DE3445192C2 - - Google Patents
Info
- Publication number
- DE3445192C2 DE3445192C2 DE3445192A DE3445192A DE3445192C2 DE 3445192 C2 DE3445192 C2 DE 3445192C2 DE 3445192 A DE3445192 A DE 3445192A DE 3445192 A DE3445192 A DE 3445192A DE 3445192 C2 DE3445192 C2 DE 3445192C2
- Authority
- DE
- Germany
- Prior art keywords
- pyridine
- tetrahydrothiazolo
- guanidino
- methyl
- general formula
- 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
- 150000001875 compounds Chemical class 0.000 claims description 42
- -1 N′-methyl-N-cyanoamidino Chemical group 0.000 claims description 19
- QSLDIPUHQBHQGY-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridine Chemical class C1NCCC2=C1SC=N2 QSLDIPUHQBHQGY-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 150000001718 carbodiimides Chemical class 0.000 claims description 4
- HSKUJSMXADGBSR-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n-(4-methylphenyl)sulfonyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)N1CC(SC(NC(N)=N)=N2)=C2CC1 HSKUJSMXADGBSR-UHFFFAOYSA-N 0.000 claims description 3
- ZZTCMGZOZSJPOV-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n-ethyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1N(C(=O)NCC)CCC2=C1SC(N=C(N)N)=N2 ZZTCMGZOZSJPOV-UHFFFAOYSA-N 0.000 claims description 3
- FTJBELIYPFVLBM-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n-methyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1N(C(=O)NC)CCC2=C1SC(N=C(N)N)=N2 FTJBELIYPFVLBM-UHFFFAOYSA-N 0.000 claims description 3
- QJHYMDXVSYZIDQ-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n-phenyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1C=2SC(NC(=N)N)=NC=2CCN1C(=O)NC1=CC=CC=C1 QJHYMDXVSYZIDQ-UHFFFAOYSA-N 0.000 claims description 3
- LNVAHBMIMOJDRD-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n-propan-2-yl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1N(C(=O)NC(C)C)CCC2=C1SC(N=C(N)N)=N2 LNVAHBMIMOJDRD-UHFFFAOYSA-N 0.000 claims description 3
- XPBZEJDGPJJTBJ-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n-propyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1N(C(=O)NCCC)CCC2=C1SC(N=C(N)N)=N2 XPBZEJDGPJJTBJ-UHFFFAOYSA-N 0.000 claims description 3
- PUFGPNZETYJFGT-UHFFFAOYSA-N n-[amino-[2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-5-yl]methylidene]benzamide Chemical compound C1C=2SC(NC(=N)N)=NC=2CCN1C(N)=NC(=O)C1=CC=CC=C1 PUFGPNZETYJFGT-UHFFFAOYSA-N 0.000 claims description 3
- OWJJIHBYBSZYGT-UHFFFAOYSA-N n-[c-[2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridin-5-yl]-n-methylcarbonimidoyl]benzamide Chemical compound C1CC=2N=C(N=C(N)N)SC=2CN1C(=NC)NC(=O)C1=CC=CC=C1 OWJJIHBYBSZYGT-UHFFFAOYSA-N 0.000 claims description 3
- GPKRPOFIRLMEOS-UHFFFAOYSA-N n-benzyl-2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1C=2SC(NC(=N)N)=NC=2CCN1C(=O)NCC1=CC=CC=C1 GPKRPOFIRLMEOS-UHFFFAOYSA-N 0.000 claims description 3
- UJGSWLRDODLNIJ-UHFFFAOYSA-N n-butyl-2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1N(C(=O)NCCCC)CCC2=C1SC(N=C(N)N)=N2 UJGSWLRDODLNIJ-UHFFFAOYSA-N 0.000 claims description 3
- RNHOTVRMOXKBBZ-UHFFFAOYSA-N n-cyclopentyl-2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1C=2SC(N=C(N)N)=NC=2CCN1C(=O)NC1CCCC1 RNHOTVRMOXKBBZ-UHFFFAOYSA-N 0.000 claims description 3
