DE4102024A1 - Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung - Google Patents
Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellungInfo
- Publication number
- DE4102024A1 DE4102024A1 DE4102024A DE4102024A DE4102024A1 DE 4102024 A1 DE4102024 A1 DE 4102024A1 DE 4102024 A DE4102024 A DE 4102024A DE 4102024 A DE4102024 A DE 4102024A DE 4102024 A1 DE4102024 A1 DE 4102024A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- biphenyl
- carbon atoms
- amidino
- radical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 92
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 title claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 239000000203 mixture Substances 0.000 claims abstract description 40
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 150000007524 organic acids Chemical class 0.000 claims abstract description 7
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
- 235000005985 organic acids Nutrition 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims abstract 2
- -1 hydroxy, amino Chemical group 0.000 claims description 118
- 125000004432 carbon atom Chemical group C* 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 125000002947 alkylene group Chemical group 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 23
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 125000004434 sulfur atom Chemical group 0.000 claims description 18
- 239000004305 biphenyl Substances 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 235000010290 biphenyl Nutrition 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 10
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000000460 chlorine Chemical group 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000004437 phosphorous atom Chemical group 0.000 claims description 8
- 229910052698 phosphorus Inorganic materials 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000000732 arylene group Chemical group 0.000 claims description 6
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 4
- 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- YOXOQMWZPSTQGQ-UHFFFAOYSA-N 5-[4-(4-carbamimidoylphenyl)phenoxy]pentanoic acid Chemical group C1=CC(C(=N)N)=CC=C1C1=CC=C(OCCCCC(O)=O)C=C1 YOXOQMWZPSTQGQ-UHFFFAOYSA-N 0.000 claims description 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 230000008619 cell matrix interaction Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 230000001681 protective effect Effects 0.000 claims description 3
- 238000001149 thermolysis Methods 0.000 claims description 3
- NOIVFVUZTWPEDG-UHFFFAOYSA-N 1-[2-[4-(4-carbamimidoylphenyl)phenoxy]acetyl]piperidine-3-carboxylic acid Chemical group C1=CC(C(=N)N)=CC=C1C(C=C1)=CC=C1OCC(=O)N1CC(C(O)=O)CCC1 NOIVFVUZTWPEDG-UHFFFAOYSA-N 0.000 claims description 2
- XRDIQQAMEJHYOK-UHFFFAOYSA-N 3-[[2-[4-(4-carbamimidoylphenyl)phenoxy]acetyl]amino]propanoic acid Chemical group C1=CC(C(=N)N)=CC=C1C1=CC=C(OCC(=O)NCCC(O)=O)C=C1 XRDIQQAMEJHYOK-UHFFFAOYSA-N 0.000 claims description 2
- JNDQKMVRZXIPBQ-UHFFFAOYSA-N 4-[[4-(4-carbamimidoylphenyl)benzoyl]amino]butanoic acid Chemical group C1=CC(C(=N)N)=CC=C1C1=CC=C(C(=O)NCCCC(O)=O)C=C1 JNDQKMVRZXIPBQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 2
- CBVBLGDTQXEDAH-UHFFFAOYSA-N 2-[[2-[4-(4-carbamimidoylphenyl)phenoxy]acetyl]amino]acetic acid Chemical group C1=CC(C(=N)N)=CC=C1C1=CC=C(OCC(=O)NCC(O)=O)C=C1 CBVBLGDTQXEDAH-UHFFFAOYSA-N 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- KALRQKZTDCDKDX-UHFFFAOYSA-N methyl 2-[1-[4-(4-carbamimidoylphenyl)benzoyl]piperidin-4-yl]acetate Chemical group C1CC(CC(=O)OC)CCN1C(=O)C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 KALRQKZTDCDKDX-UHFFFAOYSA-N 0.000 claims 1
- UBUWNPLNJJMDST-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)phenoxy]hexanoate Chemical group C1=CC(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 UBUWNPLNJJMDST-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 230000002776 aggregation Effects 0.000 abstract description 2
- 238000004220 aggregation Methods 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 90
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 238000002844 melting Methods 0.000 description 48
- 230000008018 melting Effects 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- 229960000583 acetic acid Drugs 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- 239000012362 glacial acetic acid Substances 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 238000007127 saponification reaction Methods 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 229940012952 fibrinogen Drugs 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 230000011987 methylation Effects 0.000 description 6
- 238000007069 methylation reaction Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- 102000008946 Fibrinogen Human genes 0.000 description 5
- 108010049003 Fibrinogen Proteins 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 229940099112 cornstarch Drugs 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- 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 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-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
- 230000003213 activating effect Effects 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
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- CGFPKNGIJNLHNM-UHFFFAOYSA-N methyl 2-[1-[4-(4-carbamimidoylphenyl)benzoyl]piperidin-3-yl]acetate;hydrochloride Chemical compound Cl.C1C(CC(=O)OC)CCCN1C(=O)C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 CGFPKNGIJNLHNM-UHFFFAOYSA-N 0.000 description 1
- SGBVVFODKFCERV-UHFFFAOYSA-N methyl 2-[1-[4-(4-carbamimidoylphenyl)benzoyl]piperidin-4-yl]acetate;hydrochloride Chemical compound Cl.C1CC(CC(=O)OC)CCN1C(=O)C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 SGBVVFODKFCERV-UHFFFAOYSA-N 0.000 description 1
- JYOBSAJAXCPITA-UHFFFAOYSA-N methyl 2-[1-[4-(4-cyanophenyl)benzoyl]piperidin-3-yl]acetate Chemical group C1C(CC(=O)OC)CCCN1C(=O)C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 JYOBSAJAXCPITA-UHFFFAOYSA-N 0.000 description 1
- ZEHCZVKRFUQDQO-UHFFFAOYSA-N methyl 2-[1-[4-(4-cyanophenyl)benzoyl]pyrrolidin-3-yl]acetate Chemical group C1C(CC(=O)OC)CCN1C(=O)C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 ZEHCZVKRFUQDQO-UHFFFAOYSA-N 0.000 description 1
- DMAAAHISFMCNIF-UHFFFAOYSA-N methyl 2-[1-[[4-(4-carbamimidoylphenyl)phenyl]methyl]piperidin-3-yl]acetate;hydrochloride Chemical compound Cl.C1C(CC(=O)OC)CCCN1CC1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 DMAAAHISFMCNIF-UHFFFAOYSA-N 0.000 description 1
- SRBPYZLASIJBJY-UHFFFAOYSA-N methyl 2-[1-[[4-(4-carbamimidoylphenyl)phenyl]methyl]piperidin-4-yl]acetate;hydrochloride Chemical compound Cl.C1CC(CC(=O)OC)CCN1CC1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 SRBPYZLASIJBJY-UHFFFAOYSA-N 0.000 description 1
- FWELXTWQRYDTJN-UHFFFAOYSA-N methyl 2-[1-[[4-(4-carbamimidoylphenyl)phenyl]methyl]pyrrolidin-3-yl]acetate;hydrochloride Chemical compound Cl.C1C(CC(=O)OC)CCN1CC1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 FWELXTWQRYDTJN-UHFFFAOYSA-N 0.000 description 1
- GKBXUVNNXGMLJH-UHFFFAOYSA-N methyl 2-[1-[[4-(4-cyanophenyl)phenyl]methyl]piperidin-3-yl]acetate Chemical group C1C(CC(=O)OC)CCCN1CC1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 GKBXUVNNXGMLJH-UHFFFAOYSA-N 0.000 description 1
- XCXRFCPHCSKEGK-UHFFFAOYSA-N methyl 2-[1-[[4-(4-cyanophenyl)phenyl]methyl]piperidin-4-yl]acetate Chemical group C1CC(CC(=O)OC)CCN1CC1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 XCXRFCPHCSKEGK-UHFFFAOYSA-N 0.000 description 1
- JCHPNIVUPIAFRI-UHFFFAOYSA-N methyl 2-[1-[[4-(4-cyanophenyl)phenyl]methyl]pyrrolidin-3-yl]acetate Chemical group C1C(CC(=O)OC)CCN1CC1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 JCHPNIVUPIAFRI-UHFFFAOYSA-N 0.000 description 1
- SJBORYWGFLCWHN-UHFFFAOYSA-N methyl 2-[2-[4-(4-carbamimidoylphenyl)anilino]-2-oxoethoxy]acetate;hydrochloride Chemical compound Cl.C1=CC(NC(=O)COCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 SJBORYWGFLCWHN-UHFFFAOYSA-N 0.000 description 1
- JULNAJRNHRXATQ-UHFFFAOYSA-N methyl 2-[2-[4-(4-carbamimidoylphenyl)phenyl]ethylsulfanyl]acetate;hydrochloride Chemical compound Cl.C1=CC(CCSCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 JULNAJRNHRXATQ-UHFFFAOYSA-N 0.000 description 1
- YGYVTVSHBJZLLP-UHFFFAOYSA-N methyl 2-[2-[4-(4-cyanophenyl)phenyl]ethylsulfanyl]acetate Chemical group C1=CC(CCSCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 YGYVTVSHBJZLLP-UHFFFAOYSA-N 0.000 description 1
- MQQLIILFBZRMAR-UHFFFAOYSA-N methyl 2-[3-[[2-[4-(4-carbamimidoylphenyl)phenyl]acetyl]amino]phenyl]acetate;hydrochloride Chemical compound Cl.COC(=O)CC1=CC=CC(NC(=O)CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=C1 MQQLIILFBZRMAR-UHFFFAOYSA-N 0.000 description 1
- FSZSLNFALSIVDX-UHFFFAOYSA-N methyl 2-[3-[[4-(4-carbamimidoylphenyl)benzoyl]amino]phenyl]acetate;hydrochloride Chemical compound Cl.COC(=O)CC1=CC=CC(NC(=O)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=C1 FSZSLNFALSIVDX-UHFFFAOYSA-N 0.000 description 1
- RYOHQPHMRFOAEA-UHFFFAOYSA-N methyl 2-[3-[[4-(4-cyanophenyl)benzoyl]amino]phenyl]acetate Chemical group COC(=O)CC1=CC=CC(NC(=O)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)=C1 RYOHQPHMRFOAEA-UHFFFAOYSA-N 0.000 description 1
- SCKMBMMQIPDRLV-UHFFFAOYSA-N methyl 2-[[2-[4-(4-cyanophenyl)-n-methylanilino]acetyl]amino]acetate Chemical group C1=CC(N(C)CC(=O)NCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 SCKMBMMQIPDRLV-UHFFFAOYSA-N 0.000 description 1
- PKDRUFJXUQCTJJ-UHFFFAOYSA-N methyl 2-[[2-[4-(4-cyanophenyl)anilino]-2-oxoethyl]-methylamino]acetate Chemical group C1=CC(NC(=O)CN(C)CC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 PKDRUFJXUQCTJJ-UHFFFAOYSA-N 0.000 description 1
- LWIDKNHLTIYJIS-UHFFFAOYSA-N methyl 2-[[2-[4-(4-cyanophenyl)phenoxy]acetyl]amino]acetate Chemical group C1=CC(OCC(=O)NCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 LWIDKNHLTIYJIS-UHFFFAOYSA-N 0.000 description 1
- VTNGULPXTZKJFT-UHFFFAOYSA-N methyl 2-[n-acetyl-4-(4-cyanophenyl)anilino]oxyacetate Chemical group C1=CC(N(C(C)=O)OCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 VTNGULPXTZKJFT-UHFFFAOYSA-N 0.000 description 1
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 1
- QQFTXBUEMGDUNW-UHFFFAOYSA-N methyl 3-[2-[4-(4-carbamimidoylphenyl)phenoxy]ethyl-methylsulfonylamino]propanoate;hydrochloride Chemical compound Cl.C1=CC(OCCN(CCC(=O)OC)S(C)(=O)=O)=CC=C1C1=CC=C(C(N)=N)C=C1 QQFTXBUEMGDUNW-UHFFFAOYSA-N 0.000 description 1
- GNJBMZFAGPJADC-UHFFFAOYSA-N methyl 3-[2-[4-(4-carbamimidoylphenyl)phenyl]-2-oxoethyl]sulfanylpropanoate;hydrochloride Chemical compound Cl.C1=CC(C(=O)CSCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 GNJBMZFAGPJADC-UHFFFAOYSA-N 0.000 description 1
- MMVBRGLZWZAWDX-UHFFFAOYSA-N methyl 3-[2-[4-(4-cyanophenyl)phenoxy]ethyl-methylsulfonylamino]propanoate Chemical group C1=CC(OCCN(CCC(=O)OC)S(C)(=O)=O)=CC=C1C1=CC=C(C#N)C=C1 MMVBRGLZWZAWDX-UHFFFAOYSA-N 0.000 description 1
- JJYHOILAFXFJFR-UHFFFAOYSA-N methyl 3-[2-[4-(4-cyanophenyl)phenyl]-2-oxoethyl]sulfanylpropanoate Chemical group C1=CC(C(=O)CSCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 JJYHOILAFXFJFR-UHFFFAOYSA-N 0.000 description 1
- SXWKCIISXMUSBT-UHFFFAOYSA-N methyl 3-[3-[[2-[4-(4-carbamimidoylphenyl)phenyl]acetyl]amino]phenyl]propanoate;hydrochloride Chemical compound Cl.COC(=O)CCC1=CC=CC(NC(=O)CC=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=C1 SXWKCIISXMUSBT-UHFFFAOYSA-N 0.000 description 1
- KJMXUAXIFLWADX-UHFFFAOYSA-N methyl 3-[3-[[4-(4-carbamimidoylphenyl)benzoyl]amino]phenyl]propanoate;hydrochloride Chemical compound Cl.COC(=O)CCC1=CC=CC(NC(=O)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=C1 KJMXUAXIFLWADX-UHFFFAOYSA-N 0.000 description 1
- NCSGKQZIQFQYEW-UHFFFAOYSA-N methyl 3-[3-[[4-(4-cyanophenyl)benzoyl]amino]phenyl]propanoate Chemical group COC(=O)CCC1=CC=CC(NC(=O)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C#N)=C1 NCSGKQZIQFQYEW-UHFFFAOYSA-N 0.000 description 1
- NFOOVVYDIAYTNN-UHFFFAOYSA-N methyl 3-[[2-[4-(4-carbamimidoylphenyl)phenoxy]acetyl]-methylamino]propanoate;hydrochloride Chemical compound Cl.C1=CC(OCC(=O)N(C)CCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 NFOOVVYDIAYTNN-UHFFFAOYSA-N 0.000 description 1
- HQZJNNKFFUISGU-UHFFFAOYSA-N methyl 3-[[2-[4-(4-carbamimidoylphenyl)phenoxy]acetyl]amino]propanoate;hydrochloride Chemical compound Cl.C1=CC(OCC(=O)NCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 HQZJNNKFFUISGU-UHFFFAOYSA-N 0.000 description 1
- YYGJUNTWMGTGBI-UHFFFAOYSA-N methyl 3-[[2-[4-(4-carbamimidoylphenyl)phenyl]acetyl]amino]-4-[2-(4-methoxyphenyl)ethylamino]-4-oxobutanoate Chemical group C=1C=C(OC)C=CC=1CCNC(=O)C(CC(=O)OC)NC(=O)CC(C=C1)=CC=C1C1=CC=C(C(N)=N)C=C1 YYGJUNTWMGTGBI-UHFFFAOYSA-N 0.000 description 1
- LYKFBLGSZDYIEO-UHFFFAOYSA-N methyl 3-[[2-[4-(4-carbamimidoylphenyl)phenyl]acetyl]amino]propanoate Chemical group C1=CC(CC(=O)NCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 LYKFBLGSZDYIEO-UHFFFAOYSA-N 0.000 description 1
- JDNKPAZJXJVLLR-UHFFFAOYSA-N methyl 3-[[2-[4-(4-cyanophenyl)phenoxy]acetyl]-methylamino]propanoate Chemical group C1=CC(OCC(=O)N(C)CCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 JDNKPAZJXJVLLR-UHFFFAOYSA-N 0.000 description 1
- VGRQLVGWSFLOHD-UHFFFAOYSA-N methyl 3-[[4-(4-carbamimidoylphenyl)benzoyl]amino]propanoate;hydrochloride Chemical compound Cl.C1=CC(C(=O)NCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 VGRQLVGWSFLOHD-UHFFFAOYSA-N 0.000 description 1
- YMKGGWSWILUSSB-UHFFFAOYSA-N methyl 3-[[4-(4-carbamimidoylphenyl)phenyl]carbamoylamino]propanoate;hydrochloride Chemical compound Cl.C1=CC(NC(=O)NCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 YMKGGWSWILUSSB-UHFFFAOYSA-N 0.000 description 1
- IZIAZSCWOURSLJ-UHFFFAOYSA-N methyl 3-[[4-(4-cyanophenyl)phenyl]carbamoylamino]propanoate Chemical group C1=CC(NC(=O)NCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 IZIAZSCWOURSLJ-UHFFFAOYSA-N 0.000 description 1
- KOLMVQRDUPYHEJ-UHFFFAOYSA-N methyl 3-[[[4-(4-carbamimidoylphenyl)phenyl]-methylcarbamoyl]-methylamino]propanoate;hydrochloride Chemical compound Cl.C1=CC(N(C)C(=O)N(C)CCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 KOLMVQRDUPYHEJ-UHFFFAOYSA-N 0.000 description 1
- DJSVAFSIUALNAO-UHFFFAOYSA-N methyl 3-[[[4-(4-cyanophenyl)phenyl]-methylcarbamoyl]-methylamino]propanoate Chemical group C1=CC(N(C)C(=O)N(C)CCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 DJSVAFSIUALNAO-UHFFFAOYSA-N 0.000 description 1
- DMPAUOBGJFHLKT-UHFFFAOYSA-N methyl 3-[acetyl-[2-[4-(4-carbamimidoylphenyl)phenoxy]ethyl]amino]propanoate;hydrochloride Chemical compound Cl.C1=CC(OCCN(CCC(=O)OC)C(C)=O)=CC=C1C1=CC=C(C(N)=N)C=C1 DMPAUOBGJFHLKT-UHFFFAOYSA-N 0.000 description 1
- QXKYIAFYKBQNOE-UHFFFAOYSA-N methyl 3-[benzoyl-[2-[4-(4-carbamimidoylphenyl)phenoxy]ethyl]amino]propanoate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(=O)N(CCC(=O)OC)CCOC(C=C1)=CC=C1C1=CC=C(C(N)=N)C=C1 QXKYIAFYKBQNOE-UHFFFAOYSA-N 0.000 description 1
- CSDWQCKLFCFPRR-UHFFFAOYSA-N methyl 3-[benzoyl-[2-[4-(4-cyanophenyl)phenoxy]ethyl]amino]propanoate Chemical group C=1C=CC=CC=1C(=O)N(CCC(=O)OC)CCOC(C=C1)=CC=C1C1=CC=C(C#N)C=C1 CSDWQCKLFCFPRR-UHFFFAOYSA-N 0.000 description 1
- LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 description 1
- HAMIEVLUIPBMDJ-UHFFFAOYSA-N methyl 4-(4-carbamimidoylphenyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 HAMIEVLUIPBMDJ-UHFFFAOYSA-N 0.000 description 1
- KMLLDRNKDCBRPG-UHFFFAOYSA-N methyl 4-[4-(4-carbamimidoylphenyl)-n-methylanilino]-2-methyl-4-oxobutanoate;hydrochloride Chemical compound Cl.C1=CC(N(C)C(=O)CC(C)C(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 KMLLDRNKDCBRPG-UHFFFAOYSA-N 0.000 description 1
- DZAGHYYMDQHVME-UHFFFAOYSA-N methyl 4-[4-(4-carbamimidoylphenyl)-n-methylanilino]-4-oxobutanoate;hydrochloride Chemical compound Cl.C1=CC(N(C)C(=O)CCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 DZAGHYYMDQHVME-UHFFFAOYSA-N 0.000 description 1
- PYSGCFYXBWBIHB-UHFFFAOYSA-N methyl 4-[4-(4-cyanophenyl)-n-methylanilino]-4-oxobutanoate Chemical group C1=CC(N(C)C(=O)CCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 PYSGCFYXBWBIHB-UHFFFAOYSA-N 0.000 description 1
- MRSWUTQUYSHKHS-UHFFFAOYSA-N methyl 4-[4-(4-cyanophenyl)anilino]-4-oxobutanoate Chemical group C1=CC(NC(=O)CCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 MRSWUTQUYSHKHS-UHFFFAOYSA-N 0.000 description 1
- XVRUNSDLMXWAHA-UHFFFAOYSA-N methyl 4-[4-(4-cyanophenyl)phenoxy]butanoate Chemical group C1=CC(OCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 XVRUNSDLMXWAHA-UHFFFAOYSA-N 0.000 description 1
- NPISCBCIUJGHQX-UHFFFAOYSA-N methyl 4-[[4-(4-carbamimidoylphenyl)benzoyl]-methylamino]but-2-enoate;hydrochloride Chemical compound Cl.C1=CC(C(=O)N(C)CC=CC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 NPISCBCIUJGHQX-UHFFFAOYSA-N 0.000 description 1
- KYOLOWLBVLXZSF-UHFFFAOYSA-N methyl 4-[[4-(4-carbamimidoylphenyl)benzoyl]amino]butanoate;hydrochloride Chemical compound Cl.C1=CC(C(=O)NCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 KYOLOWLBVLXZSF-UHFFFAOYSA-N 0.000 description 1
- RPMZDBFGUUVZOL-UHFFFAOYSA-N methyl 4-[[4-(4-carbamimidoylphenyl)phenyl]methylsulfanyl]butanoate;hydrochloride Chemical compound Cl.C1=CC(CSCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 RPMZDBFGUUVZOL-UHFFFAOYSA-N 0.000 description 1
- YRJQMUNFPSOJJS-UHFFFAOYSA-N methyl 4-[[4-(4-carbamimidoylphenyl)phenyl]methylsulfinyl]butanoate Chemical group C1=CC(CS(=O)CCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 YRJQMUNFPSOJJS-UHFFFAOYSA-N 0.000 description 1
- HXPWGLAQUPNMIO-UHFFFAOYSA-N methyl 4-[[4-(4-carbamimidoylphenyl)phenyl]methylsulfonyl]butanoate;hydrochloride Chemical compound Cl.C1=CC(CS(=O)(=O)CCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 HXPWGLAQUPNMIO-UHFFFAOYSA-N 0.000 description 1
- NSTFMOCMKJHNTM-UHFFFAOYSA-N methyl 4-[[4-(4-carbamimidoylphenyl)phenyl]sulfonyl-methylamino]butanoate;hydrochloride Chemical compound Cl.C1=CC(S(=O)(=O)N(C)CCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 NSTFMOCMKJHNTM-UHFFFAOYSA-N 0.000 description 1
- AOLYAQIYQMVJGF-UHFFFAOYSA-N methyl 4-[[4-(4-carbamimidoylphenyl)phenyl]sulfonylamino]butanoate;hydrochloride Chemical compound Cl.C1=CC(S(=O)(=O)NCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 AOLYAQIYQMVJGF-UHFFFAOYSA-N 0.000 description 1
- CHQUPXNRBJHEBD-UHFFFAOYSA-N methyl 4-[[4-(4-cyanophenyl)benzoyl]-methylamino]but-2-enoate Chemical group C1=CC(C(=O)N(C)CC=CC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 CHQUPXNRBJHEBD-UHFFFAOYSA-N 0.000 description 1
- MWPIUJSBZCLYBW-UHFFFAOYSA-N methyl 4-[[4-(4-cyanophenyl)phenyl]methylsulfanyl]butanoate Chemical group C1=CC(CSCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 MWPIUJSBZCLYBW-UHFFFAOYSA-N 0.000 description 1
- XXGZVVVQWOTGFT-UHFFFAOYSA-N methyl 4-[[4-(4-cyanophenyl)phenyl]methylsulfonyl]butanoate Chemical group C1=CC(CS(=O)(=O)CCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 XXGZVVVQWOTGFT-UHFFFAOYSA-N 0.000 description 1
- UENWKBGWQVHHRD-UHFFFAOYSA-N methyl 4-[[4-(4-cyanophenyl)phenyl]sulfonyl-methylamino]butanoate Chemical group C1=CC(S(=O)(=O)N(C)CCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 UENWKBGWQVHHRD-UHFFFAOYSA-N 0.000 description 1
- LHBQJMYSVZNOEH-UHFFFAOYSA-N methyl 4-[[4-[4-[(z)-n'-ethoxycarbonylcarbamimidoyl]phenyl]benzoyl]amino]butanoate Chemical group C1=CC(C(=N)NC(=O)OCC)=CC=C1C1=CC=C(C(=O)NCCCC(=O)OC)C=C1 LHBQJMYSVZNOEH-UHFFFAOYSA-N 0.000 description 1
- SVOFVQOKFYZXIO-UHFFFAOYSA-N methyl 4-[[4-[4-[(z)-n'-methoxycarbonylcarbamimidoyl]phenyl]benzoyl]amino]butanoate Chemical group C1=CC(C(=O)NCCCC(=O)OC)=CC=C1C1=CC=C(C(=N)NC(=O)OC)C=C1 SVOFVQOKFYZXIO-UHFFFAOYSA-N 0.000 description 1
- QSFBFAPFVIJGSX-UHFFFAOYSA-N methyl 4-[[4-[4-[(z)-n'-phenylmethoxycarbonylcarbamimidoyl]phenyl]benzoyl]amino]butanoate Chemical group C1=CC(C(=O)NCCCC(=O)OC)=CC=C1C1=CC=C(C(=N)NC(=O)OCC=2C=CC=CC=2)C=C1 QSFBFAPFVIJGSX-UHFFFAOYSA-N 0.000 description 1
- RBRGPPSAIUGJFQ-UHFFFAOYSA-N methyl 5-[2,6-dibromo-4-(4-carbamimidoylphenyl)anilino]-5-oxopentanoate;hydrochloride Chemical compound Cl.C1=C(Br)C(NC(=O)CCCC(=O)OC)=C(Br)C=C1C1=CC=C(C(N)=N)C=C1 RBRGPPSAIUGJFQ-UHFFFAOYSA-N 0.000 description 1
- RLLDZRDOUMMJLF-UHFFFAOYSA-N methyl 5-[2,6-dibromo-4-(4-cyanophenyl)anilino]-5-oxopentanoate Chemical group C1=C(Br)C(NC(=O)CCCC(=O)OC)=C(Br)C=C1C1=CC=C(C#N)C=C1 RLLDZRDOUMMJLF-UHFFFAOYSA-N 0.000 description 1
- JNEKHMVKTODPQD-UHFFFAOYSA-N methyl 5-[2-bromo-4-(4-carbamimidoylphenyl)anilino]-5-oxopentanoate;hydrochloride Chemical compound Cl.C1=C(Br)C(NC(=O)CCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 JNEKHMVKTODPQD-UHFFFAOYSA-N 0.000 description 1
- FVBPVOSAXAVIFC-UHFFFAOYSA-N methyl 5-[2-bromo-4-(4-cyanophenyl)anilino]-5-oxopentanoate Chemical group C1=C(Br)C(NC(=O)CCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 FVBPVOSAXAVIFC-UHFFFAOYSA-N 0.000 description 1
- CBQVNTAFWDLDGS-UHFFFAOYSA-N methyl 5-[4-(4-carbamimidoylphenyl)anilino]-5-oxopentanoate;hydrochloride Chemical compound Cl.C1=CC(NC(=O)CCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 CBQVNTAFWDLDGS-UHFFFAOYSA-N 0.000 description 1
- BEYPBRZVPOXYJC-UHFFFAOYSA-N methyl 5-[4-(4-carbamimidoylphenyl)phenoxy]pentanoate;hydrochloride Chemical compound Cl.C1=CC(OCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 BEYPBRZVPOXYJC-UHFFFAOYSA-N 0.000 description 1
- ZMOZRIAVYPTENW-UHFFFAOYSA-N methyl 5-[4-(4-carbamimidoylphenyl)phenyl]sulfanylpentanoate Chemical group C1=CC(SCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 ZMOZRIAVYPTENW-UHFFFAOYSA-N 0.000 description 1
- YCFRMTMNLAXQNQ-UHFFFAOYSA-N methyl 5-[4-(4-carbamimidoylphenyl)phenyl]sulfanylpentanoate;hydrochloride Chemical compound Cl.C1=CC(SCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 YCFRMTMNLAXQNQ-UHFFFAOYSA-N 0.000 description 1
- HUXUGTZMYFLULR-UHFFFAOYSA-N methyl 5-[4-(4-carbamimidoylphenyl)phenyl]sulfinylpentanoate Chemical group C1=CC(S(=O)CCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 HUXUGTZMYFLULR-UHFFFAOYSA-N 0.000 description 1
- NETLZUJIIQKATA-UHFFFAOYSA-N methyl 5-[4-(4-carbamimidoylphenyl)phenyl]sulfonylpentanoate;hydrochloride Chemical compound Cl.C1=CC(S(=O)(=O)CCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 NETLZUJIIQKATA-UHFFFAOYSA-N 0.000 description 1
- UUSBGKLNJCIHGJ-UHFFFAOYSA-N methyl 5-[4-(4-cyanophenyl)phenoxy]pentanoate Chemical group C1=CC(OCCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 UUSBGKLNJCIHGJ-UHFFFAOYSA-N 0.000 description 1
- VTKIFKZEFGHIEM-UHFFFAOYSA-N methyl 5-[4-(4-cyanophenyl)phenyl]sulfonylpentanoate Chemical group C1=CC(S(=O)(=O)CCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 VTKIFKZEFGHIEM-UHFFFAOYSA-N 0.000 description 1
- SCEFIXXLWWGHKO-UHFFFAOYSA-N methyl 5-[[4-(4-carbamimidoylphenyl)benzoyl]amino]pentanoate;hydrochloride Chemical compound Cl.C1=CC(C(=O)NCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 SCEFIXXLWWGHKO-UHFFFAOYSA-N 0.000 description 1
- OCVMFCUNBRVFQC-UHFFFAOYSA-N methyl 5-[[4-(4-cyanophenyl)benzoyl]amino]pentanoate Chemical group C1=CC(C(=O)NCCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 OCVMFCUNBRVFQC-UHFFFAOYSA-N 0.000 description 1
- JWLBACJGXMXNAT-UHFFFAOYSA-N methyl 5-amino-4-[4-(4-carbamimidoylphenyl)phenyl]-5-oxopentanoate Chemical group C1=CC(C(C(N)=O)CCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 JWLBACJGXMXNAT-UHFFFAOYSA-N 0.000 description 1
- VKEUHOJUOASIIZ-UHFFFAOYSA-N methyl 6-[2-(benzenesulfonamido)-4-(4-cyanophenyl)phenoxy]hexanoate Chemical group COC(=O)CCCCCOC1=CC=C(C=2C=CC(=CC=2)C#N)C=C1NS(=O)(=O)C1=CC=CC=C1 VKEUHOJUOASIIZ-UHFFFAOYSA-N 0.000 description 1
- QCDOYXLJXWBUSO-UHFFFAOYSA-N methyl 6-[2-acetamido-4-(4-carbamimidoylphenyl)phenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C(NC(C)=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 QCDOYXLJXWBUSO-UHFFFAOYSA-N 0.000 description 1
- LFVJDAMGNOXYII-UHFFFAOYSA-N methyl 6-[2-acetamido-4-(4-cyanophenyl)phenoxy]hexanoate Chemical group C1=C(NC(C)=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 LFVJDAMGNOXYII-UHFFFAOYSA-N 0.000 description 1
- YFSDSVKQDLCFML-UHFFFAOYSA-N methyl 6-[2-amino-4-(4-carbamimidoylphenyl)phenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C(N)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 YFSDSVKQDLCFML-UHFFFAOYSA-N 0.000 description 1
- XCSQJJZADQSAPQ-UHFFFAOYSA-N methyl 6-[2-amino-4-(4-cyanophenyl)phenoxy]hexanoate Chemical group C1=C(N)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 XCSQJJZADQSAPQ-UHFFFAOYSA-N 0.000 description 1
- GTPKJKKMWIDUIH-UHFFFAOYSA-N methyl 6-[2-benzamido-4-(4-carbamimidoylphenyl)phenoxy]hexanoate;hydrochloride Chemical compound Cl.COC(=O)CCCCCOC1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1NC(=O)C1=CC=CC=C1 GTPKJKKMWIDUIH-UHFFFAOYSA-N 0.000 description 1
- UJVNSUCQWBQKHL-UHFFFAOYSA-N methyl 6-[2-benzamido-4-(4-cyanophenyl)phenoxy]hexanoate Chemical group COC(=O)CCCCCOC1=CC=C(C=2C=CC(=CC=2)C#N)C=C1NC(=O)C1=CC=CC=C1 UJVNSUCQWBQKHL-UHFFFAOYSA-N 0.000 description 1
- WUMDPVDNTXWYPF-UHFFFAOYSA-N methyl 6-[3-(3-aminophenyl)anilino]-6-oxohexanoate Chemical group COC(=O)CCCCC(=O)NC1=CC=CC(C=2C=C(N)C=CC=2)=C1 WUMDPVDNTXWYPF-UHFFFAOYSA-N 0.000 description 1
- DFRVSZIDCNITOT-UHFFFAOYSA-N methyl 6-[3-[3-(diaminomethylideneamino)phenyl]anilino]-6-oxohexanoate Chemical group COC(=O)CCCCC(=O)NC1=CC=CC(C=2C=C(NC(N)=N)C=CC=2)=C1 DFRVSZIDCNITOT-UHFFFAOYSA-N 0.000 description 1
- MSOPLHIVWYZVON-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoyl-3-chlorophenyl)phenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=CC(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C(Cl)=C1 MSOPLHIVWYZVON-UHFFFAOYSA-N 0.000 description 1
- DWBCCYPZCRPINP-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoyl-3-fluorophenyl)phenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=CC(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C(F)=C1 DWBCCYPZCRPINP-UHFFFAOYSA-N 0.000 description 1
- DOKFUZLAEUGMSN-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2,3-dimethylphenoxy]hexanoate;hydrochloride Chemical compound Cl.CC1=C(C)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 DOKFUZLAEUGMSN-UHFFFAOYSA-N 0.000 description 1
- ZXCZWQMKCDGJED-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2-(methanesulfonamido)phenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C(NS(C)(=O)=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 ZXCZWQMKCDGJED-UHFFFAOYSA-N 0.000 description 1
- LQQYIGSKGGSWKB-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2-(trifluoromethyl)phenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C(C(F)(F)F)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 LQQYIGSKGGSWKB-UHFFFAOYSA-N 0.000 description 1
- BPDOODMBYRESDJ-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2-hydroxyphenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C(O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 BPDOODMBYRESDJ-UHFFFAOYSA-N 0.000 description 1
- LQCUSMNCKYWBGD-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2-methylsulfanylphenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C(SC)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 LQCUSMNCKYWBGD-UHFFFAOYSA-N 0.000 description 1
- JABWYIGTWQBZHD-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2-methylsulfinylphenoxy]hexanoate Chemical group C1=C(S(C)=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 JABWYIGTWQBZHD-UHFFFAOYSA-N 0.000 description 1
- UWBWKJKBDJDMPE-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2-methylsulfonylphenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C(S(C)(=O)=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 UWBWKJKBDJDMPE-UHFFFAOYSA-N 0.000 description 1
- KSOBRICEAULBQW-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)-2-nitrophenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=C([N+]([O-])=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 KSOBRICEAULBQW-UHFFFAOYSA-N 0.000 description 1
- RPGHSAWRJPYXBI-UHFFFAOYSA-N methyl 6-[4-(4-carbamimidoylphenyl)phenoxy]hexanoate;hydrochloride Chemical compound Cl.C1=CC(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C(N)=N)C=C1 RPGHSAWRJPYXBI-UHFFFAOYSA-N 0.000 description 1
- AIXIEXIWAYKTCJ-UHFFFAOYSA-N methyl 6-[4-(4-cyanophenyl)-2-(methanesulfonamido)phenoxy]hexanoate Chemical group C1=C(NS(C)(=O)=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 AIXIEXIWAYKTCJ-UHFFFAOYSA-N 0.000 description 1
- HYGBCTICCWEJNE-UHFFFAOYSA-N methyl 6-[4-(4-cyanophenyl)-2-methylsulfonylphenoxy]hexanoate Chemical group C1=C(S(C)(=O)=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 HYGBCTICCWEJNE-UHFFFAOYSA-N 0.000 description 1
- QMYISYPXSISLTJ-UHFFFAOYSA-N methyl 6-[4-(4-cyanophenyl)-2-nitrophenoxy]hexanoate Chemical group C1=C([N+]([O-])=O)C(OCCCCCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 QMYISYPXSISLTJ-UHFFFAOYSA-N 0.000 description 1
- KWRRDKRBMBNRLJ-UHFFFAOYSA-N methyl 6-[4-[4-[(e)-n'-methoxycarbamimidoyl]phenyl]phenoxy]hexanoate Chemical group C1=CC(C(=N)NOC)=CC=C1C1=CC=C(OCCCCCC(=O)OC)C=C1 KWRRDKRBMBNRLJ-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229940073584 methylene chloride Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000004540 pour-on Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000036633 rest Effects 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000003462 vein Anatomy 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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/18—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 acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- 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
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/36—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a ring other than a six-membered aromatic ring
-
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/10—Hydrazines
- C07C243/22—Hydrazines having nitrogen atoms of hydrazine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/56—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and doubly-bound oxygen atoms bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
- C07C255/59—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
- C07C255/60—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
-
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- 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
-
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/62—Compounds containing any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylcarbamates
- C07C271/64—Y being a hydrogen or a carbon atom, e.g. benzoylcarbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C307/04—Diamides of sulfuric acids
- C07C307/10—Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
- C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C309/07—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing oxygen atoms bound to the carbon skeleton
- C07C309/09—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing oxygen atoms bound to the carbon skeleton containing etherified hydroxy groups bound to the carbon skeleton
- C07C309/11—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing oxygen atoms bound to the carbon skeleton containing etherified hydroxy groups bound to the carbon skeleton with the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/04—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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- C—CHEMISTRY; METALLURGY
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
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- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
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- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
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- C—CHEMISTRY; METALLURGY
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
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- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/36—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 no double bonds between ring members or between ring members and non-ring members 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/36—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 no double bonds between ring members or between ring members and non-ring members 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
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
-
- 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
- C07D211/70—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- 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)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
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- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Pyrrole Compounds (AREA)
Priority Applications (23)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4102024A DE4102024A1 (de) | 1991-01-24 | 1991-01-24 | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DK92101007.0T DK0496378T3 (da) | 1991-01-24 | 1992-01-22 | Biphenylderivater, lægemidler indeholdende disse forbindelser og fremgangsmåder til deres fremstilling |
| CA002059857A CA2059857A1 (en) | 1991-01-24 | 1992-01-22 | Biphenyl derivatives, pharmaceutical compositions containing these compounds and processes for preparing them |
| TW081100460A TW257753B (enExample) | 1991-01-24 | 1992-01-22 | |
| DE59203704T DE59203704D1 (de) | 1991-01-24 | 1992-01-22 | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung. |
| NZ24135592A NZ241355A (en) | 1991-01-24 | 1992-01-22 | Substituted biphenyl derivatives and pharmaceutical compositions |
| ES92101007T ES2079694T3 (es) | 1991-01-24 | 1992-01-22 | Derivados de bifenilo, medicamentos que contienen estos compuestos y procedimiento para su preparacion. |
| EP92101007A EP0496378B1 (de) | 1991-01-24 | 1992-01-22 | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| AT92101007T ATE128120T1 (de) | 1991-01-24 | 1992-01-22 | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung. |
| MX9200269A MX9200269A (es) | 1991-01-24 | 1992-01-22 | Derivados de bifenilo, medicamentos que contienen estos compuestos y procedimientos para su preparacion |
| AU10403/92A AU648379B2 (en) | 1991-01-24 | 1992-01-23 | Biphenyl derivatives |
| HU9200212A HUT60462A (en) | 1991-01-24 | 1992-01-23 | Process for producing biphenyl derivatives and pharmaceutical compositions comprising same |
| JP4009703A JPH04334351A (ja) | 1991-01-24 | 1992-01-23 | ビフェニル誘導体、これらの化合物を含む製薬組成物及びそれらの調製法 |
| NO920320A NO177852C (no) | 1991-01-24 | 1992-01-23 | Bifenylderivater, legemidler inneholdende disse, og anvendelse av dem for fremstilling av legemidler |
| ZA92464A ZA92464B (en) | 1991-01-24 | 1992-01-23 | Diphenyl derivatives. |
| FI920286A FI920286A7 (fi) | 1991-01-24 | 1992-01-23 | Bifenyylijohdannaiset, näitä yhdisteitä sisältävät lääkeaineet ja menetelmä niiden valmistamiseksi |
| IE920199A IE69973B1 (en) | 1991-01-24 | 1992-01-23 | Biphenyl derivatives |
| IL100740A IL100740A0 (en) | 1991-01-24 | 1992-01-23 | Biphenyl derivatives,their preparation and pharmaceutical compositions containing them |
| KR1019920000983A KR920014779A (ko) | 1991-01-24 | 1992-01-24 | 비페닐 유도체. 이를 함유하는 약제학적 조성물 및 이의 제조방법 |
| US08/257,759 US5597825A (en) | 1991-01-24 | 1994-05-16 | Biphenyl derivatives, pharmaceutical compositions containing these compounds and processes for preparing them |
| GR950402905T GR3017802T3 (en) | 1991-01-24 | 1995-10-18 | Biphenylderivatives, drugs containing these compounds and processes for their preparation. |
| US08/691,107 US5736559A (en) | 1991-01-24 | 1996-08-01 | Biphenyl derivatives, pharmaceutical compositions containing these compounds and processes for preparing them |
| US08/978,739 US5922763A (en) | 1991-01-24 | 1997-11-26 | Biphenyl derivatives, pharmaceutical compositions containing these compounds and processes for preparing them |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4102024A DE4102024A1 (de) | 1991-01-24 | 1991-01-24 | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
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| DE4102024A1 true DE4102024A1 (de) | 1992-07-30 |
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| DE4102024A Withdrawn DE4102024A1 (de) | 1991-01-24 | 1991-01-24 | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE59203704T Expired - Fee Related DE59203704D1 (de) | 1991-01-24 | 1992-01-22 | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| DE59203704T Expired - Fee Related DE59203704D1 (de) | 1991-01-24 | 1992-01-22 | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung. |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US5597825A (enExample) |
| EP (1) | EP0496378B1 (enExample) |
| JP (1) | JPH04334351A (enExample) |
| KR (1) | KR920014779A (enExample) |
| AT (1) | ATE128120T1 (enExample) |
| AU (1) | AU648379B2 (enExample) |
| CA (1) | CA2059857A1 (enExample) |
| DE (2) | DE4102024A1 (enExample) |
| DK (1) | DK0496378T3 (enExample) |
| ES (1) | ES2079694T3 (enExample) |
| FI (1) | FI920286A7 (enExample) |
| GR (1) | GR3017802T3 (enExample) |
| HU (1) | HUT60462A (enExample) |
| IE (1) | IE69973B1 (enExample) |
| IL (1) | IL100740A0 (enExample) |
| MX (1) | MX9200269A (enExample) |
| NO (1) | NO177852C (enExample) |
| NZ (1) | NZ241355A (enExample) |
| TW (1) | TW257753B (enExample) |
| ZA (1) | ZA92464B (enExample) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DE4134467A1 (de) * | 1991-10-18 | 1993-04-22 | Thomae Gmbh Dr K | Heterobiarylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE4124942A1 (de) * | 1991-07-27 | 1993-01-28 | Thomae Gmbh Dr K | 5-gliedrige heterocyclen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US5674863A (en) * | 1991-10-18 | 1997-10-07 | Genentech, Inc. | Nonpeptidyl integrin inhibitors having specificity for the GPIIb IIIa receptor |
| US5250679A (en) * | 1991-10-18 | 1993-10-05 | Genentech, Inc. | Nonpeptidyl platelet aggregation inhibitors having specificity for the GPIIb III.sub. receptor |
| WO1993018058A1 (en) * | 1992-03-06 | 1993-09-16 | G.D. Searle & Co. | Peptides mimics useful as platelet aggregation inhibitors |
| KR940005271A (ko) * | 1992-04-28 | 1994-03-21 | 디터 라우딘, 게르하르트 후버 | 표지된 피브리노겐 수용체 길항제, 이의 용도 및 이의 제조방법 |
| DE4219158A1 (de) * | 1992-06-11 | 1993-12-16 | Thomae Gmbh Dr K | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE4234295A1 (de) * | 1992-10-12 | 1994-04-14 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE4241632A1 (de) * | 1992-12-10 | 1994-06-16 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| GB9406144D0 (en) * | 1993-03-29 | 1994-05-18 | Zeneca Ltd | Heterocyclic compounds |
| US5750754A (en) * | 1993-03-29 | 1998-05-12 | Zeneca Limited | Heterocyclic compounds |
| NZ262941A (en) * | 1993-03-29 | 1997-07-27 | Zeneca Ltd | Pyridine derivatives and medicaments |
| US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
| US5652242A (en) * | 1993-03-29 | 1997-07-29 | Zeneca Limited | Heterocyclic derivatives |
| GB9313268D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Chemical compounds |
| US5463011A (en) * | 1993-06-28 | 1995-10-31 | Zeneca Limited | Acid derivatives |
| GB9313285D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Acid derivatives |
| DE4326344A1 (de) * | 1993-08-05 | 1995-02-09 | Thomae Gmbh Dr K | Carbonamide, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| WO1995026328A1 (en) * | 1994-03-26 | 1995-10-05 | Smithkline Beecham Plc | Biphenyl derivatives as 5ht1d antagonists |
| HRP950558A2 (en) * | 1994-11-15 | 1997-12-31 | Scott M. Wilhelm | Substituted 4-biarylbutric or biarylpentanoic acids and derivatives as matrix metalloprotease inhibitors |
| US6100423A (en) * | 1995-08-30 | 2000-08-08 | G. D. Searle & Co. | Amino benzenepropanoic acid compounds and derivatives thereof |
| NZ318926A (en) * | 1995-08-30 | 1999-04-29 | Searle & Co | Alpha v beta 3 integrin (vitronectin) inhibitors or anatagonists derived from benzoic acid for treating diseases of cell adhesion |
| DE19636689A1 (de) * | 1996-09-10 | 1998-03-12 | Boehringer Ingelheim Kg | Neue Benzamidinderivate |
| JP2001508404A (ja) | 1996-10-11 | 2001-06-26 | ワーナー―ランバート・コンパニー | スルホンアミドインターロイキン―1β変換酵素阻害剤 |
| WO1998016504A2 (en) * | 1996-10-11 | 1998-04-23 | Warner-Lambert Company | SULFONAMIDE SUBSTITUTED ASPARTIC ACID INTERLEUKIN-1β CONVERTING ENZYME INHIBITORS |
| US5872122A (en) * | 1997-10-16 | 1999-02-16 | Monsanto Company | Pyrimidinylamidino β-amino acid derivatives useful as inhibitors of platelet aggregation |
| AU736112B2 (en) * | 1997-11-20 | 2001-07-26 | Teijin Limited | Biphenylamidine derivatives |
| PL340658A1 (en) | 1997-11-20 | 2001-02-12 | Teijin Ltd | Derivatives of biphenylamidine |
| DE19819548A1 (de) * | 1998-04-30 | 1999-11-04 | Merck Patent Gmbh | Biphenylderivate |
| US6037365A (en) * | 1998-09-25 | 2000-03-14 | G.D. Searle & Co. | Aminobenzamidinosuccinyl lactone derivatives useful as inhibitors of platelet aggregation |
| US6420396B1 (en) | 1998-12-16 | 2002-07-16 | Beiersdorf Ag | Biphenyl and biphenyl-analogous compounds as integrin antagonists |
| US6677360B2 (en) | 1998-12-16 | 2004-01-13 | Bayer Aktiengesellschaft | Biphenyl and biphenyl-analogous compounds as integrin antagonists |
| AU773156B2 (en) | 1999-01-28 | 2004-05-20 | Teijin Limited | Release-regulating preparations |
| PE20001456A1 (es) | 1999-02-02 | 2001-01-28 | Smithkline Beecham Corp | Compuestos calcioliticos |
| DE19947457A1 (de) * | 1999-10-02 | 2001-04-05 | Aventis Pharma Gmbh | 2'-Substituierte 1,1'-Biphenyl-2-carbonamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie enthaltende pharmazeutische Zubereitungen |
| AU2868601A (en) * | 2000-01-27 | 2001-08-07 | Ribotargets Ltd | Biaryl compounds, their preparation and their use in therapy |
| WO2001077203A2 (en) | 2000-04-11 | 2001-10-18 | Dupont Displays, Inc. | Soluble poly(aryl-oxadiazole) conjugated polymers |
