NO803414L - Analogifremgangsmaate for fremstilling av terapeutisk aktive guanidinderivater - Google Patents
Analogifremgangsmaate for fremstilling av terapeutisk aktive guanidinderivaterInfo
- Publication number
- NO803414L NO803414L NO803414A NO803414A NO803414L NO 803414 L NO803414 L NO 803414L NO 803414 A NO803414 A NO 803414A NO 803414 A NO803414 A NO 803414A NO 803414 L NO803414 L NO 803414L
- Authority
- NO
- Norway
- Prior art keywords
- radical
- formula
- carbon atoms
- trifluoroethyl
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 41
- 238000002360 preparation method Methods 0.000 title claims description 33
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title claims description 8
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title description 28
- -1 alkyl radicals Chemical class 0.000 claims description 213
- 150000003254 radicals Chemical class 0.000 claims description 151
- 150000001875 compounds Chemical class 0.000 claims description 143
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 137
- 125000004432 carbon atom Chemical group C* 0.000 claims description 102
- 229910021529 ammonia Inorganic materials 0.000 claims description 67
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 56
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 239000003795 chemical substances by application Substances 0.000 claims description 44
- 239000007858 starting material Substances 0.000 claims description 39
- 229910052717 sulfur Inorganic materials 0.000 claims description 34
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 32
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 32
- 125000004434 sulfur atom Chemical group 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 26
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 25
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 229920006395 saturated elastomer Polymers 0.000 claims description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 15
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 150000002357 guanidines Chemical class 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 150000005840 aryl radicals Chemical class 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 5
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 5
- QWJNFFYFEKXZBF-UHFFFAOYSA-N cyanocyanamide Chemical compound N#CNC#N QWJNFFYFEKXZBF-UHFFFAOYSA-N 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 4
- SOQLEZOUWVWHRF-UHFFFAOYSA-N 1-[4-[4-[[5-[(4-chlorophenyl)methyl]-6-oxo-1h-pyrimidin-2-yl]amino]butyl]-1,3-thiazol-2-yl]-2-(2,2,2-trifluoroethyl)guanidine Chemical compound S1C(NC(N)=NCC(F)(F)F)=NC(CCCCNC=2NC(=O)C(CC=3C=CC(Cl)=CC=3)=CN=2)=C1 SOQLEZOUWVWHRF-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 3
- 229930192474 thiophene Chemical group 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 125000002723 alicyclic group Chemical group 0.000 claims description 2
- 125000004450 alkenylene group Chemical group 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004419 alkynylene group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 150000001555 benzenes Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical group [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims description 2
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 1
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 493
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 370
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 343
- 239000000203 mixture Substances 0.000 description 231
- 239000000243 solution Substances 0.000 description 220
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 198
