WO1996010024A1 - Derive pyrimidinylpyrazole - Google Patents
Derive pyrimidinylpyrazole Download PDFInfo
- Publication number
- WO1996010024A1 WO1996010024A1 PCT/JP1995/001934 JP9501934W WO9610024A1 WO 1996010024 A1 WO1996010024 A1 WO 1996010024A1 JP 9501934 W JP9501934 W JP 9501934W WO 9610024 A1 WO9610024 A1 WO 9610024A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- pyrimidinyl
- methyl
- halogen atom
- added
- Prior art date
Links
- BWIHJLOBZMKPKS-UHFFFAOYSA-N 2-(1h-pyrazol-5-yl)pyrimidine Chemical class N1C=CC(C=2N=CC=CN=2)=N1 BWIHJLOBZMKPKS-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- 125000005843 halogen group Chemical group 0.000 claims abstract description 31
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000003277 amino group Chemical group 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 17
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 15
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- FMRFUKZPHGBWHF-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-1-ol Chemical group C1=CC=C2C(O)NCCC2=C1 FMRFUKZPHGBWHF-UHFFFAOYSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 239000011347 resin Substances 0.000 claims 1
- 229920005989 resin Polymers 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- -1 amino, hydroxy Chemical group 0.000 abstract description 54
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 4
- 239000001257 hydrogen Chemical group 0.000 abstract description 4
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 150000003573 thiols Chemical group 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 131
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 61
- 239000000203 mixture Substances 0.000 description 56
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- 238000005481 NMR spectroscopy Methods 0.000 description 47
- 239000002904 solvent Substances 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 30
- 239000011734 sodium Substances 0.000 description 30
- 229910052708 sodium Inorganic materials 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 238000000034 method Methods 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000010898 silica gel chromatography Methods 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 229930040373 Paraformaldehyde Natural products 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 229920002866 paraformaldehyde Polymers 0.000 description 12
- 239000012279 sodium borohydride Substances 0.000 description 12
- 229910000033 sodium borohydride Inorganic materials 0.000 description 12
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 11
- 238000000354 decomposition reaction Methods 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 239000000835 fiber Substances 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical compound ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 235000003642 hunger Nutrition 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 5
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000037351 starvation Effects 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- GNKZMNRKLCTJAY-UHFFFAOYSA-N 4'-Methylacetophenone Chemical compound CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 239000004210 ether based solvent Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003849 aromatic solvent Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 150000004714 phosphonium salts Chemical class 0.000 description 2
- 229910052573 porcelain Inorganic materials 0.000 description 2
- ZDHURYWHEBEGHO-UHFFFAOYSA-N potassiopotassium Chemical compound [K].[K] ZDHURYWHEBEGHO-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 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 2
- KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 1
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- JHICIIDUQBMMRM-UHFFFAOYSA-N 1-(2,5-dichlorophenyl)piperazine Chemical compound ClC1=CC=C(Cl)C(N2CCNCC2)=C1 JHICIIDUQBMMRM-UHFFFAOYSA-N 0.000 description 1
- SWQMPOXIMTYXHI-UHFFFAOYSA-N 1-(2,5-difluorophenyl)piperazine Chemical compound FC1=CC=C(F)C(N2CCNCC2)=C1 SWQMPOXIMTYXHI-UHFFFAOYSA-N 0.000 description 1
