AU720385B2 - Novel pyrimidine derivatives and processes for the preparation thereof - Google Patents
Novel pyrimidine derivatives and processes for the preparation thereof Download PDFInfo
- Publication number
- AU720385B2 AU720385B2 AU65239/98A AU6523998A AU720385B2 AU 720385 B2 AU720385 B2 AU 720385B2 AU 65239/98 A AU65239/98 A AU 65239/98A AU 6523998 A AU6523998 A AU 6523998A AU 720385 B2 AU720385 B2 AU 720385B2
- Authority
- AU
- Australia
- Prior art keywords
- methyl
- pyrimidine
- hydrogen
- dimethyl
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims description 96
- 150000003230 pyrimidines Chemical class 0.000 title claims description 27
- 238000002360 preparation method Methods 0.000 title description 27
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims description 218
- -1 CI-C 3 alkoxyethyl Chemical group 0.000 claims description 77
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 51
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 24
- 229910052736 halogen Chemical group 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
- 125000006515 benzyloxy alkyl group Chemical group 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 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 description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 claims description 3
- 229940061627 chloromethyl methyl ether Drugs 0.000 claims description 3
- 125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 230000002265 prevention Effects 0.000 claims 4
- WTEUBPBTJVSGPF-UHFFFAOYSA-N 2-pyrimidin-4-yl-3,4-dihydro-1h-isoquinoline Chemical class C1CC2=CC=CC=C2CN1C1=CC=NC=N1 WTEUBPBTJVSGPF-UHFFFAOYSA-N 0.000 claims 3
- 101100079984 Caenorhabditis elegans nhr-9 gene Proteins 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 191
- 238000005481 NMR spectroscopy Methods 0.000 description 134
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 119
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 88
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- 229940086542 triethylamine Drugs 0.000 description 63
- IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 39
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- 229940035423 ethyl ether Drugs 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 26
- 230000002829 reductive effect Effects 0.000 description 26
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 19
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 101150041968 CDC13 gene Proteins 0.000 description 13
- 229940093499 ethyl acetate Drugs 0.000 description 13
- 238000010898 silica gel chromatography Methods 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- 102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 108010083204 Proton Pumps Proteins 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 9
- BORJVRHSXJQZQT-UHFFFAOYSA-N 2-(2-chloro-5,6-dimethylpyrimidin-4-yl)-3,4-dihydro-1h-isoquinoline Chemical compound CC1=NC(Cl)=NC(N2CC3=CC=CC=C3CC2)=C1C BORJVRHSXJQZQT-UHFFFAOYSA-N 0.000 description 8
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 8
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
- 229960000381 omeprazole Drugs 0.000 description 8
