CA1097635A - 2,6-bis-(aminoacylamino)-benzo-[1,2-d:5,4-d']- bisthiazoles and 2-amino-6-(aminoacylamino)-benzo- [1,2-d:5,4-d']-bisthiazoles, processes for the production and pharmaceuticals - Google Patents
2,6-bis-(aminoacylamino)-benzo-[1,2-d:5,4-d']- bisthiazoles and 2-amino-6-(aminoacylamino)-benzo- [1,2-d:5,4-d']-bisthiazoles, processes for the production and pharmaceuticalsInfo
- Publication number
- CA1097635A CA1097635A CA309,176A CA309176A CA1097635A CA 1097635 A CA1097635 A CA 1097635A CA 309176 A CA309176 A CA 309176A CA 1097635 A CA1097635 A CA 1097635A
- Authority
- CA
- Canada
- Prior art keywords
- benzo
- bisthiazole
- bis
- group
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 54
- 238000004519 manufacturing process Methods 0.000 title claims 17
- 239000003814 drug Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 87
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 239000000460 chlorine Substances 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 22
- 239000002253 acid Substances 0.000 claims abstract description 21
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 6
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000002252 acyl group Chemical group 0.000 claims abstract description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract 3
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims abstract 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 50
- -1 piperazino group Chemical group 0.000 claims description 43
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 40
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 9
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 7
- 150000001413 amino acids Chemical class 0.000 claims description 7
- 239000012312 sodium hydride Substances 0.000 claims description 7
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 230000000802 nitrating effect Effects 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 229940060038 chlorine Drugs 0.000 claims 12
- 235000017168 chlorine Nutrition 0.000 claims 12
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 6
- OKQWARPWVZPKLV-UHFFFAOYSA-N 2-(diethylamino)-n-[2-[[2-(diethylamino)acetyl]amino]-[1,3]thiazolo[4,5-f][1,3]benzothiazol-6-yl]acetamide Chemical compound C1=C2SC(NC(=O)CN(CC)CC)=NC2=CC2=C1SC(NC(=O)CN(CC)CC)=N2 OKQWARPWVZPKLV-UHFFFAOYSA-N 0.000 claims 3
- 125000001246 bromo group Chemical group Br* 0.000 claims 3
- VBACVKROBJUHLJ-UHFFFAOYSA-N 2-(dimethylamino)-n-[2-[[2-(dimethylamino)acetyl]amino]-[1,3]thiazolo[4,5-f][1,3]benzothiazol-6-yl]acetamide Chemical compound C1=C2SC(NC(=O)CN(C)C)=NC2=CC2=C1SC(NC(=O)CN(C)C)=N2 VBACVKROBJUHLJ-UHFFFAOYSA-N 0.000 claims 2
- NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical group CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 claims 2
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical group CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 claims 2
- ALSFHDCCAKIYIQ-UHFFFAOYSA-N [1,3]thiazolo[4,5-f][1,3]benzothiazole-2,6-diamine Chemical compound C1=C2SC(N)=NC2=CC2=C1SC(N)=N2 ALSFHDCCAKIYIQ-UHFFFAOYSA-N 0.000 claims 2
- UKKUUBZCPIEACO-UHFFFAOYSA-N n-[4-bromo-8-chloro-2-[[2-(diethylamino)acetyl]amino]-[1,3]thiazolo[4,5-f][1,3]benzothiazol-6-yl]-2-(diethylamino)acetamide Chemical compound ClC1=C2SC(NC(=O)CN(CC)CC)=NC2=C(Br)C2=C1SC(NC(=O)CN(CC)CC)=N2 UKKUUBZCPIEACO-UHFFFAOYSA-N 0.000 claims 2
- YZGKGEAJWZTAFP-UHFFFAOYSA-N n-[8-bromo-4-chloro-2-[[2-(diethylamino)acetyl]amino]-[1,3]thiazolo[4,5-f][1,3]benzothiazol-6-yl]-2-(diethylamino)acetamide Chemical compound BrC1=C2SC(NC(=O)CN(CC)CC)=NC2=C(Cl)C2=C1SC(NC(=O)CN(CC)CC)=N2 YZGKGEAJWZTAFP-UHFFFAOYSA-N 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- SGXDXUYKISDCAZ-UHFFFAOYSA-N N,N-diethylglycine Chemical compound CCN(CC)CC(O)=O SGXDXUYKISDCAZ-UHFFFAOYSA-N 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- BGCNBOFPABQGNG-UHFFFAOYSA-N ethyl 2-(dimethylamino)acetate Chemical compound CCOC(=O)CN(C)C BGCNBOFPABQGNG-UHFFFAOYSA-N 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- XVFSSYSVHOICOH-UHFFFAOYSA-N n-[4,8-dichloro-2-[[2-(diethylamino)acetyl]amino]-[1,3]thiazolo[4,5-f][1,3]benzothiazol-6-yl]-2-(diethylamino)acetamide Chemical compound ClC1=C2SC(NC(=O)CN(CC)CC)=NC2=C(Cl)C2=C1SC(NC(=O)CN(CC)CC)=N2 XVFSSYSVHOICOH-UHFFFAOYSA-N 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 abstract description 5
