AU2009211004C1 - Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents - Google Patents
Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents Download PDFInfo
- Publication number
- AU2009211004C1 AU2009211004C1 AU2009211004A AU2009211004A AU2009211004C1 AU 2009211004 C1 AU2009211004 C1 AU 2009211004C1 AU 2009211004 A AU2009211004 A AU 2009211004A AU 2009211004 A AU2009211004 A AU 2009211004A AU 2009211004 C1 AU2009211004 C1 AU 2009211004C1
- Authority
- AU
- Australia
- Prior art keywords
- pyrazolo
- phenyl
- amine
- formula
- pyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical class C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 239000002246 antineoplastic agent Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 219
- 238000000034 method Methods 0.000 claims abstract description 29
- 230000008569 process Effects 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 241001465754 Metazoa Species 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- -1 hydroxy, amino Chemical group 0.000 claims description 168
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 97
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 57
- 238000010992 reflux Methods 0.000 claims description 47
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 37
- 206010028980 Neoplasm Diseases 0.000 claims description 35
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 35
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 34
- 239000007787 solid Substances 0.000 claims description 32
- 239000002904 solvent Substances 0.000 claims description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 29
- 229910052757 nitrogen Chemical group 0.000 claims description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 24
- 201000011510 cancer Diseases 0.000 claims description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 150000001412 amines Chemical class 0.000 claims description 16
- 229910021529 ammonia Inorganic materials 0.000 claims description 16
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 12
- 125000003368 amide group Chemical group 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 239000002585 base Substances 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 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 10
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class 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
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 10
- 239000011707 mineral Substances 0.000 claims description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 239000000010 aprotic solvent Substances 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
- 239000003586 protic polar solvent Substances 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000005296 thioaryloxy group Chemical group 0.000 claims description 8
- 125000005404 thioheteroaryloxy group Chemical group 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 7
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 7
- 235000010288 sodium nitrite Nutrition 0.000 claims description 7
- 239000001117 sulphuric acid Substances 0.000 claims description 7
- 235000011149 sulphuric acid Nutrition 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims description 6
- 201000002528 pancreatic cancer Diseases 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- 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 5
- LHCPRYRLDOSKHK-UHFFFAOYSA-N 7-deaza-8-aza-adenine Chemical compound NC1=NC=NC2=C1C=NN2 LHCPRYRLDOSKHK-UHFFFAOYSA-N 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- LREBRMSRVWVJGK-UHFFFAOYSA-N CC=1C=C(C=C(C1)C)C1=NNC2=NC=NC=C21 Chemical class CC=1C=C(C=C(C1)C)C1=NNC2=NC=NC=C21 LREBRMSRVWVJGK-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 5
- 235000011181 potassium carbonates Nutrition 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
- 150000003230 pyrimidines Chemical class 0.000 claims description 5
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 claims description 5
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 4
- HPARLNRMYDSBNO-UHFFFAOYSA-N 1,4-benzodioxine Chemical compound C1=CC=C2OC=COC2=C1 HPARLNRMYDSBNO-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 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 class 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 150000004679 hydroxides Chemical class 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 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
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000002560 nitrile group Chemical group 0.000 claims description 4
- 150000002829 nitrogen Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
- 239000011593 sulfur 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
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 239000001099 ammonium carbonate Substances 0.000 claims description 3
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 235000017550 sodium carbonate Nutrition 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 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 class 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
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 239000002609 medium Substances 0.000 claims description 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 description 2
- 229940067157 phenylhydrazine Drugs 0.000 claims description 2
- 208000017572 squamous cell neoplasm Diseases 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 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
- 230000003463 hyperproliferative effect Effects 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 3
- 229910052700 potassium Inorganic materials 0.000 claims 3
- 239000011591 potassium Substances 0.000 claims 3
- 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 2
- UBKSUPKIDNXMMC-UHFFFAOYSA-N 5-amino-1-phenylpyrazole-4-carboxamide Chemical class NC1=C(C(=O)N)C=NN1C1=CC=CC=C1 UBKSUPKIDNXMMC-UHFFFAOYSA-N 0.000 claims 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 2
- 230000003472 neutralizing effect Effects 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- SQAKOPVOUSLGRS-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-[2-(2-methoxyethoxy)ethyl]pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=2C(NCCOCCOC)=NC=NC=2N1C1=CC(C)=CC(C)=C1 SQAKOPVOUSLGRS-UHFFFAOYSA-N 0.000 claims 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 claims 1
- 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 1
- ROEFWOWUWFIFHP-UHFFFAOYSA-N 2-[[1-(3,5-dimethylphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]amino]acetic acid Chemical compound CC1=CC(C)=CC(N2C3=NC=NC(NCC(O)=O)=C3C=N2)=C1 ROEFWOWUWFIFHP-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- BWEHNFAHJYUHNO-UHFFFAOYSA-N 3-[4-[(4-methoxyphenyl)methylamino]pyrazolo[3,4-d]pyrimidin-1-yl]benzonitrile Chemical compound C1=CC(OC)=CC=C1CNC1=NC=NC2=C1C=NN2C1=CC=CC(C#N)=C1 BWEHNFAHJYUHNO-UHFFFAOYSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- PARWGYPSBMSXSC-UHFFFAOYSA-N [4-(2-methoxyethoxy)phenyl]methanamine Chemical compound COCCOC1=CC=C(CN)C=C1 PARWGYPSBMSXSC-UHFFFAOYSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 238000007796 conventional method Methods 0.000 claims 1
- 125000005265 dialkylamine group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000004101 esophageal cancer Diseases 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
- 201000010982 kidney cancer Diseases 0.000 claims 1
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- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 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
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 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
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 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
- FGNJVJCEKXEYDF-UHFFFAOYSA-N trimethyl-[2-(3-pyrazolo[3,4-d]pyrimidin-1-ylphenyl)ethynyl]silane Chemical class C[Si](C)(C)C#CC1=CC=CC(N2C3=NC=NC=C3C=N2)=C1 FGNJVJCEKXEYDF-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- KMIOJWCYOHBUJS-HAKPAVFJSA-N vorolanib Chemical compound C1N(C(=O)N(C)C)CC[C@@H]1NC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C KMIOJWCYOHBUJS-HAKPAVFJSA-N 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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN109/CHE/2008 | 2008-01-11 | ||
| 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 (4)
| Publication Number | Publication Date |
|---|---|
| AU2009211004A1 AU2009211004A1 (en) | 2009-08-13 |
| AU2009211004A2 AU2009211004A2 (en) | 2011-01-27 |
| AU2009211004B2 AU2009211004B2 (en) | 2011-09-01 |
| AU2009211004C1 true AU2009211004C1 (en) | 2013-08-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2009211004A Ceased AU2009211004C1 (en) | 2008-01-11 | 2009-01-12 | Novel pyrazolo [3, 4 -d] pyrimidine derivatives as anti -cancer agents |
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| EP (1) | EP2247596A2 (enExample) |
| JP (1) | JP2011509290A (enExample) |
| KR (1) | KR20100116607A (enExample) |
| CN (1) | CN101965350A (enExample) |
| AP (1) | AP2010005347A0 (enExample) |
| AU (1) | AU2009211004C1 (enExample) |
| BR (1) | BRPI0906475A2 (enExample) |
| CA (1) | CA2711777A1 (enExample) |
| CO (1) | CO6382174A2 (enExample) |
| EA (1) | EA201070841A1 (enExample) |
| GE (1) | GEP20135780B (enExample) |
| IL (1) | IL206811A0 (enExample) |
| MA (1) | MA32009B1 (enExample) |
| MX (1) | MX2010007523A (enExample) |
| NZ (1) | NZ586642A (enExample) |
| WO (1) | WO2009098715A2 (enExample) |
| ZA (1) | ZA201004823B (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20140754T2 (hr) | 2009-06-29 | 2015-07-17 | Incyte Corporation | Pirimidinoni kao inhibitori pi3k |
| AR079529A1 (es) * | 2009-12-18 | 2012-02-01 | Incyte Corp | Derivados arilo y heteroarilo sustituidos y fundidos como inhibidores de la pi3k |
| US8759359B2 (en) | 2009-12-18 | 2014-06-24 | Incyte Corporation | Substituted heteroaryl fused derivatives as PI3K inhibitors |
| WO2011130342A1 (en) | 2010-04-14 | 2011-10-20 | Incyte Corporation | FUSED DERIVATIVES AS ΡI3Κδ INHIBITORS |
| US9062055B2 (en) | 2010-06-21 | 2015-06-23 | Incyte Corporation | Fused pyrrole derivatives as PI3K inhibitors |
| WO2012087881A1 (en) | 2010-12-20 | 2012-06-28 | Incyte Corporation | N-(1-(substituted-phenyl)ethyl)-9h-purin-6-amines as pi3k inhibitors |
| WO2012125629A1 (en) | 2011-03-14 | 2012-09-20 | 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 |
| LT3196202T (lt) | 2011-09-02 | 2019-07-10 | Incyte Holdings Corporation | Heterociklilaminai, kaip pi3k slopikliai |
| AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
| 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 |
| 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 |
| 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 |
| US10077277B2 (en) | 2014-06-11 | 2018-09-18 | Incyte Corporation | Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors |
| CN117736209A (zh) | 2015-02-27 | 2024-03-22 | 因赛特控股公司 | Pi3k抑制剂的盐及其制备方法 |
| US9732097B2 (en) | 2015-05-11 | 2017-08-15 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase inhibitor |
| WO2016183063A1 (en) | 2015-05-11 | 2016-11-17 | 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 |
| PE20211208A1 (es) | 2018-06-01 | 2021-07-05 | Incyte Corp | Regimen de dosificacion para el tratamiento de trastornos relacionados con pi3k |
| US20230121698A1 (en) * | 2019-12-23 | 2023-04-20 | 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 |
| DK0836605T3 (da) | 1995-07-06 | 2002-05-13 | Novartis Ag | Pyrrolopyrimidiner og fremgangsmåder til deres fremstilling |
| JP4275733B2 (ja) | 1996-01-23 | 2009-06-10 | ノバルティス アクチエンゲゼルシャフト | ピロロピリミジンおよびその製造法 |
| 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 |
| ES2241146T3 (es) | 1997-08-05 | 2005-10-16 | Pfizer Products Inc. | 4-aminopirrol(3,2-d)pirimidinas como antagonistas del receptor del neuropeptido 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 |
| WO2000071129A1 (en) | 1999-05-21 | 2000-11-30 | Bristol-Myers Squibb Company | Pyrrolotriazine inhibitors of kinases |
| 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 |
| EA007254B1 (ru) | 2000-12-01 | 2006-08-25 | Оси Фармасьютикалз, Инк. | Соединения, специфические к аденозиновому а, аи арецептору, и их применение |
| US6673802B2 (en) | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine 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 |
| US6939874B2 (en) | 2001-08-22 | 2005-09-06 | Amgen Inc. | Substituted pyrimidinyl derivatives and methods of use |
| US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-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 CN CN2009801083051A patent/CN101965350A/zh active Pending
- 2009-01-12 BR BRPI0906475-3A patent/BRPI0906475A2/pt not_active IP Right Cessation
- 2009-01-12 CA CA2711777A patent/CA2711777A1/en not_active Abandoned
- 2009-01-12 MX MX2010007523A patent/MX2010007523A/es not_active Application Discontinuation
- 2009-01-12 EA EA201070841A patent/EA201070841A1/ru unknown
- 2009-01-12 KR KR1020107017777A patent/KR20100116607A/ko not_active Withdrawn
- 2009-01-12 WO PCT/IN2009/000037 patent/WO2009098715A2/en not_active Ceased
- 2009-01-12 GE GEAP200911914A patent/GEP20135780B/en unknown
- 2009-01-12 AU AU2009211004A patent/AU2009211004C1/en not_active Ceased
- 2009-01-12 US US12/812,405 patent/US8349847B2/en not_active Expired - Fee Related
- 2009-01-12 JP JP2010541891A patent/JP2011509290A/ja active Pending
- 2009-01-12 AP AP2010005347A patent/AP2010005347A0/en unknown
- 2009-01-12 EP EP09761144A patent/EP2247596A2/en not_active Withdrawn
- 2009-01-12 NZ NZ586642A patent/NZ586642A/en not_active IP Right Cessation
-
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
Non-Patent Citations (1)
| Title |
|---|
| Cavasotto et al., Bioorganic & Medicinal Chemistry Letters, vol. 16, 2006, pages 1969-1974 * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100116607A (ko) | 2010-11-01 |
| WO2009098715A2 (en) | 2009-08-13 |
| MX2010007523A (es) | 2010-08-18 |
| CA2711777A1 (en) | 2009-08-13 |
| IL206811A0 (en) | 2010-12-30 |
| CO6382174A2 (es) | 2012-02-15 |
| US8349847B2 (en) | 2013-01-08 |
| JP2011509290A (ja) | 2011-03-24 |
| WO2009098715A3 (en) | 2009-10-15 |
| WO2009098715A4 (en) | 2009-12-10 |
| NZ586642A (en) | 2012-04-27 |
| MA32009B1 (fr) | 2011-01-03 |
| US20100298351A1 (en) | 2010-11-25 |
| CN101965350A (zh) | 2011-02-02 |
| GEP20135780B (en) | 2013-03-11 |
| EA201070841A1 (ru) | 2011-02-28 |
| EP2247596A2 (en) | 2010-11-10 |
| AP2010005347A0 (en) | 2010-08-31 |
| AU2009211004B2 (en) | 2011-09-01 |
| AU2009211004A2 (en) | 2011-01-27 |
| AU2009211004A1 (en) | 2009-08-13 |
| BRPI0906475A2 (pt) | 2015-07-14 |
| ZA201004823B (en) | 2011-09-28 |
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