CS228534B2 - Production method of amidine derivative - Google Patents
Production method of amidine derivative Download PDFInfo
- Publication number
- CS228534B2 CS228534B2 CS816809A CS680981A CS228534B2 CS 228534 B2 CS228534 B2 CS 228534B2 CS 816809 A CS816809 A CS 816809A CS 680981 A CS680981 A CS 680981A CS 228534 B2 CS228534 B2 CS 228534B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- amidino
- acid
- compound
- group
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001409 amidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 116
- 239000002253 acid Substances 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- ULKSSXOMKDEKPC-UHFFFAOYSA-N 6-hydroxynaphthalene-2-carboximidamide Chemical compound C1=C(O)C=CC2=CC(C(=N)N)=CC=C21 ULKSSXOMKDEKPC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 46
- 230000008569 process Effects 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 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
- 239000007858 starting material Substances 0.000 claims 7
- GAVZNOLUZPCABT-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboximidamide Chemical compound NC(=N)c1c(O)ccc2ccccc12 GAVZNOLUZPCABT-UHFFFAOYSA-N 0.000 claims 1
- SXTSBZBQQRIYCU-UHFFFAOYSA-N 4-guanidinobenzoic acid Chemical compound NC(=N)NC1=CC=C(C(O)=O)C=C1 SXTSBZBQQRIYCU-UHFFFAOYSA-N 0.000 claims 1
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- -1 carboxylic acid compounds Chemical class 0.000 abstract description 30
- 239000003795 chemical substances by application Substances 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 13
- 239000002753 trypsin inhibitor Substances 0.000 abstract description 8
- 230000002391 anti-complement effect Effects 0.000 abstract description 7
- 108010008730 anticomplement Proteins 0.000 abstract description 6
- 239000004019 antithrombin Substances 0.000 abstract description 6
- 230000000288 anti-kallikrein effect Effects 0.000 abstract description 4
- 238000005886 esterification reaction Methods 0.000 abstract description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 abstract 2
- 230000032050 esterification Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 94
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 60
- 238000001914 filtration Methods 0.000 description 49
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 230000015572 biosynthetic process Effects 0.000 description 38
- 238000003786 synthesis reaction Methods 0.000 description 38
- 239000002244 precipitate Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 35
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 32
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- 239000013078 crystal Substances 0.000 description 29
- 238000001816 cooling Methods 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 23
- 230000000295 complement effect Effects 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 17
- 239000000843 powder Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 206010018910 Haemolysis Diseases 0.000 description 13
- 230000008588 hemolysis Effects 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- NCVIXRFLZFTMOS-UHFFFAOYSA-N (6-carbamimidoylnaphthalen-2-yl) methanesulfonate Chemical compound C1=C(C(N)=N)C=CC2=CC(OS(=O)(=O)C)=CC=C21 NCVIXRFLZFTMOS-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 12
- 229940088598 enzyme Drugs 0.000 description 12
- 229940098779 methanesulfonic acid Drugs 0.000 description 12
- 229940012957 plasmin Drugs 0.000 description 12
- 230000035939 shock Effects 0.000 description 12
- 108090000631 Trypsin Proteins 0.000 description 10
- 102000004142 Trypsin Human genes 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000012588 trypsin Substances 0.000 description 10
