NO843043L - Fremgangsmaate for fremstilling av forbindelser med histamin h2-antagonistvirkning - Google Patents
Fremgangsmaate for fremstilling av forbindelser med histamin h2-antagonistvirkningInfo
- Publication number
- NO843043L NO843043L NO843043A NO843043A NO843043L NO 843043 L NO843043 L NO 843043L NO 843043 A NO843043 A NO 843043A NO 843043 A NO843043 A NO 843043A NO 843043 L NO843043 L NO 843043L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- group
- compounds
- piperidinomethyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 215
- 238000000034 method Methods 0.000 title claims abstract description 24
- 239000003485 histamine H2 receptor antagonist Substances 0.000 title abstract description 6
- 230000000694 effects Effects 0.000 title description 11
- -1 2-guanidinothiazol-4-yl Chemical group 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 239000001301 oxygen Substances 0.000 claims abstract description 13
- 239000005864 Sulphur Substances 0.000 claims abstract description 11
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 10
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 7
- 230000008569 process Effects 0.000 claims abstract description 5
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 44
- 230000002829 reductive effect Effects 0.000 claims description 38
- 239000002904 solvent Substances 0.000 claims description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 21
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 20
- 229910052727 yttrium Inorganic materials 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- LAWSCRRWSNZVTC-UHFFFAOYSA-N 5-amino-2-[3-[3-(piperidin-1-ylmethyl)phenoxy]propyl]-1h-pyrimidin-6-one Chemical compound N1C(=O)C(N)=CN=C1CCCOC1=CC=CC(CN2CCCCC2)=C1 LAWSCRRWSNZVTC-UHFFFAOYSA-N 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000006308 propyl amino group Chemical group 0.000 claims description 6
- 150000003573 thiols Chemical class 0.000 claims description 6
- YGXUTHRSTDOXBA-UHFFFAOYSA-N 5-nitro-2-[3-[3-(piperidin-1-ylmethyl)phenoxy]propyl]-1h-pyrimidin-6-one Chemical compound N1C(=O)C([N+](=O)[O-])=CN=C1CCCOC1=CC=CC(CN2CCCCC2)=C1 YGXUTHRSTDOXBA-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims description 4
- QDYSILPQCCUBTG-UHFFFAOYSA-N 5-amino-2-[3-[4-(piperidin-1-ylmethyl)pyridin-2-yl]oxypropyl]-1h-pyrimidin-6-one Chemical compound N1C(=O)C(N)=CN=C1CCCOC1=CC(CN2CCCCC2)=CC=N1 QDYSILPQCCUBTG-UHFFFAOYSA-N 0.000 claims description 4
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000002243 precursor Substances 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000001119 stannous chloride Substances 0.000 claims description 4
- 235000011150 stannous chloride Nutrition 0.000 claims description 4
- PPOALEXDGIAFQH-UHFFFAOYSA-N 5-amino-2-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1h-pyrimidin-6-one Chemical compound N1C(=O)C(N)=CN=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 PPOALEXDGIAFQH-UHFFFAOYSA-N 0.000 claims description 3
- ZQGXWORHWJBZFZ-UHFFFAOYSA-N 5-amino-2-[3-[3-[(dimethylamino)methyl]phenoxy]propylamino]-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=CC(OCCCNC=2NC(=O)C(N)=CN=2)=C1 ZQGXWORHWJBZFZ-UHFFFAOYSA-N 0.000 claims description 3
- UNLICQAETKKCLB-UHFFFAOYSA-N 5-amino-2-[3-[4-(piperidin-1-ylmethyl)pyridin-2-yl]oxypropylamino]-1h-pyrimidin-6-one Chemical compound N1C(=O)C(N)=CN=C1NCCCOC1=CC(CN2CCCCC2)=CC=N1 UNLICQAETKKCLB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- TZNOVWOLKZSGNF-UHFFFAOYSA-N n-[6-oxo-2-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1h-pyrimidin-5-yl]acetamide Chemical compound N1C(=O)C(NC(=O)C)=CN=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 TZNOVWOLKZSGNF-UHFFFAOYSA-N 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- UHKTYBSUZMWAAK-UHFFFAOYSA-N 5-amino-6-methyl-2-[3-[3-(piperidin-1-ylmethyl)phenoxy]propyl]-1h-pyrimidin-4-one Chemical compound O=C1C(N)=C(C)NC(CCCOC=2C=C(CN3CCCCC3)C=CC=2)=N1 UHKTYBSUZMWAAK-UHFFFAOYSA-N 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 12
- 239000000543 intermediate Substances 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 52
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 229960001340 histamine Drugs 0.000 description 26
- 239000000203 mixture Substances 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 229910052794 bromium Chemical group 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- ZHQPCZZUXLSAAB-UHFFFAOYSA-N 2-methylsulfanyl-5-nitro-1h-pyrimidin-6-one Chemical compound CSC1=NC=C([N+]([O-])=O)C(O)=N1 ZHQPCZZUXLSAAB-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 6
- BWPREQYEXQAUOY-UHFFFAOYSA-N 5-nitro-2-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1h-pyrimidin-6-one Chemical compound N1C(=O)C([N+](=O)[O-])=CN=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 BWPREQYEXQAUOY-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 239000002026 chloroform extract Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 150000002828 nitro derivatives Chemical class 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical group O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 3
- VDIJHKXJTRVWFY-UHFFFAOYSA-N 5-nitro-2-[3-[4-(piperidin-1-ylmethyl)pyridin-2-yl]oxypropyl]-1h-pyrimidin-6-one Chemical compound N1C(=O)C([N+](=O)[O-])=CN=C1CCCOC1=CC(CN2CCCCC2)=CC=N1 VDIJHKXJTRVWFY-UHFFFAOYSA-N 0.000 description 3
- XJLMOWQXFCKYJR-UHFFFAOYSA-N 5-nitro-2-[3-[4-(piperidin-1-ylmethyl)pyridin-2-yl]oxypropylamino]-1h-pyrimidin-6-one Chemical compound N1C(=O)C([N+](=O)[O-])=CN=C1NCCCOC1=CC(CN2CCCCC2)=CC=N1 XJLMOWQXFCKYJR-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 125000005236 alkanoylamino group Chemical group 0.000 description 3
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 3
- 229960001380 cimetidine Drugs 0.000 description 3
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 3
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 2
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 description 2
- VQSXCZMVUMSITD-UHFFFAOYSA-N 3-[3-(piperidin-1-ylmethyl)phenoxy]propan-1-amine Chemical compound NCCCOC1=CC=CC(CN2CCCCC2)=C1 VQSXCZMVUMSITD-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- HSGQGWSJZKKFKE-UHFFFAOYSA-N 4-[3-(piperidin-1-ylmethyl)phenoxy]butanenitrile Chemical compound N#CCCCOC1=CC=CC(CN2CCCCC2)=C1 HSGQGWSJZKKFKE-UHFFFAOYSA-N 0.000 description 2
- OJFCZXVFDVJSNX-UHFFFAOYSA-N 5-nitro-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound [O-][N+](=O)C1=CNC(=S)NC1=O OJFCZXVFDVJSNX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 102000003710 Histamine H2 Receptors Human genes 0.000 description 2
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
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- 239000000829 suppository Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 239000012178 vegetable wax Substances 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB838320505A GB8320505D0 (en) | 1983-07-29 | 1983-07-29 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO843043L true NO843043L (no) | 1985-01-30 |
Family
ID=10546495
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO843043A NO843043L (no) | 1983-07-29 | 1984-07-27 | Fremgangsmaate for fremstilling av forbindelser med histamin h2-antagonistvirkning |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0134096B1 (fi) |
| JP (1) | JPS6051179A (fi) |
| KR (1) | KR850001174A (fi) |
| AT (1) | ATE40552T1 (fi) |
| AU (1) | AU564650B2 (fi) |
| CA (1) | CA1261831A (fi) |
| CS (1) | CS244448B2 (fi) |
| DD (1) | DD216933A5 (fi) |
| DE (1) | DE3476541D1 (fi) |
| DK (1) | DK368284A (fi) |
| ES (1) | ES534620A0 (fi) |
| FI (1) | FI842976A (fi) |
| GB (1) | GB8320505D0 (fi) |
| GR (1) | GR82226B (fi) |
| HU (1) | HUT34743A (fi) |
| IL (1) | IL72491A0 (fi) |
| JO (1) | JO1327B1 (fi) |
| NO (1) | NO843043L (fi) |
