CA2284795C - Novel pyrimidine derivatives and processes for the preparation thereof - Google Patents
Novel pyrimidine derivatives and processes for the preparation thereof Download PDFInfo
- Publication number
- CA2284795C CA2284795C CA002284795A CA2284795A CA2284795C CA 2284795 C CA2284795 C CA 2284795C CA 002284795 A CA002284795 A CA 002284795A CA 2284795 A CA2284795 A CA 2284795A CA 2284795 C CA2284795 C CA 2284795C
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- pyrimidine
- fluorophenylamino
- dimethyl
- tetrahydroisoquinolin
- 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 - Fee Related
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- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title abstract description 93
- 238000002360 preparation method Methods 0.000 title abstract description 26
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title abstract description 11
- -1 3-trifluoromethylphenylmethyl Chemical group 0.000 claims abstract description 68
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 46
- 239000001257 hydrogen Substances 0.000 claims abstract description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 229910052736 halogen Chemical group 0.000 claims abstract description 12
- 150000002367 halogens Chemical group 0.000 claims abstract description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
- 125000004849 alkoxymethyl group Chemical group 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 6
- 125000004848 alkoxyethyl group Chemical group 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 4
- 125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 202
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 59
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- HAASDWOKLDBJAK-UHFFFAOYSA-N [2-(4-fluoroanilino)-4-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-5-yl]methanol Chemical compound C1CC2=CC=CC=C2C(C)N1C(C(=C(C)N=1)CO)=NC=1NC1=CC=C(F)C=C1 HAASDWOKLDBJAK-UHFFFAOYSA-N 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- MELAICPHFIDWPI-LUTIACGYSA-N [2-(4-fluoroanilino)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]methyl (2s)-2-amino-3-methylbutanoate Chemical compound N=1C(N2C(C3=CC=CC=C3CC2)C)=C(C)C(COC(=O)[C@@H](N)C(C)C)=NC=1NC1=CC=C(F)C=C1 MELAICPHFIDWPI-LUTIACGYSA-N 0.000 claims description 2
- UTRGXAOOUSKFCH-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2,3,4,5-tetrafluorobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC(F)=C(F)C(F)=C1F UTRGXAOOUSKFCH-UHFFFAOYSA-N 0.000 claims description 2
- HLNJBKUNHKPSIF-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2,3,4-trifluorobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=C(F)C(F)=C1F HLNJBKUNHKPSIF-UHFFFAOYSA-N 0.000 claims description 2
- QQWIJYAHRQQLHU-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2,3,6-trifluorobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=C(F)C=CC(F)=C1F QQWIJYAHRQQLHU-UHFFFAOYSA-N 0.000 claims description 2
- NABQSPFBADDJQP-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2,4,5-trifluorobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC(F)=C(F)C=C1F NABQSPFBADDJQP-UHFFFAOYSA-N 0.000 claims description 2
- IEOHHYXMYBNALF-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2,4,6-trichlorobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=C(Cl)C=C(Cl)C=C1Cl IEOHHYXMYBNALF-UHFFFAOYSA-N 0.000 claims description 2
- QJEIIVUCEMBHTH-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2-(3-methoxyphenyl)acetate Chemical compound COC1=CC=CC(CC(=O)OC=2C=C3CCN(C(C)C3=CC=2)C=2C(=C(C)N=C(NC=3C=CC(F)=CC=3)N=2)C)=C1 QJEIIVUCEMBHTH-UHFFFAOYSA-N 0.000 claims description 2