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 171
- 235000019439 ethyl acetate Nutrition 0.000 description 166
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 124
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 94
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 76
- 239000002904 solvent Substances 0.000 description 74
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 74
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 73
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 69
- 239000011976 maleic acid Substances 0.000 description 69
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 62
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- 238000012746 preparative thin layer chromatography Methods 0.000 description 48
- 239000000706 filtrate Substances 0.000 description 43
- 238000010992 reflux Methods 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
- 238000001704 evaporation Methods 0.000 description 36
- 230000008020 evaporation Effects 0.000 description 36
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 36
- 238000000746 purification Methods 0.000 description 36
- 239000007787 solid Substances 0.000 description 36
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 29
- BGPJLYIFDLICMR-UHFFFAOYSA-N 1,4,2,3-dioxadithiolan-5-one Chemical compound O=C1OSSO1 BGPJLYIFDLICMR-UHFFFAOYSA-N 0.000 description 28
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 28
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- 239000002244 precipitate Substances 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000003085 diluting agent Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- GOXVPASJCHROBY-UHFFFAOYSA-N 1,1,1-trifluoro-2-isothiocyanatoethane Chemical compound FC(F)(F)CN=C=S GOXVPASJCHROBY-UHFFFAOYSA-N 0.000 description 19
- MDNHLFUZGIMIIC-UHFFFAOYSA-N 1-[4-(4-aminobutyl)-1,3-thiazol-2-yl]-2-(2,2,2-trifluoroethyl)guanidine Chemical compound NCCCCC1=CSC(NC(N)=NCC(F)(F)F)=N1 MDNHLFUZGIMIIC-UHFFFAOYSA-N 0.000 description 19
- 239000002024 ethyl acetate extract Substances 0.000 description 18
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 17
- 238000007792 addition Methods 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000001953 recrystallisation Methods 0.000 description 16
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 description 15
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 15
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 15
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 15
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 14
- 229960001340 histamine Drugs 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000000284 extract Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 12
- 229940101209 mercuric oxide Drugs 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 238000009835 boiling Methods 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- NWKIODFPRAEIBS-UHFFFAOYSA-N 1-[4-(2-aminoethylsulfanylmethyl)-1,3-thiazol-2-yl]-2-(2,2,2-trifluoroethyl)guanidine Chemical compound NCCSCC1=CSC(NC(N)=NCC(F)(F)F)=N1 NWKIODFPRAEIBS-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- ZFGQKMRUYLSJBR-UHFFFAOYSA-N 1-[2-(4-aminobutyl)pyrimidin-4-yl]-2-(2,2,2-trifluoroethyl)guanidine Chemical compound NCCCCC1=NC=CC(NC(N)=NCC(F)(F)F)=N1 ZFGQKMRUYLSJBR-UHFFFAOYSA-N 0.000 description 8
- PRQXEAOYRQKQLI-UHFFFAOYSA-N 1-[4-(2-aminoethylsulfanylmethyl)-1,3-thiazol-2-yl]-2-(2,2,3,3-tetrafluoropropyl)guanidine Chemical compound NCCSCC1=CSC(NC(N)=NCC(F)(F)C(F)F)=N1 PRQXEAOYRQKQLI-UHFFFAOYSA-N 0.000 description 8