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 108090000190 Thrombin Proteins 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 229960004072 thrombin Drugs 0.000 description 8
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 239000002198 insoluble material Substances 0.000 description 7
- 101710081722 Antitrypsin Proteins 0.000 description 6
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- 108010088842 Fibrinolysin Proteins 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 230000001475 anti-trypsic effect Effects 0.000 description 6
- 239000012467 final product Substances 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 description 4
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 4
- 241000700198 Cavia Species 0.000 description 4
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010033645 Pancreatitis Diseases 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000024203 complement activation Effects 0.000 description 4
- 230000004154 complement system Effects 0.000 description 4
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 4
- 108010052968 leupeptin Proteins 0.000 description 4
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 3
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 3
- 102000009123 Fibrin Human genes 0.000 description 3
- 108010073385 Fibrin Proteins 0.000 description 3
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 3
- 108010006464 Hemolysin Proteins Proteins 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 102000001399 Kallikrein Human genes 0.000 description 3
- 108060005987 Kallikrein Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000007514 bases Chemical class 0.000 description 3
- 229950011260 betanaphthol Drugs 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 235000013985 cinnamic acid Nutrition 0.000 description 3
- 229930016911 cinnamic acid Natural products 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
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- 229950003499 fibrin Drugs 0.000 description 3
- 239000003228 hemolysin Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 3
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- SKAWDTAMLOJQNK-UHFFFAOYSA-N 2-acetamido-3-(4-hydroxyphenyl)propanoic acid ethyl ester Chemical compound CCOC(=O)C(NC(C)=O)CC1=CC=C(O)C=C1 SKAWDTAMLOJQNK-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 2
- 108010028774 Complement C1 Proteins 0.000 description 2
- 102100025406 Complement C1s subcomponent Human genes 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
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- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
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- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 2
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- UHRXINKIUBEOBK-UHFFFAOYSA-N (6-aminonaphthalen-2-yl) methanesulfonate Chemical compound C1=C(N)C=CC2=CC(OS(=O)(=O)C)=CC=C21 UHRXINKIUBEOBK-UHFFFAOYSA-N 0.000 description 1
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- XNCRUNXWPDJHGV-BQYQJAHWSA-N (e)-2-methyl-3-phenylprop-2-enoic acid Chemical compound OC(=O)C(/C)=C/C1=CC=CC=C1 XNCRUNXWPDJHGV-BQYQJAHWSA-N 0.000 description 1
- FCEQRBOTYXIORK-UHFFFAOYSA-N 2-(diaminomethylideneamino)benzoic acid Chemical compound NC(=N)NC1=CC=CC=C1C(O)=O FCEQRBOTYXIORK-UHFFFAOYSA-N 0.000 description 1
- QWFQKRFFMIUAKT-UHFFFAOYSA-N 2-(diaminomethylideneamino)benzoic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.NC(N)=NC1=CC=CC=C1C(O)=O QWFQKRFFMIUAKT-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