- IVTZRJKKXSKXKO-UHFFFAOYSA-N 1-(2-fluorophenyl)piperazine Chemical compound FC1=CC=CC=C1N1CCNCC1 IVTZRJKKXSKXKO-UHFFFAOYSA-N 0.000 description 1
- WICKLEOONJPMEQ-UHFFFAOYSA-N 1-(2-methylphenyl)piperazine Chemical compound CC1=CC=CC=C1N1CCNCC1 WICKLEOONJPMEQ-UHFFFAOYSA-N 0.000 description 1
- LISGMSBYRAXPJH-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)piperazine Chemical compound ClC1=CC(Cl)=CC(N2CCNCC2)=C1 LISGMSBYRAXPJH-UHFFFAOYSA-N 0.000 description 1
- KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 description 1
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 1
- JIWHIRLNKIUYSM-UHFFFAOYSA-N 1-(3-methylphenyl)piperazine Chemical compound CC1=CC=CC(N2CCNCC2)=C1 JIWHIRLNKIUYSM-UHFFFAOYSA-N 0.000 description 1
- UMOPUYQHCRDESJ-UHFFFAOYSA-N 1-(5-methyl-1-pyrimidin-2-ylpyrazol-4-yl)ethanone Chemical compound CC1=C(C(=O)C)C=NN1C1=NC=CC=N1 UMOPUYQHCRDESJ-UHFFFAOYSA-N 0.000 description 1
- IKHDQPQGKVFTAZ-UHFFFAOYSA-N 1-[1-(4-methoxy-6-methylpyrimidin-2-yl)-5-methylpyrazol-4-yl]-3-[4-(2-methylphenyl)piperazin-1-yl]propan-1-one Chemical class COC1=CC(C)=NC(N2C(=C(C(=O)CCN3CCN(CC3)C=3C(=CC=CC=3)C)C=N2)C)=N1 IKHDQPQGKVFTAZ-UHFFFAOYSA-N 0.000 description 1
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- YNOOQIUSYGWMSS-UHFFFAOYSA-N 2,5-difluoroaniline Chemical compound NC1=CC(F)=CC=C1F YNOOQIUSYGWMSS-UHFFFAOYSA-N 0.000 description 1
- CNAOLBLYYSSPAO-DUXPYHPUSA-N 2-[4-[(e)-3-[4-(3,5-difluorophenyl)piperazin-1-yl]prop-1-enyl]-5-methylpyrazol-1-yl]pyrimidine Chemical compound C1=NN(C=2N=CC=CN=2)C(C)=C1\C=C\CN(CC1)CCN1C1=CC(F)=CC(F)=C1 CNAOLBLYYSSPAO-DUXPYHPUSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- UORNTHBBLYBAJJ-UHFFFAOYSA-N 2-piperazin-1-ylphenol Chemical compound OC1=CC=CC=C1N1CCNCC1 UORNTHBBLYBAJJ-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 1
- WDNBURPWRNALGP-UHFFFAOYSA-N 3,4-Dichlorophenol Chemical compound OC1=CC=C(Cl)C(Cl)=C1 WDNBURPWRNALGP-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- FDMMLBIVOFBJJT-UHFFFAOYSA-N 3-[4-(2-chlorophenyl)piperazin-1-yl]-1-(5-methyl-1-pyrimidin-2-ylpyrazol-4-yl)propan-1-one Chemical compound CC1=C(C(=O)CCN2CCN(CC2)C=2C(=CC=CC=2)Cl)C=NN1C1=NC=CC=N1 FDMMLBIVOFBJJT-UHFFFAOYSA-N 0.000 description 1
- KRXRNQIWAJLZQD-UHFFFAOYSA-N 3-[4-(3-chlorophenyl)piperazin-1-yl]-1-(5-methyl-1-pyrimidin-2-ylpyrazol-4-yl)propan-1-one Chemical compound CC1=C(C(=O)CCN2CCN(CC2)C=2C=C(Cl)C=CC=2)C=NN1C1=NC=CC=N1 KRXRNQIWAJLZQD-UHFFFAOYSA-N 0.000 description 1
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 1
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 description 1
- IZGVOANXLNJMDM-UHFFFAOYSA-N 4-methyl-1,2,3,6-tetrahydropyridine Chemical compound CC1=CCNCC1 IZGVOANXLNJMDM-UHFFFAOYSA-N 0.000 description 1
- ZVNPWFOVUDMGRP-UHFFFAOYSA-N 4-methylaminophenol sulfate Chemical compound OS(O)(=O)=O.CNC1=CC=C(O)C=C1.CNC1=CC=C(O)C=C1 ZVNPWFOVUDMGRP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101100005766 Caenorhabditis elegans cdf-1 gene Proteins 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 235000003332 Ilex aquifolium Nutrition 0.000 description 1
- 241000209027 Ilex aquifolium Species 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 241001474791 Proboscis Species 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229910052776 Thorium Inorganic materials 0.000 description 1
- GWBWGPRZOYDADH-UHFFFAOYSA-N [C].[Na] Chemical compound [C].[Na] GWBWGPRZOYDADH-UHFFFAOYSA-N 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
- DALDUXIBIKGWTK-UHFFFAOYSA-N benzene;toluene Chemical compound C1=CC=CC=C1.CC1=CC=CC=C1 DALDUXIBIKGWTK-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000005266 casting Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical group [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present invention is a novelty with:
- the present invention also relates to an anti-m using the compound ⁇ ! Background decoration
- Pyrimidinyl villasono 3 ⁇ 4 ⁇ is known for its antihypertensive and psychotropic effects (eg, Japanese Patent Publication No. 47-14233, # ⁇ 0948-42072), but its effects have not yet been reported.
- Bases include n-butyllithium, phenyllithium, sodium hydride, potassium t-butoxide, sodium ethoxide, 1,8-diazabicyclo [5.4.0] pendes-7-ene (DBU) No.
- the compound of the present invention can be converted into an inorganic acid, such as carboxylic acid, phosphoric acid, or the like, or an organic acid, such as chiral, methane, methanesulfonic acid, or the like, to give a biologically acceptable salt.
- an inorganic acid such as carboxylic acid, phosphoric acid, or the like
- an organic acid such as chiral, methane, methanesulfonic acid, or the like
- X10 6 mouse leukemia cells, P388, were implanted intravenously into 7-10 week old male CDF-1 mice (34 g from body S21, 1E), and their quality was expanded on the first and fifth days after transplantation. The drug was administered in a controlled manner to prolong its life.
- the substance was administered by dissolving or suspending it in BTC (distilled water containing 0.9X benzyl alcohol, 0.4X Tween 80, and 0.5X sodium carboxymethylcellulose).
- the agent of the present invention can be administered as a variety of ai agents intravenously, intramuscularly, subcutaneously, or by various methods such as oral administration. Among these administrations, intravenous administration with water ffira and oral administration are preferred. It can be prepared by using an acid with an acid that is acceptable for the above or an alkali metal salt such as sodium.
- the compound of the present invention represented by the formula (I) and salts thereof are useful for JiMSP as agents.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Photoreceptors In Electrophotography (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95932229A EP0784055B1 (en) | 1994-09-26 | 1995-09-25 | Pyrimidinylpyrazole derivative |
| DK95932229T DK0784055T3 (da) | 1994-09-26 | 1995-09-25 | Pyrimidinylpyrazolderivater |
| HK98100241.0A HK1001396B (en) | 1994-09-26 | 1995-09-25 | Pyrimidinylpyrazole derivative |
| RU97106768A RU2146675C1 (ru) | 1994-09-26 | 1995-09-25 | Производные пиримидинилпиразола и противоопухолевое средство |
| FI971227A FI971227A7 (fi) | 1994-09-26 | 1995-09-25 | Pyramidinyylipyratsolijohdannaisia |
| DE69529619A DE69529619D1 (en) | 1994-09-26 | 1995-09-25 | Pyrimidinylpyrazolderivate |
| US08/821,076 US5852019A (en) | 1994-09-26 | 1995-09-25 | Pyrimidinylpyrazole derivatives |
| AT95932229T ATE232528T1 (de) | 1994-09-26 | 1995-09-25 | Pyrimidinylpyrazolderivate |
| DE69529619T DE69529619T4 (de) | 1994-09-26 | 1995-09-25 | Pyrimidinylpyrazolderivative |
| NO19971384A NO313196B1 (no) | 1994-09-26 | 1997-03-24 | Pyrimidinylpyrazol-derivat, og antitumormiddel inneholdende dette |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6/229422 | 1994-09-26 | ||
| JP22942294 | 1994-09-26 | ||
| JP13501095 | 1995-06-01 | ||
| JP7/135010 | 1995-06-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996010024A1 true WO1996010024A1 (fr) | 1996-04-04 |
Family
ID=26468965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1995/001934 WO1996010024A1 (fr) | 1994-09-26 | 1995-09-25 | Derive pyrimidinylpyrazole |
Country Status (13)
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000043385A1 (fr) * | 1999-01-25 | 2000-07-27 | Zenyaku Kogyo Kabushiki Kaisha | Composes heterocycliques et agents antitumoraux les comprenant en tant que principe actif |
| EP1022270A4 (en) * | 1997-01-27 | 2002-01-30 | Daiichi Seiyaku Co | PIRAZOLE DERIVATIVES |
| US6552018B1 (en) | 1997-01-27 | 2003-04-22 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| WO2005095389A1 (ja) * | 2004-03-31 | 2005-10-13 | Zenyaku Kogyo Kabushiki Kaisha | 複素環式化合物及びそれを有効成分とする抗悪性腫瘍剤 |
| US7307077B2 (en) | 2001-04-27 | 2007-12-11 | Zenyaku Kogyo Kabushiki Kaisha | Heterocyclic compound and antitumor agent containing the same as effective ingredient |
| US7750001B2 (en) | 2005-03-11 | 2010-07-06 | Zenyaku Kogyo Kabushikikaisha | Immunosuppressive agent and anti-tumor agent comprising heterocyclic compound as active ingredient |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1103551A1 (en) * | 1998-07-24 | 2001-05-30 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives and salts thereof |
| WO2003011837A1 (en) * | 2001-08-01 | 2003-02-13 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US20050130989A1 (en) * | 2003-01-28 | 2005-06-16 | Aventis Pharma S. A. | N-arylheteroaromatic products compositions containing them and use thereof |
| CA2512243A1 (fr) * | 2003-01-28 | 2004-09-16 | Aventis Pharma S.A. | Produits n-aryl-heteroaromatiques, compositions les contenant et utilisation |
| FR2850379B1 (fr) * | 2003-01-28 | 2006-11-17 | Aventis Pharma Sa | Produits n-aryl-heteroaromatiques, compositions les contenant et utilisation |
| US7223759B2 (en) * | 2003-09-15 | 2007-05-29 | Anadys Pharmaceuticals, Inc. | Antibacterial 3,5-diaminopiperidine-substituted aromatic and heteroaromatic compounds |
| US20070244110A1 (en) * | 2006-04-14 | 2007-10-18 | Zenyaku Kogyo Kabushiki Kaisha | Treatment of prostate cancer, melanoma or hepatic cancer |
| JP2010505957A (ja) | 2006-10-10 | 2010-02-25 | アムゲン インコーポレイティッド | 糖尿病に対して使用されるｎ−アリールピラゾール化合物 |
| US10287269B2 (en) * | 2015-03-26 | 2019-05-14 | Merck Sharp & Dohme Corp. | Pyrazolyl pyrimidinone compounds as PDE2 inhibitors |
| US9963462B2 (en) | 2015-09-30 | 2018-05-08 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Sepiapterin reductase inhibitors |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5102893A (en) * | 1986-07-07 | 1992-04-07 | Warner-Lambert Company | Trans-6-(2-(n-heteroaryl-3,5-disubstituted)pyrazol-4-yl)-ethyl- or ethenyl)tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3778433A (en) * | 1969-04-18 | 1973-12-11 | Sumitomo Chemical Co | Process for producing benzodiazepine derivatives |
| JPS4842072A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1971-09-29 | 1973-06-19 | ||
| JPS61129129A (ja) * | 1984-11-28 | 1986-06-17 | Kureha Chem Ind Co Ltd | 抗腫瘍剤 |
-
1995
- 1995-09-19 TW TW084109880A patent/TW312694B/zh active
- 1995-09-25 KR KR1019970701964A patent/KR100388568B1/ko not_active Expired - Fee Related
- 1995-09-25 FI FI971227A patent/FI971227A7/fi unknown
- 1995-09-25 DE DE69529619A patent/DE69529619D1/de not_active Expired - Fee Related
- 1995-09-25 EP EP95932229A patent/EP0784055B1/en not_active Expired - Lifetime
- 1995-09-25 CA CA002201110A patent/CA2201110A1/en not_active Abandoned
- 1995-09-25 WO PCT/JP1995/001934 patent/WO1996010024A1/ja active IP Right Grant
- 1995-09-25 DE DE69529619T patent/DE69529619T4/de not_active Expired - Lifetime
- 1995-09-25 AT AT95932229T patent/ATE232528T1/de not_active IP Right Cessation
- 1995-09-25 CN CN95196449A patent/CN1071754C/zh not_active Expired - Fee Related
- 1995-09-25 DK DK95932229T patent/DK0784055T3/da active
- 1995-09-25 ES ES95932229T patent/ES2192584T3/es not_active Expired - Lifetime
- 1995-09-25 US US08/821,076 patent/US5852019A/en not_active Expired - Fee Related
-
1997
- 1997-03-24 NO NO19971384A patent/NO313196B1/no not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5102893A (en) * | 1986-07-07 | 1992-04-07 | Warner-Lambert Company | Trans-6-(2-(n-heteroaryl-3,5-disubstituted)pyrazol-4-yl)-ethyl- or ethenyl)tetrahydro-4-hydroxypyran-2-one inhibitors of cholesterol biosynthesis |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1022270A4 (en) * | 1997-01-27 | 2002-01-30 | Daiichi Seiyaku Co | PIRAZOLE DERIVATIVES |
| US6552018B1 (en) | 1997-01-27 | 2003-04-22 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| WO2000043385A1 (fr) * | 1999-01-25 | 2000-07-27 | Zenyaku Kogyo Kabushiki Kaisha | Composes heterocycliques et agents antitumoraux les comprenant en tant que principe actif |
| US7307077B2 (en) | 2001-04-27 | 2007-12-11 | Zenyaku Kogyo Kabushiki Kaisha | Heterocyclic compound and antitumor agent containing the same as effective ingredient |
| WO2005095389A1 (ja) * | 2004-03-31 | 2005-10-13 | Zenyaku Kogyo Kabushiki Kaisha | 複素環式化合物及びそれを有効成分とする抗悪性腫瘍剤 |
| US7855199B2 (en) | 2004-03-31 | 2010-12-21 | Zenyaku Kogyo Kabushiki Kaisha | Heterocyclic compound and anti-malignant-tumor agent containing the same as active ingredient |
| JP4733021B2 (ja) * | 2004-03-31 | 2011-07-27 | 全薬工業株式会社 | 複素環式化合物及びそれを有効成分とする抗悪性腫瘍剤 |
| US7750001B2 (en) | 2005-03-11 | 2010-07-06 | Zenyaku Kogyo Kabushikikaisha | Immunosuppressive agent and anti-tumor agent comprising heterocyclic compound as active ingredient |
| US8338414B2 (en) | 2005-03-11 | 2012-12-25 | Zenyaku Kogyo Kabushikikaisha | Immunosuppressive agent and anti-tumor agent comprising heterocyclic compound as active ingredient |
Also Published As
| Publication number | Publication date |
|---|---|
| FI971227L (fi) | 1997-05-23 |
| FI971227A0 (fi) | 1997-03-24 |
| US5852019A (en) | 1998-12-22 |
| NO313196B1 (no) | 2002-08-26 |
| CN1071754C (zh) | 2001-09-26 |
| HK1001396A1 (en) | 1998-06-19 |
| ATE232528T1 (de) | 2003-02-15 |
| EP0784055B1 (en) | 2003-02-12 |
| TW312694B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1997-08-11 |
| KR970706275A (ko) | 1997-11-03 |
| DE69529619T4 (de) | 2005-01-27 |
| NO971384D0 (no) | 1997-03-24 |
| ES2192584T3 (es) | 2003-10-16 |
| KR100388568B1 (ko) | 2003-10-04 |
| EP0784055A1 (en) | 1997-07-16 |
| CN1166833A (zh) | 1997-12-03 |
| DK0784055T3 (da) | 2003-06-02 |
| DE69529619T2 (de) | 2003-12-18 |
| FI971227A7 (fi) | 1997-05-23 |
| CA2201110A1 (en) | 1996-04-04 |
| EP0784055A4 (en) | 1998-01-07 |
| DE69529619D1 (en) | 2003-03-20 |
| NO971384L (no) | 1997-05-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO1996010024A1 (fr) | Derive pyrimidinylpyrazole | |
| KR870001158B1 (ko) | 항비루스활성이 있는 피리다진아민류의 제조방법 | |
| EP0464604B1 (en) | 1-Indolylalkyl-4-(alkoxy-pyrimidinyl)piperazines | |
| JP4248605B2 (ja) | ピリジン―２―イル―メチルアミン誘導体、それらの製造方法および医薬としてのそれらの適用 | |
| WO1999031062A1 (fr) | Nouveaux composes de pyridine | |
| WO1999025697A1 (fr) | Nouveaux derives de pyridazine et medicaments contenant ces composes comme principe actif | |
| AU2005272738A1 (en) | Isoindolone compounds and their use as metabotropic glutamate receptor potentiators | |
| JP4915715B2 (ja) | フェニルピリダジン誘導体及びこれを含有する医薬 | |
| HU228457B1 (en) | Substituted aza- and diazacycloheptane and cyclooctane derivatives, use thereof, pharmaceutical compositions containing there of | |
| EP1337518A1 (en) | Piperazinylpyrazines compounds as antagonists of serotonin 5-ht2 receptor | |
| EP0433149B1 (fr) | Antagonistes de la sérotonine, leur préparation et les médicaments les contenant | |
| IE61607B1 (en) | Benzimidazole derivatives, the preparation thereof and their application in therapy | |
| US4999355A (en) | Isoindolinone derivatives, processes for preparing them and medicines containing them | |
| JPS60226862A (ja) | 抗ウイルス活性ピリダジンアミン類 | |
| JP2001521035A (ja) | ３−置換テトラヒドロピリドピリミジノン−誘導体、その製造方法及びその使用 | |
| JPH08225535A (ja) | インダゾール誘導体 | |
| CA2130078A1 (en) | Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines | |
| US5401762A (en) | Aminoalkyl-substituted thiazolin-2-ones, the preparation and use thereof | |
| US5521188A (en) | Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines | |
| US20060211735A1 (en) | 4-Arylsulphonylpiperidine derivatives for antagonism of the 5-ht2a receptor | |
| JPH0948776A (ja) | ピリミジニルピラゾール誘導体 | |
| AU2002215294B2 (en) | Piperazinylpyrazines compounds as antagonists of serotonin 5-HT2 receptor | |
| WO1991018893A1 (en) | Novel 1,4-thiazine derivative and cardiotonic containing the same as active ingredient | |
| JPH02229193A (ja) | ベンズアゼピン化合物 | |
| HK1001396B (en) | Pyrimidinylpyrazole derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WWE | Wipo information: entry into national phase |
Ref document number: 95196449.6 Country of ref document: CN |
|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA CN FI KR NO RU US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 971227 Country of ref document: FI |
|
| ENP | Entry into the national phase |
Ref document number: 2201110 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1019970701964 Country of ref document: KR Ref document number: 1995932229 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 1995932229 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 1019970701964 Country of ref document: KR |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 08821076 Country of ref document: US |
|
| WWG | Wipo information: grant in national office |
Ref document number: 1995932229 Country of ref document: EP |
|
| WWG | Wipo information: grant in national office |
Ref document number: 1019970701964 Country of ref document: KR |