- WKZUFMHOHQVCJY-UHFFFAOYSA-N 1-[4-(5-aminopentyl)-1,3-thiazol-2-yl]-2-(2,2,2-trifluoroethyl)guanidine Chemical compound NCCCCCC1=CSC(NC(N)=NCC(F)(F)F)=N1 WKZUFMHOHQVCJY-UHFFFAOYSA-N 0.000 description 8
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 125000006351 ethylthiomethyl group Chemical group [H]C([H])([H])C([H])([H])SC([H])([H])* 0.000 description 8
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 8
- IXBPPZBJIFNGJJ-UHFFFAOYSA-N sodium;cyanoiminomethylideneazanide Chemical compound [Na+].N#C[N-]C#N IXBPPZBJIFNGJJ-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- INGPHSZPCRSYLB-UHFFFAOYSA-N 1-[2-(3-aminopropylsulfanyl)pyrimidin-4-yl]-2-(2,2,2-trifluoroethyl)guanidine Chemical compound NCCCSC1=NC=CC(NC(N)=NCC(F)(F)F)=N1 INGPHSZPCRSYLB-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 7
- 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 6
- WVRCYXCWGORVCA-UHFFFAOYSA-N 1-[2-(2-aminoethylsulfanylmethyl)pyrimidin-4-yl]-2-(2,2,2-trifluoroethyl)guanidine Chemical compound NCCSCC1=NC=CC(NC(N)=NCC(F)(F)F)=N1 WVRCYXCWGORVCA-UHFFFAOYSA-N 0.000 description 6
- BSCDWUNYTWSTAF-UHFFFAOYSA-N 1-[4-(2-aminoethylsulfanylmethyl)-1,3-thiazol-2-yl]-2-(2-chloro-2,2-difluoroethyl)guanidine Chemical compound NCCSCC1=CSC(NC(N)=NCC(F)(F)Cl)=N1 BSCDWUNYTWSTAF-UHFFFAOYSA-N 0.000 description 6
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- RBMKPGOYNOCWMP-UHFFFAOYSA-N methyl N-methylsulfonyl-N'-[2-[[2-[[N'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]methylsulfanyl]ethyl]carbamimidothioate Chemical compound CS(=O)(=O)N=C(SC)NCCSCC1=CSC(NC(N)=NCC(F)(F)F)=N1 RBMKPGOYNOCWMP-UHFFFAOYSA-N 0.000 description 1
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- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
- ITOJHPFMLYJRQU-UHFFFAOYSA-N n-(5-methyl-6-oxo-1h-pyrimidin-2-yl)nitramide Chemical compound CC1=CN=C(N[N+]([O-])=O)NC1=O ITOJHPFMLYJRQU-UHFFFAOYSA-N 0.000 description 1
- RVLQUZZFJPNSFR-UHFFFAOYSA-N n-(6-methyl-4-oxo-1h-pyrimidin-2-yl)nitramide Chemical compound CC1=CC(=O)N=C(N[N+]([O-])=O)N1 RVLQUZZFJPNSFR-UHFFFAOYSA-N 0.000 description 1
- IHBCKBDJTATIDP-UHFFFAOYSA-N n-[4-[2-[[n'-(2,2,2-trifluoroethyl)carbamimidoyl]amino]-1,3-thiazol-4-yl]butyl]acetamide Chemical compound CC(=O)NCCCCC1=CSC(NC(N)=NCC(F)(F)F)=N1 IHBCKBDJTATIDP-UHFFFAOYSA-N 0.000 description 1
- DQMWMUMCNOJLSI-UHFFFAOYSA-N n-carbamothioylbenzamide Chemical compound NC(=S)NC(=O)C1=CC=CC=C1 DQMWMUMCNOJLSI-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
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- 230000001175 peptic effect Effects 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
- 229960002695 phenobarbital Drugs 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
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- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 230000001681 protective effect Effects 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- KKKDGYXNGYJJRX-UHFFFAOYSA-M silver nitrite Chemical compound [Ag+].[O-]N=O KKKDGYXNGYJJRX-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
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- 238000011105 stabilization Methods 0.000 description 1
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- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- PGWMQVQLSMAHHO-UHFFFAOYSA-N sulfanylidenesilver Chemical compound [Ag]=S PGWMQVQLSMAHHO-UHFFFAOYSA-N 0.000 description 1
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- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000003357 wound healing promoting agent Substances 0.000 description 1
- GKIRPKYJQBWNGO-QPLCGJKRSA-N zuclomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-QPLCGJKRSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/43—Y being a hetero atom