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical class C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 210000004051 gastric juice Anatomy 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- SCFDZWASOUFVBE-UHFFFAOYSA-N 2-(2-chloro-5,6-dimethylpyrimidin-4-yl)-1-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC=CC=C2C(C)N1C1=NC(Cl)=NC(C)=C1C SCFDZWASOUFVBE-UHFFFAOYSA-N 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- SCPUERXVEBRZMV-UHFFFAOYSA-N 2,4-dichloro-6-(methoxymethyl)-5-methylpyrimidine Chemical compound COCC1=NC(Cl)=NC(Cl)=C1C SCPUERXVEBRZMV-UHFFFAOYSA-N 0.000 description 5
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229940126409 proton pump inhibitor Drugs 0.000 description 5
- 239000000612 proton pump inhibitor Substances 0.000 description 5
- ZYJPUMXJBDHSIF-NSHDSACASA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-NSHDSACASA-N 0.000 description 4
- BFXIDUSEHNCLTP-UHFFFAOYSA-N 2,4-dichloro-5,6-dimethylpyrimidine Chemical compound CC1=NC(Cl)=NC(Cl)=C1C BFXIDUSEHNCLTP-UHFFFAOYSA-N 0.000 description 4
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 4
- ICGYBJNONRDZOP-UHFFFAOYSA-N 2-morpholin-4-ium-4-ylacetic acid;chloride Chemical compound Cl.OC(=O)CN1CCOCC1 ICGYBJNONRDZOP-UHFFFAOYSA-N 0.000 description 4
- WKVJGLBBPPFCGD-UHFFFAOYSA-N 2-piperidin-1-ium-1-ylacetic acid;chloride Chemical compound Cl.OC(=O)CN1CCCCC1 WKVJGLBBPPFCGD-UHFFFAOYSA-N 0.000 description 4
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 4
- ATDWJOOPFDQZNK-UHFFFAOYSA-N N-acetyltyramine Chemical compound CC(=O)NCCC1=CC=C(O)C=C1 ATDWJOOPFDQZNK-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 description 3
- PGASJMSZUPLNTH-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)acetic acid;dihydrochloride Chemical compound Cl.Cl.C1CN(CC(=O)O)CCN1CC1=CC=CC=C1 PGASJMSZUPLNTH-UHFFFAOYSA-N 0.000 description 3
- NRHPBXWENYCPFC-UHFFFAOYSA-N 2-[2-chloro-6-(methoxymethyl)-5-methylpyrimidin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound COCC1=NC(Cl)=NC(N2CC3=CC=CC=C3CC2)=C1C NRHPBXWENYCPFC-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- VMIDQQQAEQXCDJ-UHFFFAOYSA-N 7-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound C1CNC(C)C2=CC(OC)=CC=C21 VMIDQQQAEQXCDJ-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
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 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 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DOIJQFXXQBGGDO-UHFFFAOYSA-N 2-(4-fluoroanilino)-6-methyl-1h-pyrimidin-4-one Chemical compound N1C(C)=CC(=O)N=C1NC1=CC=C(F)C=C1 DOIJQFXXQBGGDO-UHFFFAOYSA-N 0.000 description 2
- DYXPYDSFGXASRO-UHFFFAOYSA-N 2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-7-ol Chemical compound C1CC2=CC=C(O)C=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 DYXPYDSFGXASRO-UHFFFAOYSA-N 0.000 description 2
- DQXIHLOJSHOJMV-UHFFFAOYSA-N 2-[2-chloro-6-(methoxymethyl)-5-methylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinoline Chemical compound COCC1=NC(Cl)=NC(N2C(C3=CC=CC=C3CC2)C)=C1C DQXIHLOJSHOJMV-UHFFFAOYSA-N 0.000 description 2
- GMCUTBZAYPXCOC-UHFFFAOYSA-N 2-methoxy-n-(2-phenylethyl)acetamide Chemical compound COCC(=O)NCCC1=CC=CC=C1 GMCUTBZAYPXCOC-UHFFFAOYSA-N 0.000 description 2
- QKPVEISEHYYHRH-UHFFFAOYSA-N 2-methoxyacetonitrile Chemical compound COCC#N QKPVEISEHYYHRH-UHFFFAOYSA-N 0.000 description 2
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
- XBPOHKGSTPBJOS-UHFFFAOYSA-N 4-(3,4-dihydro-1h-isoquinolin-2-yl)-6-(methoxymethyl)-5-methyl-n-(2-methylphenyl)pyrimidin-2-amine;hydrochloride Chemical compound Cl.N=1C(N2CC3=CC=CC=C3CC2)=C(C)C(COC)=NC=1NC1=CC=CC=C1C XBPOHKGSTPBJOS-UHFFFAOYSA-N 0.000 description 2
