JP3176379B2 - 新規ピリミジン誘導体およびその製造方法 - Google Patents
新規ピリミジン誘導体およびその製造方法Info
- Publication number
- JP3176379B2 JP3176379B2 JP54148798A JP54148798A JP3176379B2 JP 3176379 B2 JP3176379 B2 JP 3176379B2 JP 54148798 A JP54148798 A JP 54148798A JP 54148798 A JP54148798 A JP 54148798A JP 3176379 B2 JP3176379 B2 JP 3176379B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- mmol
- pyrimidine
- dimethyl
- hydrogen
- 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
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 33
- 150000003230 pyrimidines Chemical class 0.000 title claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 214
- -1 C 1 -C 3 alkoxyethyl Chemical group 0.000 claims description 179
- 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 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 150000003839 salts Chemical class 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
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 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
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 4
- 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
- 125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([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
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 claims description 2
- 229940061627 chloromethyl methyl ether Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 234
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 150
- 238000005481 NMR spectroscopy Methods 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 110
- 239000000243 solution Substances 0.000 description 83
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 238000005160 1H NMR spectroscopy Methods 0.000 description 55
- 238000006243 chemical reaction Methods 0.000 description 52
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 46
- 238000002844 melting Methods 0.000 description 46
- 230000008018 melting Effects 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 27
- 230000002829 reductive effect Effects 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 21
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 17
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000010898 silica gel chromatography Methods 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 description 11
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical class C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 10
- 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
- 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 9
- 230000000694 effects Effects 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 239000011259 mixed solution Substances 0.000 description 8
- FEOTVFZHCHZXJX-UHFFFAOYSA-N 2-[2-(4-fluoroanilino)-5,6-dimethylpyrimidin-4-yl]-1-methyl-3,4-dihydro-1h-isoquinolin-6-ol Chemical compound C1CC2=CC(O)=CC=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 FEOTVFZHCHZXJX-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 238000001914 filtration Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229960000381 omeprazole Drugs 0.000 description 7
- BFXIDUSEHNCLTP-UHFFFAOYSA-N 2,4-dichloro-5,6-dimethylpyrimidine Chemical compound CC1=NC(Cl)=NC(Cl)=C1C BFXIDUSEHNCLTP-UHFFFAOYSA-N 0.000 description 6
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 6
- 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 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 229940126409 proton pump inhibitor Drugs 0.000 description 6
- 239000000612 proton pump inhibitor Substances 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 210000004211 gastric acid Anatomy 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000004474 valine Substances 0.000 description 5
- 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 4
- QLJDWNGVIXFBPK-UHFFFAOYSA-N 2-[[4,5-dimethyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-yl]amino]-5-fluorophenol Chemical compound C1CC2=CC=CC=C2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1O QLJDWNGVIXFBPK-UHFFFAOYSA-N 0.000 description 4
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-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
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- SCPUERXVEBRZMV-UHFFFAOYSA-N 2,4-dichloro-6-(methoxymethyl)-5-methylpyrimidine Chemical compound COCC1=NC(Cl)=NC(Cl)=C1C SCPUERXVEBRZMV-UHFFFAOYSA-N 0.000 description 3
- 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 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
- ICGYBJNONRDZOP-UHFFFAOYSA-N 2-morpholin-4-ium-4-ylacetic acid;chloride Chemical compound Cl.OC(=O)CN1CCOCC1 ICGYBJNONRDZOP-UHFFFAOYSA-N 0.000 description 3
- VRDBIJCCXDEZJN-UHFFFAOYSA-N 2-piperidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCCC1 VRDBIJCCXDEZJN-UHFFFAOYSA-N 0.000 description 3
- RQCWFLTXPVGHLK-UHFFFAOYSA-N 4-fluoroaniline;hydrochloride Chemical compound Cl.NC1=CC=C(F)C=C1 RQCWFLTXPVGHLK-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
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- WQVIQDPUBXGLNR-UHFFFAOYSA-N n-(4-fluorophenyl)-4-(methoxymethyl)-6-(6-methoxy-1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)-5-methylpyrimidin-2-amine Chemical compound N=1C(N2C(C3=CC=C(OC)C=C3CC2)C)=C(C)C(COC)=NC=1NC1=CC=C(F)C=C1 WQVIQDPUBXGLNR-UHFFFAOYSA-N 0.000 description 3
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 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
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 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
- CVQNVDFNUAHUOO-UHFFFAOYSA-N 1-(methoxymethyl)-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2C(COC)NCCC2=C1 CVQNVDFNUAHUOO-UHFFFAOYSA-N 0.000 description 2
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 2
- QPILYVQSKNWRDD-UHFFFAOYSA-N 1-methyl-1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2C(C)NCCC2=C1 QPILYVQSKNWRDD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 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
- WKVJGLBBPPFCGD-UHFFFAOYSA-N 2-piperidin-1-ium-1-ylacetic acid;chloride Chemical compound Cl.OC(=O)CN1CCCCC1 WKVJGLBBPPFCGD-UHFFFAOYSA-N 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 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
- BRXVPTDTGZQYPL-UHFFFAOYSA-N 4-(5,8-dimethoxy-1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)-n-(4-fluorophenyl)-5,6-dimethylpyrimidin-2-amine Chemical compound C1CC=2C(OC)=CC=C(OC)C=2C(C)N1C(C(=C(C)N=1)C)=NC=1NC1=CC=C(F)C=C1 BRXVPTDTGZQYPL-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 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 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- VIWZVFVJPXTXPA-UHFFFAOYSA-N N-(2-Carboxymethyl)-morpholine Chemical compound OC(=O)CN1CCOCC1 VIWZVFVJPXTXPA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
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- 230000001262 anti-secretory effect Effects 0.000 description 2
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- 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
- BQKQARGTZMWTMS-GSFCWMEHSA-N [2-[[4,5-dimethyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-yl]amino]-5-fluorophenyl] (2s)-2-amino-3-phenylpropanoate;dihydrochloride Chemical compound Cl.Cl.C([C@H](N)C(=O)OC1=CC(F)=CC=C1NC=1N=C(C(=C(C)N=1)C)N1C(C2=CC=CC=C2CC1)C)C1=CC=CC=C1 BQKQARGTZMWTMS-GSFCWMEHSA-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
- 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 1
- ITEHFPLUJYTGEO-UHFFFAOYSA-N [5-methyl-2-(2-methylanilino)-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=C1C ITEHFPLUJYTGEO-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 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
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 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
- 238000005660 chlorination reaction Methods 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
- 229940125846 compound 25 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000001335 demethylating effect Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 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
- 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 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000002427 irreversible effect Effects 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
- JJUSTAVGGFEOJN-UHFFFAOYSA-N morpholin-4-yl acetate Chemical compound CC(=O)ON1CCOCC1 JJUSTAVGGFEOJN-UHFFFAOYSA-N 0.000 description 1
- MLUPNFFGUXLYQX-UHFFFAOYSA-N n-(2-methoxyethyl)-4,5-dimethyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine;hydrochloride Chemical compound Cl.COCCNC1=NC(C)=C(C)C(N2C(C3=CC=CC=C3CC2)C)=N1 MLUPNFFGUXLYQX-UHFFFAOYSA-N 0.000 description 1
- DJXUZFZDNCZADC-UHFFFAOYSA-N n-(4-fluoro-2-methoxyphenyl)-4,5-dimethyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine Chemical compound COC1=CC(F)=CC=C1NC1=NC(C)=C(C)C(N2C(C3=CC=CC=C3CC2)C)=N1 DJXUZFZDNCZADC-UHFFFAOYSA-N 0.000 description 1
- CHBIIIQJTQLZHT-UHFFFAOYSA-N n-(4-fluorophenyl)-4-(methoxymethyl)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine Chemical compound N=1C(N2C(C3=CC=CC=C3CC2)C)=C(C)C(COC)=NC=1NC1=CC=C(F)C=C1 CHBIIIQJTQLZHT-UHFFFAOYSA-N 0.000 description 1
- RDQUNPMTLOWDGZ-UHFFFAOYSA-N n-(4-fluorophenyl)-4-(methoxymethyl)-5-methyl-6-(1-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyrimidin-2-amine;hydrochloride Chemical compound Cl.N=1C(N2C(C3=CC=CC=C3CC2)C)=C(C)C(COC)=NC=1NC1=CC=C(F)C=C1 RDQUNPMTLOWDGZ-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
- ZDNZYULNJBSIJH-UHFFFAOYSA-N n-(4-fluorophenyl)pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1NC1=NC=CC=N1 ZDNZYULNJBSIJH-UHFFFAOYSA-N 0.000 description 1
- FLOPYZXYIGHBJL-UHFFFAOYSA-N n-[2-(3-methoxyphenyl)ethyl]acetamide Chemical compound COC1=CC=CC(CCNC(C)=O)=C1 FLOPYZXYIGHBJL-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
- 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
- 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
- 239000013642 negative control Substances 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
- 229940117803 phenethylamine Drugs 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
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000013641 positive control Substances 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
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 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
- 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
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 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
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride 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
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 229940095064 tartrate Drugs 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
- 238000005303 weighing Methods 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (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 |
|---|---|---|---|
| KR19970010862 | 1997-03-27 | ||
| KR1997/10862 | 1997-03-27 | ||
| KR1997/10863 | 1997-03-27 | ||
| KR19970010863 | 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 |
|---|---|
| JP2000513014A JP2000513014A (ja) | 2000-10-03 |
| JP3176379B2 true JP3176379B2 (ja) | 2001-06-18 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| JP54148798A Expired - Fee Related JP3176379B2 (ja) | 1997-03-27 | 1998-03-24 | 新規ピリミジン誘導体およびその製造方法 |
Country Status (21)
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|---|---|---|---|---|
| US7721894B2 (en) | 2007-02-08 | 2010-05-25 | Funai Electric Co., Ltd. | Shock-absorbing packing material, and shock-absorbing packing material for television receiver |
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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 |
| TW200302728A (en) | 2002-02-01 | 2003-08-16 | Novartis Ag | Substituted amines as IgE inhibitors |
| WO2004012659A2 (en) | 2002-08-01 | 2004-02-12 | Nitromed, Inc. | Nitrosated proton pump inhibitors, compositions and methods of use |
| WO2005009980A1 (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 |
| WO2005041961A1 (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 |
| 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 |
| US8367684B2 (en) * | 2007-06-13 | 2013-02-05 | Valeant Pharmaceuticals International | Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators |
| CN102171210B (zh) | 2008-08-05 | 2014-04-23 | 第一三共株式会社 | 咪唑并吡啶-2-酮衍生物 |
| 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 |
| MX2013005478A (es) | 2010-11-15 | 2013-08-29 | Univ Leuven Kath | Compuestos heterociclicos condensados antivirales. |
| JP5980236B2 (ja) | 2011-02-25 | 2016-08-31 | ユーハン・コーポレイションＹＵＨＡＮ Ｃｏｒｐｏｒａｔｉｏｎ | ジアミノピリミジン誘導体及びその製造方法 |
| US9447051B2 (en) * | 2012-02-17 | 2016-09-20 | Abbvie Inc. | Diaminopyrimidines and uses thereof |
| CA2873674A1 (en) | 2012-05-29 | 2013-12-05 | Momentive Performance Materials Gmbh | Preparation of isocyanato silanes |
| JP6412503B2 (ja) | 2012-11-21 | 2018-10-24 | ピーティーシー セラピューティクス， インコーポレイテッド | 置換逆ピリミジンＢｍｉ−１阻害剤 |
| WO2014139326A1 (en) | 2013-03-13 | 2014-09-18 | Genentech, Inc. | Pyrazolo compounds and uses thereof |
| JP6524094B2 (ja) * | 2013-08-30 | 2019-06-05 | ピーティーシー セラピューティクス， インコーポレイテッド | 置換ピリミジンＢｍｉ−１阻害剤 |
| US10125144B2 (en) | 2013-10-07 | 2018-11-13 | Kadmon Corporation, Llc | Rho kinase inhibitors |
| EP3071553A4 (en) | 2013-11-21 | 2017-08-02 | PTC Therapeutics, Inc. | Substituted pyridine and pyrazine bmi-1 inhibitors |
| WO2016064970A1 (en) * | 2014-10-22 | 2016-04-28 | The Board Of Regents Of The University Of Texas System | 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 |
| CA3009573A1 (en) * | 2016-01-04 | 2017-07-13 | ObsEva S.A. | Alpha-amino esters of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof |
| JP7107962B2 (ja) * | 2017-04-05 | 2022-07-27 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | ２－アミノ－５－オキシアルキル－ピリミジン誘導体および望ましくない植物成長を防除するためのその使用 |
| US12023335B2 (en) | 2018-08-17 | 2024-07-02 | Ptc Therapeutics, Inc. | Method for treating pancreatic cancer |
| 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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| WO1992018498A1 (en) | 1991-04-17 | 1992-10-29 | Pfizer Inc. | Pyrimidine derivatives for enhancing antitumor activity |
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| US4000138A (en) | 1966-03-31 | 1976-12-28 | Imperial Chemical Industries Limited | Organic compounds and compositions containing them |
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| EP0388838B1 (de) | 1989-03-22 | 1996-01-10 | 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 |
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| SK16396A3 (en) * | 1993-08-12 | 1996-09-04 | Astra Ab | Amidine derivatives with nitric oxide synthetase activities |
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-
1998
- 1998-03-23 IN IN724DE1998 patent/IN188411B/en unknown
- 1998-03-24 AU AU65239/98A patent/AU720385B2/en not_active Ceased
- 1998-03-24 ES ES98911242T patent/ES2200324T3/es not_active Expired - Lifetime
- 1998-03-24 JP JP54148798A patent/JP3176379B2/ja not_active Expired - Fee Related
- 1998-03-24 CA CA002284795A patent/CA2284795C/en not_active Expired - Fee Related
- 1998-03-24 AT AT98911242T patent/ATE241613T1/de not_active IP Right Cessation
- 1998-03-24 HU HU0000851A patent/HUP0000851A3/hu unknown
- 1998-03-24 CN CN98803765A patent/CN1118464C/zh not_active Expired - Fee Related
- 1998-03-24 TR TR1999/02383T patent/TR199902383T2/xx unknown
- 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 RU RU99122603/04A patent/RU2203894C2/ru not_active IP Right Cessation
- 1998-03-24 DK DK98911242T patent/DK1015444T3/da active
- 1998-03-24 DE DE69815126T patent/DE69815126T2/de not_active Expired - Fee Related
- 1998-03-24 EP EP98911242A patent/EP1015444B1/en not_active Expired - Lifetime
- 1998-03-24 BR BR9808070-9A patent/BR9808070A/pt not_active Application Discontinuation
- 1998-03-24 WO PCT/KR1998/000058 patent/WO1998043968A1/en active IP Right Grant
- 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
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| WO1992018498A1 (en) | 1991-04-17 | 1992-10-29 | Pfizer Inc. | Pyrimidine derivatives for enhancing antitumor activity |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7721894B2 (en) | 2007-02-08 | 2010-05-25 | Funai Electric Co., Ltd. | Shock-absorbing packing material, and shock-absorbing packing material for television receiver |
Also Published As
| Publication number | Publication date |
|---|---|
| KR19980080789A (ko) | 1998-11-25 |
| CA2284795A1 (en) | 1998-10-08 |
| WO1998043968A1 (en) | 1998-10-08 |
| RU2203894C2 (ru) | 2003-05-10 |
| AR012181A1 (es) | 2000-09-27 |
| HUP0000851A3 (en) | 2002-04-29 |
| UY24938A1 (es) | 2001-01-31 |
| EP1015444B1 (en) | 2003-05-28 |
| JP2000513014A (ja) | 2000-10-03 |
| TW542831B (en) | 2003-07-21 |
| DE69815126T2 (de) | 2004-04-08 |
| DE69815126D1 (de) | 2003-07-03 |
| US6352993B1 (en) | 2002-03-05 |
| AU6523998A (en) | 1998-10-22 |
| TR199902383T2 (xx) | 2000-06-21 |
| AU720385B2 (en) | 2000-06-01 |
| CN1118464C (zh) | 2003-08-20 |
| BR9808070A (pt) | 2000-03-08 |
| HK1026418A1 (en) | 2000-12-15 |
| CA2284795C (en) | 2004-01-20 |
| ES2200324T3 (es) | 2004-03-01 |
| CN1251586A (zh) | 2000-04-26 |
| ATE241613T1 (de) | 2003-06-15 |
| PT1015444E (pt) | 2003-10-31 |
| HUP0000851A1 (hu) | 2001-04-28 |
| EP1015444A1 (en) | 2000-07-05 |
| IN188411B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2002-09-21 |
| DK1015444T3 (da) | 2003-08-18 |
| KR100278857B1 (ko) | 2001-01-15 |
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