ES2334641T3 - Derivados aza heterociclicos y su uso terapeutico. - Google Patents
Derivados aza heterociclicos y su uso terapeutico. Download PDFInfo
- Publication number
- ES2334641T3 ES2334641T3 ES01973678T ES01973678T ES2334641T3 ES 2334641 T3 ES2334641 T3 ES 2334641T3 ES 01973678 T ES01973678 T ES 01973678T ES 01973678 T ES01973678 T ES 01973678T ES 2334641 T3 ES2334641 T3 ES 2334641T3
- Authority
- ES
- Spain
- Prior art keywords
- groups
- substituted
- unsubstituted
- alkyl
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 230000001225 therapeutic effect Effects 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 562
- 125000003118 aryl group Chemical group 0.000 claims abstract description 518
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 499
- 150000001875 compounds Chemical class 0.000 claims abstract description 294
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 156
- -1 guanidinyl groups Chemical group 0.000 claims abstract description 104
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 96
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims abstract description 69
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims abstract description 66
- 125000005128 aryl amino alkyl group Chemical group 0.000 claims abstract description 58
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 52
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims abstract description 50
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 42
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims abstract description 42
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 42
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 39
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 34
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 33
- 125000003277 amino group Chemical group 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 27
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 18
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 17
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 16
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 16
- 125000004986 diarylamino group Chemical group 0.000 claims abstract description 16
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 16
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 16
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 12
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims abstract description 8
- 108091008605 VEGF receptors Proteins 0.000 claims abstract description 7
- 101150020251 NR13 gene Proteins 0.000 claims abstract description 6
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 claims abstract 3
- 229910052799 carbon Inorganic materials 0.000 claims description 77
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 54
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 50
- 125000004429 atom Chemical group 0.000 claims description 48
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 42
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 40
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 24
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 23
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 22
- 206010028980 Neoplasm Diseases 0.000 claims description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 20
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 19
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 14
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 13
- 150000003536 tetrazoles Chemical class 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 9
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 9
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 229930192474 thiophene Natural products 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 6
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 6
- 230000004614 tumor growth Effects 0.000 claims description 6
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 5
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 5
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 5
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 18
- 125000004434 sulfur atom Chemical group 0.000 abstract description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 238000000034 method Methods 0.000 description 40
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 30
- 239000007787 solid Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 229920006395 saturated elastomer Polymers 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 239000000460 chlorine Substances 0.000 description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 18
- 150000001412 amines Chemical group 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 14
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 14
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 13
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 13
- 125000004093 cyano group Chemical group *C#N 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 150000003222 pyridines Chemical class 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 10
- 230000033115 angiogenesis Effects 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 150000003852 triazoles Chemical class 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 9
- 125000003418 alkyl amino alkoxy group Chemical group 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 150000002460 imidazoles Chemical class 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 150000003854 isothiazoles Chemical class 0.000 description 9
- 150000002545 isoxazoles Chemical group 0.000 description 9
- 150000002916 oxazoles Chemical class 0.000 description 9
- 125000003386 piperidinyl group Chemical group 0.000 description 9