- BNRRMRUVYDETQC-UHFFFAOYSA-N 4-fluoro-2-methoxyaniline Chemical compound COC1=CC(F)=CC=C1N BNRRMRUVYDETQC-UHFFFAOYSA-N 0.000 description 2
- KMHLGVTVACLEJE-UHFFFAOYSA-N 4-fluoro-2-methylaniline Chemical compound CC1=CC(F)=CC=C1N KMHLGVTVACLEJE-UHFFFAOYSA-N 0.000 description 2
- RPAIHIMDLRNHLQ-UHFFFAOYSA-N 5,6-dimethyl-2-[(4-methyl-1,3-thiazol-2-yl)amino]-1h-pyrimidin-4-one Chemical compound CC1=CSC(NC=2N=C(O)C(C)=C(C)N=2)=N1 RPAIHIMDLRNHLQ-UHFFFAOYSA-N 0.000 description 2
- XXJBJACMXXZTEM-UHFFFAOYSA-N 5-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound CC1NCCC2=C1C=CC=C2OC XXJBJACMXXZTEM-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- MXMLBPWGHPXZRW-UHFFFAOYSA-N [2-(4-fluoroanilino)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]methanol Chemical compound C1CC2=CC=CC=C2C(C)N1C(C(=C(CO)N=1)C)=NC=1NC1=CC=C(F)C=C1 MXMLBPWGHPXZRW-UHFFFAOYSA-N 0.000 description 2
- RNDRBPVTMKQIBA-UHFFFAOYSA-N [4-(2-acetamidoethyl)phenyl] acetate Chemical compound CC(=O)NCCC1=CC=C(OC(C)=O)C=C1 RNDRBPVTMKQIBA-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 description 2
- 230000001262 anti-secretory effect Effects 0.000 description 2
- 239000012320 chlorinating reagent Substances 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- ODDDUGHVGAOYKN-UHFFFAOYSA-N ethyl 4-methoxy-2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(=O)COC ODDDUGHVGAOYKN-UHFFFAOYSA-N 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 2
- PZTJJIUPKAYECR-UHFFFAOYSA-N n-(4-chloro-5,6-dimethylpyrimidin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=C(Cl)C(C)=C(C)N=2)=N1 PZTJJIUPKAYECR-UHFFFAOYSA-N 0.000 description 2
- AXIVWCJVHLOIHJ-UHFFFAOYSA-N n-(4-fluorophenyl)-4-(methoxymethyl)-6-(6-methoxy-1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)-5-methylpyrimidin-2-amine;hydrochloride Chemical compound Cl.N=1C(N2C(C3=CC=C(OC)C=C3CC2)C)=C(C)C(COC)=NC=1NC1=CC=C(F)C=C1 AXIVWCJVHLOIHJ-UHFFFAOYSA-N 0.000 description 2
- FLOPYZXYIGHBJL-UHFFFAOYSA-N n-[2-(3-methoxyphenyl)ethyl]acetamide Chemical compound COC1=CC=CC(CCNC(C)=O)=C1 FLOPYZXYIGHBJL-UHFFFAOYSA-N 0.000 description 2
- NVSYANRBXPURRQ-UHFFFAOYSA-N naphthalen-1-ylmethanamine Chemical compound C1=CC=C2C(CN)=CC=CC2=C1 NVSYANRBXPURRQ-UHFFFAOYSA-N 0.000 description 2
- 229940117803 phenethylamine Drugs 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 150000003246 quinazolines Chemical class 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 150000003526 tetrahydroisoquinolines Chemical group 0.000 description 2
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- CVQNVDFNUAHUOO-UHFFFAOYSA-N 1-(methoxymethyl)-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2C(COC)NCCC2=C1 CVQNVDFNUAHUOO-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- QPILYVQSKNWRDD-UHFFFAOYSA-N 1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2C(C)NCCC2=C1 QPILYVQSKNWRDD-UHFFFAOYSA-N 0.000 description 1
- REIIYHICFMKMJN-UHFFFAOYSA-N 2-(2-chloro-5,6-dimethylpyrimidin-4-yl)-1-(methoxymethyl)-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC=CC=C2C(COC)N1C1=NC(Cl)=NC(C)=C1C REIIYHICFMKMJN-UHFFFAOYSA-N 0.000 description 1
- WJBMRZAHTUFBGE-UHFFFAOYSA-N 2-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC(CCN)=C1 WJBMRZAHTUFBGE-UHFFFAOYSA-N 0.000 description 1
- FNCALUISHXHMND-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-ium-1-yl)acetate Chemical compound C1CN(CC(=O)[O-])CC[NH+]1CC1=CC=CC=C1 FNCALUISHXHMND-UHFFFAOYSA-N 0.000 description 1