- 230000002456 anti-arthritic effect Effects 0.000 abstract description 3
- 239000003435 antirheumatic agent Substances 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 3
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 90
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 84
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 82
- 239000000203 mixture Substances 0.000 description 49
- 229960001701 chloroform Drugs 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 25
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
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- 239000000725 suspension Substances 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
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- 125000000623 heterocyclic group Chemical group 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
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- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
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- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- YJKWUTICFWAHDC-UHFFFAOYSA-N 2-[di(propan-2-yl)amino]butanoic acid Chemical compound CCC(C(O)=O)N(C(C)C)C(C)C YJKWUTICFWAHDC-UHFFFAOYSA-N 0.000 description 1
- YCWXOQCYLKOSKL-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)benzene-1,3-diamine Chemical compound NC1=CC(C(F)(F)F)=CC(N)=C1Cl YCWXOQCYLKOSKL-UHFFFAOYSA-N 0.000 description 1
- AJYCIEHSLYUBEI-UHFFFAOYSA-N 3,5-diamino-4-chlorobenzonitrile Chemical compound NC1=CC(C#N)=CC(N)=C1Cl AJYCIEHSLYUBEI-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- JEGMWWXJUXDNJN-UHFFFAOYSA-N 3-methylpiperidine Chemical compound CC1CCCNC1 JEGMWWXJUXDNJN-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 241000518994 Conta Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910001963 alkali metal nitrate Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229940089960 chloroacetate Drugs 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 239000001926 citrus aurantium l. subsp. bergamia wright et arn. oil Substances 0.000 description 1
- 239000008199 coating composition Substances 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- ORRQJZMYQQDYDX-UHFFFAOYSA-N ethyl 2-(diethylamino)acetate Chemical compound CCOC(=O)CN(CC)CC ORRQJZMYQQDYDX-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- KUHRIIPUCPOQMQ-UHFFFAOYSA-N n,n-diethyl-3-(ethyliminomethylideneamino)propan-1-amine Chemical compound CCN=C=NCCCN(CC)CC KUHRIIPUCPOQMQ-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- FRZHHZDISMDVDV-UHFFFAOYSA-N phenyl 2-(diethylamino)acetate Chemical compound CCN(CC)CC(=O)OC1=CC=CC=C1 FRZHHZDISMDVDV-UHFFFAOYSA-N 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[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
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000008096 xylene Substances 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP2736652.5 | 1977-08-13 | ||
| DE19772736652 DE2736652A1 (de) | 1977-08-13 | 1977-08-13 | 2,6-bis-(aminocylamino)-benzo- eckige klammer auf 1,2-d zu 5,4-d' eckige klammer zu -bisthiazole und 2-amino-6-(aminoacylamino)-benzo- eckige klammer auf 1,2-d zu 5,4-d' eckige klammer zu -bisthiazole, verfahren zu ihrer herstellung und arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1097635A true CA1097635A (en) | 1981-03-17 |
Family
ID=6016379
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA309,176A Expired CA1097635A (en) | 1977-08-13 | 1978-08-11 | 2,6-bis-(aminoacylamino)-benzo-[1,2-d:5,4-d']- bisthiazoles and 2-amino-6-(aminoacylamino)-benzo- [1,2-d:5,4-d']-bisthiazoles, processes for the production and pharmaceuticals |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US4344946A (en, 2012) |
| JP (1) | JPS5432495A (en, 2012) |
| AT (1) | AT356664B (en, 2012) |
| AU (1) | AU518652B2 (en, 2012) |
| BE (1) | BE869714A (en, 2012) |
| BG (1) | BG30774A3 (en, 2012) |
| CA (1) | CA1097635A (en, 2012) |
| CH (1) | CH639976A5 (en, 2012) |
| CS (1) | CS209542B2 (en, 2012) |
| DD (1) | DD140253A5 (en, 2012) |
| DE (1) | DE2736652A1 (en, 2012) |
| DK (1) | DK157762C (en, 2012) |
| ES (1) | ES472544A1 (en, 2012) |
| FI (1) | FI63415C (en, 2012) |
| FR (1) | FR2400027A1 (en, 2012) |
| GB (2) | GB2002383B (en, 2012) |
| GR (1) | GR65027B (en, 2012) |
| HU (1) | HU176066B (en, 2012) |
| IE (1) | IE47308B1 (en, 2012) |
| IL (1) | IL55335A0 (en, 2012) |
| IT (1) | IT1107969B (en, 2012) |
| LU (1) | LU80103A1 (en, 2012) |
| NL (1) | NL189611C (en, 2012) |
| NO (1) | NO153851C (en, 2012) |
| NZ (1) | NZ188122A (en, 2012) |
| PL (1) | PL118018B1 (en, 2012) |
| PT (1) | PT68418A (en, 2012) |
| RO (1) | RO75639A (en, 2012) |
| SE (1) | SE442511B (en, 2012) |
| SU (1) | SU847924A3 (en, 2012) |
| ZA (1) | ZA784569B (en, 2012) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8203001B2 (en) | 2006-06-14 | 2012-06-19 | Boehringer Ingelheim International Gmbh | Chemical compounds |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2833671A1 (de) * | 1978-08-01 | 1980-02-21 | Boehringer Sohn Ingelheim | 2,6-bis- (aminoacylamino) - benzo - eckige klammer auf 1,2-d zu 5,4-d' eckige klammer zu -bisthiazole und 2-amino-6- (aminoacylamino) - benzo - eckige klammer auf 1,2-d zu 5,4-d' eckige klammer zu - bisthiazole, verfahren zu ihrer herstellung und arzneimittel |
| JPS59138758U (ja) * | 1983-03-08 | 1984-09-17 | 株式会社トクヤマ | 酸素検知装置 |
| US4628052A (en) * | 1985-05-28 | 1986-12-09 | Peat Raymond F | Pharmaceutical compositions containing dehydroepiandrosterone and other anesthetic steroids in the treatment of arthritis and other joint disabilities |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2562830A (en) * | 1951-07-31 | Derivatives | ||
| US2140540A (en) * | 1937-02-19 | 1938-12-20 | Du Pont Film Mfg Corp | Color photography |
| US2182815A (en) * | 1938-11-23 | 1939-12-12 | Du Pont Film Mfg Corp | Color-forming photographic compositions and processes |
| US3489558A (en) * | 1967-09-18 | 1970-01-13 | Ibm | Photoconductive benzobisthiazoles and their use in electrophotographic processes |
| US3501293A (en) * | 1967-09-18 | 1970-03-17 | Ibm | Photoconductive benzobisthiazoles and their use in electrophotographic processes |
| CH606335A5 (en, 2012) * | 1974-10-17 | 1978-10-31 | Ciba Geigy Ag |
-
1977
- 1977-08-13 DE DE19772736652 patent/DE2736652A1/de active Granted
-
1978
- 1978-08-02 GR GR56913A patent/GR65027B/el unknown
- 1978-08-03 AT AT562778A patent/AT356664B/de not_active IP Right Cessation
- 1978-08-09 DD DD78207187A patent/DD140253A5/de unknown
- 1978-08-09 CH CH845878A patent/CH639976A5/de not_active IP Right Cessation
- 1978-08-10 RO RO7894947A patent/RO75639A/ro unknown
- 1978-08-11 CS CS785273A patent/CS209542B2/cs unknown
- 1978-08-11 IL IL7855335A patent/IL55335A0/xx not_active IP Right Cessation
- 1978-08-11 FI FI782459A patent/FI63415C/fi not_active IP Right Cessation
- 1978-08-11 NL NLAANVRAGE7808391,A patent/NL189611C/xx not_active IP Right Cessation
- 1978-08-11 FR FR7823802A patent/FR2400027A1/fr active Granted
- 1978-08-11 IT IT50705/78A patent/IT1107969B/it active
- 1978-08-11 CA CA309,176A patent/CA1097635A/en not_active Expired
- 1978-08-11 PT PT68418A patent/PT68418A/pt unknown
- 1978-08-11 NO NO782734A patent/NO153851C/no unknown
- 1978-08-11 BE BE78189868A patent/BE869714A/xx not_active IP Right Cessation
- 1978-08-11 LU LU80103A patent/LU80103A1/de unknown
- 1978-08-11 JP JP9812178A patent/JPS5432495A/ja active Granted
- 1978-08-11 SE SE7808589A patent/SE442511B/sv not_active IP Right Cessation
- 1978-08-11 ZA ZA784569A patent/ZA784569B/xx unknown
- 1978-08-11 SU SU782646503A patent/SU847924A3/ru active
- 1978-08-11 IE IE1635/78A patent/IE47308B1/en not_active IP Right Cessation
- 1978-08-11 HU HU78BO1730A patent/HU176066B/hu not_active IP Right Cessation
- 1978-08-11 GB GB7833028A patent/GB2002383B/en not_active Expired
- 1978-08-11 DK DK356578A patent/DK157762C/da not_active IP Right Cessation
- 1978-08-11 NZ NZ188122A patent/NZ188122A/xx unknown
- 1978-08-11 GB GB8040967A patent/GB2062639B/en not_active Expired
- 1978-08-11 AU AU38822/78A patent/AU518652B2/en not_active Expired
- 1978-08-12 ES ES472544A patent/ES472544A1/es not_active Expired
- 1978-08-12 PL PL1978209009A patent/PL118018B1/pl unknown
- 1978-08-14 BG BG040662A patent/BG30774A3/xx unknown
-
1980
- 1980-08-28 US US06/182,077 patent/US4344946A/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8203001B2 (en) | 2006-06-14 | 2012-06-19 | Boehringer Ingelheim International Gmbh | Chemical compounds |
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