| US20020183316A1 (en) * | 2000-10-27 | 2002-12-05 | Kevin Pan | Amidoalkyl-piperidine and amidoalkyl-piperazine derivatives useful for the treatment of nervous system disorders |
| AR035425A1 (es) * | 2001-01-30 | 2004-05-26 | Teijin Ltd | Cristal de diclorhidrato del acido 3-(3-amidinofenil)-5-[({[1-(iminoetil)-4-piperidil]metil}amino)metil]benzoico y proceso para prepararlo |
| AU2003207567B2 (en) * | 2002-01-18 | 2008-01-24 | Merck Sharp & Dohme Corp. | Edg receptor agonists |
| WO2004056774A2 (en) * | 2002-12-19 | 2004-07-08 | Neurogen Corporation | Substituted biphenyl-4-carboxylic acid arylamide analogues as capsaicin receptor modulators |
| GB0321538D0 (en) * | 2003-09-13 | 2003-10-15 | Glaxo Group Ltd | Therapeutically useful compounds |
| US7534894B2 (en) | 2003-09-25 | 2009-05-19 | Wyeth | Biphenyloxy-acids |
| EP1723132A1 (en) * | 2004-02-12 | 2006-11-22 | Asterand Uk Limited | Ep2 receptor agonists |
| JP4697415B2 (ja) * | 2004-09-09 | 2011-06-08 | 信越化学工業株式会社 | ポリフェニレンエーテルオリゴマー体のスルホン酸塩及びその製造方法 |
| JP4697416B2 (ja) * | 2004-10-26 | 2011-06-08 | 信越化学工業株式会社 | 難燃性ポリカーボネート樹脂組成物及びその成型品 |
| JP4697417B2 (ja) * | 2004-10-26 | 2011-06-08 | 信越化学工業株式会社 | 難燃性樹脂組成物及びその成形品 |
| WO2007008994A2 (en) | 2005-07-11 | 2007-01-18 | Wyeth | Glutamate aggrecanase inhibitors |
| 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 |
| KR20080058436A (ko) | 2005-10-13 | 2008-06-25 | 와이어쓰 | 글루탐산 유도체의 제조 방법 |
| US8399451B2 (en) * | 2009-08-07 | 2013-03-19 | Bristol-Myers Squibb Company | Heterocyclic compounds |
| WO2011133734A1 (en) | 2010-04-23 | 2011-10-27 | Bristol-Myers Squibb Company | 4 - (5 - isoxazolyl or 5 - pyrrazolyl -1,2,4- oxadiazol - 3 - yl) -mandelic acid amides as sphingosin- 1 - phosphate 1 rreceptor agonists |
| CN103237795B (zh) | 2010-09-24 | 2015-10-21 | 百时美施贵宝公司 | 经取代的噁二唑化合物及其作为s1p1激动剂的用途 |
| WO2012115177A1 (ja) * | 2011-02-25 | 2012-08-30 | 第一三共株式会社 | N-[(ビアリールオキシ)アルキルカルボニル]スルホンアミド誘導体 |
| WO2012115176A1 (ja) * | 2011-02-25 | 2012-08-30 | 第一三共株式会社 | 3-(ビアリールオキシ)プロピオン酸誘導体 |
| CN102805751B (zh) * | 2012-08-27 | 2014-07-02 | 澳门科技大学 | 治疗心脑血管疾病的药物组合物及其制备方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3821268A (en) * | 1970-05-05 | 1974-06-28 | Rorer Inc William H | Alpha-acylthio biphenylylacetic acids |
| AU527371B2 (en) * | 1980-09-16 | 1983-03-03 | Torii & Co., Ltd. | Amidine |
| JPS57179147A (en) * | 1981-04-28 | 1982-11-04 | Torii Yakuhin Kk | Amidine derivative |
| FR2522325B1 (fr) * | 1982-02-26 | 1985-08-09 | Delalande Sa | Nouveaux derives aryliques de la piperazine, de l'homopiperazine et de n,n'-dialkyl diamino-1,2 ethane, leur procede de preparation et leur application en therapeutique |
| US4661522A (en) * | 1984-05-24 | 1987-04-28 | Akzo N.V. | Cycloalkane-indene-carboximidamide derivatives |
| US4746737A (en) * | 1985-07-26 | 1988-05-24 | Kowa Co., Ltd. | Phenyl guanidinobenzoate derivatives which have protease inhibitory activity |
| US4927509A (en) * | 1986-06-04 | 1990-05-22 | H-D Tech Inc. | Bipolar electrolyzer |
| US5084466A (en) * | 1989-01-31 | 1992-01-28 | Hoffmann-La Roche Inc. | Novel carboxamide pyridine compounds which have useful pharmaceutical utility |
| US5061693A (en) * | 1989-07-28 | 1991-10-29 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
-
1991
- 1991-01-24 DE DE4102024A patent/DE4102024A1/de not_active Withdrawn
-
1992
- 1992-01-22 EP EP92101007A patent/EP0496378B1/de not_active Expired - Lifetime
- 1992-01-22 AT AT92101007T patent/ATE128120T1/de not_active IP Right Cessation
- 1992-01-22 CA CA002059857A patent/CA2059857A1/en not_active Abandoned
- 1992-01-22 DE DE59203704T patent/DE59203704D1/de not_active Expired - Fee Related
- 1992-01-22 TW TW081100460A patent/TW257753B/zh active
- 1992-01-22 DK DK92101007.0T patent/DK0496378T3/da active
- 1992-01-22 NZ NZ24135592A patent/NZ241355A/xx unknown
- 1992-01-22 ES ES92101007T patent/ES2079694T3/es not_active Expired - Lifetime
- 1992-01-22 MX MX9200269A patent/MX9200269A/es not_active IP Right Cessation
- 1992-01-23 NO NO920320A patent/NO177852C/no unknown
- 1992-01-23 ZA ZA92464A patent/ZA92464B/xx unknown
- 1992-01-23 IL IL100740A patent/IL100740A0/xx unknown
- 1992-01-23 IE IE920199A patent/IE69973B1/en not_active IP Right Cessation
- 1992-01-23 JP JP4009703A patent/JPH04334351A/ja active Pending
- 1992-01-23 AU AU10403/92A patent/AU648379B2/en not_active Ceased
- 1992-01-23 FI FI920286A patent/FI920286A7/fi not_active Application Discontinuation
- 1992-01-23 HU HU9200212A patent/HUT60462A/hu unknown
- 1992-01-24 KR KR1019920000983A patent/KR920014779A/ko not_active Ceased
-
1994
- 1994-05-16 US US08/257,759 patent/US5597825A/en not_active Expired - Fee Related
-
1995
- 1995-10-18 GR GR950402905T patent/GR3017802T3/el unknown
-
1996
- 1996-08-01 US US08/691,107 patent/US5736559A/en not_active Expired - Fee Related
-
1997
- 1997-11-26 US US08/978,739 patent/US5922763A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR920014779A (ko) | 1992-08-25 |
| NO920320D0 (no) | 1992-01-23 |
| JPH04334351A (ja) | 1992-11-20 |
| DE59203704D1 (de) | 1995-10-26 |
| ATE128120T1 (de) | 1995-10-15 |
| ES2079694T3 (es) | 1996-01-16 |
| NO177852B (no) | 1995-08-28 |
| IE69973B1 (en) | 1996-10-16 |
| IL100740A0 (en) | 1992-09-06 |
| FI920286A0 (fi) | 1992-01-23 |
| HUT60462A (en) | 1992-09-28 |
| US5597825A (en) | 1997-01-28 |
| TW257753B (enExample) | 1995-09-21 |
| AU648379B2 (en) | 1994-04-21 |
| HU9200212D0 (en) | 1992-04-28 |
| NO177852C (no) | 1995-12-06 |
| US5922763A (en) | 1999-07-13 |
| ZA92464B (en) | 1993-07-23 |
| FI920286L (fi) | 1992-07-25 |
| US5736559A (en) | 1998-04-07 |
| FI920286A7 (fi) | 1992-07-25 |
| EP0496378B1 (de) | 1995-09-20 |
| NZ241355A (en) | 1994-07-26 |
| GR3017802T3 (en) | 1996-01-31 |
| NO920320L (no) | 1992-07-27 |
| CA2059857A1 (en) | 1992-07-25 |
| EP0496378A1 (de) | 1992-07-29 |
| MX9200269A (es) | 1992-07-01 |
| DK0496378T3 (da) | 1996-02-05 |
| AU1040392A (en) | 1992-07-30 |
| IE920199A1 (en) | 1992-07-29 |
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