- ATKMTPLTVGOTNA-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)acetic acid ethyl 2-(4-benzylpiperazin-1-yl)acetate dihydrochloride Chemical compound C(C1=CC=CC=C1)N1CCN(CC1)CC(=O)OCC.Cl.Cl.C(C1=CC=CC=C1)N1CCN(CC1)CC(=O)O ATKMTPLTVGOTNA-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- PJHXVERCMAXEDT-UHFFFAOYSA-N 2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol;hydrochloride Chemical compound Cl.C1CC2=CC(O)=C(O)C=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 PJHXVERCMAXEDT-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-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=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-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)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-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)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-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)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-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)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- VXJIVGHBVZDQRF-UHFFFAOYSA-N 2-amino-4-(methoxymethyl)-5-methyl-1H-pyrimidin-6-one 6-(methoxymethyl)-5-methyl-1H-pyrimidine-2,4-dione Chemical compound NC1=NC(=C(C(=N1)O)C)COC.OC1=NC(=C(C(=N1)O)C)COC VXJIVGHBVZDQRF-UHFFFAOYSA-N 0.000 description 1
- BZXNIJWQTYBJGO-UHFFFAOYSA-N 2-amino-6-(methoxymethyl)-5-methyl-1h-pyrimidin-4-one Chemical compound COCC1=NC(N)=NC(O)=C1C BZXNIJWQTYBJGO-UHFFFAOYSA-N 0.000 description 1
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
- QPMFDSFYGZZZFZ-UHFFFAOYSA-N 4-(3,4-dihydro-1h-isoquinolin-2-yl)-5,6-dimethyl-n-propylpyrimidin-2-amine;hydrochloride Chemical compound Cl.CCCNC1=NC(C)=C(C)C(N2CC3=CC=CC=C3CC2)=N1 QPMFDSFYGZZZFZ-UHFFFAOYSA-N 0.000 description 1
- QDKRBQKYUIRUPV-UHFFFAOYSA-N 4-(3,4-dihydro-1h-isoquinolin-2-yl)-n-(4-fluoro-2-methylphenyl)-6-(methoxymethyl)-5-methylpyrimidin-2-amine;hydrochloride Chemical compound Cl.N=1C(N2CC3=CC=CC=C3CC2)=C(C)C(COC)=NC=1NC1=CC=C(F)C=C1C QDKRBQKYUIRUPV-UHFFFAOYSA-N 0.000 description 1
- BHVPHTSORHVUJR-UHFFFAOYSA-N 4-(3,4-dihydro-1h-isoquinolin-2-yl)-n-(4-fluorophenyl)-6-(methoxymethyl)-5-methylpyrimidin-2-amine;hydrochloride Chemical compound Cl.N=1C(N2CC3=CC=CC=C3CC2)=C(C)C(COC)=NC=1NC1=CC=C(F)C=C1 BHVPHTSORHVUJR-UHFFFAOYSA-N 0.000 description 1
- DAERKFQKSUQXQL-UHFFFAOYSA-N 4-(methoxymethyl)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)-n-phenylpyrimidin-2-amine Chemical compound N=1C(N2C(C3=CC=CC=C3CC2)C)=C(C)C(COC)=NC=1NC1=CC=CC=C1 DAERKFQKSUQXQL-UHFFFAOYSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- JTSACJNLRWGUPN-UHFFFAOYSA-N 4-chloro-n-(4-fluorophenyl)-6-methylpyrimidin-2-amine Chemical compound CC1=CC(Cl)=NC(NC=2C=CC(F)=CC=2)=N1 JTSACJNLRWGUPN-UHFFFAOYSA-N 0.000 description 1
- WLKUSVNHZXUEFO-UHFFFAOYSA-N 4-fluoro-2-methoxy-1-nitrobenzene Chemical compound COC1=CC(F)=CC=C1[N+]([O-])=O WLKUSVNHZXUEFO-UHFFFAOYSA-N 0.000 description 1
- SDEBYHVDMCQKNZ-UHFFFAOYSA-N 4-methoxy-6-piperazin-1-ylpyrimidine;hydrochloride Chemical compound Cl.C1=NC(OC)=CC(N2CCNCC2)=N1 SDEBYHVDMCQKNZ-UHFFFAOYSA-N 0.000 description 1
- YQDZFUGKZPLFIH-UHFFFAOYSA-N 4-methyl-1,3-thiazole-2-carboximidamide Chemical compound CC1=CSC(C(N)=N)=N1 YQDZFUGKZPLFIH-UHFFFAOYSA-N 0.000 description 1