- IDLFGBDIKSBCRO-UHFFFAOYSA-N n-cyclopropyl-2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1C=2SC(N=C(N)N)=NC=2CCN1C(=O)NC1CC1 IDLFGBDIKSBCRO-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- ZCBZWGQVGHFAOB-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n-propan-2-yl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carbothioamide Chemical compound C1N(C(=S)NC(C)C)CCC2=C1SC(N=C(N)N)=N2 ZCBZWGQVGHFAOB-UHFFFAOYSA-N 0.000 claims description 2
- SWGBJYABDRJAGL-UHFFFAOYSA-N 2-[cyclohexyl-(n'-cyclohexylcarbamimidoyl)amino]-n-propan-2-yl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound S1C=2CN(C(=O)NC(C)C)CCC=2N=C1N(C(N)=NC1CCCCC1)C1CCCCC1 SWGBJYABDRJAGL-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000012948 isocyanate Substances 0.000 claims description 2
- 150000002513 isocyanates Chemical class 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 150000002540 isothiocyanates Chemical class 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- VHBFEIBMZHEWSX-UHFFFAOYSA-N 2-isothiocyanatopropane Chemical compound CC(C)N=C=S VHBFEIBMZHEWSX-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 241000700159 Rattus Species 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 208000007107 Stomach Ulcer Diseases 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 208000025865 Ulcer Diseases 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 231100000397 ulcer Toxicity 0.000 description 6
- RUIDGPOZILPJAW-UHFFFAOYSA-N 2-(4,5,6,7-tetrahydro-[1,3]thiazolo[5,4-c]pyridin-2-yl)guanidine Chemical compound C1CNCC2=C1N=C(NC(=N)N)S2 RUIDGPOZILPJAW-UHFFFAOYSA-N 0.000 description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 3
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 3
- 208000000718 duodenal ulcer Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000026 anti-ulcerogenic effect Effects 0.000 description 2
- 239000003699 antiulcer agent Substances 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 210000001187 pylorus Anatomy 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000013222 sprague-dawley male rat Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- GOPPRSAKKXCXHN-UHFFFAOYSA-N 2-(diaminomethylideneamino)-n'-methyl-n-(4-methylphenyl)sulfonyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboximidamide Chemical compound C1CC=2N=C(N=C(N)N)SC=2CN1C(=NC)NS(=O)(=O)C1=CC=C(C)C=C1 GOPPRSAKKXCXHN-UHFFFAOYSA-N 0.000 description 1
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 1
- PZRSRAUPUQOYQX-UHFFFAOYSA-N 3-bromopiperidin-4-one Chemical compound BrC1CNCCC1=O PZRSRAUPUQOYQX-UHFFFAOYSA-N 0.000 description 1
- VLJQDHDVZJXNQL-UHFFFAOYSA-N 4-methyl-n-(oxomethylidene)benzenesulfonamide Chemical compound CC1=CC=C(S(=O)(=O)N=C=O)C=C1 VLJQDHDVZJXNQL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- JUJABTAZEDTRRH-UHFFFAOYSA-N CS(C)C(S)=NC#N Chemical compound CS(C)C(S)=NC#N JUJABTAZEDTRRH-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010030201 Oesophageal ulcer Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010042220 Stress ulcer Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 1
- FHIMYVFGWKCROK-UHFFFAOYSA-N [1,3]thiazolo[5,4-c]pyridine Chemical compound C1=NC=C2SC=NC2=C1 FHIMYVFGWKCROK-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- CZALJDQHONFVFU-UHFFFAOYSA-N isocyanatocyclopentane Chemical compound O=C=NC1CCCC1 CZALJDQHONFVFU-UHFFFAOYSA-N 0.000 description 1