- PRMHQZZFAQHHOP-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2-(4-methoxyphenyl)acetate Chemical compound C1=CC(OC)=CC=C1CC(=O)OC1=CC=C(C(C)N(CC2)C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)C2=C1 PRMHQZZFAQHHOP-UHFFFAOYSA-N 0.000 claims description 2
- RXVSMDZYRCAYMM-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 3-(trifluoromethyl)benzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=CC(C(F)(F)F)=C1 RXVSMDZYRCAYMM-UHFFFAOYSA-N 0.000 claims description 2
- XTGQLXDKMQDORS-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2,3-difluorobenzoate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)C1=CC=CC(F)=C1F XTGQLXDKMQDORS-UHFFFAOYSA-N 0.000 claims description 2
- PCNQAMUFPURFQL-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2-(3-methoxyphenyl)acetate Chemical compound COC1=CC=CC(CC(=O)OC=2C=C3C(C)N(CCC3=CC=2)C=2C(=C(C)N=C(NC=3C=CC(F)=CC=3)N=2)C)=C1 PCNQAMUFPURFQL-UHFFFAOYSA-N 0.000 claims description 2
- SKLJBQAVAONXEO-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2-(4-methoxyphenyl)acetate Chemical compound C1=CC(OC)=CC=C1CC(=O)OC1=CC=C(CCN(C2C)C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)C2=C1 SKLJBQAVAONXEO-UHFFFAOYSA-N 0.000 claims description 2
- BGBCLJIKHCPCGO-UHFFFAOYSA-N [[2-(4-fluoroanilino)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]-thiophen-2-ylmethyl] acetate Chemical compound C1CC2=CC=CC=C2C(C)N1C(C(=C(C(OC(C)=O)C=1SC=CC=1)N=1)C)=NC=1NC1=CC=C(F)C=C1 BGBCLJIKHCPCGO-UHFFFAOYSA-N 0.000 claims description 2
- XOFRRCLMKZCDIZ-YQAGWJQESA-N [2-(4-fluoroanilino)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]methyl (2s)-2-amino-3-phenylpropanoate Chemical compound C1CC2=CC=CC=C2C(C)N1C(C(=C(COC(=O)[C@@H](N)CC=1C=CC=CC=1)N=1)C)=NC=1NC1=CC=C(F)C=C1 XOFRRCLMKZCDIZ-YQAGWJQESA-N 0.000 claims 1
- NZVQGOFXUNABDV-UHFFFAOYSA-N [2-(4-fluoroanilino)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]methyl 4-propylbenzoate Chemical compound C1=CC(CCC)=CC=C1C(=O)OCC1=NC(NC=2C=CC(F)=CC=2)=NC(N2C(C3=CC=CC=C3CC2)C)=C1C NZVQGOFXUNABDV-UHFFFAOYSA-N 0.000 claims 1
- ZVOANXVHMLFIDF-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2-chlorobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=CC=C1Cl ZVOANXVHMLFIDF-UHFFFAOYSA-N 0.000 claims 1
- DQWINXRKSPEREL-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2-phenylmethoxyacetate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)COCC1=CC=CC=C1 DQWINXRKSPEREL-UHFFFAOYSA-N 0.000 claims 1
- GIJCCRIGUVYBSN-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 3-cyanobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=CC(C#N)=C1 GIJCCRIGUVYBSN-UHFFFAOYSA-N 0.000 claims 1
- KSGDVBXJPNXIKX-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 3-phenylprop-2-enoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C=CC1=CC=CC=C1 KSGDVBXJPNXIKX-UHFFFAOYSA-N 0.000 claims 1
- RIKPEGNSHSCKKI-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-(trifluoromethyl)benzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=C(C(F)(F)F)C=C1 RIKPEGNSHSCKKI-UHFFFAOYSA-N 0.000 claims 1
- AIKIFAMWBPZEDX-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-butoxybenzoate Chemical compound C1=CC(OCCCC)=CC=C1C(=O)OC1=CC=C(C(C)N(CC2)C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)C2=C1 AIKIFAMWBPZEDX-UHFFFAOYSA-N 0.000 claims 1
- KLBZEZIEIVPJGX-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-chlorobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=C(Cl)C=C1 KLBZEZIEIVPJGX-UHFFFAOYSA-N 0.000 claims 1
- MWCOKDSJYBTTDD-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-ethylbenzoate Chemical compound C1=CC(CC)=CC=C1C(=O)OC1=CC=C(C(C)N(CC2)C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)C2=C1 MWCOKDSJYBTTDD-UHFFFAOYSA-N 0.000 claims 1