- JRTPSRIDBWIDOB-UHFFFAOYSA-N 5,6-dimethyl-2-[(4-phenyl-1,3-thiazol-2-yl)amino]-1h-pyrimidin-4-one Chemical compound OC1=C(C)C(C)=NC(NC=2SC=C(N=2)C=2C=CC=CC=2)=N1 JRTPSRIDBWIDOB-UHFFFAOYSA-N 0.000 description 1
- JVPBCCHBTQZAKW-UHFFFAOYSA-N 5,8-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound CC1NCCC2=C1C(OC)=CC=C2OC JVPBCCHBTQZAKW-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- QQURWFRNETXFTN-UHFFFAOYSA-N 5-fluoro-2-nitrophenol Chemical compound OC1=CC(F)=CC=C1[N+]([O-])=O QQURWFRNETXFTN-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- MUFBHPRPPXNRKQ-UHFFFAOYSA-N 6-(methoxymethyl)-5-methyl-1h-pyrimidine-2,4-dione Chemical compound COCC1=NC(O)=NC(O)=C1C MUFBHPRPPXNRKQ-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- FSCCJTKQQGRDAT-UHFFFAOYSA-N 6-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound CC1NCCC2=CC(OC)=CC=C21 FSCCJTKQQGRDAT-UHFFFAOYSA-N 0.000 description 1
- YRRBATAVUCSTRH-UHFFFAOYSA-N 6-methoxy-1-methyl-3,4-dihydroisoquinoline Chemical compound CC1=NCCC2=CC(OC)=CC=C21 YRRBATAVUCSTRH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- RNXTVCGTCBDFNC-UHFFFAOYSA-N COC=1C=C2CCN=C(C2=CC1)C.COC=1C=C2CCNC(C2=CC1)C Chemical compound COC=1C=C2CCN=C(C2=CC1)C.COC=1C=C2CCNC(C2=CC1)C RNXTVCGTCBDFNC-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 101000659324 Homo sapiens Twinfilin-1 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- VIFWHZYHQSVJGD-UHFFFAOYSA-N N-[2-(4-methoxyphenyl)ethyl]acetamide Chemical compound COC1=CC=C(CCNC(C)=O)C=C1 VIFWHZYHQSVJGD-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- QEXPWXSTGQYTDF-UHFFFAOYSA-N N1(CCCCC1)CC(=O)OCC.Cl.N1(CCCCC1)CC(=O)O Chemical compound N1(CCCCC1)CC(=O)OCC.Cl.N1(CCCCC1)CC(=O)O QEXPWXSTGQYTDF-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100036223 Twinfilin-1 Human genes 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- 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 description 1
- DULGCBBSWTWAKF-UHFFFAOYSA-N [2-(4-fluoroanilino)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]methyl 4-pentylbenzoate Chemical compound C1=CC(CCCCC)=CC=C1C(=O)OCC1=NC(NC=2C=CC(F)=CC=2)=NC(N2C(C3=CC=CC=C3CC2)C)=C1C DULGCBBSWTWAKF-UHFFFAOYSA-N 0.000 description 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 description 1
- DHFLPMASGULHNZ-UHFFFAOYSA-N [2-(4-fluoroanilino)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-4-yl]methyl cyclohexanecarboxylate Chemical compound C1CC2=CC=CC=C2C(C)N1C(C(=C(COC(=O)C1CCCCC1)N=1)C)=NC=1NC1=CC=C(F)C=C1 DHFLPMASGULHNZ-UHFFFAOYSA-N 0.000 description 1
- ZPFZAPAWVYPQQX-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-yl] 2,3-difluorobenzoate 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(F)=C1F ZPFZAPAWVYPQQX-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
- 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
- UUXZYDCWPSFNLU-UHFFFAOYSA-N [2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-3,4-dihydro-1h-isoquinolin-1-yl]methanol Chemical compound N=1C(N2C(C3=CC=CC=C3CC2)CO)=C(C)C(C)=NC=1NC1=CC=C(F)C=C1 UUXZYDCWPSFNLU-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
- YKNZTUQUXUXTLE-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=CC(C(F)(F)F)=C1 YKNZTUQUXUXTLE-UHFFFAOYSA-N 0.000 description 1
- 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
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000004848 alkoxyethyl group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 230000037396 body weight Effects 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