- C07C323/44—X or Y being nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/24—Derivatives of thiourea containing any of the groups, X being a hetero atom, Y being any atom
- C07C335/28—Y being a hetero atom, e.g. thiobiuret
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
-
- 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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
-
- 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
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
- C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/08—1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB7939232 | 1979-11-13 | ||
GB8012789 | 1980-04-18 | ||
GB8026420 | 1980-08-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
NO803414L true NO803414L (no) | 1981-05-14 |
Family
ID=27260797
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO803414A NO803414L (no) | 1979-11-13 | 1980-11-12 | Analogifremgangsmaate for fremstilling av terapeutisk aktive guanidinderivater |
Country Status (15)
Country | Link |
---|---|
US (3) | US4362728A (ja) |
EP (1) | EP0030092B1 (ja) |
JP (1) | JPH02191247A (ja) |
AU (1) | AU544314B2 (ja) |
CA (1) | CA1136135A (ja) |
DE (1) | DE3070127D1 (ja) |
DK (1) | DK485080A (ja) |
ES (2) | ES496810A0 (ja) |
FI (1) | FI803540L (ja) |
GR (1) | GR71929B (ja) |
IE (1) | IE50440B1 (ja) |
IL (1) | IL61468A0 (ja) |
NO (1) | NO803414L (ja) |
NZ (1) | NZ195568A (ja) |
PT (1) | PT72057B (ja) |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ196923A (en) * | 1980-04-29 | 1983-12-16 | Shionogi & Co | 2-guanidino-4-(-acylaminoalkyl(thio)methyl)thiazoles and analogs |
DE3168031D1 (en) * | 1980-07-30 | 1985-02-14 | Ici Plc | Guanidine derivatives |
WO1982000462A1 (en) * | 1980-08-11 | 1982-02-18 | Rech Syntheses Organ | Imino-alkyl and amino-nitrile cyano-guanidines |
DE3270716D1 (en) * | 1981-02-27 | 1986-05-28 | Ici Plc | Guanidino-substituted heterocyclic derivatives having histamine h-2 antagonist activity |
CA1233818A (en) * | 1981-03-09 | 1988-03-08 | David J. Gilman | Guanidine derivatives as histamine h-2 receptor antagonists |
US4460584A (en) * | 1981-03-13 | 1984-07-17 | Imperial Chemical Industries Plc | Nitrogen heterocycles |
US4463005A (en) * | 1981-03-18 | 1984-07-31 | Imperial Chemical Industries Plc | Bicyclic guanidines |
IN158869B (ja) * | 1981-03-18 | 1987-02-07 | Ici Plc | |
EP0060730A3 (en) * | 1981-03-18 | 1982-12-08 | Imperial Chemical Industries Plc | Bicyclic derivatives |
US4451463A (en) * | 1981-03-24 | 1984-05-29 | Imperial Chemical Industries Plc | Alcohol derivatives |
EP0065823A1 (en) * | 1981-05-13 | 1982-12-01 | Imperial Chemical Industries Plc | Heterocyclic guanidines as histamine H-2 antagonists |
US4526973A (en) * | 1981-05-18 | 1985-07-02 | Bristol-Myers Company | Chemical compounds |
DE3267110D1 (de) * | 1981-05-18 | 1985-12-05 | Ici Plc | Amidine derivatives |
US4522943A (en) * | 1981-05-18 | 1985-06-11 | Bristol-Myers Company | Chemical compounds |
US4546188A (en) * | 1981-05-18 | 1985-10-08 | Bristol-Myers Company | Substituted 1,2-diaminocyclobutene-3,4-diones |
IE53068B1 (en) * | 1981-06-15 | 1988-05-25 | Merck & Co Inc | Diamino isothiazole-1-oxides and -1,1-dioxides as gastic secretion inhibitors |
FI832520L (fi) * | 1982-07-12 | 1984-01-13 | Bristol Myers Co | Farmaceutiska foerfaranden och sammansaettningar |
US4466965A (en) * | 1982-07-26 | 1984-08-21 | American Hospital Supply Corporation | Phthalazine compounds, compositions and use |
GR79384B (ja) * | 1982-08-20 | 1984-10-22 | Hoechst Uk Ltd | |
US4466970A (en) * | 1982-10-02 | 1984-08-21 | Smith Kline & French Laboratories Limited | Dioxocyclobutene compounds |
JPS5995281A (ja) * | 1982-11-19 | 1984-06-01 | Kotobuki Seiyaku Kk | チアゾ−ル誘導体及びその製造方法 |
JPS59104370A (ja) * | 1982-12-03 | 1984-06-16 | Kotobuki Seiyaku Kk | チアゾ−ル誘導体及びその製造方法 |
US4585781A (en) * | 1982-12-31 | 1986-04-29 | Glaxo Group Limited | Heterocyclic derivatives |
DE3334455A1 (de) * | 1983-03-04 | 1984-09-06 | Bayer Ag, 5090 Leverkusen | Guanidin - derivate |
JPS59167570A (ja) * | 1983-03-04 | 1984-09-21 | バイエル・アクチエンゲゼルシヤフト | グアニジン誘導体 |
ES521588A0 (es) * | 1983-03-30 | 1984-08-16 | Ferrer Int | Procedimiento de obtencion de nuevas n-ciano-formamidinas. |
US4567191A (en) * | 1983-06-07 | 1986-01-28 | Merck & Co., Inc. | Amino-phenyl-thiadiazoledioxides as gastric secretion inhibitors |
US4985459A (en) * | 1984-02-08 | 1991-01-15 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising diphenhydramine and methods of using same |
US4906625A (en) * | 1984-02-08 | 1990-03-06 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising diphenhydramine and metyhods of using same |
US4522826A (en) * | 1984-02-08 | 1985-06-11 | Richardson-Vicks Inc. | Analgesic and anti-inflammatory compositions comprising diphenhydramine and methods of using same |
US4683243A (en) * | 1984-02-08 | 1987-07-28 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising diphenhydramine and methods of using same |
US4755532A (en) * | 1984-02-08 | 1988-07-05 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising diphenhydramine and methods of using same |
US4560690A (en) * | 1984-04-30 | 1985-12-24 | Pfizer Inc. | 2-(N-substituted guanidino)-4-hetero-arylthiazole antiulcer agents |
GB8417194D0 (en) * | 1984-07-05 | 1984-08-08 | Boots Co Plc | Therapeutic agents |
KR890014504A (ko) * | 1988-03-11 | 1989-10-24 | 우대규 | 4-(2'-시아노 에틸티오)메틸-2-구아니디노티아졸의 제조방법 |
AU618355B2 (en) * | 1988-05-19 | 1991-12-19 | Hu-Metal Engineering Pty. Ltd. | Improvements relating to plate bending |
US5028716A (en) * | 1989-01-30 | 1991-07-02 | Taisho Pharmaceutical Co., Ltd. | 3,5-diamino-1,2,4-triazole derivatives |
FR2647112A1 (fr) * | 1989-05-22 | 1990-11-23 | Atochem | Composes polyfluoralkyle azotes, leurs procedes de preparation et leurs applications |
WO1994021621A1 (en) * | 1993-03-23 | 1994-09-29 | Astra Aktiebolag | Guanidine derivatives useful in therapy |
US6066740A (en) * | 1997-11-25 | 2000-05-23 | The Procter & Gamble Company | Process for making 2-amino-2-imidazoline, guanidine and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives |
EP2725021A1 (de) | 2008-06-13 | 2014-04-30 | Bayer CropScience AG | Neue heteroaromatische Thioamide als Schädlingsbekämpfungsmittel |
EP2161259A1 (de) | 2008-09-03 | 2010-03-10 | Bayer CropScience AG | 4-Halogenalkylsubstituierte Diaminopyrimidine als Fungizide |
EP4196793A1 (en) | 2020-08-11 | 2023-06-21 | Université de Strasbourg | H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer |
USD1035780S1 (en) * | 2021-01-29 | 2024-07-16 | Fuzhou Leisiao Information Technology Co., Ltd. | Electric scooter |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4165378A (en) * | 1977-04-20 | 1979-08-21 | Ici Americas Inc. | Guanidine derivatives of imidazoles and thiazoles |
IE47044B1 (en) * | 1977-04-20 | 1983-12-14 | Ici Ltd | Guanidine derivatives |
GB2001624B (en) * | 1977-04-20 | 1982-03-03 | Ici Ltd | Guanidine derivatives processes for their manufacture and pharmaceutical compositions containing them |
EP0006679B1 (en) * | 1978-05-24 | 1982-07-21 | Imperial Chemical Industries Plc | Antisecretory thiadiazole derivatives, processes for their manufacture and pharmaceutical compositions containing them |
US4374836A (en) * | 1978-10-16 | 1983-02-22 | Imperial Chemical Industries Ltd. | Antisecretory heterocyclic derivatives, process for their manufacture and pharmaceutical compositions containing them |
EP0010893B1 (en) * | 1978-10-16 | 1984-02-08 | Imperial Chemical Industries Plc | Antisecretory branched-chain heterocyclic guanidine derivatives, processes for their manufacture, intermediates, and pharmaceutical compositions containing said derivatives |
US4200578A (en) * | 1978-12-18 | 1980-04-29 | Bristol-Myers Company | Thiazole derivatives |
JPS6056143B2 (ja) * | 1979-08-02 | 1985-12-09 | 山之内製薬株式会社 | アミジン誘導体ならびにその製造法 |
US4242351A (en) * | 1979-05-07 | 1980-12-30 | Imperial Chemical Industries Limited | Antisecretory oxadiazoles and pharmaceutical compositions containing them |
US4239908A (en) * | 1979-12-10 | 1980-12-16 | G.D. Searle & Co. | N-aralkenyl-N'-cyano-N"-(heterocyclylthioalkyl)-guanidines |
DE3270716D1 (en) * | 1981-02-27 | 1986-05-28 | Ici Plc | Guanidino-substituted heterocyclic derivatives having histamine h-2 antagonist activity |
US4451463A (en) * | 1981-03-24 | 1984-05-29 | Imperial Chemical Industries Plc | Alcohol derivatives |
US4336255A (en) * | 1981-03-24 | 1982-06-22 | Smithkline Corporation | Pharmaceutical compositions containing guanidinopyrimidines |
US4464378A (en) * | 1981-04-28 | 1984-08-07 | University Of Kentucky Research Foundation | Method of administering narcotic antagonists and analgesics and novel dosage forms containing same |
JPS59227870A (ja) * | 1983-06-07 | 1984-12-21 | Yamanouchi Pharmaceut Co Ltd | 新規2−グアニジノチアゾリン誘導体ならびにその製造法 |
-
1980
- 1980-11-07 GR GR63338A patent/GR71929B/el unknown
- 1980-11-11 DE DE8080304023T patent/DE3070127D1/de not_active Expired
- 1980-11-11 EP EP80304023A patent/EP0030092B1/en not_active Expired
- 1980-11-12 FI FI803540A patent/FI803540L/fi not_active Application Discontinuation
- 1980-11-12 US US06/206,005 patent/US4362728A/en not_active Expired - Lifetime
- 1980-11-12 NO NO803414A patent/NO803414L/no unknown
- 1980-11-12 CA CA000364482A patent/CA1136135A/en not_active Expired
- 1980-11-12 IL IL61468A patent/IL61468A0/xx unknown
- 1980-11-13 DK DK485080A patent/DK485080A/da unknown
- 1980-11-13 ES ES496810A patent/ES496810A0/es active Granted
- 1980-11-13 IE IE2359/80A patent/IE50440B1/en unknown
- 1980-11-13 PT PT72057A patent/PT72057B/pt unknown
- 1980-11-14 AU AU64420/80A patent/AU544314B2/en not_active Expired
- 1980-11-17 NZ NZ195568A patent/NZ195568A/xx unknown
-
1981
- 1981-11-30 ES ES507570A patent/ES507570A0/es active Granted
-
1982
- 1982-09-21 US US06/420,863 patent/US4604465A/en not_active Expired - Fee Related
-
1986
- 1986-06-02 US US06/869,615 patent/US4762932A/en not_active Expired - Fee Related
-
1989
- 1989-11-22 JP JP1302281A patent/JPH02191247A/ja active Granted
Also Published As
Publication number | Publication date |
---|---|
US4604465A (en) | 1986-08-05 |
ES8203076A1 (es) | 1982-03-01 |
DK485080A (da) | 1981-05-14 |
EP0030092A1 (en) | 1981-06-10 |
IL61468A0 (en) | 1980-12-31 |
IE50440B1 (en) | 1986-04-16 |
ES8207136A1 (es) | 1982-09-01 |
ES496810A0 (es) | 1982-03-01 |
AU544314B2 (en) | 1985-05-23 |
JPH02191247A (ja) | 1990-07-27 |
GR71929B (ja) | 1983-08-19 |
US4762932A (en) | 1988-08-09 |
AU6438480A (en) | 1981-09-17 |
EP0030092B1 (en) | 1985-02-06 |
NZ195568A (en) | 1983-04-12 |
ES507570A0 (es) | 1982-09-01 |
CA1136135A (en) | 1982-11-23 |
IE802359L (en) | 1981-05-13 |
US4362728A (en) | 1982-12-07 |
PT72057B (en) | 1981-09-24 |
DE3070127D1 (en) | 1985-03-21 |
FI803540L (fi) | 1981-05-14 |
JPH0262547B2 (ja) | 1990-12-26 |
PT72057A (en) | 1980-12-01 |
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