- PWWLUWYTNHXCDJ-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-methylbenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=C(C)C=C1 PWWLUWYTNHXCDJ-UHFFFAOYSA-N 0.000 claims 1
- UFINUWFRDLBXEV-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-nitrobenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=C([N+]([O-])=O)C=C1 UFINUWFRDLBXEV-UHFFFAOYSA-N 0.000 claims 1
- ROKRZOVDIJHWIB-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-propylbenzoate Chemical compound C1=CC(CCC)=CC=C1C(=O)OC1=CC=C(C(C)N(CC2)C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)C2=C1 ROKRZOVDIJHWIB-UHFFFAOYSA-N 0.000 claims 1
- WJQGMXFNVJFELI-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 4-tert-butylbenzoate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1=CC=C(C(C)(C)C)C=C1 WJQGMXFNVJFELI-UHFFFAOYSA-N 0.000 claims 1
- MIUZSFKJCQNNLJ-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2-chlorobenzoate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)C1=CC=CC=C1Cl MIUZSFKJCQNNLJ-UHFFFAOYSA-N 0.000 claims 1
- JURVLKRHZDVLSE-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 3-(trifluoromethyl)benzoate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)C1=CC=CC(C(F)(F)F)=C1 JURVLKRHZDVLSE-UHFFFAOYSA-N 0.000 claims 1
- AEKZJUBETLRWAH-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 3-cyanobenzoate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)C1=CC=CC(C#N)=C1 AEKZJUBETLRWAH-UHFFFAOYSA-N 0.000 claims 1
- IGHOKMXMBOWXHL-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 3-fluorobenzoate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)C1=CC=CC(F)=C1 IGHOKMXMBOWXHL-UHFFFAOYSA-N 0.000 claims 1
- ILIPORGEJNIDGJ-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 4-methylbenzoate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)C1=CC=C(C)C=C1 ILIPORGEJNIDGJ-UHFFFAOYSA-N 0.000 claims 1
- RSBGNYFOPWXZBK-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 4-nitrobenzoate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)C1=CC=C([N+]([O-])=O)C=C1 RSBGNYFOPWXZBK-UHFFFAOYSA-N 0.000 claims 1
- SMJQMCAVHIEZKG-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 4-pentylbenzoate Chemical compound C1=CC(CCCCC)=CC=C1C(=O)OC1=CC=C(CCN(C2C)C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)C2=C1 SMJQMCAVHIEZKG-UHFFFAOYSA-N 0.000 claims 1
- IWSDEZHPXNCUHQ-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 4-propylbenzoate Chemical compound C1=CC(CCC)=CC=C1C(=O)OC1=CC=C(CCN(C2C)C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)C2=C1 IWSDEZHPXNCUHQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 5
- 239000004480 active ingredient Substances 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 230000001262 anti-secretory effect Effects 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 abstract description 3
- 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 abstract description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 abstract description 2
- 125000006515 benzyloxy alkyl group Chemical group 0.000 abstract description 2
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 abstract 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 229
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 192
- 238000005481 NMR spectroscopy Methods 0.000 description 152
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 147
- 101150041968 CDC13 gene Proteins 0.000 description 114
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 229940086542 triethylamine Drugs 0.000 description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