- 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
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 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
- 229940079593 drug Drugs 0.000 description 1
- 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
- FNENWZWNOPCZGK-UHFFFAOYSA-N ethyl 2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(C)=O FNENWZWNOPCZGK-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
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 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
- 229910052749 magnesium 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
- JJUSTAVGGFEOJN-UHFFFAOYSA-N morpholin-4-yl acetate Chemical compound CC(=O)ON1CCOCC1 JJUSTAVGGFEOJN-UHFFFAOYSA-N 0.000 description 1
- VTSRQYDCXGTZMF-UHFFFAOYSA-N n-(4-fluorophenyl)-4-[1-(methoxymethyl)-3,4-dihydro-1h-isoquinolin-2-yl]-5,6-dimethylpyrimidin-2-amine Chemical compound C1CC2=CC=CC=C2C(COC)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 VTSRQYDCXGTZMF-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
- IRPWSONINNCTCG-UHFFFAOYSA-N n-[4,5-dimethyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-yl]-4-methyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=NC(C)=CS1 IRPWSONINNCTCG-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
- BUYRIMYOSPUNJD-UHFFFAOYSA-N n-[4-(3,4-dihydro-1h-isoquinolin-2-yl)-5,6-dimethylpyrimidin-2-yl]-4-phenyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.N=1C(N2CC3=CC=CC=C3CC2)=C(C)C(C)=NC=1NC(SC=1)=NC=1C1=CC=CC=C1 BUYRIMYOSPUNJD-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
- 230000003287 optical effect Effects 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
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 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
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000028327 secretion Effects 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
- 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 |
|---|---|---|---|
| KR19970010863 | 1997-03-27 | ||
| KR9710863 | 1997-03-27 | ||
| KR9710862 | 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 |
|---|---|
| AU6523998A AU6523998A (en) | 1998-10-22 |
| AU720385B2 true AU720385B2 (en) | 2000-06-01 |
Family
ID=26632616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU65239/98A Ceased AU720385B2 (en) | 1997-03-27 | 1998-03-24 | Novel pyrimidine derivatives and processes for the preparation thereof |
Country Status (21)
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO2004012659A2 (en) | 2002-08-01 | 2004-02-12 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| CA2533397A1 (en) * | 2003-07-22 | 2005-02-03 | Neurogen Corporation | Substituted pyridin-2-ylamine analogues |
| US7816353B2 (en) * | 2003-10-24 | 2010-10-19 | Exelixis, Inc. | P70S6 kinase modulators and method of use |
| CA2544325A1 (en) | 2003-11-03 | 2005-05-12 | Astrazeneca Ab | Imidazo [1,2-a] pyridine derivatives for the treatment of silent gastro-esophageal reflux |
| KR101122376B1 (ko) * | 2005-03-09 | 2012-03-26 | 주식회사유한양행 | 신규의 5,6-다이메틸피리미딘 유도체 및 그의 제조방법 |
| JP2009511548A (ja) * | 2005-10-14 | 2009-03-19 | ノイロサーチ アクティーゼルスカブ | 新規ピリミジン−２，４−ジアミン誘導体及び小コンダクタンスのカルシウム依存性カリウムチャネルのモジュレーターとしてのこれらの使用 |
| 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 |
| NZ590688A (en) | 2008-08-05 | 2012-09-28 | Daiichi Sankyo Co Ltd | imidazo[4,5-b]pyridin-2-one derivatives |
