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
- 238000005345 coagulation Methods 0.000 description 3
- 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
- 210000000056 organ Anatomy 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000012048 reactive intermediate Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000013566 Plasminogen Human genes 0.000 description 2
- 108010051456 Plasminogen Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108010027252 Trypsinogen Proteins 0.000 description 2
- 102000018690 Trypsinogen Human genes 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 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
- 230000036772 blood pressure Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 239000007806 chemical reaction intermediate Substances 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000010908 decantation Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 208000031169 hemorrhagic disease Diseases 0.000 description 2
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229940049953 phenylacetate Drugs 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 230000008728 vascular permeability Effects 0.000 description 2
- YETFLAUJROGBMC-UHFFFAOYSA-N (4-carboxyphenyl)-(diaminomethylidene)azanium;chloride Chemical compound Cl.NC(N)=NC1=CC=C(C(O)=O)C=C1 YETFLAUJROGBMC-UHFFFAOYSA-N 0.000 description 1
- 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
- AMXYRRJBEFJXDJ-UHFFFAOYSA-N (6-carbamimidoylnaphthalen-2-yl) 2-methylbenzoate methanesulfonic acid Chemical compound CS(O)(=O)=O.CC1=CC=CC=C1C(=O)OC1=CC=C(C=C(C=C2)C(N)=N)C2=C1 AMXYRRJBEFJXDJ-UHFFFAOYSA-N 0.000 description 1
- MSIUVCDNLRNVIQ-UHFFFAOYSA-N (6-carbamimidoylnaphthalen-2-yl) 2-phenoxyacetate Chemical compound C1=CC2=CC(C(=N)N)=CC=C2C=C1OC(=O)COC1=CC=CC=C1 MSIUVCDNLRNVIQ-UHFFFAOYSA-N 0.000 description 1
- SEPJQQWQYNEMDL-UHFFFAOYSA-N (6-carbamimidoylnaphthalen-2-yl) benzoate Chemical compound C1=CC2=CC(C(=N)N)=CC=C2C=C1OC(=O)C1=CC=CC=C1 SEPJQQWQYNEMDL-UHFFFAOYSA-N 0.000 description 1
- IYDDBJZGJTWRSA-UHFFFAOYSA-N (6-carbamimidoylnaphthalen-2-yl) benzoate;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC2=CC(C(=N)N)=CC=C2C=C1OC(=O)C1=CC=CC=C1 IYDDBJZGJTWRSA-UHFFFAOYSA-N 0.000 description 1
- 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
- BAHOXMFOYPPFNP-UHFFFAOYSA-N 2-chloro-4-(diaminomethylideneamino)benzoic acid Chemical compound NC(=N)NC1=CC=C(C(O)=O)C(Cl)=C1 BAHOXMFOYPPFNP-UHFFFAOYSA-N 0.000 description 1
- 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
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- OFJWFSNDPCAWDK-UHFFFAOYSA-N 2-phenylbutyric acid Chemical compound CCC(C(O)=O)C1=CC=CC=C1 OFJWFSNDPCAWDK-UHFFFAOYSA-N 0.000 description 1
- VNDWQCSOSCCWIP-UHFFFAOYSA-N 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one Chemical compound C1=2C=CNC(=O)C=2C2=CC(F)=CC=C2C2=C1NC(C(C)(C)C)=N2 VNDWQCSOSCCWIP-UHFFFAOYSA-N 0.000 description 1
- NEGFNJRAUMCZMY-UHFFFAOYSA-N 3-(dimethylamino)benzoic acid Chemical compound CN(C)C1=CC=CC(C(O)=O)=C1 NEGFNJRAUMCZMY-UHFFFAOYSA-N 0.000 description 1
- YDIYEOMDOWUDTJ-UHFFFAOYSA-N 4-(dimethylamino)benzoic acid Chemical compound CN(C)C1=CC=C(C(O)=O)C=C1 YDIYEOMDOWUDTJ-UHFFFAOYSA-N 0.000 description 1
- KMGGGMYCWLXSJT-UHFFFAOYSA-N 4-(methylamino)benzoic acid;hydrochloride Chemical compound Cl.CNC1=CC=C(C(O)=O)C=C1 KMGGGMYCWLXSJT-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 101100126625 Caenorhabditis elegans itr-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 102100030556 Coagulation factor XII Human genes 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010080865 Factor XII Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 239000005562 Glyphosate Substances 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 101000975003 Homo sapiens Kallistatin Proteins 0.000 description 1
- 101001077723 Homo sapiens Serine protease inhibitor Kazal-type 6 Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 229940122920 Kallikrein inhibitor Drugs 0.000 description 1
- 102100023012 Kallistatin Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229910006121 SOBr2 Inorganic materials 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- SFRAURMUQMJLPG-ZIKNSQGESA-N [4-[(e)-2-carboxyethenyl]phenyl]azanium;chloride Chemical compound Cl.NC1=CC=C(\C=C\C(O)=O)C=C1 SFRAURMUQMJLPG-ZIKNSQGESA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 229940009550 c1 esterase inhibitor Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 206010024378 leukocytosis Diseases 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- GPSDUZXPYCFOSQ-UHFFFAOYSA-M m-toluate Chemical compound CC1=CC=CC(C([O-])=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-M 0.000 description 1
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 1
- 210000004923 pancreatic tissue Anatomy 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000004526 pharmaceutical effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 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 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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)
- Peptides Or Proteins (AREA)
- Superconductors And Manufacturing Methods Therefor (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Heat Treatment Of Sheet Steel (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Medicinal Preparation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Power Steering Mechanism (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 (da) |
| EP (1) | EP0048433B1 (da) |
| KR (1) | KR860000264B1 (da) |
| AT (1) | ATE20051T1 (da) |
| AU (1) | AU527371B2 (da) |
| CA (1) | CA1177488A (da) |
| CS (1) | CS228534B2 (da) |
| DD (1) | DD201779A5 (da) |
| DE (1) | DE3174717D1 (da) |
| DK (1) | DK155003C (da) |
| ES (1) | ES505460A0 (da) |
| FI (1) | FI73975C (da) |
| GB (1) | GB2083818B (da) |
| HU (1) | HU185956B (da) |
| NO (1) | NO153568C (da) |
| PH (1) | PH18109A (da) |
| SU (1) | SU1176832A3 (da) |
Families Citing this family (64)
| 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 |
| AU584502B2 (en) * | 1987-03-30 | 1989-05-25 | Shosuke Okamoto | Phenylalanine derivatives and proteinase inhibitor |
| US4990537A (en) * | 1988-07-11 | 1991-02-05 | Banyu Pharmaceutical Co., Ltd. | Anti influenza agent |
| US5116985A (en) * | 1989-12-28 | 1992-05-26 | Snow Brand Milk Products Co., Ltd. | Isoquinoline derivatives and salts thereof |
| EP0435235B1 (en) * | 1989-12-28 | 1995-03-08 | Snow Brand Milk Products Co., Ltd. | Isoquinoline derivatives and salts thereof as protease inhibitors. |
| US5238964A (en) * | 1990-04-05 | 1993-08-24 | Torii & Co., Ltd. | Agent for treatment of cerebrovascular contraction |
| JPH078789B2 (ja) * | 1990-04-05 | 1995-02-01 | 鳥居薬品株式会社 | 脳血管攣縮治療剤 |
| 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. |
| ES2132535T3 (es) * | 1994-09-20 | 1999-08-16 | Ono Pharmaceutical Co | Derivados de amidinofenol como inhibidores de proteasa. |
| ES2193202T3 (es) * | 1994-12-02 | 2003-11-01 | Yamanouchi Pharma Co Ltd | Nuevo derivado de amidinonaftilo o sal de este. |
| DE69527854T2 (de) * | 1995-01-05 | 2003-03-27 | Torii Pharmaceutical Co., Ltd. | Derivate substituierter amidinonaphthylester |
| US6388122B1 (en) | 1996-04-10 | 2002-05-14 | Ono Pharmaceutical Co., Ltd. | Tryptase inhibitor and novel guanidino derivatives |
| AU7808198A (en) | 1997-06-03 | 1998-12-21 | Biocryst Pharmaceuticals, Inc. | Novel compounds useful in the complement, coagulat and kallikrein pathways and method for their preparation |
| AU1208999A (en) * | 1997-11-10 | 1999-05-31 | Array Biopharma, Inc. | Compounds which inhibit tryptase activity |
| US6066673A (en) | 1998-03-12 | 2000-05-23 | The Procter & Gamble Company | Enzyme inhibitors |
| AP1224A (en) | 1998-03-19 | 2003-11-14 | Bristol Myers Squibb Co | Biphasic controlled release delivery system for high solubility pharmaceuticals and method. |
| EP1066272A4 (en) * | 1998-03-27 | 2002-03-13 | Biocryst Pharm Inc | NEW CONNECTIONS USEFUL IN THE COMPLEMENT, COAGULATE AND KALLIKREIN REACTION WAY AND METHOD FOR THEIR PRODUCTION |
| AU3620099A (en) * | 1998-04-24 | 1999-11-16 | Proteus Molecular Design Limited | Aminomethyl-benzoic ester derivatives as tryptase inhibitors |
| US6362216B1 (en) | 1998-10-27 | 2002-03-26 | Array Biopharma Inc. | Compounds which inhibit tryptase activity |
| AR037097A1 (es) | 2001-10-05 | 2004-10-20 | Novartis Ag | Compuestos acilsulfonamidas, composiciones farmaceuticas y el uso de dichos compuestos para la preparacion de un medicamento |
| JP2006096668A (ja) * | 2002-11-08 | 2006-04-13 | Ono Pharmaceut Co Ltd | エラスターゼ阻害剤と血液凝固系および／または線溶系酵素阻害剤との組み合わせからなる医薬 |
| BR0315942A (pt) | 2002-11-27 | 2005-10-04 | Dmi Biosciences Inc | Tratamento de doenças e condições mediadas pelo aumento de fosforilação |
| CA2538352A1 (en) * | 2003-09-25 | 2005-04-07 | Dmi Biosciences Inc. | Methods and products which utilize n-acyl-l-aspartic acid |
| US20090253765A1 (en) * | 2005-05-17 | 2009-10-08 | Santen Pharmaceutical Co., Ltd. | Angiogenesis Inhibitor Containing Amine Derivative as Active Ingredient |
| US20090088472A1 (en) * | 2005-05-17 | 2009-04-02 | Kouji Oohashi | Protective Agent for Neuronal Cell Comprising Amidino Derivative as Active Ingredient |
| GB2445920A (en) * | 2007-01-25 | 2008-07-30 | Mucokinetica Ltd | Amidino compounds for treatment of respiratory disease |
| EP2311810A4 (en) * | 2008-07-11 | 2012-04-04 | Ajinomoto Kk | AMIDINE DERIVATIVE |
| WO2010045599A1 (en) | 2008-10-17 | 2010-04-22 | Pharmacofore, Inc. | Pharmaceutical compositions with attenuated release of phenolic opioids |
| CN102695545B (zh) | 2009-09-08 | 2016-08-17 | 特色疗法股份有限公司 | 包括酶可剪切的酮改性的阿片样物质药物前体以及其可任选的抑制剂的组合物 |
| US20110262355A1 (en) | 2010-04-21 | 2011-10-27 | Jenkins Thomas E | Compositions comprising enzyme-cleavable opioid prodrugs and inhibitors thereof |
| US20130059914A1 (en) | 2010-04-21 | 2013-03-07 | Signature Therapeutics, Inc. | Compositions Comprising Enzyme-Cleavable Amphetamine Prodrugs and Inhibitors Thereof |
| WO2011133178A1 (en) | 2010-04-21 | 2011-10-27 | Pharmacofore, Inc | Compositions comprising enzyme-cleavable phenol-modified tapentadol prodrug |
| MY161846A (en) | 2010-07-09 | 2017-05-15 | James Trinca Green | Combination immediate/delayed release delivery system for short half-life pharmaceuticals including remogliflozin |
| US8497237B2 (en) | 2011-01-11 | 2013-07-30 | Signature Therapeutics, Inc. | Compositions comprising enzyme-cleavable oxycodone prodrug |
| AU2012205733B2 (en) | 2011-01-11 | 2015-10-08 | Signature Therapeutics, Inc. | Compositions comprising enzyme-cleavable oxycodone prodrug |
| JP6148182B2 (ja) | 2011-03-09 | 2017-06-14 | シグネーチャー セラピューティクス, インク.Signature Therapeutics, Inc. | 複素環式リンカーを有する活性薬剤プロドラッグ |
| WO2012122420A2 (en) | 2011-03-09 | 2012-09-13 | Pharmacofore, Inc. | Opioid prodrugs with heterocyclic linkers |
| KR101981347B1 (ko) | 2011-09-15 | 2019-05-22 | 아스텔라스세이야쿠 가부시키가이샤 | 구아니디노벤조산 화합물 |
| CN103012214A (zh) * | 2011-09-28 | 2013-04-03 | 南京长澳医药科技有限公司 | 一种萘莫司他盐酸盐及萘莫司他甲磺酸盐的制备方法 |
| SG10201707504VA (en) * | 2013-03-13 | 2017-10-30 | Takeda Pharmaceuticals Co | Guanidinobenzoic acid ester compound |
| CN103641749B (zh) * | 2013-12-02 | 2016-02-10 | 山东永泰化工有限公司 | 一种甲磺酸萘莫司他的制备方法 |
| US9428470B2 (en) | 2014-02-13 | 2016-08-30 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| US9346776B2 (en) | 2014-02-13 | 2016-05-24 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
| CN110330447B (zh) * | 2019-07-16 | 2022-04-15 | 北京赛升药业股份有限公司 | 一种甲磺酸萘莫司他中间体的制备方法及其应用 |
| JP2023512628A (ja) * | 2020-01-21 | 2023-03-28 | アカデミー オブ ミリタリー メディカル サイエンシズ | ＳＡＲＳ－ＣｏＶ－２感染症の治療における安息香酸塩化合物の利用 |
| US20230218644A1 (en) | 2020-04-16 | 2023-07-13 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus |
| CN111574409A (zh) * | 2020-05-14 | 2020-08-25 | 河北省医疗器械与药品包装材料检验研究院(河北省医疗器械技术审评中心) | 一种甲磺酸萘莫司他的重结晶工艺方法 |
| IL305493A (en) | 2021-03-09 | 2023-10-01 | Ensysce Biosciences Inc | Compositions comprising enzyme-cleavable prodrugs and controlled release nafamostat and methods of use thereof |
| CA3230025A1 (en) | 2021-09-29 | 2023-04-06 | Lynn Kirkpatrick | Enzyme-cleavable methadone prodrugs and methods of use thereof |
| CN113999145B (zh) * | 2021-11-12 | 2023-02-03 | 开封明仁药业有限公司 | 一种甲磺酸萘莫司他的合成方法 |
| EP4452220A1 (en) | 2021-12-23 | 2024-10-30 | Subintro Limited | Novel antiviral compositions comprising oleic acid |
| WO2023148783A1 (en) * | 2022-02-07 | 2023-08-10 | Council Of Scientific & Industrial Research | Process for the preparation of nafamostat, camostat and their derivatives |
| CN118439976A (zh) * | 2024-04-25 | 2024-08-06 | 南京海纳医药科技股份有限公司 | 一种甲磺酸萘莫司他晶型及其制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD89611A (da) * | ||||
| 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 KR KR1019810003427A patent/KR860000264B1/ko not_active Expired
- 1981-09-15 CS CS816809A patent/CS228534B2/cs unknown
- 1981-09-15 SU SU813384251A patent/SU1176832A3/ru active
- 1981-09-15 GB GB8127837A patent/GB2083818B/en not_active Expired
- 1981-09-15 DK DK410681A patent/DK155003C/da not_active IP Right Cessation
- 1981-09-15 AT AT81107274T patent/ATE20051T1/de not_active IP Right Cessation
- 1981-09-15 DE DE8181107274T patent/DE3174717D1/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 HU HU812665A patent/HU185956B/hu unknown
- 1981-09-15 EP EP81107274A patent/EP0048433B1/en not_active Expired
- 1981-09-15 FI FI812876A patent/FI73975C/fi not_active IP Right Cessation
- 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 |
|---|---|
| DE3174717D1 (en) | 1986-07-03 |
| DK155003C (da) | 1989-05-29 |
| SU1176832A3 (ru) | 1985-08-30 |
| ES8206443A1 (es) | 1982-08-16 |
| NO153568C (no) | 1986-05-21 |
| DD201779A5 (de) | 1983-08-10 |
| DK155003B (da) | 1989-01-23 |
| FI73975C (fi) | 1987-12-10 |
| FI812876L (fi) | 1982-03-17 |
| KR860000264B1 (ko) | 1986-03-22 |
| NO813138L (no) | 1982-03-17 |
| ATE20051T1 (de) | 1986-06-15 |
| GB2083818B (en) | 1984-05-10 |
| ES505460A0 (es) | 1982-08-16 |
| EP0048433A2 (en) | 1982-03-31 |
| AU527371B2 (en) | 1983-03-03 |
| HU185956B (en) | 1985-04-28 |
| PH18109A (en) | 1985-03-22 |
| DK410681A (da) | 1982-03-17 |
| AU7506281A (en) | 1982-03-25 |
| NO153568B (no) | 1986-01-06 |
| US4454338A (en) | 1984-06-12 |
| EP0048433B1 (en) | 1986-05-28 |
| CA1177488A (en) | 1984-11-06 |
| GB2083818A (en) | 1982-03-31 |
| FI73975B (fi) | 1987-08-31 |
| KR830007527A (ko) | 1983-10-21 |
| US4532255A (en) | 1985-07-30 |
| EP0048433A3 (en) | 1982-07-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CS228534B2 (en) | Production method of amidine derivative | |
| GB2134901A (en) | Amidine compounds | |
| DE60122750T2 (de) | Amidin-Inhibitoren von Serin-Proteasen | |
| JP2844329B2 (ja) | 選択的トロンビン抑制剤 | |
| DK169069B1 (da) | 6-Amidino-2-naphthyl-4-amino-benzoat-derivater og farmaceutisk acceptable syreadditionssalte deraf | |
| US4563527A (en) | Amidine compounds | |
| US6989401B2 (en) | Sulfonic acid derivatives of hydroxamic acids and their use as medicinal products | |
| RU2017748C1 (ru) | Производные нитратоалкановых кислот или их фармацевтически приемлемые соли | |
| JPH0259145B2 (da) | ||
| US3816531A (en) | (2,6-disubstituted benzylidene)amino guanidines and related compounds | |
| GB2096598A (en) | Novel amidine compounds | |
| JPH037663B2 (da) | ||
| US3324124A (en) | Thiamine derivatives | |
| JPH0210822B2 (da) | ||
| GB2162171A (en) | Amidine compounds | |
| JPS6360738B2 (da) | ||
| FR2568253A1 (fr) | Nouvelle amidine | |
| JPS6360739B2 (da) | ||
| HK1053829A (en) | Sulfonic acid derivatives of hydroxamic acids and their use as medicinal products |