| PT (1) | PT78977B (fi) |
| ZA (1) | ZA845820B (fi) |
| ZW (1) | ZW11584A1 (fi) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4772704A (en) * | 1983-09-21 | 1988-09-20 | Bristol-Myers Company | 2,5-disubstituted-4(3H)-pyrimidones having histamine H2 -receptor antagonist activity |
| GB8421427D0 (en) * | 1984-08-23 | 1984-09-26 | Smith Kline French Lab | Chemical compounds |
| JP2007531753A (ja) | 2004-03-31 | 2007-11-08 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 非イミダゾール系複素環式化合物 |
| AU2007256931B2 (en) | 2006-05-30 | 2013-01-24 | Janssen Pharmaceutica N.V. | Substituted pyridyl amide compounds as modulators of the histamine H3 receptor |
| KR101546712B1 (ko) | 2007-11-20 | 2015-08-24 | 얀센 파마슈티카 엔.브이. | 히스타민 ｈ3 수용체의 조절제로서 사이클로알킬옥시- 및 헤테로사이클로알킬옥시피리딘 화합물 |
| WO2022034121A1 (en) | 2020-08-11 | 2022-02-17 | Université De Strasbourg | H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN151188B (fi) * | 1978-02-13 | 1983-03-05 | Smith Kline French Lab | |
| ZA793443B (en) * | 1978-07-26 | 1980-12-31 | Glaxo Group Ltd | Heterocyclic derivatives |
| US4496567A (en) * | 1978-11-13 | 1985-01-29 | Smith Kline & French Laboratories Limited | Phenyl alkylaminopyrimidones |
| US4521418A (en) * | 1979-02-21 | 1985-06-04 | Smith Kline & French Laboratories Limited | Guanidinothiazolyl derivatives |
| ZW21281A1 (en) * | 1980-10-01 | 1981-11-18 | Smith Kline French Lab | Amine derivatives |
| NZ202797A (en) * | 1981-12-28 | 1985-08-30 | Lilly Co Eli | Pyrimidine derivatives and pharmaceutical compositions |
-
1983
- 1983-07-29 GB GB838320505A patent/GB8320505D0/en active Pending
-
1984
- 1984-07-18 JO JO19841327A patent/JO1327B1/en active
- 1984-07-23 GR GR75407A patent/GR82226B/el unknown
- 1984-07-24 AU AU30991/84A patent/AU564650B2/en not_active Ceased
- 1984-07-24 CA CA000459505A patent/CA1261831A/en not_active Expired
- 1984-07-25 IL IL72491A patent/IL72491A0/xx unknown
- 1984-07-25 PT PT78977A patent/PT78977B/pt unknown
- 1984-07-25 AT AT84305045T patent/ATE40552T1/de not_active IP Right Cessation
- 1984-07-25 EP EP84305045A patent/EP0134096B1/en not_active Expired
- 1984-07-25 DE DE8484305045T patent/DE3476541D1/de not_active Expired
- 1984-07-26 ES ES534620A patent/ES534620A0/es active Granted
- 1984-07-26 FI FI842976A patent/FI842976A/fi not_active Application Discontinuation
- 1984-07-27 JP JP59158537A patent/JPS6051179A/ja active Pending
- 1984-07-27 ZW ZW115/84A patent/ZW11584A1/xx unknown
- 1984-07-27 ZA ZA845820A patent/ZA845820B/xx unknown
- 1984-07-27 DK DK368284A patent/DK368284A/da not_active Application Discontinuation
- 1984-07-27 DD DD84265728A patent/DD216933A5/de unknown
- 1984-07-27 CS CS845810A patent/CS244448B2/cs unknown
- 1984-07-27 KR KR1019840004474A patent/KR850001174A/ko not_active Application Discontinuation
- 1984-07-27 HU HU842902A patent/HUT34743A/hu unknown
- 1984-07-27 NO NO843043A patent/NO843043L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS581084A2 (en) | 1985-08-15 |
| FI842976A (fi) | 1985-01-30 |
| DE3476541D1 (de) | 1989-03-09 |
| ES8600254A1 (es) | 1985-09-16 |
| PT78977B (en) | 1986-06-05 |
| EP0134096B1 (en) | 1989-02-01 |
| GB8320505D0 (en) | 1983-09-01 |
| GR82226B (fi) | 1984-12-13 |
| EP0134096A2 (en) | 1985-03-13 |
| FI842976A0 (fi) | 1984-07-26 |
| ES534620A0 (es) | 1985-09-16 |
| ZW11584A1 (en) | 1985-04-17 |
| KR850001174A (ko) | 1985-03-16 |
| IL72491A0 (en) | 1984-11-30 |
| ZA845820B (en) | 1985-06-26 |
| DK368284D0 (da) | 1984-07-27 |
| JO1327B1 (en) | 1986-11-30 |
| EP0134096A3 (en) | 1985-12-18 |
| AU564650B2 (en) | 1987-08-20 |
| HUT34743A (en) | 1985-04-28 |
| ATE40552T1 (de) | 1989-02-15 |
| CS244448B2 (en) | 1986-07-17 |
| AU3099184A (en) | 1985-01-31 |
| DD216933A5 (de) | 1985-01-02 |
| PT78977A (en) | 1984-08-01 |
| CA1261831A (en) | 1989-09-26 |
| DK368284A (da) | 1985-01-30 |
| JPS6051179A (ja) | 1985-03-22 |
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