 0.000 claims abstract description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims abstract description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims abstract description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims abstract description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims abstract description 4
- 206010017758 gastric cancer Diseases 0.000 claims abstract description 4
- 208000032839 leukemia Diseases 0.000 claims abstract description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 claims abstract description 4
- 201000011549 stomach cancer Diseases 0.000 claims abstract description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims abstract description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 3
- 201000005202 lung cancer Diseases 0.000 claims abstract description 3
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 3
- 208000017572 squamous cell neoplasm Diseases 0.000 claims abstract description 3
- 201000002510 thyroid cancer Diseases 0.000 claims abstract description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims abstract 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims abstract 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims abstract 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims abstract 2
- 206010025323 Lymphomas Diseases 0.000 claims abstract 2
- 206010060862 Prostate cancer Diseases 0.000 claims abstract 2
- 206010038389 Renal cancer Diseases 0.000 claims abstract 2
- 201000004101 esophageal cancer Diseases 0.000 claims abstract 2
- 201000010982 kidney cancer Diseases 0.000 claims abstract 2
- 208000026037 malignant tumor of neck Diseases 0.000 claims abstract 2
- SJBHYUWNPFYYNI-UHFFFAOYSA-N n-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-1-(3,5-dimethylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC(C)=CC(N2C3=NC=NC(NCC=4C=C5OCCOC5=CC=4)=C3C=N2)=C1 SJBHYUWNPFYYNI-UHFFFAOYSA-N 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 82
- 238000006243 chemical reaction Methods 0.000 claims description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 51
- 238000010992 reflux Methods 0.000 claims description 41
- 239000007787 solid Substances 0.000 claims description 32
- 230000008569 process Effects 0.000 claims description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 28
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 21
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000002585 base Substances 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 229910021529 ammonia Inorganic materials 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical group OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 11
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 11
- 239000011707 mineral Substances 0.000 claims description 11
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical group OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 10
- 150000001340 alkali metals Chemical class 0.000 claims description 10
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000003586 protic polar solvent Substances 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 239000000010 aprotic solvent Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 7
- 239000001117 sulphuric acid Substances 0.000 claims description 7
- 235000011149 sulphuric acid Nutrition 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 6
- 125000003368 amide group Chemical group 0.000 claims description 6
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- 235000010288 sodium nitrite Nutrition 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 claims description 6
- GSILHXSZYLRDCW-UHFFFAOYSA-N 1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidine Chemical compound CC1=CC=CC(N2C3=NC=NC=C3C=N2)=C1 GSILHXSZYLRDCW-UHFFFAOYSA-N 0.000 claims description 5
- PNAQLBVTHVBJOU-UHFFFAOYSA-N 3,5-dimethylpyrazolo[3,4-d]pyrimidine Chemical compound N1=CN(C)C=C2C(C)=NN=C21 PNAQLBVTHVBJOU-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 5
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 5
- STYVEAOALAEULT-UHFFFAOYSA-N 1-(3-iodophenyl)pyrazolo[3,4-d]pyrimidine Chemical class IC1=CC=CC(N2C3=NC=NC=C3C=N2)=C1 STYVEAOALAEULT-UHFFFAOYSA-N 0.000 claims description 4
- UBKSUPKIDNXMMC-UHFFFAOYSA-N 5-amino-1-phenylpyrazole-4-carboxamide Chemical compound NC1=C(C(=O)N)C=NN1C1=CC=CC=C1 UBKSUPKIDNXMMC-UHFFFAOYSA-N 0.000 claims description 4
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical group [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 239000001099 ammonium carbonate Chemical group 0.000 claims description 4
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- KFVUXNKQQOUCAH-UHFFFAOYSA-N butan-1-ol;propan-2-ol Chemical compound CC(C)O.CCCCO KFVUXNKQQOUCAH-UHFFFAOYSA-N 0.000 claims description 4
- 150000004649 carbonic acid derivatives Chemical group 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
- 150000004679 hydroxides Chemical group 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical class Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 claims description 4
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 claims description 4
- 150000004031 phenylhydrazines Chemical class 0.000 claims description 4
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 4
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 4
- 125000005296 thioaryloxy group Chemical group 0.000 claims description 4
- 125000005404 thioheteroaryloxy group Chemical group 0.000 claims description 4
- 125000005270 trialkylamine group Chemical group 0.000 claims description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 3
- MYAMRGRIEXIPDC-UHFFFAOYSA-N n-methyl-2,3-dihydro-1,4-benzodioxin-6-amine;hydrochloride Chemical compound Cl.O1CCOC2=CC(NC)=CC=C21 MYAMRGRIEXIPDC-UHFFFAOYSA-N 0.000 claims description 3
- 125000002560 nitrile group Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229940067157 phenylhydrazine Drugs 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- HPARLNRMYDSBNO-UHFFFAOYSA-N 1,4-benzodioxine Chemical compound C1=CC=C2OC=COC2=C1 HPARLNRMYDSBNO-UHFFFAOYSA-N 0.000 claims description 2
- GETXGBDZZACJPV-UHFFFAOYSA-N 1-(3-methylphenyl)-n-[(3,4,5-trimethoxyphenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound COC1=C(OC)C(OC)=CC(CNC=2C=3C=NN(C=3N=CN=2)C=2C=C(C)C=CC=2)=C1 GETXGBDZZACJPV-UHFFFAOYSA-N 0.000 claims description 2
- VLVZKHQSYVUBEA-UHFFFAOYSA-N 1-(3-methylphenyl)-n-[[4-(3-morpholin-4-ylpropoxy)phenyl]methyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(N2C3=NC=NC(NCC=4C=CC(OCCCN5CCOCC5)=CC=4)=C3C=N2)=C1 VLVZKHQSYVUBEA-UHFFFAOYSA-N 0.000 claims description 2
- DTTHGYPBDBANKG-UHFFFAOYSA-N 2-[[1-(3-cyanophenyl)pyrazolo[3,4-d]pyrimidin-4-yl]amino]acetic acid Chemical compound N1=CC=2C(NCC(=O)O)=NC=NC=2N1C1=CC=CC(C#N)=C1 DTTHGYPBDBANKG-UHFFFAOYSA-N 0.000 claims description 2
- KDMNJOUCLAIXDH-UHFFFAOYSA-N 2-[[1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]amino]acetic acid Chemical compound CC1=CC=CC(N2C3=NC=NC(NCC(O)=O)=C3C=N2)=C1 KDMNJOUCLAIXDH-UHFFFAOYSA-N 0.000 claims description 2
- PNSVHQUIJWZNRG-UHFFFAOYSA-N 3-[4-[(3,4,5-trimethoxyphenyl)methylamino]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile Chemical compound COC1=C(OC)C(OC)=CC(CNC=2C=3C=NN(C=3N=CN=2)C=2C=C(C=CC=2)C#N)=C1 PNSVHQUIJWZNRG-UHFFFAOYSA-N 0.000 claims description 2
- NLEPMVNTYFGIJQ-UHFFFAOYSA-N 3-[4-[(3,4-diethoxyphenyl)methylamino]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile Chemical compound C1=C(OCC)C(OCC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC=CC(C#N)=C1 NLEPMVNTYFGIJQ-UHFFFAOYSA-N 0.000 claims description 2
- WJHAGGMBBWXXCU-UHFFFAOYSA-N 3-pyrazolo[3,4-d]pyrimidin-1-ylbenzonitrile Chemical class N#CC1=CC=CC(N2C3=NC=NC=C3C=N2)=C1 WJHAGGMBBWXXCU-UHFFFAOYSA-N 0.000 claims description 2
- YMXQUFUYCADCFL-UHFFFAOYSA-N 4-chloro-1h-pyrazolo[3,4-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=NN2 YMXQUFUYCADCFL-UHFFFAOYSA-N 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- PARWGYPSBMSXSC-UHFFFAOYSA-N [4-(2-methoxyethoxy)phenyl]methanamine Chemical compound COCCOC1=CC=C(CN)C=C1 PARWGYPSBMSXSC-UHFFFAOYSA-N 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000002609 medium Substances 0.000 claims description 2
- KSESLOVJGZDCDV-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC=CC(C)=C1 KSESLOVJGZDCDV-UHFFFAOYSA-N 0.000 claims description 2
- UXLQRQRZMYFOJQ-UHFFFAOYSA-N n-[2-(2-methoxyethoxy)ethyl]-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=2C(NCCOCCOC)=NC=NC=2N1C1=CC=CC(C)=C1 UXLQRQRZMYFOJQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- MAKQREKUUHPPIS-UHFFFAOYSA-N 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C=NN1C1=CC=CC=C1 MAKQREKUUHPPIS-UHFFFAOYSA-N 0.000 claims 4
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 claims 2
- 229940127271 compound 49 Drugs 0.000 claims 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 2
- 230000003472 neutralizing effect Effects 0.000 claims 2
- MBQGTSVBBOSEBW-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC1=CC(C)=CC(N2C3=NC=NC(N)=C3C=N2)=C1 MBQGTSVBBOSEBW-UHFFFAOYSA-N 0.000 claims 1
- BPQDBXIAZHFVOV-UHFFFAOYSA-N 3-[4-[[4-(2-methoxyethoxy)phenyl]methylamino]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile Chemical compound C1=CC(OCCOC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC=CC(C#N)=C1 BPQDBXIAZHFVOV-UHFFFAOYSA-N 0.000 claims 1
- DWRMZQCPYGFIGS-UHFFFAOYSA-N 3-[4-[[4-(3-morpholin-4-ylpropoxy)phenyl]methylamino]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile Chemical compound N#CC1=CC=CC(N2C3=NC=NC(NCC=4C=CC(OCCCN5CCOCC5)=CC=4)=C3C=N2)=C1 DWRMZQCPYGFIGS-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 238000007796 conventional method Methods 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 230000003463 hyperproliferative effect Effects 0.000 claims 1
- XYFNVSNOCNUOOR-UHFFFAOYSA-N n-[(3,4-dimethoxyphenyl)methyl]-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=C(OC)C(OC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC=CC(C)=C1 XYFNVSNOCNUOOR-UHFFFAOYSA-N 0.000 claims 1
- DVQNZXMUTFGQDI-UHFFFAOYSA-N n-[[3,4-bis(2-methoxyethoxy)phenyl]methyl]-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=C(OCCOC)C(OCCOC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC=CC(C)=C1 DVQNZXMUTFGQDI-UHFFFAOYSA-N 0.000 claims 1
- UYWJCYDXLYIFMY-UHFFFAOYSA-N n-[[4-(2-methoxyethoxy)phenyl]methyl]-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(OCCOC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC=CC(C)=C1 UYWJCYDXLYIFMY-UHFFFAOYSA-N 0.000 claims 1
- 150000002829 nitrogen Chemical group 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 6
- 206010006187 Breast cancer Diseases 0.000 abstract description 5
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 abstract 1
- 238000010189 synthetic method Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 21
- 239000000126 substance Substances 0.000 description 19
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 17
- 239000003112 inhibitor Substances 0.000 description 16
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 16
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 16
- 230000003595 spectral effect Effects 0.000 description 16
- 229940073584 methylene chloride Drugs 0.000 description 14
- 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 14
- 101800003838 Epidermal growth factor Proteins 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 229940116977 epidermal growth factor Drugs 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 10
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 10
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 10
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 10
- 229910000564 Raney nickel Inorganic materials 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 9
- 239000007868 Raney catalyst Substances 0.000 description 9
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 8
- 102000001301 EGF receptor Human genes 0.000 description 8
- 108060006698 EGF receptor Proteins 0.000 description 8
- 239000010779 crude oil Substances 0.000 description 8
- 229960001433 erlotinib Drugs 0.000 description 8
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 8
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 7
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 description 6
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 108700020796 Oncogene Proteins 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 150000003230 pyrimidines Chemical class 0.000 description 5
- 150000004944 pyrrolopyrimidines Chemical class 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 4
- IFYKTCBGIXRDLX-UHFFFAOYSA-N 4-chloro-1-(3,5-dimethylphenyl)pyrazolo[3,4-d]pyrimidine Chemical compound CC1=CC(C)=CC(N2C3=NC=NC(Cl)=C3C=N2)=C1 IFYKTCBGIXRDLX-UHFFFAOYSA-N 0.000 description 4
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 4
- 229940121647 egfr inhibitor Drugs 0.000 description 4
- 229960002584 gefitinib Drugs 0.000 description 4
- 229910052735 hafnium Inorganic materials 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 229940086542 triethylamine Drugs 0.000 description 4
- QWCGXANSAOXRFE-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanamine Chemical compound COCCOCCN QWCGXANSAOXRFE-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 230000010355 oscillation Effects 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
- 239000002525 vasculotropin inhibitor Substances 0.000 description 3
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
- RSBQANBNDXZFIY-UHFFFAOYSA-N (3,5-dimethylphenyl)hydrazine;hydrochloride Chemical compound [Cl-].CC1=CC(C)=CC(N[NH3+])=C1 RSBQANBNDXZFIY-UHFFFAOYSA-N 0.000 description 2
- WTEKLOBVBASOSY-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethyl benzenesulfonate Chemical compound COCCOCCOS(=O)(=O)C1=CC=CC=C1 WTEKLOBVBASOSY-UHFFFAOYSA-N 0.000 description 2
- GPEGMQBVLGNIMY-UHFFFAOYSA-N 3,4-bis(2-methoxyethoxy)benzaldehyde Chemical compound COCCOC1=CC=C(C=O)C=C1OCCOC GPEGMQBVLGNIMY-UHFFFAOYSA-N 0.000 description 2
- IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 description 2
- MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 2
- ANMRILZEEWJAOZ-UHFFFAOYSA-N 4-chloro-1-(3-iodophenyl)pyrazolo[3,4-d]pyrimidine Chemical compound N1=CC=2C(Cl)=NC=NC=2N1C1=CC=CC(I)=C1 ANMRILZEEWJAOZ-UHFFFAOYSA-N 0.000 description 2
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 241001227713 Chiron Species 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000003445 Mouth Neoplasms Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 206010043515 Throat cancer Diseases 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- LOGUAPASTBWDAO-UHFFFAOYSA-M [NH4+].[K+].OC([O-])=O.OC([O-])=O Chemical compound [NH4+].[K+].OC([O-])=O.OC([O-])=O LOGUAPASTBWDAO-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 201000001514 prostate carcinoma Diseases 0.000 description 2
- 239000003909 protein kinase inhibitor Substances 0.000 description 2
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 2
- 206010038038 rectal cancer Diseases 0.000 description 2
- 201000001275 rectum cancer Diseases 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000001119 stannous chloride Substances 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 150000003440 styrenes Chemical class 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- BIIBYWQGRFWQKM-JVVROLKMSA-N (2S)-N-[4-(cyclopropylamino)-3,4-dioxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl]-2-[[(E)-3-(2,4-dichlorophenyl)prop-2-enoyl]amino]-4,4-dimethylpentanamide Chemical compound CC(C)(C)C[C@@H](C(NC(C[C@H](CCN1)C1=O)C(C(NC1CC1)=O)=O)=O)NC(/C=C/C(C=CC(Cl)=C1)=C1Cl)=O BIIBYWQGRFWQKM-JVVROLKMSA-N 0.000 description 1
- VKYOURQWEVCZSX-UHFFFAOYSA-N (3,5-dimethylphenyl)hydrazine Chemical compound CC1=CC(C)=CC(NN)=C1 VKYOURQWEVCZSX-UHFFFAOYSA-N 0.000 description 1
- BOMBFECOZPIPOX-UHFFFAOYSA-N (3-iodophenyl)hydrazine;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=CC(I)=C1 BOMBFECOZPIPOX-UHFFFAOYSA-N 0.000 description 1
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
- KMPLYESDOZJASB-PAHRJMAXSA-N (6s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-hydroxy-6-methoxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one;(z)-n-carbamoyl-2-ethylbut-2-enamide;6-ethoxy-1,3-benzothiazole-2-sulfonamide Chemical compound CC\C(=C\C)C(=O)NC(N)=O.CCOC1=CC=C2N=C(S(N)(=O)=O)SC2=C1.C([C@@]12C)CC(=O)C=C1[C@@H](OC)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 KMPLYESDOZJASB-PAHRJMAXSA-N 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- PJQFZUZMLYDYIR-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CC1=CC(C)=CC(N2C3=C(C(NC=N3)=O)C=N2)=C1 PJQFZUZMLYDYIR-UHFFFAOYSA-N 0.000 description 1
- YSWUDFATSBPVFL-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-[(3,4,5-trimethoxyphenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound COC1=C(OC)C(OC)=CC(CNC=2C=3C=NN(C=3N=CN=2)C=2C=C(C)C=C(C)C=2)=C1 YSWUDFATSBPVFL-UHFFFAOYSA-N 0.000 description 1
- LXJPKKQQUDYLSN-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-[[4-methoxy-3-(3-morpholin-4-ylpropoxy)phenyl]methyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=C(OCCCN2CCOCC2)C(OC)=CC=C1CNC(C=1C=N2)=NC=NC=1N2C1=CC(C)=CC(C)=C1 LXJPKKQQUDYLSN-UHFFFAOYSA-N 0.000 description 1
- IDJVYPSFBOXUPW-UHFFFAOYSA-N 1-(3-ethynylphenyl)pyrazolo[3,4-d]pyrimidine Chemical class C#CC1=CC=CC(N2C3=NC=NC=C3C=N2)=C1 IDJVYPSFBOXUPW-UHFFFAOYSA-N 0.000 description 1
- SZCAORBAQHOJQI-UHFFFAOYSA-N 1-iodo-2-methoxyethane Chemical compound COCCI SZCAORBAQHOJQI-UHFFFAOYSA-N 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- BDGADLKNLKXJNY-UHFFFAOYSA-N 2-(3-morpholin-4-ylpropoxy)benzaldehyde Chemical compound O=CC1=CC=CC=C1OCCCN1CCOCC1 BDGADLKNLKXJNY-UHFFFAOYSA-N 0.000 description 1
- DWKNOLCXIFYNFV-HSZRJFAPSA-N 2-[[(2r)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-n,n,6-trimethylpyridine-4-carboxamide Chemical compound CN(C)C(=O)C1=CC(C)=NC(NC(=O)[C@@H]2N(C(=O)CC2)C2CCN(CC=3C=C(C)C(Cl)=CC=3)CC2)=C1 DWKNOLCXIFYNFV-HSZRJFAPSA-N 0.000 description 1
- PCYGLFXKCBFGPC-UHFFFAOYSA-N 3,4-Dihydroxy hydroxymethyl benzene Natural products OCC1=CC=C(O)C(O)=C1 PCYGLFXKCBFGPC-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 description 1
- BFTOEGBZMXUJPJ-UHFFFAOYSA-N 3-[4-(1,3-benzodioxol-5-ylmethylamino)pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile Chemical compound N#CC1=CC=CC(N2C3=NC=NC(NCC=4C=C5OCOC5=CC=4)=C3C=N2)=C1 BFTOEGBZMXUJPJ-UHFFFAOYSA-N 0.000 description 1
- XFOOBWTXCQRRJW-UHFFFAOYSA-N 3-n-[(3-aminophenyl)methyl]-4-n-(3-chlorophenyl)-1h-pyrazolo[3,4-d]pyrimidine-3,4-diamine Chemical compound NC1=CC=CC(CNC=2C3=C(NC=4C=C(Cl)C=CC=4)N=CN=C3NN=2)=C1 XFOOBWTXCQRRJW-UHFFFAOYSA-N 0.000 description 1
- UXHQLGLGLZKHTC-CUNXSJBXSA-N 4-[(3s,3ar)-3-cyclopentyl-7-(4-hydroxypiperidine-1-carbonyl)-3,3a,4,5-tetrahydropyrazolo[3,4-f]quinolin-2-yl]-2-chlorobenzonitrile Chemical compound C1CC(O)CCN1C(=O)C1=CC=C(C=2[C@@H]([C@H](C3CCCC3)N(N=2)C=2C=C(Cl)C(C#N)=CC=2)CC2)C2=N1 UXHQLGLGLZKHTC-CUNXSJBXSA-N 0.000 description 1
- DLHSWXBXKPTYSR-UHFFFAOYSA-N 4-chloro-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidine Chemical compound CC1=CC=CC(N2C3=NC=NC(Cl)=C3C=N2)=C1 DLHSWXBXKPTYSR-UHFFFAOYSA-N 0.000 description 1
- YVQRRWURNBYPII-UHFFFAOYSA-N 5-amino-1-(3,5-dimethylphenyl)pyrazole-4-carboxamide Chemical compound CC1=CC(C)=CC(N2C(=C(C(N)=O)C=N2)N)=C1 YVQRRWURNBYPII-UHFFFAOYSA-N 0.000 description 1
- XELVAUKJXKPSRP-UHFFFAOYSA-N 5-amino-1-(3,5-dimethylphenyl)pyrazole-4-carboxylic acid Chemical compound CC1=CC(C)=CC(N2C(=C(C(O)=O)C=N2)N)=C1 XELVAUKJXKPSRP-UHFFFAOYSA-N 0.000 description 1
- FZLSDZZNPXXBBB-KDURUIRLSA-N 5-chloro-N-[3-cyclopropyl-5-[[(3R,5S)-3,5-dimethylpiperazin-1-yl]methyl]phenyl]-4-(6-methyl-1H-indol-3-yl)pyrimidin-2-amine Chemical compound C[C@H]1CN(Cc2cc(Nc3ncc(Cl)c(n3)-c3c[nH]c4cc(C)ccc34)cc(c2)C2CC2)C[C@@H](C)N1 FZLSDZZNPXXBBB-KDURUIRLSA-N 0.000 description 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
- SUPXSFXAMJPEPH-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]triazine Chemical compound N1=NC=C2NC=CC2=N1 SUPXSFXAMJPEPH-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 102100038778 Amphiregulin Human genes 0.000 description 1
- 108010033760 Amphiregulin Proteins 0.000 description 1
- 108090000644 Angiozyme Proteins 0.000 description 1
- 101100005765 Arabidopsis thaliana CDF1 gene Proteins 0.000 description 1
- 101100007579 Arabidopsis thaliana CPP1 gene Proteins 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- 238000007809 Boyden Chamber assay Methods 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 101100123850 Caenorhabditis elegans her-1 gene Proteins 0.000 description 1
- 101100127890 Caenorhabditis elegans let-23 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 101800000155 Epiregulin Proteins 0.000 description 1
- 102000044591 ErbB-4 Receptor Human genes 0.000 description 1
- 208000009849 Female Genital Neoplasms Diseases 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 238000007807 Matrigel invasion assay Methods 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- FTFRZXFNZVCRSK-UHFFFAOYSA-N N4-(3-chloro-4-fluorophenyl)-N6-(1-methyl-4-piperidinyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FTFRZXFNZVCRSK-UHFFFAOYSA-N 0.000 description 1
- 102000014413 Neuregulin Human genes 0.000 description 1
- 108050003475 Neuregulin Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 101150057744 PDGFA gene Proteins 0.000 description 1
- 101150093908 PDGFRB gene Proteins 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102100029837 Probetacellulin Human genes 0.000 description 1
- 102100025498 Proepiregulin Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 101150109894 TGFA gene Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 101100429091 Xiphophorus maculatus xmrk gene Proteins 0.000 description 1
- MCRWZBYTLVCCJJ-DKALBXGISA-N [(1s,3r)-3-[[(3s,4s)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[(1s,4s)-5-[6-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)[C@@]1(C[C@@H](CC1)N[C@@H]1[C@@H](COCC1)OC)C(C)C)[H])N2C1=CC(C(F)(F)F)=NC=N1 MCRWZBYTLVCCJJ-DKALBXGISA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- WDENQIQQYWYTPO-IBGZPJMESA-N acalabrutinib Chemical compound CC#CC(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C(=O)NC=2N=CC=CC=2)=C2N1C=CN=C2N WDENQIQQYWYTPO-IBGZPJMESA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 1
- 125000005001 aminoaryl group Chemical group 0.000 description 1
- 150000005005 aminopyrimidines Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 239000002839 antibiotic anticancer agent Substances 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 108010044165 crotoxin drug combination cardiotoxin Proteins 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- SIHZWGODIRRSRA-ONEGZZNKSA-N erbstatin Chemical compound OC1=CC=C(O)C(\C=C\NC=O)=C1 SIHZWGODIRRSRA-ONEGZZNKSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- HOXINJBQVZWYGZ-UHFFFAOYSA-N fenbutatin oxide Chemical compound C=1C=CC=CC=1C(C)(C)C[Sn](O[Sn](CC(C)(C)C=1C=CC=CC=1)(CC(C)(C)C=1C=CC=CC=1)CC(C)(C)C=1C=CC=CC=1)(CC(C)(C)C=1C=CC=CC=1)CC(C)(C)C1=CC=CC=C1 HOXINJBQVZWYGZ-UHFFFAOYSA-N 0.000 description 1
- JUQAECQBUNODQP-UHFFFAOYSA-N furo[3,2-d]pyrimidine Chemical class C1=NC=C2OC=CC2=N1 JUQAECQBUNODQP-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- XQAOUDWGZHEVBU-UHFFFAOYSA-N methyl 3,5-bis(dimethylaminomethylideneamino)-1h-pyrazole-4-carboxylate Chemical compound COC(=O)C=1C(N=CN(C)C)=NNC=1N=CN(C)C XQAOUDWGZHEVBU-UHFFFAOYSA-N 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- MDKOLQNIIBHLBX-UHFFFAOYSA-N n'-[4-cyano-3-(dimethylaminomethylideneamino)-1h-pyrazol-5-yl]-n,n-dimethylmethanimidamide Chemical class CN(C)C=NC1=NNC(N=CN(C)C)=C1C#N MDKOLQNIIBHLBX-UHFFFAOYSA-N 0.000 description 1
- JUIGKLFOQNJFIC-UHFFFAOYSA-N n-[(3,4-dimethoxyphenyl)methyl]-1-(3,5-dimethylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=C(OC)C(OC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC(C)=CC(C)=C1 JUIGKLFOQNJFIC-UHFFFAOYSA-N 0.000 description 1
- VOVZXURTCKPRDQ-CQSZACIVSA-N n-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-5-(1h-pyrazol-5-yl)pyridine-3-carboxamide Chemical compound C1[C@H](O)CCN1C1=NC=C(C(=O)NC=2C=CC(OC(F)(F)Cl)=CC=2)C=C1C1=CC=NN1 VOVZXURTCKPRDQ-CQSZACIVSA-N 0.000 description 1
- IJTBHPAXFRYDQY-UHFFFAOYSA-N n-[[4-methoxy-3-(3-morpholin-4-ylpropoxy)phenyl]methyl]-1-(3-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=C(OCCCN2CCOCC2)C(OC)=CC=C1CNC(C=1C=N2)=NC=NC=1N2C1=CC=CC(C)=C1 IJTBHPAXFRYDQY-UHFFFAOYSA-N 0.000 description 1
- 208000025402 neoplasm of esophagus Diseases 0.000 description 1
- 208000025440 neoplasm of neck Diseases 0.000 description 1
- 239000002660 neuropeptide Y receptor antagonist Substances 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M nitrite group Chemical group N(=O)[O-] IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 101710135378 pH 6 antigen Proteins 0.000 description 1
- VFXXDLSJPITVGX-UHFFFAOYSA-H palladium(2+) hexaacetate Chemical compound [Pd+2].[Pd+2].[Pd+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O VFXXDLSJPITVGX-UHFFFAOYSA-H 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229950003647 semaxanib Drugs 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000013076 thyroid tumor Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN109CH2008 | 2008-01-11 | ||
| PCT/IN2009/000037 WO2009098715A2 (en) | 2008-01-11 | 2009-01-12 | Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ586642A true NZ586642A (en) | 2012-04-27 |
Family
ID=40933862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ586642A NZ586642A (en) | 2008-01-11 | 2009-01-12 | Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US8349847B2 (https=) |
| EP (1) | EP2247596A2 (https=) |
| JP (1) | JP2011509290A (https=) |
| KR (1) | KR20100116607A (https=) |
| CN (1) | CN101965350A (https=) |
| AP (1) | AP2010005347A0 (https=) |
| AU (1) | AU2009211004C1 (https=) |
| BR (1) | BRPI0906475A2 (https=) |
| CA (1) | CA2711777A1 (https=) |
| CO (1) | CO6382174A2 (https=) |
| EA (1) | EA201070841A1 (https=) |
| GE (1) | GEP20135780B (https=) |
| IL (1) | IL206811A0 (https=) |
| MA (1) | MA32009B1 (https=) |
| MX (1) | MX2010007523A (https=) |
| NZ (1) | NZ586642A (https=) |
| WO (1) | WO2009098715A2 (https=) |
| ZA (1) | ZA201004823B (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945420A (zh) | 2009-06-29 | 2015-09-30 | 因塞特公司 | 作为pi3k抑制剂的嘧啶酮类 |
| US8680108B2 (en) * | 2009-12-18 | 2014-03-25 | Incyte Corporation | Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors |
| WO2011075643A1 (en) | 2009-12-18 | 2011-06-23 | Incyte Corporation | Substituted heteroaryl fused derivatives as pi3k inhibitors |
| AR081823A1 (es) | 2010-04-14 | 2012-10-24 | Incyte Corp | DERIVADOS FUSIONADOS COMO INHIBIDORES DE PI3Kd |
| US9062055B2 (en) | 2010-06-21 | 2015-06-23 | Incyte Corporation | Fused pyrrole derivatives as PI3K inhibitors |
| EP2655374B1 (en) | 2010-12-20 | 2019-10-23 | Incyte Holdings Corporation | N-(1-(substituted-phenyl)ethyl)-9h-purin-6-amines as pi3k inhibitors |
| US9108984B2 (en) | 2011-03-14 | 2015-08-18 | Incyte Corporation | Substituted diamino-pyrimidine and diamino-pyridine derivatives as PI3K inhibitors |
| WO2012135009A1 (en) | 2011-03-25 | 2012-10-04 | Incyte Corporation | Pyrimidine-4,6-diamine derivatives as pi3k inhibitors |
| KR102507287B1 (ko) | 2011-09-02 | 2023-03-07 | 인사이트 홀딩스 코포레이션 | Ｐｉ３ｋ 억제제로서 헤테로시클릴아민 |
| AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
| CN102746309B (zh) * | 2012-07-09 | 2013-06-05 | 四川大学 | 1-N-乙基-4-N-2′-取代酰基肼-1H-吡唑[3,4-d]嘧啶类衍生物及其制备方法和用途 |
| CN102746307B (zh) * | 2012-07-09 | 2013-07-31 | 四川大学 | 1-n-苄基别嘌醇衍生物及其制备方法和用途 |
| CN103965202B (zh) * | 2014-05-21 | 2016-01-20 | 邹宏丽 | 二环稠合杂环化合物、其制备方法及用途 |
| WO2015191677A1 (en) | 2014-06-11 | 2015-12-17 | Incyte Corporation | Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors |
| SI3831833T1 (sl) | 2015-02-27 | 2023-03-31 | Incyte Holdings Corporation | Postopki za pripravo inhibitorja PI3K |
| US9732097B2 (en) | 2015-05-11 | 2017-08-15 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase inhibitor |
| US9988401B2 (en) | 2015-05-11 | 2018-06-05 | Incyte Corporation | Crystalline forms of a PI3K inhibitor |
| CN106008527B (zh) * | 2016-06-29 | 2018-05-15 | 四川大学华西医院 | 吡唑并[3,4-d]嘧啶衍生物 |
| CN107698596A (zh) * | 2017-11-15 | 2018-02-16 | 双鹤药业（商丘）有限责任公司 | 一种别嘌醇的合成方法 |
| CA3101323A1 (en) | 2018-06-01 | 2019-12-05 | Incyte Corporation | Dosing regimen for the treatment of pi3k related disorders |
| EP4081528A4 (en) * | 2019-12-23 | 2024-03-13 | Sanford Burnham Prebys Medical Discovery Institute | ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF |
| CN115304607B (zh) * | 2022-07-06 | 2023-06-27 | 华南农业大学 | 吡唑并嘧啶衍生物的制备方法 |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3000688A (en) | 1961-09-19 | Process for vatting of vat dyestuffs | ||
| US3551428A (en) | 1956-02-10 | 1970-12-29 | Ciba Geigy Corp | New 1- (or 2-) substituted 4-mercapto-pyrazolo(3,4-d)pyrimidines |
| JPS5439096A (en) | 1977-08-27 | 1979-03-24 | Lion Dentifrice Co Ltd | 11phenyll1hhpyrazolo*3*44d*pyrimidinee44 carbonitrile |
| US5958930A (en) | 1991-04-08 | 1999-09-28 | Duquesne University Of The Holy Ghost | Pyrrolo pyrimidine and furo pyrimidine derivatives |
| US5877178A (en) | 1991-04-08 | 1999-03-02 | Duquesne University Of The Holy Ghost | Pyrimidine derivatives and methods of making and using these derivatives |
| US5593997A (en) | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
| MX9800215A (es) | 1995-07-06 | 1998-03-31 | Novartis Ag | Pirrolopirimidas y procesos para su preparacion. |
| ATE217873T1 (de) | 1996-01-23 | 2002-06-15 | Novartis Erfind Verwalt Gmbh | Pyrrolopyrimidinen und verfahren zu deren herstellung |
| CH690773A5 (de) | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| US6537999B2 (en) | 1996-06-06 | 2003-03-25 | Duquesne University Of The Holy Ghost | Pyrimidine derivatives and methods of making and using these derivatives |
| WO1998007726A1 (en) | 1996-08-23 | 1998-02-26 | Novartis Ag | Substituted pyrrolopyrimidines and processes for their preparation |
| DE19709488A1 (de) | 1997-03-07 | 1998-09-10 | Basf Ag | Verfahren zur N-Alkylierung von Aminen |
| ID24300A (id) | 1997-08-05 | 2000-07-13 | Pfizer Prod Inc | 4-AMINOPIROL(3,2-d)PIRIMIDIN SEBAGAI ANTAGONIS-ANTAGONIS RESEPTOR NEUROPEPTIDA Y |
| US6686366B1 (en) | 1998-06-02 | 2004-02-03 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| US6423871B1 (en) | 1999-02-26 | 2002-07-23 | University Of South Florida | Efficient synthesis of secondary amines by selective alkylation of primary amines |
| DE60026297T2 (de) | 1999-05-21 | 2006-11-02 | Bristol-Myers Squibb Co. | Pyrrolotriazin kinasehemmer |
| ITMI992711A1 (it) | 1999-12-27 | 2001-06-27 | Novartis Ag | Composti organici |
| WO2001072751A1 (en) | 2000-03-29 | 2001-10-04 | Knoll Gesellschaft Mit Beschraenkter Haftung | Pyrrolopyrimidines as tyrosine kinase inhibitors |
| US6673802B2 (en) | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| AP1893A (en) | 2000-12-01 | 2008-09-23 | Osi Pharm Inc | Compounds specific to adenosine A1, A2A and A3 receptor and uses thereof |
| US6680324B2 (en) | 2000-12-01 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
| DE10060388A1 (de) * | 2000-12-05 | 2002-06-06 | Merck Patent Gmbh | Verwendung von Pyrazolo [4,3-d]pyrimidinen |
| AR035885A1 (es) | 2001-05-14 | 2004-07-21 | Novartis Ag | Derivados de 4-amino-5-fenil-7-ciclobutilpirrolo (2,3-d)pirimidina, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos derivados para la preparacion de una composicion farmaceutica |
| AU2002315389A1 (en) | 2001-06-21 | 2003-01-08 | Ariad Pharmaceuticals, Inc. | Novel pyrazolo-and pyrrolo-pyrimidines and uses thereof |
| GB0115393D0 (en) | 2001-06-23 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-substituted pyrimidinyl derivatives and methods of use |
| US6939874B2 (en) | 2001-08-22 | 2005-09-06 | Amgen Inc. | Substituted pyrimidinyl derivatives and methods of use |
| ATE323702T1 (de) | 2002-08-06 | 2006-05-15 | Astrazeneca Ab | Kondensierte pyridine und pyrimidine mit tie2 (tek) aktivität |
| US20040138238A1 (en) | 2002-08-08 | 2004-07-15 | Dhanoa Dale S. | Substituted aminopyrimidine compounds as neurokinin antagonists |
-
2009
- 2009-01-12 EP EP09761144A patent/EP2247596A2/en not_active Withdrawn
- 2009-01-12 GE GEAP200911914A patent/GEP20135780B/en unknown
- 2009-01-12 CN CN2009801083051A patent/CN101965350A/zh active Pending
- 2009-01-12 KR KR1020107017777A patent/KR20100116607A/ko not_active Withdrawn
- 2009-01-12 AU AU2009211004A patent/AU2009211004C1/en not_active Ceased
- 2009-01-12 AP AP2010005347A patent/AP2010005347A0/en unknown
- 2009-01-12 US US12/812,405 patent/US8349847B2/en not_active Expired - Fee Related
- 2009-01-12 BR BRPI0906475-3A patent/BRPI0906475A2/pt not_active IP Right Cessation
- 2009-01-12 NZ NZ586642A patent/NZ586642A/en not_active IP Right Cessation
- 2009-01-12 CA CA2711777A patent/CA2711777A1/en not_active Abandoned
- 2009-01-12 JP JP2010541891A patent/JP2011509290A/ja active Pending
- 2009-01-12 MX MX2010007523A patent/MX2010007523A/es not_active Application Discontinuation
- 2009-01-12 EA EA201070841A patent/EA201070841A1/ru unknown
- 2009-01-12 WO PCT/IN2009/000037 patent/WO2009098715A2/en not_active Ceased
-
2010
- 2010-07-05 IL IL206811A patent/IL206811A0/en unknown
- 2010-07-08 ZA ZA2010/04823A patent/ZA201004823B/en unknown
- 2010-07-09 MA MA33007A patent/MA32009B1/fr unknown
- 2010-08-11 CO CO10098749A patent/CO6382174A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EA201070841A1 (ru) | 2011-02-28 |
| IL206811A0 (en) | 2010-12-30 |
| AP2010005347A0 (en) | 2010-08-31 |
| MX2010007523A (es) | 2010-08-18 |
| AU2009211004C1 (en) | 2013-08-01 |
| WO2009098715A2 (en) | 2009-08-13 |
| AU2009211004A1 (en) | 2009-08-13 |
| WO2009098715A4 (en) | 2009-12-10 |
| WO2009098715A3 (en) | 2009-10-15 |
| US20100298351A1 (en) | 2010-11-25 |
| KR20100116607A (ko) | 2010-11-01 |
| CN101965350A (zh) | 2011-02-02 |
| AU2009211004B2 (en) | 2011-09-01 |
| ZA201004823B (en) | 2011-09-28 |
| CA2711777A1 (en) | 2009-08-13 |
| JP2011509290A (ja) | 2011-03-24 |
| BRPI0906475A2 (pt) | 2015-07-14 |
| GEP20135780B (en) | 2013-03-11 |
| AU2009211004A2 (en) | 2011-01-27 |
| US8349847B2 (en) | 2013-01-08 |
| CO6382174A2 (es) | 2012-02-15 |
| EP2247596A2 (en) | 2010-11-10 |
| MA32009B1 (fr) | 2011-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009211004C1 (en) | Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents | |
| CA2127411C (en) | Tricyclic derivatives | |
| JP4134227B2 (ja) | 縮合複素環化合物 | |
| TWI385174B (zh) | 作為酪胺酸激酶抑制劑之稠合雙環及多環嘧啶化合物 | |
| KR101362621B1 (ko) | 화합물 | |
| CN111936499A (zh) | Mat2a的杂二环抑制剂和用于治疗癌症的方法 | |
| CN103122001A (zh) | Polo样激酶抑制剂 | |
| JP2010509242A (ja) | イミダゾ［１，２−ｂ］ピリダジン誘導体およびピラゾロ［１，５−ａ］ピリダジン誘導体およびプロテインキナーゼインヒビターとしてのこれらの使用 | |
| MXPA04001191A (es) | Derivados de 4-amino-6-fenil-pirrolo[2,3-d]pirimidina. | |
| CN111386273A (zh) | 可用作tam抑制剂的吡咯并三嗪衍生物的盐 | |
| US9156853B2 (en) | AKT inhibitor compounds for treatment of cancer | |
| CN101189239A (zh) | 蛋白激酶抑制剂 | |
| AU2008320342A1 (en) | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents | |
| KR20200078610A (ko) | 아미노치환 질소함유 축합고리 화합물 및 그의 제조방법과 용도 | |
| TW202045509A (zh) | 7H-吡咯并[2,3-d]嘧啶-4-胺衍生物 | |
| KR101767260B1 (ko) | 피리미도 옥사진 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 pi3 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 | |
| CN115210236A (zh) | 作为Toll样受体7(TLR7)激动剂的1H-吡唑并[4,3-d]嘧啶化合物 | |
| CN116283994A (zh) | 作为mat2a抑制剂的杂环化合物 | |
| TW200530245A (en) | Pyrrolo pyrimidine derivatives useful for treating proliferative diseases | |
| CN107629057A (zh) | Bet蛋白抑制剂及其应用 | |
| KR101796779B1 (ko) | 다이하이드로프테리딘-온 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 pi3 키나아제 관련 질환의 예방 또는 치료용 약학적 조성물 | |
| CN118772113A (zh) | 作为DNA聚合酶Theta抑制剂的含氮杂环化合物 | |
| TWI602818B (zh) | 稠合雜環化合物作爲蛋白激酶抑制劑 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Patent lapsed |