- 150000003217 pyrazoles Chemical group 0.000 description 9
- HNJBEVLQSNELDL-YZRHJBSPSA-N pyrrolidin-2-one Chemical group O=C1CC[14CH2]N1 HNJBEVLQSNELDL-YZRHJBSPSA-N 0.000 description 9
- 150000003235 pyrrolidines Chemical group 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- SFDJOSRHYKHMOK-UHFFFAOYSA-N nitramide Chemical compound N[N+]([O-])=O SFDJOSRHYKHMOK-UHFFFAOYSA-N 0.000 description 8
- 125000004193 piperazinyl group Chemical group 0.000 description 8
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical class C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 7
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical class NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 6
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 6
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
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- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 150000002780 morpholines Chemical class 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 150000003233 pyrroles Chemical class 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- SHCCOLNEBLEONP-UHFFFAOYSA-N 2-(1h-imidazo[4,5-b]pyridin-2-yl)acetic acid Chemical compound C1=CC=C2NC(CC(=O)O)=NC2=N1 SHCCOLNEBLEONP-UHFFFAOYSA-N 0.000 description 5
- PEZNQSQPDQLHPN-UHFFFAOYSA-N 3-aminopyridine-4-carbonitrile Chemical group NC1=CN=CC=C1C#N PEZNQSQPDQLHPN-UHFFFAOYSA-N 0.000 description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 5
- PEDMFCHWOVJDNW-UHFFFAOYSA-N 5-fluoro-2-nitroaniline Chemical compound NC1=CC(F)=CC=C1[N+]([O-])=O PEDMFCHWOVJDNW-UHFFFAOYSA-N 0.000 description 5
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 5
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 5
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- 229910021529 ammonia Inorganic materials 0.000 description 5
- 230000005907 cancer growth Effects 0.000 description 5
- 125000004984 dialkylaminoalkoxy group Chemical group 0.000 description 5
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- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
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- 238000002347 injection Methods 0.000 description 5
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- 238000002360 preparation method Methods 0.000 description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 150000003557 thiazoles Chemical class 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 4
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 4
- GFTPLFVZKMIYAP-UHFFFAOYSA-N 2-(1h-benzimidazol-1-ium-2-yl)acetate Chemical compound C1=CC=C2NC(CC(=O)O)=NC2=C1 GFTPLFVZKMIYAP-UHFFFAOYSA-N 0.000 description 4
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 4
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- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 4
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
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- 125000005843 halogen group Chemical group 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
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- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 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 4
- AHEBVWXGBJJXSF-UHFFFAOYSA-N 3-[(3-methoxy-3-oxopropanoyl)amino]pyridine-4-carboxylic acid Chemical compound COC(=O)CC(=O)NC1=CN=CC=C1C(O)=O AHEBVWXGBJJXSF-UHFFFAOYSA-N 0.000 description 3
- IQXUIDYRTHQTET-UHFFFAOYSA-N 4-amino-3-nitrophenol Chemical compound NC1=CC=C(O)C=C1[N+]([O-])=O IQXUIDYRTHQTET-UHFFFAOYSA-N 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23182900P | 2000-09-01 | 2000-09-01 | |
| US231829P | 2000-09-01 |
Publications (1)
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|---|---|
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| KR101387985B1 (ko) | 2005-01-27 | 2014-04-25 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 전이 종양의 치료 |
-
2001
- 2001-08-30 ES ES01973678T patent/ES2334641T3/es not_active Expired - Lifetime
- 2001-08-30 AU AU2001293233A patent/AU2001293233A1/en not_active Abandoned
- 2001-08-30 DE DE60140456T patent/DE60140456D1/de not_active Expired - Lifetime
- 2001-08-30 JP JP2002523898A patent/JP4341949B2/ja not_active Expired - Fee Related
- 2001-08-30 US US09/943,382 patent/US6756383B2/en not_active Expired - Fee Related
- 2001-08-30 WO PCT/US2001/041942 patent/WO2002018383A2/en not_active Ceased
- 2001-08-30 EP EP01973678A patent/EP1313734B1/en not_active Expired - Lifetime
- 2001-08-30 PT PT01973678T patent/PT1313734E/pt unknown
- 2001-08-30 AT AT01973678T patent/ATE448226T1/de not_active IP Right Cessation
-
2003
- 2003-06-02 US US10/452,786 patent/US6759417B2/en not_active Expired - Fee Related
-
2004
- 2004-04-14 US US10/823,995 patent/US7138409B2/en not_active Expired - Fee Related
-
2006
- 2006-10-11 US US11/546,814 patent/US7368459B2/en not_active Expired - Fee Related
-
2007
- 2007-05-16 JP JP2007131084A patent/JP2007217427A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US6759417B2 (en) | 2004-07-06 |
| ATE448226T1 (de) | 2009-11-15 |
| WO2002018383A3 (en) | 2002-08-29 |
| DE60140456D1 (de) | 2009-12-24 |
| JP2007217427A (ja) | 2007-08-30 |
| US6756383B2 (en) | 2004-06-29 |
| US7138409B2 (en) | 2006-11-21 |
| US7368459B2 (en) | 2008-05-06 |
| JP2004507543A (ja) | 2004-03-11 |
| PT1313734E (pt) | 2010-02-09 |
| AU2001293233A1 (en) | 2002-03-13 |
| US20020103230A1 (en) | 2002-08-01 |
| US20050137188A1 (en) | 2005-06-23 |
| US20040002518A1 (en) | 2004-01-01 |
| JP4341949B2 (ja) | 2009-10-14 |
| EP1313734B1 (en) | 2009-11-11 |
| WO2002018383A2 (en) | 2002-03-07 |
| EP1313734A2 (en) | 2003-05-28 |
| US20070032528A1 (en) | 2007-02-08 |
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