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- AAJLPPDFIRPBDA-UHFFFAOYSA-N 2-cyclohexyl-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)C1CCCCC1 AAJLPPDFIRPBDA-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07C257/18—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 having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Superconductors And Manufacturing Methods Therefor (AREA)
- Peptides Or Proteins (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Power Steering Mechanism (AREA)
- Heat Treatment Of Sheet Steel (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12826980A JPS5753454A (en) | 1980-09-16 | 1980-09-16 | Guanidinobenzoate and anticomplementary agent |
| JP6494281A JPS57179146A (en) | 1981-04-28 | 1981-04-28 | Amidine compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS228534B2 true CS228534B2 (en) | 1984-05-14 |
Family
ID=26406084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS816809A CS228534B2 (en) | 1980-09-16 | 1981-09-15 | Production method of amidine derivative |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US4454338A (de) |
| EP (1) | EP0048433B1 (de) |
| KR (1) | KR860000264B1 (de) |
| AT (1) | ATE20051T1 (de) |
| AU (1) | AU527371B2 (de) |
| CA (1) | CA1177488A (de) |
| CS (1) | CS228534B2 (de) |
| DD (1) | DD201779A5 (de) |
| DE (1) | DE3174717D1 (de) |
| DK (1) | DK155003C (de) |
| ES (1) | ES505460A0 (de) |
| FI (1) | FI73975C (de) |
| GB (1) | GB2083818B (de) |
| HU (1) | HU185956B (de) |
| NO (1) | NO153568C (de) |
| PH (1) | PH18109A (de) |
| SU (1) | SU1176832A3 (de) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU527371B2 (en) * | 1980-09-16 | 1983-03-03 | Torii & Co., Ltd. | Amidine |
| GB2095239B (en) * | 1981-02-27 | 1985-03-06 | Torii & Co Ltd | Novel amidine compounds |
| JPS57179147A (en) * | 1981-04-28 | 1982-11-04 | Torii Yakuhin Kk | Amidine derivative |
| JPS59139357A (ja) * | 1983-01-28 | 1984-08-10 | Torii Yakuhin Kk | アミジン誘導体 |
| US4818273A (en) * | 1983-11-14 | 1989-04-04 | The Dow Chemical Company | Substituted 1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamides, compositions containing them, and their utility as herbicides |
| US4563527A (en) * | 1984-07-19 | 1986-01-07 | Torii & Co., Ltd. | Amidine compounds |
| JPS6133173A (ja) * | 1984-07-25 | 1986-02-17 | Torii Yakuhin Kk | アミジン化合物 |
| FR2568253B1 (fr) * | 1984-07-26 | 1987-01-30 | Torii Co | Nouvelle amidine |
| GB2162171B (en) * | 1984-07-26 | 1988-01-27 | Torii & Co Ltd | Amidine compounds |
| DE3427865A1 (de) * | 1984-07-27 | 1986-02-06 | Torii & Co., Tokio/Tokyo | Amidinoverbindungen, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische mittel |
| US4709082A (en) * | 1984-10-25 | 1987-11-24 | Nissan Chemical Industries, Ltd. | 2-phenylpropionic acid esters, method for optical resolution thereof and optically active substance thereof |
| US4873253A (en) * | 1987-03-30 | 1989-10-10 | Shosuke Okamoto | Phenylalanine derivative and proteinase inhibitor |
| US4990537A (en) * | 1988-07-11 | 1991-02-05 | Banyu Pharmaceutical Co., Ltd. | Anti influenza agent |
| ATE119523T1 (de) * | 1989-12-28 | 1995-03-15 | Snow Brand Milk Products Co Ltd | Isochinolinderivate und ihre salze als proteasehemmer. |
| US5116985A (en) * | 1989-12-28 | 1992-05-26 | Snow Brand Milk Products Co., Ltd. | Isoquinoline derivatives and salts thereof |
| JPH078789B2 (ja) * | 1990-04-05 | 1995-02-01 | 鳥居薬品株式会社 | 脳血管攣縮治療剤 |
| US5238964A (en) * | 1990-04-05 | 1993-08-24 | Torii & Co., Ltd. | Agent for treatment of cerebrovascular contraction |
| DE4102024A1 (de) * | 1991-01-24 | 1992-07-30 | Thomae Gmbh Dr K | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| ZA928276B (en) * | 1991-10-31 | 1993-05-06 | Daiichi Seiyaku Co | Aromatic amidine derivates and salts thereof. |
| DE69508875T2 (de) * | 1994-09-20 | 1999-09-16 | Ono Pharmaceutical Co. Ltd., Osaka | Amidinophenol-Derivate als Protease-hemmende Verbindungen |
| NZ296210A (en) * | 1994-12-02 | 1998-05-27 | Yamanouchi Pharma Co Ltd | Amidinonaphthyl derivatives to inhibit activated blood coagulation factor x |
| WO1996020917A1 (en) * | 1995-01-05 | 1996-07-11 | Torii Pharmaceutical Co., Ltd. | Substituted amidinonaphthyl ester derivatives |
| EP0893437A4 (de) | 1996-04-10 | 2000-12-27 | Ono Pharmaceutical Co | Tryptase-Inhibitor und Guanidino-Derivate |
| WO1998055471A1 (en) | 1997-06-03 | 1998-12-10 | Biocryst Pharmaceuticals, Inc. | Novel compounds useful in the complement, coagulat and kallikrein pathways and method for their preparation |
| EP1030844A1 (de) * | 1997-11-10 | 2000-08-30 | Array Biopharma Inc. | Verbindungen, die die aktivität von tryptase hemmen |
| US6066673A (en) * | 1998-03-12 | 2000-05-23 | The Procter & Gamble Company | Enzyme inhibitors |
| WO1999047128A1 (en) | 1998-03-19 | 1999-09-23 | Bristol-Myers Squibb Company | Biphasic controlled release delivery system for high solubility pharmaceuticals and method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD89611A (de) * | ||||
| DE1905813A1 (de) * | 1968-07-04 | 1970-03-05 | Akad Wissenschaften Ddr | 3- oder 4-Guanidobenzoesaeurebenzyl- oder -phenylestern und deren Verwendung als Inhibitoren |
| GB1472700A (en) * | 1974-11-01 | 1977-05-04 | Ono Pharmaceutical Co | Guanidinobehzoic acid derivatives and process for preparing the same |
| AU527371B2 (en) * | 1980-09-16 | 1983-03-03 | Torii & Co., Ltd. | Amidine |
-
1981
- 1981-09-08 AU AU75062/81A patent/AU527371B2/en not_active Expired
- 1981-09-09 US US06/300,534 patent/US4454338A/en not_active Expired - Lifetime
- 1981-09-10 CA CA000385570A patent/CA1177488A/en not_active Expired
- 1981-09-14 ES ES505460A patent/ES505460A0/es active Granted
- 1981-09-15 HU HU812665A patent/HU185956B/hu unknown
- 1981-09-15 GB GB8127837A patent/GB2083818B/en not_active Expired
- 1981-09-15 CS CS816809A patent/CS228534B2/cs unknown
- 1981-09-15 AT AT81107274T patent/ATE20051T1/de not_active IP Right Cessation
- 1981-09-15 EP EP81107274A patent/EP0048433B1/de not_active Expired
- 1981-09-15 NO NO813138A patent/NO153568C/no unknown
- 1981-09-15 PH PH26206A patent/PH18109A/en unknown
- 1981-09-15 FI FI812876A patent/FI73975C/fi not_active IP Right Cessation
- 1981-09-15 DK DK410681A patent/DK155003C/da not_active IP Right Cessation
- 1981-09-15 KR KR1019810003427A patent/KR860000264B1/ko not_active Expired
- 1981-09-15 SU SU813384251A patent/SU1176832A3/ru active
- 1981-09-15 DE DE8181107274T patent/DE3174717D1/de not_active Expired
- 1981-09-16 DD DD81233339A patent/DD201779A5/de not_active IP Right Cessation
-
1984
- 1984-01-20 US US06/572,269 patent/US4532255A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| FI73975C (fi) | 1987-12-10 |
| ES8206443A1 (es) | 1982-08-16 |
| EP0048433B1 (de) | 1986-05-28 |
| FI73975B (fi) | 1987-08-31 |
| HU185956B (en) | 1985-04-28 |
| DD201779A5 (de) | 1983-08-10 |
| CA1177488A (en) | 1984-11-06 |
| FI812876L (fi) | 1982-03-17 |
| GB2083818B (en) | 1984-05-10 |
| US4454338A (en) | 1984-06-12 |
| DK155003C (da) | 1989-05-29 |
| NO153568B (no) | 1986-01-06 |
| SU1176832A3 (ru) | 1985-08-30 |
| EP0048433A2 (de) | 1982-03-31 |
| US4532255A (en) | 1985-07-30 |
| GB2083818A (en) | 1982-03-31 |
| AU7506281A (en) | 1982-03-25 |
| ATE20051T1 (de) | 1986-06-15 |
| KR860000264B1 (ko) | 1986-03-22 |
| DK155003B (da) | 1989-01-23 |
| NO813138L (no) | 1982-03-17 |
| DE3174717D1 (en) | 1986-07-03 |
| NO153568C (no) | 1986-05-21 |
| PH18109A (en) | 1985-03-22 |
| DK410681A (da) | 1982-03-17 |
| ES505460A0 (es) | 1982-08-16 |
| KR830007527A (ko) | 1983-10-21 |
| AU527371B2 (en) | 1983-03-03 |
| EP0048433A3 (en) | 1982-07-21 |
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