| 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 |
| JP2013542243A (ja) | 2010-11-15 | 2013-11-21 | カトリーケ ウニヴェルシテイト ルーヴェン | 新規な抗ウイルス性化合物 |
| BR112013019942B1 (pt) | 2011-02-25 | 2022-01-11 | Yuhan Corporation | Uso de composto ou de seu sal farmaceuticamente aceitável, composição farmacêutica, compostos ou seus sais farmaceuticamente aceitáveis e respectivos processos de preparação |
| CA2864825C (en) * | 2012-02-17 | 2021-01-26 | Abbvie Inc. | Diaminopyrimidines useful as inhibitors of the human respiratory syncytial virus (rsv) |
| KR102080782B1 (ko) | 2012-05-29 | 2020-02-27 | 모멘티브 퍼포먼스 머티리얼즈 게엠베하 | 이소시아네이토 실란의 제조 |
| SG11201503982XA (en) | 2012-11-21 | 2015-06-29 | Ptc Therapeutics Inc | Substituted reverse pyrimidine bmi-1 inhibitors |
| US10035801B2 (en) | 2013-03-13 | 2018-07-31 | Genentech, Inc. | Pyrazolo compounds and uses thereof |
| EP3039015B1 (en) * | 2013-08-30 | 2019-10-30 | PTC Therapeutics, Inc. | Substituted pyrimidine bmi-1 inhibitors |
| ES2779152T3 (es) * | 2013-10-07 | 2020-08-13 | Kadmon Corporation Llc | Derivados de (2-(5-isoindolin-2-il)pirimidin-4-il)-amina como inhibidores de Rho-quinasa para tratar enfermedades autoinmunes |
| US10584115B2 (en) | 2013-11-21 | 2020-03-10 | Ptc Therapeutics, Inc. | Substituted pyridine and pyrazine BMI-1 inhibitors |
| JP2018502900A (ja) * | 2014-10-22 | 2018-02-01 | ザ ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム | ジスコイジンドメイン受容体１を標的化する小分子阻害剤およびその使用 |
| 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 |
| SG10202009769WA (en) * | 2016-01-04 | 2020-11-27 | Merck Serono Sa | L-valinate of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof |
| BR112019020877A2 (pt) * | 2017-04-05 | 2020-05-12 | Bayer Cropscience Aktiengesellschaft | Derivados de 2-amino-5-oxialquil-pirimidina e seu uso para controlar o crescimento de plantas indesejadas |
| CN113164479A (zh) | 2018-08-17 | 2021-07-23 | Ptc医疗公司 | 用于治疗胰腺癌的方法 |
| 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 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| FI95376C (fi) | 1989-03-22 | 1996-01-25 | Ciba Geigy Ag | Mikrobisidiset 2-anilino-pyrimidiinijohdannaiset |
| 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 |
| SK400992A3 (en) | 1990-11-06 | 1995-08-09 | Pfizer | Quinazolines derivatives for enhancing antitumor activity |
| FI934565A7 (fi) | 1991-04-17 | 1993-10-15 | Pfizer | Pyrimidiinijohdannaisia kasvaimenvastaisen vaikutuksen lisäämiseksi |
| 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 |
| WO1995005363A1 (en) * | 1993-08-12 | 1995-02-23 | Astra Aktiebolag | Amidine derivatives with nitric oxide synthetase activities |
| EP0640599B1 (en) | 1993-08-26 | 1998-03-04 | Ono Pharmaceutical Co., Ltd. | 4-Aminopyrimidine derivatives |
| JP3398152B2 (ja) | 1993-10-12 | 2003-04-21 | ブリストル‐マイヤーズ・スクイブ・ファーマ・カンパニー | １ｎ−アルキル−ｎ−アリールピリミジンアミンおよびその誘導体 |
| RU2129549C1 (ru) * | 1994-08-13 | 1999-04-27 | Юхан Корпорейшн | Производные пиримидина и способы их получения |
| CA2358479C (en) * | 1996-05-04 | 2004-07-13 | Yuhan Corporation | 4-substituted-2-(4-fluorophenylamino)-5,6 dimethylpyrimidine |
-
1998
- 1998-03-23 IN IN724DE1998 patent/IN188411B/en unknown
- 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 ES ES98911242T patent/ES2200324T3/es not_active Expired - Lifetime
- 1998-03-24 AU AU65239/98A patent/AU720385B2/en not_active Ceased
- 1998-03-24 AT AT98911242T patent/ATE241613T1/de not_active IP Right Cessation
- 1998-03-24 DE DE69815126T patent/DE69815126T2/de not_active Expired - Fee Related
- 1998-03-24 BR BR9808070-9A patent/BR9808070A/pt not_active Application Discontinuation
- 1998-03-24 PT PT98911242T patent/PT1015444E/pt unknown
- 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 RU RU99122603/04A patent/RU2203894C2/ru not_active IP Right Cessation
- 1998-03-24 JP JP54148798A patent/JP3176379B2/ja not_active Expired - Fee Related
- 1998-03-24 HU HU0000851A patent/HUP0000851A3/hu unknown
- 1998-03-24 TR TR1999/02383T patent/TR199902383T2/xx unknown
- 1998-03-24 EP EP98911242A patent/EP1015444B1/en not_active Expired - Lifetime
- 1998-03-24 DK DK98911242T patent/DK1015444T3/da active
- 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 |
|---|---|
| KR100278857B1 (ko) | 2001-01-15 |
| DK1015444T3 (da) | 2003-08-18 |
| US6352993B1 (en) | 2002-03-05 |
| ES2200324T3 (es) | 2004-03-01 |
| KR19980080789A (ko) | 1998-11-25 |
| TR199902383T2 (xx) | 2000-06-21 |
| WO1998043968A1 (en) | 1998-10-08 |
| EP1015444A1 (en) | 2000-07-05 |
| RU2203894C2 (ru) | 2003-05-10 |
| TW542831B (en) | 2003-07-21 |
| CA2284795C (en) | 2004-01-20 |
| IN188411B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2002-09-21 |
| CA2284795A1 (en) | 1998-10-08 |
| CN1251586A (zh) | 2000-04-26 |
| BR9808070A (pt) | 2000-03-08 |
| DE69815126D1 (de) | 2003-07-03 |
| JP2000513014A (ja) | 2000-10-03 |
| UY24938A1 (es) | 2001-01-31 |
| JP3176379B2 (ja) | 2001-06-18 |
| AR012181A1 (es) | 2000-09-27 |
| EP1015444B1 (en) | 2003-05-28 |
| PT1015444E (pt) | 2003-10-31 |
| HUP0000851A1 (hu) | 2001-04-28 |
| AU6523998A (en) | 1998-10-22 |
| HUP0000851A3 (en) | 2002-04-29 |
| DE69815126T2 (de) | 2004-04-08 |
| HK1026418A1 (en) | 2000-12-15 |
| CN1118464C (zh) | 2003-08-20 |
| ATE241613T1 (de) | 2003-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU720385B2 (en) | Novel pyrimidine derivatives and processes for the preparation thereof | |
| US7094781B2 (en) | Sulfamides and their use as endothelin receptor antagonists | |
| EP1979341B1 (en) | Trisubstituted amine compound | |
| US7173042B2 (en) | Quinoline inhibitors of cGMP phosphodiesterase | |
| ES2381042T3 (es) | Compuestos de amina trisubstituidos como inhibidores de la proteína de transferencia del éster de colesterilo CETP | |
| CN101360723A (zh) | 制备嘧啶二酮衍生物的方法 | |
| JP2018536648A (ja) | 血漿カリクレイン阻害薬としてのヘテロアリールカルボキサミド誘導体 | |
| DK150142B (da) | Analogifremgangsmaade til fremstilling af 5-(2-imidazolin-2-yl)-aminopyrimidiner eller syreadditionssalte deraf | |
| EP1137642B1 (en) | Bis-sulfonamides | |
| CA2241891A1 (en) | Quinolones and their therapeutic use | |
| WO2007075194A1 (en) | Selective benzylamine derivatives and their utility as cholesterol ester-transfer protein inhibitors | |
| KR100835770B1 (ko) | 엔도텔린 길항 활성을 갖는 아릴알칸-설폰아마이드 | |
| US6951856B2 (en) | Arylethene-sulfonamides | |
| CN113891879B (zh) | 3,6-二取代的-2-吡啶醛肟骨架 | |
| KR100272471B1 (ko) | 신규의 피리미딘 유도체 및 그의 제조방법 | |
| CZ12097A3 (en) | Trifluoromethylquinolinecarboxylic acid derivatives and pharmaceutical composition containing thereof | |
| KR20000017194A (ko) | 치환된 피리딘의 제조방법 | |
| WO2002083650A1 (en) | Novel sulfonylamino-pyrimidines | |
| MXPA99008822A (en) | Novel pyrimidine derivatives and processes for the preparation thereof | |
| JPH07238071A (ja) | 置換アミノ基を有する新規キノリン誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |