DE4129603A1 - Kondensierte 5-gliedrige heterocyclen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel - Google Patents

Info

Publication number

DE4129603A1

DE4129603A1 DE4129603A DE4129603A DE4129603A1 DE 4129603 A1 DE4129603 A1 DE 4129603A1 DE 4129603 A DE4129603 A DE 4129603A DE 4129603 A DE4129603 A DE 4129603A DE 4129603 A1 DE4129603 A1 DE 4129603A1

Authority

DE

Germany

Prior art keywords

group

carbon atoms

alkyl

phenyl

atom

Prior art date

1991-09-06

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Withdrawn

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• 150000001875 compounds Chemical class 0.000 title claims description 85
• 238000004519 manufacturing process Methods 0.000 title claims description 10
• 238000000034 method Methods 0.000 title claims description 9
• 239000003814 drug Substances 0.000 title claims description 4
• -1 acetamido, pyrrolidino, hexamethyleneimino Chemical group 0.000 claims description 282
• 125000004432 carbon atom Chemical group C* 0.000 claims description 188
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 110
• 125000000217 alkyl group Chemical group 0.000 claims description 104
• 229910052757 nitrogen Chemical group 0.000 claims description 80
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 78
• 125000003545 alkoxy group Chemical group 0.000 claims description 36
• 239000000203 mixture Substances 0.000 claims description 35
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 34
• 229910052799 carbon Inorganic materials 0.000 claims description 33
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 31
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 28
• 239000002253 acid Substances 0.000 claims description 27
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
• 238000002360 preparation method Methods 0.000 claims description 24
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
• 239000000460 chlorine Chemical group 0.000 claims description 23
• 125000002947 alkylene group Chemical group 0.000 claims description 22
• 125000003118 aryl group Chemical group 0.000 claims description 22
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 22
• 229910052801 chlorine Inorganic materials 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
• 229910052731 fluorine Inorganic materials 0.000 claims description 19
• 239000011737 fluorine Chemical group 0.000 claims description 19
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
• 238000006243 chemical reaction Methods 0.000 claims description 18
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• 239000001257 hydrogen Substances 0.000 claims description 17
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 16
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 16
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 125000004646 sulfenyl group Chemical group S(*)* 0.000 claims description 16
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 15
• 125000003282 alkyl amino group Chemical group 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 12
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
• 125000003277 amino group Chemical group 0.000 claims description 12
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
• 125000004956 cyclohexylene group Chemical group 0.000 claims description 12
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
• 239000001301 oxygen Substances 0.000 claims description 12
• 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 10
• 125000004076 pyridyl group Chemical group 0.000 claims description 10
• 125000001424 substituent group Chemical group 0.000 claims description 10
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
• 125000004450 alkenylene group Chemical group 0.000 claims description 8
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
• 150000007524 organic acids Chemical class 0.000 claims description 8
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
• 239000000126 substance Substances 0.000 claims description 8
• 239000011593 sulfur Chemical group 0.000 claims description 8
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
• 150000007522 mineralic acids Chemical class 0.000 claims description 7
• 239000011541 reaction mixture Substances 0.000 claims description 7
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
• 125000004419 alkynylene group Chemical group 0.000 claims description 6
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
• 125000001246 bromo group Chemical group Br* 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 235000005985 organic acids Nutrition 0.000 claims description 6
• 150000007513 acids Chemical class 0.000 claims description 5
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 5
• 230000007062 hydrolysis Effects 0.000 claims description 5
• 238000006460 hydrolysis reaction Methods 0.000 claims description 5
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 125000005277 alkyl imino group Chemical group 0.000 claims description 4
• 125000000304 alkynyl group Chemical group 0.000 claims description 4
• 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 4
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
• 125000005101 aryl methoxy carbonyl group Chemical group 0.000 claims description 4
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• 125000004122 cyclic group Chemical group 0.000 claims description 4
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 4
• NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical group N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 4
• 238000007327 hydrogenolysis reaction Methods 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
• 230000000269 nucleophilic effect Effects 0.000 claims description 4
• 125000005551 pyridylene group Chemical group 0.000 claims description 4
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
• 150000001412 amines Chemical class 0.000 claims description 3
• 239000000969 carrier Substances 0.000 claims description 3
• 230000008619 cell matrix interaction Effects 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 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
• 229910052740 iodine Inorganic materials 0.000 claims description 3
• 238000001149 thermolysis Methods 0.000 claims description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 2
• RUOBLLKIDKODAH-UHFFFAOYSA-N 3-[[2-(4-carbamimidoylphenyl)-1-methylbenzimidazole-5-carbonyl]amino]propanoic acid Chemical compound N=1C2=CC(C(=O)NCCC(O)=O)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 RUOBLLKIDKODAH-UHFFFAOYSA-N 0.000 claims description 2
• ZGEVVZKTSQYJBQ-UHFFFAOYSA-N 4-[[2-(4-carbamimidoylphenyl)-1-methylbenzimidazole-5-carbonyl]amino]butanoic acid Chemical compound N=1C2=CC(C(=O)NCCCC(O)=O)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 ZGEVVZKTSQYJBQ-UHFFFAOYSA-N 0.000 claims description 2
• 101100295738 Gallus gallus COR3 gene Proteins 0.000 claims description 2
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
• 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
• 125000004104 aryloxy group Chemical group 0.000 claims description 2
• 150000001556 benzimidazoles Chemical class 0.000 claims description 2
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 2
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
• 125000005842 heteroatom Chemical group 0.000 claims description 2
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 230000008569 process Effects 0.000 claims description 2
• 230000001681 protective effect Effects 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
• 239000002904 solvent Substances 0.000 description 30
• 239000000243 solution Substances 0.000 description 23
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 22
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• 229960000583 acetic acid Drugs 0.000 description 22
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 150000003254 radicals Chemical class 0.000 description 20
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• 239000012362 glacial acetic acid Substances 0.000 description 18
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 239000000741 silica gel Substances 0.000 description 14
• 229910002027 silica gel Inorganic materials 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 238000002844 melting Methods 0.000 description 13
• 230000008018 melting Effects 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 9
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 8
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 7
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
• 239000002775 capsule Substances 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• JMPDNWCGVRZKBK-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-methylbenzimidazole-5-carbonyl]-methylamino]propanoate Chemical compound N=1C2=CC(C(=O)N(C)CCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 JMPDNWCGVRZKBK-UHFFFAOYSA-N 0.000 description 7
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
• 239000013543 active substance Substances 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
• 150000002148 esters Chemical class 0.000 description 6
• 229940012952 fibrinogen Drugs 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• MWZYKPYLGSSSIX-UHFFFAOYSA-N methyl 3-[[1-methyl-2-[4-(methylaminomethyl)phenyl]benzimidazole-5-carbonyl]amino]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(CNC)=CC=C1C1=NC2=CC(C(=O)NCCC(=O)OC)=CC=C2N1C MWZYKPYLGSSSIX-UHFFFAOYSA-N 0.000 description 6
• SXUOSJRAGNDVCF-UHFFFAOYSA-N methyl 4-[2-[4-(2-aminoethyl)phenyl]-1-methylbenzimidazol-5-yl]-4-oxobutanoate;dihydrochloride Chemical compound Cl.Cl.N=1C2=CC(C(=O)CCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(CCN)C=C1 SXUOSJRAGNDVCF-UHFFFAOYSA-N 0.000 description 6
• 230000007017 scission Effects 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
• 229920002261 Corn starch Polymers 0.000 description 5
• 108010049003 Fibrinogen Proteins 0.000 description 5
• 102000008946 Fibrinogen Human genes 0.000 description 5
• 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 5
• 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 5
• 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 5
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 229910021529 ammonia Inorganic materials 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
• 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
• 229940093915 gynecological organic acid Drugs 0.000 description 5
• 235000019359 magnesium stearate Nutrition 0.000 description 5
• GXJYZKVMVZHJCX-UHFFFAOYSA-N methyl 5-[2-[4-(2-aminoethyl)phenyl]-1-methylbenzimidazol-5-yl]-5-oxopentanoate;dihydrochloride Chemical compound Cl.Cl.N=1C2=CC(C(=O)CCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(CCN)C=C1 GXJYZKVMVZHJCX-UHFFFAOYSA-N 0.000 description 5
• 230000003287 optical effect Effects 0.000 description 5
• 239000007800 oxidant agent Substances 0.000 description 5
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• UIHXIRZDZYHVPF-UHFFFAOYSA-N methyl 2-[4-[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]piperazin-1-yl]acetate Chemical compound C1CN(CC(=O)OC)CCN1C1=CC=C(N=C(C=2C=CC(=CC=2)C(N)=N)N2C)C2=N1 UIHXIRZDZYHVPF-UHFFFAOYSA-N 0.000 description 3
• OBRCINFBIRWWTI-UHFFFAOYSA-N methyl 2-[[2-[8-(4-carbamimidoylphenyl)-3-methyl-2,6-dioxo-7h-purin-1-yl]acetyl]-methylamino]acetate Chemical compound N1C=2C(=O)N(CC(=O)N(C)CC(=O)OC)C(=O)N(C)C=2N=C1C1=CC=C(C(N)=N)C=C1 OBRCINFBIRWWTI-UHFFFAOYSA-N 0.000 description 3
• BINREBULYXUQOS-UHFFFAOYSA-N methyl 3-[[1-(6-aminohexyl)-2-(4-carbamimidoylphenyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CCCCCCN)C=1C1=CC=C(C(N)=N)C=C1 BINREBULYXUQOS-UHFFFAOYSA-N 0.000 description 3
• DFHZGRALQWQYPY-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoyl-2-fluorophenyl)-1-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1F DFHZGRALQWQYPY-UHFFFAOYSA-N 0.000 description 3
• JERPZYHADCTEHG-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoyl-2-methylphenyl)-1-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1C JERPZYHADCTEHG-UHFFFAOYSA-N 0.000 description 3
• FMCBLDLEJGUEQI-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-methoxy-3-oxopropyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CCC(=O)OC)C=1C1=CC=C(C(N)=N)C=C1 FMCBLDLEJGUEQI-UHFFFAOYSA-N 0.000 description 3
• MKYXSGXPIJHLIZ-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-methylsulfinylpropyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CCCS(C)=O)C=1C1=CC=C(C(N)=N)C=C1 MKYXSGXPIJHLIZ-UHFFFAOYSA-N 0.000 description 3
• UJWKVRHGSBMFEW-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-methylsulfonylphenyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C=2C=C(C=CC=2)S(C)(=O)=O)C=1C1=CC=C(C(N)=N)C=C1 UJWKVRHGSBMFEW-UHFFFAOYSA-N 0.000 description 3
• GWGYPURVPKFHPR-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-[3-(1,1-dioxo-1,4-thiazinan-4-yl)-3-oxopropyl]benzimidazole-5-carbonyl]amino]propanoate Chemical compound C=1C=C(C(N)=N)C=CC=1C1=NC2=CC(C(=O)NCCC(=O)OC)=CC=C2N1CCC(=O)N1CCS(=O)(=O)CC1 GWGYPURVPKFHPR-UHFFFAOYSA-N 0.000 description 3
• IGINJILFIRVIIT-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-[3-(dimethylamino)-3-oxopropyl]benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CCC(=O)N(C)C)C=1C1=CC=C(C(N)=N)C=C1 IGINJILFIRVIIT-UHFFFAOYSA-N 0.000 description 3
• QTPBPXRRMHWIKW-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-[3-[(2-methoxy-2-oxoethyl)amino]-3-oxopropyl]benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CCC(=O)NCC(=O)OC)C=1C1=CC=C(C(N)=N)C=C1 QTPBPXRRMHWIKW-UHFFFAOYSA-N 0.000 description 3
• OLGNFSIAOFVJHH-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-methylbenzimidazol-5-yl]sulfonyl-methylamino]propanoate Chemical compound N=1C2=CC(S(=O)(=O)N(C)CCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 OLGNFSIAOFVJHH-UHFFFAOYSA-N 0.000 description 3
• NHIWFSFOWIBBPW-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-methylbenzimidazol-5-yl]sulfonylamino]propanoate Chemical compound N=1C2=CC(S(=O)(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 NHIWFSFOWIBBPW-UHFFFAOYSA-N 0.000 description 3
• NLCXNFBAJDBZNU-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-prop-2-ynylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CC#C)C=1C1=CC=C(C(N)=N)C=C1 NLCXNFBAJDBZNU-UHFFFAOYSA-N 0.000 description 3
• FLWTWONHWMPICG-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-3-methylimidazo[1,2-a]pyridine-6-carbonyl]amino]propanoate Chemical compound CC=1N2C=C(C(=O)NCCC(=O)OC)C=CC2=NC=1C1=CC=C(C(N)=N)C=C1 FLWTWONHWMPICG-UHFFFAOYSA-N 0.000 description 3
• UWVMWYSAUKYRJD-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridine-6-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CN=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 UWVMWYSAUKYRJD-UHFFFAOYSA-N 0.000 description 3
• SVVZFINLVYKAFY-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-6-hydroxy-1-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound CN1C=2C=C(O)C(C(=O)NCCC(=O)OC)=CC=2N=C1C1=CC=C(C(N)=N)C=C1 SVVZFINLVYKAFY-UHFFFAOYSA-N 0.000 description 3
• HRCCOVZMAKFOBD-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-7-fluoro-1-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC(F)=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 HRCCOVZMAKFOBD-UHFFFAOYSA-N 0.000 description 3
• FKHIZLGVNMLKJS-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)imidazo[1,2-a]pyrimidine-6-carbonyl]amino]propanoate Chemical compound C=1N2C=C(C(=O)NCCC(=O)OC)C=NC2=NC=1C1=CC=C(C(N)=N)C=C1 FKHIZLGVNMLKJS-UHFFFAOYSA-N 0.000 description 3
• MYHWMXFMANPZDY-UHFFFAOYSA-N methyl 4-[[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]-methylamino]cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OC)CCC1N(C)C1=CC=C(N=C(C=2C=CC(=CC=2)C(N)=N)N2C)C2=N1 MYHWMXFMANPZDY-UHFFFAOYSA-N 0.000 description 3
• NSGRWWGEHARXOR-UHFFFAOYSA-N methyl 4-[[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]amino]cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OC)CCC1NC1=CC=C(N=C(C=2C=CC(=CC=2)C(N)=N)N2C)C2=N1 NSGRWWGEHARXOR-UHFFFAOYSA-N 0.000 description 3
• KWXZGQWDVMKVOD-UHFFFAOYSA-N methyl 4-[[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-6-yl]-methylsulfonylamino]butanoate Chemical compound N=1C2=CC(N(CCCC(=O)OC)S(C)(=O)=O)=CN=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 KWXZGQWDVMKVOD-UHFFFAOYSA-N 0.000 description 3
• 150000002825 nitriles Chemical class 0.000 description 3
• 150000007530 organic bases Chemical group 0.000 description 3
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
• 229920000137 polyphosphoric acid Polymers 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
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• 239000000047 product Substances 0.000 description 3
• 239000001509 sodium citrate Substances 0.000 description 3
• 239000011975 tartaric acid Substances 0.000 description 3
• 235000002906 tartaric acid Nutrition 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 125000000026 trimethylsilyl group Chemical class [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
• XCGZLOITJDKNGC-UHFFFAOYSA-N 1-[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]piperidine-4-carboxylic acid Chemical compound N1=C2N(C)C(C=3C=CC(=CC=3)C(N)=N)=NC2=CC=C1N1CCC(C(O)=O)CC1 XCGZLOITJDKNGC-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• MHRWGWOMBHCBAT-UHFFFAOYSA-N 2-[1-[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]piperidin-4-yl]acetic acid Chemical compound N1=C2N(C)C(C=3C=CC(=CC=3)C(N)=N)=NC2=CC=C1N1CCC(CC(O)=O)CC1 MHRWGWOMBHCBAT-UHFFFAOYSA-N 0.000 description 2
• KNEKADCHOFVOSH-UHFFFAOYSA-N 2-[4-[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]-2-oxopiperazin-1-yl]acetic acid Chemical compound N1=C2N(C)C(C=3C=CC(=CC=3)C(N)=N)=NC2=CC=C1N1CCN(CC(O)=O)C(=O)C1 KNEKADCHOFVOSH-UHFFFAOYSA-N 0.000 description 2
• OQUFLRMXUFSQEP-UHFFFAOYSA-N 2-[4-[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]piperazin-1-yl]acetic acid Chemical compound N1=C2N(C)C(C=3C=CC(=CC=3)C(N)=N)=NC2=CC=C1N1CCN(CC(O)=O)CC1 OQUFLRMXUFSQEP-UHFFFAOYSA-N 0.000 description 2
• UCUCEMXBIQQXSH-UHFFFAOYSA-N 2-[[2-(4-carbamimidoylphenyl)-1-methylbenzimidazol-5-yl]sulfonylamino]acetic acid Chemical compound N=1C2=CC(S(=O)(=O)NCC(O)=O)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 UCUCEMXBIQQXSH-UHFFFAOYSA-N 0.000 description 2
• KBSPCAHLMCRVEA-UHFFFAOYSA-N 2-[[2-[8-(4-carbamimidoylphenyl)-2,6-dioxo-3,7-dihydropurin-1-yl]acetyl]-methylamino]acetic acid Chemical compound N1C=2C(=O)N(CC(=O)N(CC(O)=O)C)C(=O)NC=2N=C1C1=CC=C(C(N)=N)C=C1 KBSPCAHLMCRVEA-UHFFFAOYSA-N 0.000 description 2
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• QAKYPGWLNBAUFM-UHFFFAOYSA-N 2-[[2-[8-(4-carbamimidoylphenyl)-6-oxo-7H-purin-1-yl]acetyl]-methylamino]acetic acid Chemical compound C(N)(=N)C1=CC=C(C=C1)C1=NC=2N=CN(C(C=2N1)=O)CC(=O)N(CC(=O)O)C QAKYPGWLNBAUFM-UHFFFAOYSA-N 0.000 description 2
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 2
• MUOYWBBVPYKDAF-UHFFFAOYSA-N 3-[[1-(6-aminohexyl)-2-(4-carbamimidoylphenyl)benzimidazole-5-carbonyl]amino]propanoic acid Chemical compound N=1C2=CC(C(=O)NCCC(O)=O)=CC=C2N(CCCCCCN)C=1C1=CC=C(C(N)=N)C=C1 MUOYWBBVPYKDAF-UHFFFAOYSA-N 0.000 description 2
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• KEJQEMSPZBUQRQ-UHFFFAOYSA-N 3-[[2-(4-carbamimidoylphenyl)-1-(3-morpholin-4-yl-3-oxopropyl)benzimidazole-5-carbonyl]amino]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=NC2=CC(C(=O)NCCC(O)=O)=CC=C2N1CCC(=O)N1CCOCC1 KEJQEMSPZBUQRQ-UHFFFAOYSA-N 0.000 description 2
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• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• TUJGPQRDPQVUSX-UHFFFAOYSA-N methyl 1-[2-(4-carbamimidoylphenyl)-3-methylimidazo[4,5-b]pyridin-5-yl]piperidine-2-carboxylate Chemical compound COC(=O)C1CCCCN1C1=CC=C(N=C(C=2C=CC(=CC=2)C(N)=N)N2C)C2=N1 TUJGPQRDPQVUSX-UHFFFAOYSA-N 0.000 description 1
• TYKHJXSANIQTHZ-UHFFFAOYSA-N methyl 2-[[2-(4-carbamimidoylphenyl)-1-methylbenzimidazol-5-yl]sulfonylamino]acetate Chemical compound N=1C2=CC(S(=O)(=O)NCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 TYKHJXSANIQTHZ-UHFFFAOYSA-N 0.000 description 1
• WBEUQJXFLNOGNN-UHFFFAOYSA-N methyl 3-[(1-methyl-2-piperidin-4-ylbenzimidazole-5-carbonyl)amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1CCNCC1 WBEUQJXFLNOGNN-UHFFFAOYSA-N 0.000 description 1
• KFUXEBJPKNJRHT-UHFFFAOYSA-N methyl 3-[[1-methyl-2-[4-(n'-methylcarbamimidoyl)phenyl]benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=NC)C=C1 KFUXEBJPKNJRHT-UHFFFAOYSA-N 0.000 description 1
• KDEGQFSGVHVGGT-UHFFFAOYSA-N methyl 3-[[1-methyl-2-[4-[(e)-n'-(2-methylpropoxycarbonyl)carbamimidoyl]phenyl]benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(=N)NC(=O)OCC(C)C)C=C1 KDEGQFSGVHVGGT-UHFFFAOYSA-N 0.000 description 1
• VPXGSWHPJRUPIU-UHFFFAOYSA-N methyl 3-[[2-(1-carbamimidoylpiperidin-4-yl)-1-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1CCN(C(N)=N)CC1 VPXGSWHPJRUPIU-UHFFFAOYSA-N 0.000 description 1
• GQAMIPLPFNWGGA-UHFFFAOYSA-N methyl 3-[[2-(4-aminocyclohexyl)-1-methylbenzimidazole-5-carbonyl]amino]propanoate;dihydrochloride Chemical compound Cl.Cl.N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1CCC(N)CC1 GQAMIPLPFNWGGA-UHFFFAOYSA-N 0.000 description 1
• FWXPVSFGTMKSCQ-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1,3-benzothiazole-6-carbonyl]amino]propanoate Chemical compound S1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N=C1C1=CC=C(C(N)=N)C=C1 FWXPVSFGTMKSCQ-UHFFFAOYSA-N 0.000 description 1
• JHQYYDKIDXCWSH-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(2-pyrrolidin-1-ylethyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound C=1C=C(C(N)=N)C=CC=1C1=NC2=CC(C(=O)NCCC(=O)OC)=CC=C2N1CCN1CCCC1 JHQYYDKIDXCWSH-UHFFFAOYSA-N 0.000 description 1
• FFNLPDSRIAQRKG-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-methylsulfanylphenyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C=2C=C(SC)C=CC=2)C=1C1=CC=C(C(N)=N)C=C1 FFNLPDSRIAQRKG-UHFFFAOYSA-N 0.000 description 1
• TZCVRJAVXPRFNR-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-methylsulfanylpropyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CCCSC)C=1C1=CC=C(C(N)=N)C=C1 TZCVRJAVXPRFNR-UHFFFAOYSA-N 0.000 description 1
• CLPAWQFHCRIQPV-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-methylsulfinylphenyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C=2C=C(C=CC=2)S(C)=O)C=1C1=CC=C(C(N)=N)C=C1 CLPAWQFHCRIQPV-UHFFFAOYSA-N 0.000 description 1
• SDCNFFYDTUJVEU-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-methylsulfonylpropyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(CCCS(C)(=O)=O)C=1C1=CC=C(C(N)=N)C=C1 SDCNFFYDTUJVEU-UHFFFAOYSA-N 0.000 description 1
• FFOANSHZINNJNX-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-(3-morpholin-4-yl-3-oxopropyl)benzimidazole-5-carbonyl]amino]propanoate Chemical compound C=1C=C(C(N)=N)C=CC=1C1=NC2=CC(C(=O)NCCC(=O)OC)=CC=C2N1CCC(=O)N1CCOCC1 FFOANSHZINNJNX-UHFFFAOYSA-N 0.000 description 1
• ZEWNPZWLHMLFBN-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-[3-oxo-3-(1-oxo-1,4-thiazinan-4-yl)propyl]benzimidazole-5-carbonyl]amino]propanoate Chemical compound C=1C=C(C(N)=N)C=CC=1C1=NC2=CC(C(=O)NCCC(=O)OC)=CC=C2N1CCC(=O)N1CCS(=O)CC1 ZEWNPZWLHMLFBN-UHFFFAOYSA-N 0.000 description 1
• IJOFDTQRTJKYHI-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-1-methyl-3-oxidobenzimidazol-3-ium-5-carbonyl]amino]propanoate Chemical compound [O-][N+]=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=C1 IJOFDTQRTJKYHI-UHFFFAOYSA-N 0.000 description 1
• OHVRQKFUPYPILR-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-3-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound CN1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N=C1C1=CC=C(C(N)=N)C=C1 OHVRQKFUPYPILR-UHFFFAOYSA-N 0.000 description 1
• NOHALRCXOUZRSG-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-7-chloro-3h-benzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC(Cl)=C2NC=1C1=CC=C(C(N)=N)C=C1 NOHALRCXOUZRSG-UHFFFAOYSA-N 0.000 description 1
• LVVCXIVMDOAZGT-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylphenyl)-[1,3]oxazolo[5,4-b]pyridine-5-carbonyl]amino]propanoate Chemical compound O1C2=NC(C(=O)NCCC(=O)OC)=CC=C2N=C1C1=CC=C(C(N)=N)C=C1 LVVCXIVMDOAZGT-UHFFFAOYSA-N 0.000 description 1
• NJRCKFUWBCMHFY-UHFFFAOYSA-N methyl 3-[[2-(4-carbamimidoylpiperazin-1-yl)-1-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1N1CCN(C(N)=N)CC1 NJRCKFUWBCMHFY-UHFFFAOYSA-N 0.000 description 1
• TXWZETWCIXQOLL-UHFFFAOYSA-N methyl 3-[[2-(5-carbamimidoylpyridin-2-yl)-1-methylbenzimidazole-5-carbonyl]amino]propanoate Chemical compound N=1C2=CC(C(=O)NCCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(C(N)=N)C=N1 TXWZETWCIXQOLL-UHFFFAOYSA-N 0.000 description 1
• SXQRXKGQZDARRJ-UHFFFAOYSA-N methyl 3-[[2-[4-(aminomethyl)phenyl]-1h-imidazo[4,5-b]pyridine-6-carbonyl]amino]propanoate Chemical compound N1C2=CC(C(=O)NCCC(=O)OC)=CN=C2N=C1C1=CC=C(CN)C=C1 SXQRXKGQZDARRJ-UHFFFAOYSA-N 0.000 description 1
• CAVKRHDUJIHGRT-UHFFFAOYSA-N methyl 3-[[4-[(4-cyanobenzoyl)-methylamino]-3-nitrobenzoyl]amino]propanoate Chemical compound [O-][N+](=O)C1=CC(C(=O)NCCC(=O)OC)=CC=C1N(C)C(=O)C1=CC=C(C#N)C=C1 CAVKRHDUJIHGRT-UHFFFAOYSA-N 0.000 description 1
• RUJMPEWZLDVEAV-UHFFFAOYSA-N methyl 4-(methylamino)-3-nitrobenzoate Chemical compound CNC1=CC=C(C(=O)OC)C=C1[N+]([O-])=O RUJMPEWZLDVEAV-UHFFFAOYSA-N 0.000 description 1
• IFZHVIHFTUSTMO-UHFFFAOYSA-N methyl 4-[2-[4-[(diaminomethylideneamino)methyl]phenyl]-1-methylbenzimidazol-5-yl]-4-oxobutanoate Chemical compound N=1C2=CC(C(=O)CCC(=O)OC)=CC=C2N(C)C=1C1=CC=C(CN=C(N)N)C=C1 IFZHVIHFTUSTMO-UHFFFAOYSA-N 0.000 description 1
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