- DBBRJAWSDTYYBM-UHFFFAOYSA-N isocyanatocyclopropane Chemical compound O=C=NC1CC1 DBBRJAWSDTYYBM-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- BVWJSDIBIJPJDY-UHFFFAOYSA-N methyl 2-(diaminomethylideneamino)-n-(4-methylphenyl)sulfonyl-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboximidothioate Chemical compound C1CC=2N=C(N=C(N)N)SC=2CN1C(SC)=NS(=O)(=O)C1=CC=C(C)C=C1 BVWJSDIBIJPJDY-UHFFFAOYSA-N 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- IXWOGVZXMCVHTQ-UHFFFAOYSA-N methyl n-cyano-2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboximidothioate Chemical compound C1N(C(=NC#N)SC)CCC2=C1SC(NC(N)=N)=N2 IXWOGVZXMCVHTQ-UHFFFAOYSA-N 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- DBFAKALHTSOYSG-UHFFFAOYSA-N n-cyanobenzamide Chemical compound N#CNC(=O)C1=CC=CC=C1 DBFAKALHTSOYSG-UHFFFAOYSA-N 0.000 description 1
- QCXNBYRUMAYSHF-UHFFFAOYSA-N n-cyclohexyl-2-(diaminomethylideneamino)-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxamide Chemical compound C1C=2SC(N=C(N)N)=NC=2CCN1C(=O)NC1CCCCC1 QCXNBYRUMAYSHF-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- 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
-
- 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
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)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB838333514A GB8333514D0 (en) | 1983-12-16 | 1983-12-16 | Tetrahydrothiazolo(5 4-c)pyridine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3445192A1 DE3445192A1 (de) | 1985-06-27 |
| DE3445192C2 true DE3445192C2 (en, 2012) | 1993-02-18 |
Family
ID=10553370
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19843445192 Granted DE3445192A1 (de) | 1983-12-16 | 1984-12-11 | 4,5,6,7-tetrahydrothiazolo(5,4-c) pyridinderivate, verfahren zu deren hestellung und pharmazeutische mittel |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US4624956A (en, 2012) |
| JP (1) | JPS60146893A (en, 2012) |
| KR (1) | KR910009213B1 (en, 2012) |
| AT (1) | AT391701B (en, 2012) |
| AU (1) | AU568894B2 (en, 2012) |
| BE (1) | BE901278A (en, 2012) |
| CA (1) | CA1244827A (en, 2012) |
| CH (1) | CH660739A5 (en, 2012) |
| CS (1) | CS244145B2 (en, 2012) |
| DE (1) | DE3445192A1 (en, 2012) |
| DK (1) | DK598284A (en, 2012) |
| ES (1) | ES8604603A1 (en, 2012) |
| FI (1) | FI77248C (en, 2012) |
| FR (1) | FR2556725B1 (en, 2012) |
| GB (2) | GB8333514D0 (en, 2012) |
| GR (1) | GR81232B (en, 2012) |
| HU (1) | HU193724B (en, 2012) |
| IL (1) | IL73810A (en, 2012) |
| IT (1) | IT1221007B (en, 2012) |
| NL (1) | NL8403801A (en, 2012) |
| NO (1) | NO165595C (en, 2012) |
| NZ (1) | NZ210519A (en, 2012) |
| PH (1) | PH21312A (en, 2012) |
| PT (1) | PT79681B (en, 2012) |
| SE (1) | SE455096B (en, 2012) |
| SU (1) | SU1364240A3 (en, 2012) |
| ZA (1) | ZA849770B (en, 2012) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2173187B (en) * | 1985-03-23 | 1988-05-18 | Erba Farmitalia | Condensed 2-substituted thiazole derivatives |
| JPH03148283A (ja) * | 1989-11-02 | 1991-06-25 | Terumo Corp | チアゾール誘導体またはその塩ならびにこれらを含有する抗潰瘍剤 |
| JPH0618334A (ja) * | 1992-06-29 | 1994-01-25 | Mikuni Seisakusho:Kk | 被加熱物の温度測定装置 |
| CU22676A1 (es) | 1996-06-21 | 2001-11-16 | Univ Las Villas | Composición microcida para el control de contaminantes en procesos de producción de vitroplantas |
| US5718151A (en) * | 1996-10-01 | 1998-02-17 | Breed Automotive Technology, Inc. | Steering wheel mounting |
| AR041952A1 (es) * | 2002-11-14 | 2005-06-01 | Novartis Ag | N-sulfonilaminotiazol |
| CL2004000553A1 (es) * | 2003-03-20 | 2005-02-04 | Actelion Pharmaceuticals Ltd | Uso de compuestos derivados de guanidina como antagonistas del receptor de neuropeptido ff; compuestos derivados de guanidina; procedimientos de preparacion; y composicion farmaceutica que los comprende. |