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- JCYCBQQUWMNQQI-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2-morpholin-4-ylacetate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)CN1CCOCC1 JCYCBQQUWMNQQI-UHFFFAOYSA-N 0.000 description 1
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- SBSHVCBGGJGHKB-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] cyclohexanecarboxylate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1CCCCC1 SBSHVCBGGJGHKB-UHFFFAOYSA-N 0.000 description 1
- VGRYGMABBBLWTJ-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] cyclopropanecarboxylate Chemical compound C=1C=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=1OC(=O)C1CC1 VGRYGMABBBLWTJ-UHFFFAOYSA-N 0.000 description 1
- QCEZGQNHNOZBIN-KEASEGHRSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoate Chemical compound C([C@@H](C(=O)OC1=CC=C2CCN(C(C2=C1)C)C=1C(=C(C)N=C(NC=2C=CC(F)=CC=2)N=1)C)NC(=O)OC(C)(C)C)C1=CC=CC=C1 QCEZGQNHNOZBIN-KEASEGHRSA-N 0.000 description 1
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- NCTDLRAGHORHMC-BIAFCPFJSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] (2s)-4-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate Chemical compound C1CC2=CC=C(OC(=O)[C@H](CC(N)=O)NC(=O)OC(C)(C)C)C=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 NCTDLRAGHORHMC-BIAFCPFJSA-N 0.000 description 1
- HXGGLOQWHMQFPU-GHZUAHJPSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] (2s)-5-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate Chemical compound C1CC2=CC=C(OC(=O)[C@H](CCC(N)=O)NC(=O)OC(C)(C)C)C=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 HXGGLOQWHMQFPU-GHZUAHJPSA-N 0.000 description 1
- RXTZJHRFTRTELV-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound C1CC2=CC=C(OC(=O)CNC(=O)OC(C)(C)C)C=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 RXTZJHRFTRTELV-UHFFFAOYSA-N 0.000 description 1
- OFHRKYRYPQLXPV-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2-morpholin-4-ylacetate;dihydrochloride Chemical compound Cl.Cl.C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)CN1CCOCC1 OFHRKYRYPQLXPV-UHFFFAOYSA-N 0.000 description 1
- AFCZJUXSPKGQAK-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2-phenylmethoxyacetate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)COCC1=CC=CC=C1 AFCZJUXSPKGQAK-UHFFFAOYSA-N 0.000 description 1
- PEKYRTKWJBIZIG-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-yl] 2-thiophen-2-ylacetate Chemical compound C1=C2C(C)N(C=3C(=C(C)N=C(NC=4C=CC(F)=CC=4)N=3)C)CCC2=CC=C1OC(=O)CC1=CC=CS1 PEKYRTKWJBIZIG-UHFFFAOYSA-N 0.000 description 1
- PJTBIKZSXHGTKZ-UHFFFAOYSA-N [2-anilino-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]methanol;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(C)N1C(C(=C(CO)N=1)C)=NC=1NC1=CC=CC=C1 PJTBIKZSXHGTKZ-UHFFFAOYSA-N 0.000 description 1
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- MPDUQYWJSYTCST-UHFFFAOYSA-N [K].FC1=CC(=C(C=C1)[N+](=O)[O-])OC Chemical compound [K].FC1=CC(=C(C=C1)[N+](=O)[O-])OC MPDUQYWJSYTCST-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
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- ZXPJBQLFCRVBDR-UHFFFAOYSA-N acetic acid;methanesulfonic acid Chemical compound CC(O)=O.CS(O)(=O)=O ZXPJBQLFCRVBDR-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
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- 239000003159 antacid agent Substances 0.000 description 1
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- 230000037396 body weight Effects 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-M bromoacetate Chemical compound [O-]C(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-M 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- LLADPGXAIXIKNJ-UHFFFAOYSA-N carbonic acid;2-(4-fluorophenyl)guanidine Chemical compound OC(O)=O.NC(N)=NC1=CC=C(F)C=C1 LLADPGXAIXIKNJ-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229940047583 cetamide Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- AKBSCGOUXFRZRP-UHFFFAOYSA-L dipotassium N-[2-(4-methoxyphenyl)ethyl]acetamide carbonate Chemical compound C([O-])([O-])=O.[K+].COC1=CC=C(C=C1)CCNC(C)=O.[K+] AKBSCGOUXFRZRP-UHFFFAOYSA-L 0.000 description 1
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- 238000006911 enzymatic reaction Methods 0.000 description 1
- CGEGJBMEYWWPNX-UHFFFAOYSA-N ethyl 2-(4-benzylpiperazin-1-yl)acetate Chemical compound C1CN(CC(=O)OCC)CCN1CC1=CC=CC=C1 CGEGJBMEYWWPNX-UHFFFAOYSA-N 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- SITMDWHJQROIPF-UHFFFAOYSA-N ethyl 2-morpholin-4-ylacetate Chemical compound CCOC(=O)CN1CCOCC1 SITMDWHJQROIPF-UHFFFAOYSA-N 0.000 description 1
- LXZHLNWWDDNIOJ-UHFFFAOYSA-N ethyl 2-piperidin-1-ylacetate Chemical compound CCOC(=O)CN1CCCCC1 LXZHLNWWDDNIOJ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229960002523 mercuric chloride Drugs 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- JJUSTAVGGFEOJN-UHFFFAOYSA-N morpholin-4-yl acetate Chemical compound CC(=O)ON1CCOCC1 JJUSTAVGGFEOJN-UHFFFAOYSA-N 0.000 description 1
- MEJJSNJRZUBVCN-UHFFFAOYSA-N n-(4-chloro-5,6-dimethylpyrimidin-2-yl)-4-phenyl-1,3-thiazol-2-amine Chemical compound ClC1=C(C)C(C)=NC(NC=2SC=C(N=2)C=2C=CC=CC=2)=N1 MEJJSNJRZUBVCN-UHFFFAOYSA-N 0.000 description 1
- MDTAQVYGCCBSQV-UHFFFAOYSA-N n-(4-fluorophenyl)-4-(5-methoxy-1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)-5,6-dimethylpyrimidin-2-amine;hydrochloride Chemical compound Cl.C1CC=2C(OC)=CC=CC=2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 MDTAQVYGCCBSQV-UHFFFAOYSA-N 0.000 description 1
- ISUQYJHOJGBBGT-UHFFFAOYSA-N n-(4-fluorophenyl)-4-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine Chemical compound C1CC2=CC=CC=C2C(C)N1C(N=1)=CC(C)=NC=1NC1=CC=C(F)C=C1 ISUQYJHOJGBBGT-UHFFFAOYSA-N 0.000 description 1
- RFOBMWYZVKNDGE-UHFFFAOYSA-N n-(4-fluorophenyl)-5-(methoxymethyl)-4-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine;hydrochloride Chemical compound Cl.N1=C(N2C(C3=CC=CC=C3CC2)C)C(COC)=C(C)N=C1NC1=CC=C(F)C=C1 RFOBMWYZVKNDGE-UHFFFAOYSA-N 0.000 description 1
- BCXMZTBSKMPBRL-UHFFFAOYSA-N n-[4-(3,4-dihydro-1h-isoquinolin-2-yl)-5,6-dimethylpyrimidin-2-yl]-4-methyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=C(C(C)=C(C)N=2)N2CC3=CC=CC=C3CC2)=N1 BCXMZTBSKMPBRL-UHFFFAOYSA-N 0.000 description 1
- KWBOCIMQNXGNRM-UHFFFAOYSA-N n-butyl-4,5-dimethyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine;hydrochloride Chemical compound Cl.CCCCNC1=NC(C)=C(C)C(N2C(C3=CC=CC=C3CC2)C)=N1 KWBOCIMQNXGNRM-UHFFFAOYSA-N 0.000 description 1
- CYLFNDMUNBOSNU-UHFFFAOYSA-N n-butyl-4-(3,4-dihydro-1h-isoquinolin-2-yl)-5,6-dimethylpyrimidin-2-amine;hydrochloride Chemical compound Cl.CCCCNC1=NC(C)=C(C)C(N2CC3=CC=CC=C3CC2)=N1 CYLFNDMUNBOSNU-UHFFFAOYSA-N 0.000 description 1
- XVAPMDMOXIUMHE-UHFFFAOYSA-N n-cyclohexyl-4,5-dimethyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1CCCCC1 XVAPMDMOXIUMHE-UHFFFAOYSA-N 0.000 description 1
- YXJWRKDDWQEOEL-UHFFFAOYSA-N n-cyclohexyl-4-(3,4-dihydro-1h-isoquinolin-2-yl)-5,6-dimethylpyrimidin-2-amine;hydrochloride Chemical compound Cl.N=1C(N2CC3=CC=CC=C3CC2)=C(C)C(C)=NC=1NC1CCCCC1 YXJWRKDDWQEOEL-UHFFFAOYSA-N 0.000 description 1
- CRRTZEDGZCXUFD-UHFFFAOYSA-N n-cyclopentyl-4-(3,4-dihydro-1h-isoquinolin-2-yl)-5,6-dimethylpyrimidin-2-amine;hydrochloride Chemical compound Cl.N=1C(N2CC3=CC=CC=C3CC2)=C(C)C(C)=NC=1NC1CCCC1 CRRTZEDGZCXUFD-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- OEBIHOVSAMBXIB-SJKOYZFVSA-N selitrectinib Chemical compound C[C@@H]1CCC2=NC=C(F)C=C2[C@H]2CCCN2C2=NC3=C(C=NN3C=C2)C(=O)N1 OEBIHOVSAMBXIB-SJKOYZFVSA-N 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1997/10863 | 1997-03-27 | ||
| KR19970010863 | 1997-03-27 | ||
| KR1997/10862 | 1997-03-27 | ||
| KR19970010862 | 1997-03-27 | ||
| PCT/KR1998/000058 WO1998043968A1 (en) | 1997-03-27 | 1998-03-24 | Novel pyrimidine derivatives and processes for the preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2284795A1 CA2284795A1 (en) | 1998-10-08 |
| CA2284795C true CA2284795C (en) | 2004-01-20 |
Family
ID=26632616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002284795A Expired - Fee Related CA2284795C (en) | 1997-03-27 | 1998-03-24 | Novel pyrimidine derivatives and processes for the preparation thereof |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US6352993B1 (OSRAM) |
| EP (1) | EP1015444B1 (OSRAM) |
| JP (1) | JP3176379B2 (OSRAM) |
| KR (1) | KR100278857B1 (OSRAM) |
| CN (1) | CN1118464C (OSRAM) |
| AR (1) | AR012181A1 (OSRAM) |
| AT (1) | ATE241613T1 (OSRAM) |
| AU (1) | AU720385B2 (OSRAM) |
| BR (1) | BR9808070A (OSRAM) |
| CA (1) | CA2284795C (OSRAM) |
| DE (1) | DE69815126T2 (OSRAM) |
| DK (1) | DK1015444T3 (OSRAM) |
| ES (1) | ES2200324T3 (OSRAM) |
| HU (1) | HUP0000851A3 (OSRAM) |
| IN (1) | IN188411B (OSRAM) |
| PT (1) | PT1015444E (OSRAM) |
| RU (1) | RU2203894C2 (OSRAM) |
| TR (1) | TR199902383T2 (OSRAM) |
| TW (1) | TW542831B (OSRAM) |
| UY (1) | UY24938A1 (OSRAM) |
| WO (1) | WO1998043968A1 (OSRAM) |
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| KR100272471B1 (ko) | 1998-11-17 | 2000-11-15 | 김선진 | 신규의 피리미딘 유도체 및 그의 제조방법 |
| US6852739B1 (en) | 1999-02-26 | 2005-02-08 | Nitromed Inc. | Methods using proton pump inhibitors and nitric oxide donors |
| AR038368A1 (es) | 2002-02-01 | 2005-01-12 | Novartis Ag | Compuestos n-pirimidin-2-il-aminas sustituidas como inhibidores de ige, una composicion farmaceutica y el uso de dichos compuestos para la preparacion de un medicamento |
| JP4634144B2 (ja) | 2002-08-01 | 2011-02-16 | ニコックス エスエー | ニトロソ化プロトンポンプ阻害剤、組成物および使用方法 |
| CA2533397A1 (en) * | 2003-07-22 | 2005-02-03 | Neurogen Corporation | Substituted pyridin-2-ylamine analogues |
| WO2005039506A2 (en) * | 2003-10-24 | 2005-05-06 | Exelixis, Inc. | P70s6 kinase modulators and method of use |
| EP1974730A1 (en) | 2003-11-03 | 2008-10-01 | AstraZeneca AB | Imidazo[1,2-a]pyridine derivatives for use in the treatment of sleep disturbance due to silent gastro-esophageal reflux |
| KR101122376B1 (ko) * | 2005-03-09 | 2012-03-26 | 주식회사유한양행 | 신규의 5,6-다이메틸피리미딘 유도체 및 그의 제조방법 |
| US20090124645A1 (en) * | 2005-10-14 | 2009-05-14 | Neurosearch A/S | Novel Pyrimidine-2,4-Diamine Derivatives and their Use as Modulators of Small-Conductance Calcium-Activated Potassium Channels |
| JP4946482B2 (ja) | 2007-02-08 | 2012-06-06 | 船井電機株式会社 | 緩衝用梱包材及びｔｖ受像機の緩衝用梱包材 |
| US8367684B2 (en) * | 2007-06-13 | 2013-02-05 | Valeant Pharmaceuticals International | Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators |
| PL2308877T3 (pl) | 2008-08-05 | 2014-07-31 | Daiichi Sankyo Co Ltd | Pochodne imidazopirydyn-2-onu |
| GB0908394D0 (en) | 2009-05-15 | 2009-06-24 | Univ Leuven Kath | Novel viral replication inhibitors |
| GB0913636D0 (en) | 2009-08-05 | 2009-09-16 | Univ Leuven Kath | Novel viral replication inhibitors |
| US9132129B2 (en) | 2010-11-15 | 2015-09-15 | Katholieke Universiteit Leuven | Antiviral compounds |
| AU2012221925B2 (en) | 2011-02-25 | 2016-05-05 | Yuhan Corporation | Diaminopyrimidine derivatives and processes for the preparation thereof |
| MX2014009933A (es) * | 2012-02-17 | 2015-12-16 | Abbvie Inc | Diaminopirimidinas utiles como inhibidores del virus sincitial respiratorio humano (rsv). |
| US9309271B2 (en) | 2012-05-29 | 2016-04-12 | Momentive Performance Materials Gmbh | Preparation of isocyanato silanes |
| AR093579A1 (es) | 2012-11-21 | 2015-06-10 | Ptc Therapeutics Inc | Inhibidores de bmi-1 de pirimidina inversa sustituida |
| CN105980386B (zh) | 2013-03-13 | 2021-08-13 | 基因泰克公司 | 吡唑并化合物及其用途 |
| EA034866B1 (ru) * | 2013-08-30 | 2020-03-31 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Замещенные пиримидиновые ингибиторы bmi-1 |
| US10125144B2 (en) | 2013-10-07 | 2018-11-13 | Kadmon Corporation, Llc | Rho kinase inhibitors |
| WO2015076800A1 (en) | 2013-11-21 | 2015-05-28 | Ptc Therapeutics, Inc. | Substituted pyridine and pyrazine bmi-1 inhibitors |
| AU2015335980A1 (en) * | 2014-10-22 | 2017-05-18 | Guangzhou Institutes Of Biomedicine And Health, Chinese Academy Of Sciences | Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof |
| CN105669642B (zh) * | 2014-11-19 | 2020-06-09 | 江苏天士力帝益药业有限公司 | 一种盐酸洛氟普啶的制备方法 |
| AU2017205254B2 (en) * | 2016-01-04 | 2021-05-20 | Xoma (Us) Lcc | Alpha-amino esters of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof |
| WO2018184978A1 (de) * | 2017-04-05 | 2018-10-11 | Bayer Cropscience Aktiengesellschaft | 2-amino-5-oxyalkyl-pyrimidinderivate und deren verwendung zur bekämpfung unerwünschten pflanzenwachstums |
| BR112021002630A2 (pt) | 2018-08-17 | 2021-05-11 | Ptc Therapeutics, Inc. | método para tratar câncer pancreático |
| CN114685369B (zh) * | 2022-05-17 | 2024-02-02 | 河南省科学院高新技术研究中心 | 一种利用离子液体制备1-甲基-1,2,3,4-四氢异喹啉的方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US4000138A (en) | 1966-03-31 | 1976-12-28 | Imperial Chemical Industries Limited | Organic compounds and compositions containing them |
| GB1182584A (en) | 1966-03-31 | 1970-02-25 | Ici Ltd | Pyrimidine derivates and the use thereof as fungicides |
| US3980781A (en) | 1966-03-31 | 1976-09-14 | Imperial Chemical Industries Limited | Fungicidal composition and method containing 2-amino-pyrimidines |
| US4044136A (en) | 1972-09-09 | 1977-08-23 | Pfizer Inc. | Aminoquinazoline therapeutic agents |
| GB1383409A (en) | 1972-09-09 | 1974-02-12 | Pfizer Ltd | Derivatives of 2-amino- and 4-amino-quinazoline and pharmaceutical compositions containing them |
| US3956495A (en) | 1973-10-30 | 1976-05-11 | Eli Lilly And Company | 2,4-Diaminoquinazolines as antithrombotic agents |
| US4755218A (en) | 1985-12-31 | 1988-07-05 | Monsanto Company | Haloacyl 1-substituted-1,2,3,4-tetrahydro-isoquinolines as herbicide antidotes |
| GB8621425D0 (en) * | 1986-09-05 | 1986-10-15 | Smith Kline French Lab | Compounds |
| IL88507A (en) * | 1987-12-03 | 1993-02-21 | Smithkline Beckman Intercredit | 2,4-diaminoquinazolines, process for their preparation and pharmaceutical compositions comprising them |
| US4966622A (en) | 1988-04-12 | 1990-10-30 | Ciba-Geigy Corporation | N-phenyl-N-pyrimidin-2-ylureas |
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
| DE3901448A1 (de) | 1989-01-19 | 1990-07-26 | Basf Ag | Emulsionscopolymerisate |
| DE59010042D1 (de) | 1989-03-22 | 1996-02-22 | Ciba Geigy Ag | Schädlingsbekämpfungsmittel |
| CA2015981A1 (en) * | 1989-05-10 | 1990-11-10 | Thomas H. Brown | Compounds |
| GB8910722D0 (en) | 1989-05-10 | 1989-06-28 | Smithkline Beckman Intercredit | Compounds |
| GB9012592D0 (en) | 1990-06-06 | 1990-07-25 | Smithkline Beecham Intercredit | Compounds |
| ATE124694T1 (de) | 1990-11-06 | 1995-07-15 | Pfizer | Chinazolinderivate um die antitumorwirkung zu verbessern. |
| CA2108561A1 (en) * | 1991-04-17 | 1992-10-18 | Jotham W. Coe | Pyrimidine derivatives for enhancing antitumor activity |
| US5276186A (en) | 1992-03-11 | 1994-01-04 | Ciba-Geigy Corporation | Process for the production of guanidine derivatives |
| KR0144833B1 (ko) | 1992-12-28 | 1998-07-15 | 김태훈 | 신규의 퀴나졸린 유도체 및 그의 제조방법 |
| CA2169280A1 (en) * | 1993-08-12 | 1995-02-23 | Robert James Gentile | Amidine derivatives with nitric oxide synthetase activities |
| DK0640599T3 (da) | 1993-08-26 | 1998-09-28 | Ono Pharmaceutical Co | 4-Aminopyrimidin-derivater |
| RU2153494C2 (ru) | 1993-10-12 | 2000-07-27 | Дзе Дюпон Мерк Фармасьютикал Компани | 1-n-алкил-n-арилпиримидинамины, способ лечения заболеваний, фармацевтическая композиция |
| EP0775120B1 (en) * | 1994-08-13 | 2003-06-04 | Yuhan Corporation | Novel pyrimidine derivatives and processes for the preparation thereof |
| ES2165052T3 (es) * | 1996-05-04 | 2002-03-01 | Yuhan Corp | Procedimiento para la preparacion de derivados de pirimidina. |
-
1998
- 1998-03-23 IN IN724DE1998 patent/IN188411B/en unknown
- 1998-03-24 RU RU99122603/04A patent/RU2203894C2/ru not_active IP Right Cessation
- 1998-03-24 DE DE69815126T patent/DE69815126T2/de not_active Expired - Fee Related
- 1998-03-24 AT AT98911242T patent/ATE241613T1/de not_active IP Right Cessation
- 1998-03-24 ES ES98911242T patent/ES2200324T3/es not_active Expired - Lifetime
- 1998-03-24 CA CA002284795A patent/CA2284795C/en not_active Expired - Fee Related
- 1998-03-24 CN CN98803765A patent/CN1118464C/zh not_active Expired - Fee Related
- 1998-03-24 JP JP54148798A patent/JP3176379B2/ja not_active Expired - Fee Related
- 1998-03-24 PT PT98911242T patent/PT1015444E/pt unknown
- 1998-03-24 DK DK98911242T patent/DK1015444T3/da active
- 1998-03-24 EP EP98911242A patent/EP1015444B1/en not_active Expired - Lifetime
- 1998-03-24 TR TR1999/02383T patent/TR199902383T2/xx unknown
- 1998-03-24 HU HU0000851A patent/HUP0000851A3/hu unknown
- 1998-03-24 AU AU65239/98A patent/AU720385B2/en not_active Ceased
- 1998-03-24 US US09/381,814 patent/US6352993B1/en not_active Expired - Fee Related
- 1998-03-24 WO PCT/KR1998/000058 patent/WO1998043968A1/en active IP Right Grant
- 1998-03-24 BR BR9808070-9A patent/BR9808070A/pt not_active Application Discontinuation
- 1998-03-26 UY UY24938A patent/UY24938A1/es not_active IP Right Cessation
- 1998-03-26 AR ARP980101380A patent/AR012181A1/es unknown
- 1998-03-27 KR KR1019980010754A patent/KR100278857B1/ko not_active Expired - Fee Related
- 1998-03-27 TW TW087104605A patent/TW542831B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| UY24938A1 (es) | 2001-01-31 |
| BR9808070A (pt) | 2000-03-08 |
| AU720385B2 (en) | 2000-06-01 |
| HUP0000851A1 (hu) | 2001-04-28 |
| TR199902383T2 (xx) | 2000-06-21 |
| EP1015444A1 (en) | 2000-07-05 |
| RU2203894C2 (ru) | 2003-05-10 |
| KR100278857B1 (ko) | 2001-01-15 |
| JP3176379B2 (ja) | 2001-06-18 |
| ES2200324T3 (es) | 2004-03-01 |
| HUP0000851A3 (en) | 2002-04-29 |
| KR19980080789A (ko) | 1998-11-25 |
| DK1015444T3 (da) | 2003-08-18 |
| PT1015444E (pt) | 2003-10-31 |
| AU6523998A (en) | 1998-10-22 |
| US6352993B1 (en) | 2002-03-05 |
| TW542831B (en) | 2003-07-21 |
| DE69815126D1 (de) | 2003-07-03 |
| WO1998043968A1 (en) | 1998-10-08 |
| HK1026418A1 (en) | 2000-12-15 |
| DE69815126T2 (de) | 2004-04-08 |
| IN188411B (OSRAM) | 2002-09-21 |
| CA2284795A1 (en) | 1998-10-08 |
| AR012181A1 (es) | 2000-09-27 |
| ATE241613T1 (de) | 2003-06-15 |
| EP1015444B1 (en) | 2003-05-28 |
| CN1251586A (zh) | 2000-04-26 |
| CN1118464C (zh) | 2003-08-20 |
| JP2000513014A (ja) | 2000-10-03 |
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