JP2002522535A5

JP2002522535A5 -

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Publication number: JP2002522535A5
Authority: JP; Japan
Prior art keywords: acid; phenyl; formula; compound; substituted
Prior art date: 1999-08-09
Legal status : Granted

Application number

JP2000564947A

Other languages

English (en)

Japanese (ja)

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JP2002522535A (ja

JP4516690B2 (ja

Filing date

1999-08-09

Publication date

2006-10-05

1999-08-09 Application filed filed Critical

1999-08-09 Priority claimed from PCT/EP1999/005781 external-priority patent/WO2000009495A1/en

2002-07-23 Publication of JP2002522535A publication Critical patent/JP2002522535A/ja

2006-10-05 Publication of JP2002522535A5 publication Critical patent/JP2002522535A5/ja

2010-08-04 Application granted granted Critical

2010-08-04 Publication of JP4516690B2 publication Critical patent/JP4516690B2/ja

2019-08-09 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

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-1 di-substituted amino Chemical group 0.000 description 143
150000001875 compounds Chemical class 0.000 description 68
125000000217 alkyl group Chemical group 0.000 description 46
239000002253 acid Substances 0.000 description 44
150000003839 salts Chemical class 0.000 description 37
238000000034 method Methods 0.000 description 31
229910052757 nitrogen Inorganic materials 0.000 description 30
125000003282 alkyl amino group Chemical group 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
150000001204 N-oxides Chemical class 0.000 description 23
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
229910052736 halogen Inorganic materials 0.000 description 20
150000002367 halogens Chemical class 0.000 description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 20
238000011282 treatment Methods 0.000 description 20
125000004356 hydroxy functional group Chemical group O* 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
125000001424 substituent group Chemical group 0.000 description 17
150000008064 anhydrides Chemical class 0.000 description 14
125000001589 carboacyl group Chemical group 0.000 description 14
125000003545 alkoxy group Chemical group 0.000 description 13
125000004414 alkyl thio group Chemical group 0.000 description 13
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
239000000203 mixture Substances 0.000 description 12
125000004390 alkyl sulfonyl group Chemical group 0.000 description 11
125000002947 alkylene group Chemical group 0.000 description 11
150000002148 esters Chemical class 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 10
125000001841 imino group Chemical group [H]N=* 0.000 description 10
230000005764 inhibitory process Effects 0.000 description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 10
239000000243 solution Substances 0.000 description 10
239000007858 starting material Substances 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
241000534944 Thia Species 0.000 description 9
150000007513 acids Chemical class 0.000 description 9
239000002904 solvent Substances 0.000 description 9
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
125000003277 amino group Chemical group 0.000 description 8
125000003118 aryl group Chemical group 0.000 description 8
201000010099 disease Diseases 0.000 description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
239000008194 pharmaceutical composition Substances 0.000 description 8
238000007792 addition Methods 0.000 description 7
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
206010028980 Neoplasm Diseases 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
150000001718 carbodiimides Chemical class 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
125000000623 heterocyclic group Chemical group 0.000 description 6
238000012360 testing method Methods 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
108091000080 Phosphotransferase Proteins 0.000 description 5
125000005236 alkanoylamino group Chemical group 0.000 description 5
230000033115 angiogenesis Effects 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000011065 in-situ storage Methods 0.000 description 5
125000004433 nitrogen atom Chemical group N* 0.000 description 5
102000020233 phosphotransferase Human genes 0.000 description 5
238000010992 reflux Methods 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
125000004423 acyloxy group Chemical group 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 description 4
125000005530 alkylenedioxy group Chemical group 0.000 description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
239000003814 drug Substances 0.000 description 4
150000004678 hydrides Chemical class 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 description 4
239000002953 phosphate buffered saline Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000000547 substituted alkyl group Chemical group 0.000 description 4
229940124597 therapeutic agent Drugs 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
241000208199 Buxus sempervirens Species 0.000 description 3
UIOAQJNADLELPQ-UHFFFAOYSA-N C[C]1OCCO1 Chemical group C[C]1OCCO1 UIOAQJNADLELPQ-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
102000001253 Protein Kinase Human genes 0.000 description 3
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
150000001350 alkyl halides Chemical class 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
125000004093 cyano group Chemical group *C#N 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
230000014399 negative regulation of angiogenesis Effects 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
125000004430 oxygen atom Chemical group O* 0.000 description 3
229910052698 phosphorus Inorganic materials 0.000 description 3
239000011574 phosphorus Substances 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
108060006633 protein kinase Proteins 0.000 description 3
235000018102 proteins Nutrition 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000011734 sodium Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000758 substrate Substances 0.000 description 3
RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-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
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 2
229910004298 SiO 2 Inorganic materials 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
125000005115 alkyl carbamoyl group Chemical group 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
150000007860 aryl ester derivatives Chemical class 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
150000003950 cyclic amides Chemical class 0.000 description 2
150000004292 cyclic ethers Chemical class 0.000 description 2
239000000824 cytostatic agent Substances 0.000 description 2
230000001085 cytostatic effect Effects 0.000 description 2
229940127089 cytotoxic agent Drugs 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
230000003054 hormonal effect Effects 0.000 description 2
239000005556 hormone Substances 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
150000002460 imidazoles Chemical class 0.000 description 2
238000011534 incubation Methods 0.000 description 2
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JP2000564947A 1998-08-11 1999-08-09 血管形成阻害活性を有するイソキノリン誘導体 Expired - Fee Related JP4516690B2 (ja)