| SG11202104132WA (en) * | 2018-11-02 | 2021-05-28 | Aicuris Gmbh & Co Kg | Novel urea 6,7-dihydro-4h-thiazolo[5,4-c]pyridines active against the hepatitis b virus (hbv) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1620508A1 (de) * | 1965-07-23 | 1969-09-18 | Thomae Gmbh Dr K | Verfahren zur Herstellung neuer 4,5,6,7-Tetrahydrothiazolo-[5,4-c]-pyridine |
| DE2205065A1 (de) * | 1972-02-03 | 1973-08-16 | Thomae Gmbh Dr K | Neue 4,5,6,7-tetrahydro-thiazolo eckige klammer auf 4,5-c eckige klammer zu pyridine |
| AR208500A1 (es) * | 1972-06-14 | 1977-02-15 | Merck & Co Inc | Procedimiento para la preparacion de derivados de oxazolo(4,5-b)-piridinas |
| CA1131226A (en) * | 1978-09-28 | 1982-09-07 | Tomohiko Munakata | Heterocyclic compounds |
| DE3134933A1 (de) * | 1981-09-03 | 1983-03-31 | Hoechst Ag, 6230 Frankfurt | "harnstoffderivate, verfahren zu ihrer herstellung und diese enthaltende medikamente sowie deren verwendung" |
| CA1260474A (en) * | 1984-12-03 | 1989-09-26 | Raymond A. Stokbroekx | Benzoxazol- and benzothiazolamine derivatives |
-
1983
- 1983-12-16 GB GB838333514A patent/GB8333514D0/en active Pending
-
1984
- 1984-12-05 ES ES538305A patent/ES8604603A1/es not_active Expired
- 1984-12-11 CH CH5893/84A patent/CH660739A5/de not_active IP Right Cessation
- 1984-12-11 GR GR81233A patent/GR81232B/el unknown
- 1984-12-11 AT AT0392484A patent/AT391701B/de not_active IP Right Cessation
- 1984-12-11 CS CS852669A patent/CS244145B2/cs unknown
- 1984-12-11 NZ NZ210519A patent/NZ210519A/en unknown
- 1984-12-11 GB GB08431161A patent/GB2153816B/en not_active Expired
- 1984-12-11 US US06/680,566 patent/US4624956A/en not_active Expired - Fee Related
- 1984-12-11 DE DE19843445192 patent/DE3445192A1/de active Granted
- 1984-12-11 AU AU36517/84A patent/AU568894B2/en not_active Ceased
- 1984-12-12 CA CA000469943A patent/CA1244827A/en not_active Expired
- 1984-12-12 IL IL73810A patent/IL73810A/xx unknown
- 1984-12-12 FI FI844900A patent/FI77248C/fi not_active IP Right Cessation
- 1984-12-12 SE SE8406338A patent/SE455096B/sv not_active IP Right Cessation
- 1984-12-13 DK DK598284A patent/DK598284A/da not_active Application Discontinuation
- 1984-12-13 IT IT24039/84A patent/IT1221007B/it active
- 1984-12-14 PT PT79681A patent/PT79681B/pt unknown
- 1984-12-14 NL NL8403801A patent/NL8403801A/nl not_active Application Discontinuation
- 1984-12-14 PH PH31585A patent/PH21312A/en unknown
- 1984-12-14 HU HU844680A patent/HU193724B/hu not_active IP Right Cessation
- 1984-12-14 KR KR1019840007963A patent/KR910009213B1/ko not_active Expired
- 1984-12-14 BE BE0/214166A patent/BE901278A/fr not_active IP Right Cessation
- 1984-12-14 NO NO845038A patent/NO165595C/no unknown
- 1984-12-14 ZA ZA849770A patent/ZA849770B/xx unknown
- 1984-12-14 JP JP59263149A patent/JPS60146893A/ja active Granted
- 1984-12-14 SU SU843824691A patent/SU1364240A3/ru active
- 1984-12-14 FR FR8419145A patent/FR2556725B1/fr not_active Expired
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| 8127 | New person/name/address of the applicant |
Owner name: FARMITALIA CARLO ERBA S.R.L., MAILAND/MILANO, IT |
|
| 8128 | New person/name/address of the agent |
Representative=s name: EITLE, W., DIPL.-ING. HOFFMANN, K., DIPL.-ING. DR. |
|
| 8110 | Request for examination paragraph 44 | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |