LT3958B - Process for preparing hypoglycemic guanidine derivatives - Google Patents
Process for preparing hypoglycemic guanidine derivatives Download PDFInfo
- Publication number
- LT3958B LT3958B LTIP1646A LTIP1646A LT3958B LT 3958 B LT3958 B LT 3958B LT IP1646 A LTIP1646 A LT IP1646A LT IP1646 A LTIP1646 A LT IP1646A LT 3958 B LT3958 B LT 3958B
- Authority
- LT
- Lithuania
- Prior art keywords
- morpholinophenyl
- formula
- hours
- methyl
- compounds
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 230000002218 hypoglycaemic effect Effects 0.000 title description 5
- 150000002357 guanidines Chemical class 0.000 title 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 51
- -1 N-ethylamino Chemical group 0.000 claims description 18
- 238000010992 reflux Methods 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- PLYTVAFAKDFFKM-UHFFFAOYSA-N 3,4-dimethylmorpholine Chemical compound CC1COCCN1C PLYTVAFAKDFFKM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
- KOHBEDRJXKOYHL-UHFFFAOYSA-N 2-methoxy-n-methylethanamine Chemical compound CNCCOC KOHBEDRJXKOYHL-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 2
- 229940126904 hypoglycaemic agent Drugs 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 3
- 125000001931 aliphatic group Chemical group 0.000 abstract 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 3
- 125000000623 heterocyclic group Chemical group 0.000 abstract 3
- 125000000217 alkyl group Chemical group 0.000 abstract 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 abstract 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 238000000034 method Methods 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 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 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- AQYPBQKDGHHKBD-UHFFFAOYSA-N (2-morpholin-4-ylphenyl)cyanamide Chemical compound N#CNC1=CC=CC=C1N1CCOCC1 AQYPBQKDGHHKBD-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- KQNKJJBFUFKYFX-UHFFFAOYSA-N acetic acid;trihydrate Chemical compound O.O.O.CC(O)=O KQNKJJBFUFKYFX-UHFFFAOYSA-N 0.000 description 5
- 229940046892 lead acetate Drugs 0.000 description 5
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- CMMLLKHOSNEVFO-UHFFFAOYSA-N (2-morpholin-4-ylphenyl)thiourea Chemical compound NC(=S)NC1=CC=CC=C1N1CCOCC1 CMMLLKHOSNEVFO-UHFFFAOYSA-N 0.000 description 2
- LOPWBKHHJFJKPO-UHFFFAOYSA-N (3-methyl-2-morpholin-4-ylphenyl)cyanamide Chemical compound CC1=CC=CC(NC#N)=C1N1CCOCC1 LOPWBKHHJFJKPO-UHFFFAOYSA-N 0.000 description 2
- VGICPVCQAZPROO-UHFFFAOYSA-N (3-methyl-2-morpholin-4-ylphenyl)thiourea Chemical compound CC1=CC=CC(NC(N)=S)=C1N1CCOCC1 VGICPVCQAZPROO-UHFFFAOYSA-N 0.000 description 2
- AHVKUQNZOIILGF-UHFFFAOYSA-N (4-methoxy-2-morpholin-4-ylphenyl)cyanamide Chemical compound COC1=CC=C(NC#N)C(N2CCOCC2)=C1 AHVKUQNZOIILGF-UHFFFAOYSA-N 0.000 description 2
- LGVPAWVLLZMLPB-UHFFFAOYSA-N (4-methoxy-2-morpholin-4-ylphenyl)thiourea Chemical compound COC1=CC=C(NC(N)=S)C(N2CCOCC2)=C1 LGVPAWVLLZMLPB-UHFFFAOYSA-N 0.000 description 2
- KUYYWVDLLLFAAA-UHFFFAOYSA-N (5-chloro-2-morpholin-4-ylphenyl)cyanamide Chemical compound N#CNC1=CC(Cl)=CC=C1N1CCOCC1 KUYYWVDLLLFAAA-UHFFFAOYSA-N 0.000 description 2
- FDOGAHCLAIGGEZ-UHFFFAOYSA-N (5-chloro-2-morpholin-4-ylphenyl)thiourea Chemical compound NC(=S)NC1=CC(Cl)=CC=C1N1CCOCC1 FDOGAHCLAIGGEZ-UHFFFAOYSA-N 0.000 description 2
- YIMGGHGOVMBIJO-UHFFFAOYSA-N 1,1-dimethyl-2-(2-morpholin-4-ylphenyl)guanidine Chemical compound CN(C)C(N)=NC1=CC=CC=C1N1CCOCC1 YIMGGHGOVMBIJO-UHFFFAOYSA-N 0.000 description 2
- ZTNWZRBNTYKWHF-UHFFFAOYSA-N 2-(5-fluoro-2-morpholin-4-ylphenyl)-1,1-dimethylguanidine Chemical compound CN(C)C(N)=NC1=CC(F)=CC=C1N1CCOCC1 ZTNWZRBNTYKWHF-UHFFFAOYSA-N 0.000 description 2
- OKTXVZOPNMPSAU-UHFFFAOYSA-N 4-(2-isothiocyanato-5-methoxyphenyl)morpholine Chemical compound COC1=CC=C(N=C=S)C(N2CCOCC2)=C1 OKTXVZOPNMPSAU-UHFFFAOYSA-N 0.000 description 2
- GYILGUCNWIUUOX-UHFFFAOYSA-N 4-(2-isothiocyanato-6-methylphenyl)morpholine Chemical compound CC1=CC=CC(N=C=S)=C1N1CCOCC1 GYILGUCNWIUUOX-UHFFFAOYSA-N 0.000 description 2
- OFWPPBDBRPIZRT-UHFFFAOYSA-N 4-(4-chloro-2-isothiocyanatophenyl)morpholine Chemical compound S=C=NC1=CC(Cl)=CC=C1N1CCOCC1 OFWPPBDBRPIZRT-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000002332 glycine derivatives Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003585 thioureas Chemical class 0.000 description 2
- DYMVJWOTOQCATD-UHFFFAOYSA-N (5-fluoro-2-morpholin-4-ylphenyl)cyanamide Chemical compound N#CNC1=CC(F)=CC=C1N1CCOCC1 DYMVJWOTOQCATD-UHFFFAOYSA-N 0.000 description 1
- SOWKCCAHSVVGPU-UHFFFAOYSA-N (5-fluoro-2-morpholin-4-ylphenyl)thiourea Chemical compound NC(=S)NC1=CC(F)=CC=C1N1CCOCC1 SOWKCCAHSVVGPU-UHFFFAOYSA-N 0.000 description 1
- BRKNKZKJTGFCIB-UHFFFAOYSA-N 1,1-dimethyl-2-(3-methyl-2-morpholin-4-ylphenyl)guanidine Chemical compound CN(C)C(N)=NC1=CC=CC(C)=C1N1CCOCC1 BRKNKZKJTGFCIB-UHFFFAOYSA-N 0.000 description 1
- OZTPZKOTNKOWFT-UHFFFAOYSA-N 1,1-dimethyl-2-[5-(2-methylpropyl)-2-morpholin-4-ylphenyl]guanidine Chemical compound CN(C)C(N)=NC1=CC(CC(C)C)=CC=C1N1CCOCC1 OZTPZKOTNKOWFT-UHFFFAOYSA-N 0.000 description 1
- GJWWEGYULZSQLT-UHFFFAOYSA-N 1-(2-methoxyethyl)-1-methyl-2-(2-morpholin-4-ylphenyl)guanidine Chemical compound COCCN(C)C(N)=NC1=CC=CC=C1N1CCOCC1 GJWWEGYULZSQLT-UHFFFAOYSA-N 0.000 description 1
- WJPCLVRIKPPQNQ-UHFFFAOYSA-N 1-ethyl-1-(2-methoxyethyl)-2-(2-morpholin-4-ylphenyl)guanidine Chemical compound COCCN(CC)C(N)=NC1=CC=CC=C1N1CCOCC1 WJPCLVRIKPPQNQ-UHFFFAOYSA-N 0.000 description 1
- FGFWHCOPGCHCKF-UHFFFAOYSA-N 1-ethyl-1-methyl-2-(2-morpholin-4-ylphenyl)guanidine Chemical compound CCN(C)C(N)=NC1=CC=CC=C1N1CCOCC1 FGFWHCOPGCHCKF-UHFFFAOYSA-N 0.000 description 1
- ZWXTUKIOAVCZIO-UHFFFAOYSA-N 1-methyl-1-(2-methylsulfanylethyl)-2-(2-morpholin-4-ylphenyl)guanidine Chemical compound CSCCN(C)C(N)=NC1=CC=CC=C1N1CCOCC1 ZWXTUKIOAVCZIO-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- WFDMHFWYPBYQMA-UHFFFAOYSA-N 2,6-dimethyl-n'-(2-morpholin-4-ylphenyl)morpholine-4-carboximidamide Chemical compound C1C(C)OC(C)CN1C(=N)NC1=CC=CC=C1N1CCOCC1 WFDMHFWYPBYQMA-UHFFFAOYSA-N 0.000 description 1
- VFQRQOCAKNYDLF-UHFFFAOYSA-N 2-(4-methoxy-2-morpholin-4-ylphenyl)-1,1-dimethylguanidine Chemical compound COC1=CC=C(N=C(N)N(C)C)C(N2CCOCC2)=C1 VFQRQOCAKNYDLF-UHFFFAOYSA-N 0.000 description 1
- FQSYRJIMZVMLBM-UHFFFAOYSA-N 2-(5-chloro-2-morpholin-4-ylphenyl)-1,1-dimethylguanidine Chemical compound CN(C)C(N)=NC1=CC(Cl)=CC=C1N1CCOCC1 FQSYRJIMZVMLBM-UHFFFAOYSA-N 0.000 description 1
- ZZBWWVDBMBNDSI-UHFFFAOYSA-N 2-[methyl(naphthalene-1-carbonyl)amino]acetic acid Chemical class C1=CC=C2C(C(=O)N(CC(O)=O)C)=CC=CC2=C1 ZZBWWVDBMBNDSI-UHFFFAOYSA-N 0.000 description 1
- BMKNHYSUYQXQBX-UHFFFAOYSA-N 2-butyl-1-(2-morpholin-4-ylphenyl)guanidine Chemical compound CCCCNC(N)=NC1=CC=CC=C1N1CCOCC1 BMKNHYSUYQXQBX-UHFFFAOYSA-N 0.000 description 1
- KXOGDEVRJMWOSP-UHFFFAOYSA-N 2-ethyl-1-(2-morpholin-4-ylphenyl)guanidine Chemical compound CCNC(N)=NC1=CC=CC=C1N1CCOCC1 KXOGDEVRJMWOSP-UHFFFAOYSA-N 0.000 description 1
- HSFSECZWADULIV-UHFFFAOYSA-N 2-methyl-1-(2-morpholin-4-ylphenyl)guanidine Chemical compound CNC(N)=NC1=CC=CC=C1N1CCOCC1 HSFSECZWADULIV-UHFFFAOYSA-N 0.000 description 1
- CIRFKYGQEXNBBW-UHFFFAOYSA-N 3-methyl-2-morpholin-4-ylaniline Chemical compound CC1=CC=CC(N)=C1N1CCOCC1 CIRFKYGQEXNBBW-UHFFFAOYSA-N 0.000 description 1
- PKZODHURUCXOAG-UHFFFAOYSA-N 4-(2-isothiocyanatophenyl)morpholine Chemical compound S=C=NC1=CC=CC=C1N1CCOCC1 PKZODHURUCXOAG-UHFFFAOYSA-N 0.000 description 1
- JDXRMEMHYIYRAN-UHFFFAOYSA-N 4-methoxy-2-morpholin-4-ylaniline Chemical compound COC1=CC=C(N)C(N2CCOCC2)=C1 JDXRMEMHYIYRAN-UHFFFAOYSA-N 0.000 description 1
- DZXPRKXHRYJXIX-UHFFFAOYSA-N 4-methyl-n'-(2-morpholin-4-ylphenyl)piperazine-1-carboximidamide Chemical compound C1CN(C)CCN1C(=N)NC1=CC=CC=C1N1CCOCC1 DZXPRKXHRYJXIX-UHFFFAOYSA-N 0.000 description 1
- XLTKBLYQTBYDDN-UHFFFAOYSA-N 4-methyl-n'-(2-morpholin-4-ylphenyl)piperidine-1-carboximidamide Chemical compound C1CC(C)CCN1C(=N)NC1=CC=CC=C1N1CCOCC1 XLTKBLYQTBYDDN-UHFFFAOYSA-N 0.000 description 1
- UNDBLGNMBLCRNJ-UHFFFAOYSA-N 5-chloro-2-morpholin-4-ylaniline Chemical compound NC1=CC(Cl)=CC=C1N1CCOCC1 UNDBLGNMBLCRNJ-UHFFFAOYSA-N 0.000 description 1
- NSVHSRBHIFWVGP-UHFFFAOYSA-N 5-fluoro-2-morpholin-4-ylaniline Chemical compound NC1=CC(F)=CC=C1N1CCOCC1 NSVHSRBHIFWVGP-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101000986989 Naja kaouthia Acidic phospholipase A2 CM-II Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical class Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- MPTQRFCYZCXJFQ-UHFFFAOYSA-L copper(II) chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Cu+2] MPTQRFCYZCXJFQ-UHFFFAOYSA-L 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- GRHBQAYDJPGGLF-UHFFFAOYSA-N isothiocyanic acid Chemical compound N=C=S GRHBQAYDJPGGLF-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- VGEMYWDUTPQWBN-UHFFFAOYSA-N n-ethyl-2-methoxyethanamine Chemical compound CCNCCOC VGEMYWDUTPQWBN-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 150000003892 tartrate salts Chemical class 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
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/18—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/50—Nitrogen atoms not forming part of a nitro radical with carbocyclic radicals directly attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Emergency Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
- Thermotherapy And Cooling Therapy Devices (AREA)
- Soy Sauces And Products Related Thereto (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB898903592A GB8903592D0 (en) | 1989-02-16 | 1989-02-16 | Therapeutic agents |
Publications (2)
Publication Number | Publication Date |
---|---|
LTIP1646A LTIP1646A (en) | 1995-07-25 |
LT3958B true LT3958B (en) | 1996-05-27 |
Family
ID=10651840
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LTIP1647A LT3960B (en) | 1989-02-16 | 1993-12-21 | Process for preparing hypoglycemic compounds |
LTIP1648A LT3961B (en) | 1989-02-16 | 1993-12-21 | Hypoglycemic compounds, process for preparing thereof and pharmaceutical compositions containing them |
LTIP1646A LT3958B (en) | 1989-02-16 | 1993-12-21 | Process for preparing hypoglycemic guanidine derivatives |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
LTIP1647A LT3960B (en) | 1989-02-16 | 1993-12-21 | Process for preparing hypoglycemic compounds |
LTIP1648A LT3961B (en) | 1989-02-16 | 1993-12-21 | Hypoglycemic compounds, process for preparing thereof and pharmaceutical compositions containing them |
Country Status (26)
Country | Link |
---|---|
US (2) | US5223498A (ro) |
EP (1) | EP0385038B1 (ro) |
JP (1) | JP2545475B2 (ro) |
AT (1) | ATE90074T1 (ro) |
BG (1) | BG60557B1 (ro) |
CS (1) | CS277609B6 (ro) |
DD (1) | DD294023A5 (ro) |
DE (1) | DE68906880T2 (ro) |
DK (1) | DK640889A (ro) |
ES (1) | ES2055115T3 (ro) |
FI (1) | FI95565C (ro) |
GB (1) | GB8903592D0 (ro) |
GE (1) | GEP19981040B (ro) |
HU (1) | HU211571A9 (ro) |
IL (1) | IL92963A (ro) |
LT (3) | LT3960B (ro) |
LV (1) | LV10619B (ro) |
MY (1) | MY105052A (ro) |
NO (1) | NO177993C (ro) |
PL (2) | PL161961B1 (ro) |
PT (1) | PT92770B (ro) |
RO (2) | RO105807B1 (ro) |
RU (3) | RU1826969C (ro) |
UA (2) | UA27713C2 (ro) |
YU (1) | YU48164B (ro) |
ZA (1) | ZA899941B (ro) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3766696D1 (de) * | 1986-12-27 | 1991-01-24 | Konishiroku Photo Ind | Lichtempfindliches photographisches silberhalogenidmaterial. |
IN172842B (ro) * | 1990-05-17 | 1993-12-11 | Boots Pharmaceuticals Limited | |
GB9418912D0 (en) * | 1994-09-20 | 1994-11-09 | Fisons Corp | Pharmaceutically active compounds |
AU4176396A (en) * | 1994-12-08 | 1996-06-26 | Knoll Aktiengesellschaft | Use of substituted phenylamidine and phenylguanidine compounds for the treatment of cerebral and cardiac ischaemia, convulsion and sickle cell anaemia |
TW397812B (en) * | 1995-02-11 | 2000-07-11 | Astra Ab | Bicyclic isothiourea derivatives useful in therapy |
WO1997046515A1 (fr) * | 1996-06-04 | 1997-12-11 | Chugai Seiyaku Kabushiki Kaisha | Benzenes substitues ne presentant pas d'effets inhibiteurs |
US6756389B2 (en) * | 1996-08-09 | 2004-06-29 | Cambridge Neuroscience, Inc. | Pharmaceutically active compounds and methods of use |
US6187203B1 (en) * | 1998-12-01 | 2001-02-13 | Academia Sinica | Sample purification apparatus and method |
US20030212116A1 (en) * | 1999-12-28 | 2003-11-13 | Toshio Niki | Heterocyclic imino compounds and fungicides and insecticides for agricultural and horitcultural use |
BR0107179A (pt) * | 2000-09-07 | 2002-07-02 | Bayer Ag | Amidinas cìclicas e acìclicas e composições farmacêuticas contendo as mesmas para uso como agentes de ligação de receptor de progesterona |
PE20070182A1 (es) * | 2005-07-29 | 2007-03-06 | Wyeth Corp | Derivados cianopirrol-fenil amida como moduladores del receptor de progesterona |
PE20070341A1 (es) * | 2005-07-29 | 2007-04-13 | Wyeth Corp | Derivados de pirrol como moduladores del receptor de progesterona |
PE20070404A1 (es) * | 2005-07-29 | 2007-05-10 | Wyeth Corp | Compuestos derivados de cianopirrol-sulfonamida como moduladores del receptor de progesterona |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US77978A (en) | 1868-05-19 | Improvement in low-water indicators |
Family Cites Families (85)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DD81857A (ro) * | ||||
CA372219A (en) | 1938-03-01 | Kienzle Fritz | Perforating device | |
US672015A (en) | 1900-10-05 | 1901-04-16 | Alfred Schlatter | Automatic switch for groups of transformers. |
GB861527A (en) * | 1958-05-16 | 1961-02-22 | Ici Ltd | New salts of penicillins |
US3622596A (en) * | 1960-10-14 | 1971-11-23 | A Wander Sa Dr | Carbanilide compounds |
CH459172A (de) * | 1961-09-11 | 1968-07-15 | Wander Ag Dr A | Verfahren zur Herstellung mehrbasischer Verbindungen |
US3867448A (en) * | 1962-03-08 | 1975-02-18 | Ciba Geigy Ag | Trifluoromethylphenyl-formamadines and acetamidines |
BE639393A (ro) * | 1962-10-30 | |||
US3320229A (en) * | 1963-08-26 | 1967-05-16 | Stauffer Chemical Co | Complexes of guanidines with completely halogenated acetones |
US3479437A (en) * | 1963-08-26 | 1969-11-18 | Stauffer Chemical Co | Guanidine complexes as fungicides |
US3636219A (en) * | 1964-03-02 | 1972-01-18 | Du Pont | Anticholinergic compositions containing certain thiazolines or imidazolines |
US3399211A (en) * | 1964-03-10 | 1968-08-27 | Merck & Co Inc | Production of 2-aryl-4(5)-nitroimidazoles |
US3479401A (en) * | 1966-06-28 | 1969-11-18 | Merck & Co Inc | Guanidinoaryl and guanidinomethylaryl compounds |
DE1670274A1 (de) * | 1966-10-31 | 1970-07-16 | Boehringer Sohn Ingelheim | Neues Verfahren zur Herstellung von 2-Arylamino-1,3-diazacycloalkenen-(2) |
IL30281A (en) * | 1967-07-11 | 1971-12-29 | Chinoin Gyogyszer Es Vegyeszet | Amidine history and process for their preparation |
DE2029297A1 (de) * | 1970-06-13 | 1971-12-30 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Neue Aminophenyl-cycloamidine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
US3911014A (en) * | 1970-06-13 | 1975-10-07 | Bayer Ag | Aminophenylamidines, their production and their medicinal use |
US3903302A (en) * | 1970-06-13 | 1975-09-02 | Bayer Ag | Aminophenylamidines as anthelmintic agents |
US3919315A (en) * | 1970-06-13 | 1975-11-11 | Bayer Ag | New aminophenylamidines, their production and their medicinal use |
US3925471A (en) * | 1970-06-13 | 1975-12-09 | Bayer Ag | Aminophenylamidines their production and their medicinal use |
US3925470A (en) * | 1970-06-13 | 1975-12-09 | Bayer Ag | Aminophenylamidines, their production and their medicinal use |
US3911013A (en) * | 1970-06-13 | 1975-10-07 | Bayer Ag | New aminophenylamidines, their production and their medicinal use |
US4018814A (en) * | 1970-06-13 | 1977-04-19 | Bayer Aktiengesellschaft | Aromatic amides and carbomates of phenylamidines |
US3923888A (en) * | 1970-06-13 | 1975-12-02 | Bayer Ag | Aminophenylamidines, their production and their medicinal use |
DE2029298C3 (de) * | 1970-06-13 | 1980-04-17 | Bayer Ag, 5090 Leverkusen | Aminophenylamidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
DE2029299C3 (de) * | 1970-06-13 | 1980-08-21 | Bayer Ag, 5090 Leverkusen | Neue Aminophenylamidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
US4013676A (en) * | 1970-06-13 | 1977-03-22 | Bayer Aktiengesellschaft | Aminophenylamidines, their production and their pharmaceutical use |
US3911010A (en) * | 1970-06-13 | 1975-10-07 | Bayer Ag | Aminophenylamidines, their production and their pharmaceutical use |
US3996247A (en) * | 1970-06-13 | 1976-12-07 | Bayer Aktiengesellschaft | Substituted 4-aminophenylamidines |
FR2098352A7 (en) * | 1970-07-13 | 1972-03-10 | Fahlberg List Veb | Hydroxyguanidines - with selective herbicidal activity |
GB1311913A (en) * | 1970-09-05 | 1973-03-28 | Fahlberg List Veb | Herbicidal hydroxyguanidines |
DE2350696A1 (de) * | 1972-10-12 | 1974-04-18 | Ciba Geigy Ag | Neue ester |
US3965176A (en) * | 1973-06-20 | 1976-06-22 | Schering Corporation | Novel substituted amidines |
IL44905A (en) * | 1973-06-25 | 1977-03-31 | Ciba Geigy Ag | N-alkyl-n-(n-alkylformimidoyl)-n'-phenylformamidine derivatives their preparation and use in pest control |
SE7411169L (sv) * | 1974-09-04 | 1976-03-05 | Wander Ag Dr A | Forfarande for framstellning av nya organiska foreningar |
JPS51118832A (en) * | 1975-04-09 | 1976-10-19 | Sumitomo Chem Co Ltd | A non-medical antibacterial, 3-pyridyl substituted guanidine |
US4211867A (en) * | 1976-03-19 | 1980-07-08 | Mcneil Laboratories, Incorporated | Nitrogen heterocyclic carboximidamide compounds |
DE2626128A1 (de) * | 1976-06-11 | 1977-12-22 | Beiersdorf Ag | N-substituierte benzimidazolin-2-one und verfahren zu deren herstellung |
US4182865A (en) * | 1978-09-18 | 1980-01-08 | Mcneil Laboratories, Inc. | Diaza-cyclic derivatives of guanidine |
US4414211A (en) * | 1978-09-18 | 1983-11-08 | Mcneilab, Inc. | Heterocyclic derivatives of guanidine |
DE2848786C3 (de) * | 1978-11-10 | 1981-05-21 | Ibm Deutschland Gmbh, 7000 Stuttgart | Schaltungsanordnung für die Synchronisierung der Auftrittszeitpunkte von Druckhammeraufschlag mit dem Eintreffen der Drucktype an der Druckstelle |
AU5263779A (en) * | 1978-11-29 | 1980-05-29 | Beecham Group Limited | Derivatives of thiazolidin-2-ylidene and oxazolidin-2-ylidene with hypoglycaemic acitivity |
US4247705A (en) * | 1979-02-06 | 1981-01-27 | A. H. Robins Company, Inc. | 4-Substituted 2-iminoimidazolidine compounds |
ZA801680B (en) * | 1979-04-03 | 1981-03-25 | Fujisawa Pharmaceutical Co | 2-imidazoline derivatives,process for the preparation thereof and the pharmaceutical composition of the same |
ZA802161B (en) * | 1979-04-11 | 1981-04-29 | Ciba Geigy Ag | Guanidines,processes for producing them,and pharmaceutical preparations containing sucn compounds |
IN150250B (ro) * | 1979-04-16 | 1982-08-28 | Ciba Geigy India Ltd | |
EP0018134B1 (en) * | 1979-04-21 | 1984-03-14 | Beecham Group Plc | Dihydropyridine derivatives, processes for their preparation and pharmaceutical compositions containing them |
US4342764A (en) * | 1979-05-29 | 1982-08-03 | Ciba-Geigy Corporation | Guanidine compounds, pharmaceutical compositions and use |
JPS55160764A (en) * | 1979-05-29 | 1980-12-13 | Ciba Geigy Ag | Guanidine* its manufacture and pharmaceutic medicine containing same |
DD144919A1 (de) * | 1979-07-20 | 1980-11-12 | Rainer Beckert | Verfahren zur herstellung von 2,5-diaryl-3,4-diarylimino-1,2,5-thiadiazolidin-s-oxiden |
JPS5618969A (en) * | 1979-07-24 | 1981-02-23 | Toyama Chem Co Ltd | Novel 1-(4-aminobenzyl)-2,3-dioxopiperazine derivative, its acid addition salt, and their preparation |
US4340609A (en) * | 1980-01-02 | 1982-07-20 | William H. Rorer, Inc. | Amidinourea derivative veterinary compositions for suppression of parasitemia |
US4287201A (en) * | 1980-03-03 | 1981-09-01 | Merck & Co., Inc. | Anovulatory method and chicken feed compositions |
US4281004A (en) * | 1980-03-31 | 1981-07-28 | Pfizer Inc. | Phenylguanidine therapeutic agents |
DE3168754D1 (en) * | 1980-07-09 | 1985-03-21 | Beecham Group Plc | Clonidine derivatives useful in the treatment of diarrhoea |
US4348406A (en) * | 1980-10-20 | 1982-09-07 | Schering Corporation | Novel guanidine derivatives |
DE3100575A1 (de) * | 1981-01-10 | 1982-09-02 | Dr. Karl Thomae Gmbh, 7950 Biberach | "neue benzoesaeuren, ihre herstellung und ihre verwendung als arzneimittel" |
US4735959A (en) * | 1981-01-10 | 1988-04-05 | Dr. Karl Thomae Gmbh | Carboxylic acid amides and pharmaceutical compositions containing them |
DE3225188A1 (de) * | 1982-07-06 | 1984-01-12 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue phenylessigsaeurederivate, ihre herstellung und diese verbindungen enthaltende arzneimittel |
EP0070084A3 (en) * | 1981-04-24 | 1983-02-16 | Beecham Group Plc | Imidazoline derivatives |
US4461904A (en) * | 1981-11-20 | 1984-07-24 | Alcon Laboratories, Inc. | 2-(Trisubstituted phenylimino)-imidazolines |
DE3375783D1 (en) * | 1982-07-06 | 1988-04-07 | Thomae Gmbh Dr K | Phenyl-acetic-acid derivatives, their preparation and pharmaceutical compostions containing them |
US4533739A (en) * | 1982-10-12 | 1985-08-06 | G. D. Searle & Co. | 2-[(Aminophenyl and amidophenyl)amino]-1-azacycloalkanes having antidiarrheal activity |
IL70665A (en) * | 1983-01-13 | 1987-08-31 | Rhone Poulenc Sante | Condensed pyrrole carboxylic acid derivative intermediates for pharmaceuticals and their preparation |
FR2539417A1 (fr) * | 1983-01-13 | 1984-07-20 | Rhone Poulenc Sante | Nouveaux pyrrolo-1, 2 heterocycles, leur preparation et les medicaments qui les contiennent |
SU1114674A1 (ru) * | 1983-02-08 | 1984-09-23 | Предприятие П/Я Р-6913 | Способ получени гидрохлоридов производных @ , @ -дифенил бензамидина |
GB8304593D0 (en) * | 1983-02-18 | 1983-03-23 | Beecham Group Plc | Amidines |
US4619931A (en) * | 1983-02-28 | 1986-10-28 | Janssen Pharmaceutica, N.V. | [[4-[4-(4-phenyl-1-piperazinyl)phenoxymethyl]-1,3-dioxolan-2-yl]methyl]-1H-imidazoles and 1H-1,2,4-triazoles |
US4735942A (en) * | 1984-01-09 | 1988-04-05 | Janssen Pharmaceutica, N.V. | [[4-[4-(4-phenyl-1-piperazinyl)phenoxymethyl]-1,3-dioxolan-2-yl]-methyl]-1H-imidazoles and 1H-1,2,4-triazoles having antimicrobial properties |
US4861879A (en) * | 1983-02-28 | 1989-08-29 | Janssen Pharmaceutica N.V. | [[4-[4-Phenyl-1-piperazinyl)phenoxymethyl]-1-3-dioxolan-2-yl]-methyl]-1H-imidazoles and 1H-1,2,4-triazoles |
FR2549049B1 (fr) * | 1983-07-13 | 1986-06-20 | Chauvin Blache Lab | Nouvelles amidines, leur procede de preparation et leur application therapeutique |
US4723029A (en) * | 1983-09-23 | 1988-02-02 | Schering Corporation | Organic acid-substituted guanidine anthelmintics |
US4701447A (en) * | 1983-09-23 | 1987-10-20 | Schering Corporation | N-((2-nitro)phenyl)-N' (organic acid) guanidine anthelmintics |
JPS60100559A (ja) * | 1983-11-05 | 1985-06-04 | Morishita Seiyaku Kk | 2−アニリノ−1,6−ジヒドロ−6−オキソ−5−ピリミジンカルボン酸誘導体,その製法及び該化合物を含有する抗アレルギ−剤 |
US4579951A (en) * | 1984-03-19 | 1986-04-01 | G. D. Searle & Co. | Substituted (azacycloalk-2-yl)iminophenols and esters thereof |
US4560690A (en) * | 1984-04-30 | 1985-12-24 | Pfizer Inc. | 2-(N-substituted guanidino)-4-hetero-arylthiazole antiulcer agents |
EP0164204A1 (en) * | 1984-05-12 | 1985-12-11 | FISONS plc | Novel pharmaceutically useful pyrimidines |
HU192986B (en) * | 1984-05-23 | 1987-08-28 | Egyt Gyogyszervegyeszeti Gyar | Process for production of imidasodiline derivatives |
US4693850A (en) * | 1985-03-15 | 1987-09-15 | Mcneilab, Inc. | Methane sulfonic acid derivatives |
US4656270A (en) * | 1985-03-15 | 1987-04-07 | Mcneilab, Inc. | Process for producing guanidines such as linogliride |
DE3518917A1 (de) * | 1985-05-25 | 1986-11-27 | Bayer Ag, 5090 Leverkusen | Substituierte benzochinolizine, verfahren zur herstellung und ihre verwendung in arzneimitteln |
DE3529692A1 (de) * | 1985-08-20 | 1987-02-26 | Bayer Ag | Verwendung von lactamamiden als leistungsfoerderer bei tieren |
CA1292472C (en) * | 1985-12-03 | 1991-11-26 | Alfonsus Guilielmus Knaeps | Derivatives of ¬¬4-¬4-(4-phenyl-1-piperazinyl)- phenoxymethyl|-1,3-dioxolan-2-yl|methyl|-1h-imidazoles and 1h-1,2,4-triazoles |
ATE135699T1 (de) * | 1986-01-13 | 1996-04-15 | American Cyanamid Co | 4,5,6-substituierte 2-pyrimidinamine |
GB8602025D0 (en) | 1986-01-28 | 1986-03-05 | Reid M | Orthopaedic trolley |
-
1989
- 1989-02-16 GB GB898903592A patent/GB8903592D0/en active Pending
- 1989-12-13 FI FI895956A patent/FI95565C/fi not_active IP Right Cessation
- 1989-12-14 NO NO895023A patent/NO177993C/no not_active IP Right Cessation
- 1989-12-18 DK DK640889A patent/DK640889A/da not_active Application Discontinuation
- 1989-12-19 MY MYPI89001812A patent/MY105052A/en unknown
- 1989-12-27 CS CS897433A patent/CS277609B6/cs not_active IP Right Cessation
- 1989-12-28 BG BG90783A patent/BG60557B1/bg unknown
- 1989-12-28 ES ES89313636T patent/ES2055115T3/es not_active Expired - Lifetime
- 1989-12-28 US US07/458,237 patent/US5223498A/en not_active Expired - Lifetime
- 1989-12-28 YU YU248589A patent/YU48164B/sh unknown
- 1989-12-28 EP EP89313636A patent/EP0385038B1/en not_active Expired - Lifetime
- 1989-12-28 DE DE8989313636T patent/DE68906880T2/de not_active Expired - Fee Related
- 1989-12-28 AT AT89313636T patent/ATE90074T1/de not_active IP Right Cessation
- 1989-12-28 ZA ZA899941A patent/ZA899941B/xx unknown
- 1989-12-29 PL PL89295913A patent/PL161961B1/pl unknown
- 1989-12-29 RU SU894742813A patent/RU1826969C/ru active
- 1989-12-29 PT PT92770A patent/PT92770B/pt not_active IP Right Cessation
- 1989-12-29 DD DD89336816A patent/DD294023A5/de unknown
- 1989-12-29 PL PL28307489A patent/PL162960B1/pl unknown
- 1989-12-29 UA UA5011043A patent/UA27713C2/uk unknown
- 1989-12-29 JP JP1345135A patent/JP2545475B2/ja not_active Expired - Fee Related
- 1989-12-29 UA UA4742813A patent/UA19156A/uk unknown
- 1989-12-30 RO RO143555A patent/RO105807B1/ro unknown
- 1989-12-30 RO RO147103A patent/RO107945B1/ro unknown
-
1990
- 1990-01-03 IL IL9296390A patent/IL92963A/en not_active IP Right Cessation
- 1990-12-03 RU SU904831862A patent/RU1797610C/ru active
-
1992
- 1992-02-27 RU SU925011043A patent/RU2052452C1/ru active
-
1993
- 1993-01-27 US US08/009,807 patent/US5373008A/en not_active Expired - Fee Related
- 1993-06-30 LV LVP-93-815A patent/LV10619B/en unknown
- 1993-12-21 LT LTIP1647A patent/LT3960B/lt not_active IP Right Cessation
- 1993-12-21 LT LTIP1648A patent/LT3961B/lt not_active IP Right Cessation
- 1993-12-21 LT LTIP1646A patent/LT3958B/lt not_active IP Right Cessation
-
1994
- 1994-10-06 GE GEAP19942233A patent/GEP19981040B/en unknown
-
1995
- 1995-06-30 HU HU95P/P00688P patent/HU211571A9/hu unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US77978A (en) | 1868-05-19 | Improvement in low-water indicators |
Non-Patent Citations (1)
Title |
---|
KADISH A.H.: "A new and rapid method for the determination of glucose by measurement of rate of oxygen consumption", CLIN CHEM., 1968, pages 116 - 131 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7085566B2 (ja) | アポトーシス誘発剤 | |
CA2655654C (en) | New carbonylated (aza)cyclohexanes as dopamine d3 receptor ligands | |
DE69418601T2 (de) | Guanidinderivate mit therapeutischer wirkung | |
JP5754040B2 (ja) | TNFαシグナル伝達のモジュレータ | |
JP3067807B2 (ja) | 4−フェニルアミノチアゾール誘導体、その製造方法、および該誘導体を含有してなる医薬組成物 | |
SK188399A3 (en) | Substituted 1,2,3,4-tetrahydronaphthalene derivatives | |
AU616907B2 (en) | Melatonin analogues | |
NO170883B (no) | Fremgangsmaate for fremstilling av 2-amino-5-hydroksy-4-metylpyrimidin-derivater | |
LT3958B (en) | Process for preparing hypoglycemic guanidine derivatives | |
IE55798B1 (en) | 2-substituted 4-amino-6,7-dimethoxyquinolines | |
JPH09505030A (ja) | ヒドロイソキノリン誘導体 | |
SK12332002A3 (sk) | Deriváty chinolínu ako alfa 2 antagonisty | |
NZ551509A (en) | Tetrahydroisoquinoline sulfonamide derivatives, the preparation thereof, and the use of the same in therapeutics | |
KR20070045290A (ko) | Hsp90의 억제제 | |
DE69708968T2 (de) | Arylacrylamidderivate als 5HT1 Agoniste oder Antagoniste | |
CS249544B2 (en) | Method of new imidazolylphenylamidines production | |
DE4243287A1 (de) | N-Substituierte Azabicycloheptan-Derivate, ihre Herstellung und Verwendung | |
JP2003300875A (ja) | インターロイキン12抑制剤 | |
SU1156593A3 (ru) | Способ получени производных бензамида или их кислотно-аддитивных солей,или оптических изомеров | |
US6028073A (en) | N-substituted 3-azabicyclo (3.2.0)heptane derivatives useful as neuroleptics | |
JP2008515884A (ja) | 新規なヒドロキシメチルベンゾチアゾールアミド | |
FR2593818A1 (fr) | Derives d'acylaminomethyl-3 imidazo(1,2-a)pyridine, leur preparation et leur application en therapeutique | |
JPH08502057A (ja) | カルモジュリン拮抗特性を有する複素環式アミン | |
DE69215482T2 (de) | 2,2'-Alkylendiindolderivate, Verfahren zu ihrer Herstellung, sie enthaltende Arzneimittel und deren Verwendung als Ulcustherapeutikum | |
KR20240115232A (ko) | Sik3 억제제 및 이의 중간체를 제조하기 위한 합성 반응식 및 과정 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM9A | Lapsed patents |
Effective date: 20021221 |