IL101203A - History of cyclic urea, their preparation and pharmaceutical preparations containing them - Google Patents
History of cyclic urea, their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL101203A IL101203A IL10120392A IL10120392A IL101203A IL 101203 A IL101203 A IL 101203A IL 10120392 A IL10120392 A IL 10120392A IL 10120392 A IL10120392 A IL 10120392A IL 101203 A IL101203 A IL 101203A
- Authority
- IL
- Israel
- Prior art keywords
- group
- phenyl
- groups
- formula
- ethyl
- Prior art date
Links
- ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical class OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims description 12
- 238000000034 method Methods 0.000 claims abstract description 18
- 230000008569 process Effects 0.000 claims abstract description 7
- -1 sulphinyl Chemical group 0.000 claims description 412
- 150000001875 compounds Chemical class 0.000 claims description 188
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 160
- 229910052757 nitrogen Inorganic materials 0.000 claims description 123
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 95
- 239000000203 mixture Substances 0.000 claims description 95
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 125000003118 aryl group Chemical group 0.000 claims description 76
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 65
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 55
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
- 239000000460 chlorine Substances 0.000 claims description 49
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 48
- 229910052801 chlorine Inorganic materials 0.000 claims description 48
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 46
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 239000011737 fluorine Substances 0.000 claims description 42
- 229910052731 fluorine Inorganic materials 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 41
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 34
- 125000005551 pyridylene group Chemical group 0.000 claims description 32
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 125000002947 alkylene group Chemical group 0.000 claims description 27
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 27
- 239000002585 base Substances 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 25
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 24
- 125000005550 pyrazinylene group Chemical group 0.000 claims description 24
- 125000005576 pyrimidinylene group Chemical group 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 23
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 23
- 125000001246 bromo group Chemical group Br* 0.000 claims description 23
- 125000004450 alkenylene group Chemical group 0.000 claims description 22
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 21
- 125000001153 fluoro group Chemical group F* 0.000 claims description 21
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 239000011541 reaction mixture Substances 0.000 claims description 17
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 230000000269 nucleophilic effect Effects 0.000 claims description 13
- 238000000926 separation method Methods 0.000 claims description 13
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 230000002776 aggregation Effects 0.000 claims description 10
- 238000004220 aggregation Methods 0.000 claims description 10
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 10
- 125000005835 indanylene group Chemical group 0.000 claims description 10
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 9
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 229910052701 rubidium Inorganic materials 0.000 claims description 8
- 125000005558 triazinylene group Chemical group 0.000 claims description 8
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 7
- 239000005864 Sulphur Substances 0.000 claims description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 7
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 7
- 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 claims description 6
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 230000008619 cell matrix interaction Effects 0.000 claims description 6
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 6
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 6
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 150000003951 lactams Chemical group 0.000 claims description 6
- 150000007524 organic acids Chemical class 0.000 claims description 6
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 6
- 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 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 5
- 150000007513 acids Chemical class 0.000 claims description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 229910001516 alkali metal iodide Inorganic materials 0.000 claims description 4
- 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 4
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
- 125000006356 alkylene carbonyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 4
- 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 4
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 125000006357 methylene carbonyl group Chemical group [H]C([H])([*:1])C([*:2])=O 0.000 claims description 4
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 238000001149 thermolysis Methods 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- LZTSCEYDCZBRCJ-UHFFFAOYSA-N 1,2-dihydro-1,2,4-triazol-3-one Chemical compound OC=1N=CNN=1 LZTSCEYDCZBRCJ-UHFFFAOYSA-N 0.000 claims description 2
- AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 claims description 2
- ZUQJRIFSHOJWJR-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]cyclohexyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C2CCC(CCC(O)=O)CC2)CC1 ZUQJRIFSHOJWJR-UHFFFAOYSA-N 0.000 claims description 2
- FCMUCMIRXTVDTH-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 FCMUCMIRXTVDTH-UHFFFAOYSA-N 0.000 claims description 2
- 101150063022 CHRD gene Proteins 0.000 claims description 2
- 101100274355 Danio rerio chd gene Proteins 0.000 claims description 2
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 2
- PVYPYTKOKJWDHC-UHFFFAOYSA-N methyl 3-[4-[1-(4-carbamimidoylphenyl)-5-oxo-1,2,4-triazol-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)N=C1 PVYPYTKOKJWDHC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims 2
- 125000005654 1,2-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([*:2])C([H])([*:1])C1([H])[H] 0.000 claims 1
- 125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims 1
- BQUXTYDUWQRCNT-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2,5-dioxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C(=O)C1 BQUXTYDUWQRCNT-UHFFFAOYSA-N 0.000 claims 1
- SVJLCBSOQHZDOO-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-5-methyl-2-oxoimidazol-1-yl]phenyl]propanoic acid Chemical compound O=C1N(C=2C=CC(CCC(O)=O)=CC=2)C(C)=CN1C1=CC=C(C(N)=N)C=C1 SVJLCBSOQHZDOO-UHFFFAOYSA-N 0.000 claims 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims 1
- 125000002993 cycloalkylene group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 421
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 330
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 327
- 238000002844 melting Methods 0.000 description 142
- 230000008018 melting Effects 0.000 description 142
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 141
- 239000000741 silica gel Substances 0.000 description 141
- 229910002027 silica gel Inorganic materials 0.000 description 141
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 93
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 81
- 239000002904 solvent Substances 0.000 description 75
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 74
- 239000000243 solution Substances 0.000 description 72
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 66
- 235000002639 sodium chloride Nutrition 0.000 description 64
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 62
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 239000012071 phase Substances 0.000 description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 41
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 39
- 239000011780 sodium chloride Substances 0.000 description 37
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000004202 carbamide Substances 0.000 description 32
- 229960000583 acetic acid Drugs 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 239000012362 glacial acetic acid Substances 0.000 description 27
- 239000001257 hydrogen Substances 0.000 description 26
- 229910052739 hydrogen Inorganic materials 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 19
- 229910021529 ammonia Inorganic materials 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
- 239000013543 active substance Substances 0.000 description 14
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 13
- 238000009835 boiling Methods 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 235000011121 sodium hydroxide Nutrition 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 229940012952 fibrinogen Drugs 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102000008946 Fibrinogen Human genes 0.000 description 9
- 108010049003 Fibrinogen Proteins 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- BHPVZDLRVSTGQL-UHFFFAOYSA-N methyl 3-[4-[3-[4-[(e)-n'-(2-methylpropoxycarbonyl)carbamimidoyl]phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(=N)NC(=O)OCC(C)C)CC1 BHPVZDLRVSTGQL-UHFFFAOYSA-N 0.000 description 8
- OVHDVVYBQZFGIK-UHFFFAOYSA-N methyl 3-[4-[3-[4-[(e)-n'-ethoxycarbonylcarbamimidoyl]phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(C(=N)NC(=O)OCC)=CC=C1N1C(=O)N(C=2C=CC(CCC(=O)OC)=CC=2)CC1 OVHDVVYBQZFGIK-UHFFFAOYSA-N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 239000001117 sulphuric acid Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- QIJYIKYSGQORDP-UHFFFAOYSA-N methyl 3-[4-[1-(4-cyanophenyl)-3-methyl-2-oxoimidazol-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(N(C1=O)C)=CN1C1=CC=C(C#N)C=C1 QIJYIKYSGQORDP-UHFFFAOYSA-N 0.000 description 7
- QKFJBLNKZTZBAH-UHFFFAOYSA-N methyl 3-[4-[3-(4-carbamimidoyl-2-methylsulfinylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C(=CC(=CC=2)C(N)=N)S(C)=O)CC1 QKFJBLNKZTZBAH-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000007800 oxidant agent Substances 0.000 description 7
- 229910052697 platinum Inorganic materials 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 235000011149 sulphuric acid Nutrition 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 210000001772 blood platelet Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- TZNFQXFLCGDGRU-UHFFFAOYSA-N methyl 3-[3-chloro-4-[2-(oxan-2-yloxy)ethyl-(2,2,2-trifluoroacetyl)amino]phenyl]propanoate Chemical compound ClC1=CC(CCC(=O)OC)=CC=C1N(C(=O)C(F)(F)F)CCOC1OCCCC1 TZNFQXFLCGDGRU-UHFFFAOYSA-N 0.000 description 6
- QPBHEVGUVOAUOI-UHFFFAOYSA-N methyl 3-[4-[1-(4-carbamimidoylphenyl)-2-oxo-3-phenylimidazolidin-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1N(C=2C=CC=CC=2)C(=O)N(C=2C=CC(=CC=2)C(N)=N)C1 QPBHEVGUVOAUOI-UHFFFAOYSA-N 0.000 description 6
- BMEKBURGTHNGHC-UHFFFAOYSA-N methyl 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]-3-methylsulfinylphenyl]propanoate Chemical compound CS(=O)C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 BMEKBURGTHNGHC-UHFFFAOYSA-N 0.000 description 6
- HRJXXNZRKFCHPF-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]-3-fluorophenyl]propanoate Chemical compound FC1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 HRJXXNZRKFCHPF-UHFFFAOYSA-N 0.000 description 6
- UTUSIPFCGQBTDC-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]-3-methoxyphenyl]propanoate Chemical compound COC1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 UTUSIPFCGQBTDC-UHFFFAOYSA-N 0.000 description 6
- FZWLRIGVADSRAH-UHFFFAOYSA-N methyl 3-[4-[3-[4-[n'-(2-methylpropanoyl)carbamimidoyl]phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(=N)NC(=O)C(C)C)CC1 FZWLRIGVADSRAH-UHFFFAOYSA-N 0.000 description 6
- 150000007530 organic bases Chemical group 0.000 description 6
- 235000009518 sodium iodide Nutrition 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- 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 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000007868 Raney catalyst Substances 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- 150000002513 isocyanates Chemical class 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- QBEANVPHYOGWIN-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)-5-methyl-2-oxo-3-phenylimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC=CC=2)C(C=2C=CC(=CC=2)C#N)=C1C QBEANVPHYOGWIN-UHFFFAOYSA-N 0.000 description 5
- SIGWQHYLVMKNLH-UHFFFAOYSA-N methyl 3-[4-[4-[4-(aminomethyl)phenyl]-5-oxo-1,2,4-triazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(CN)=CC=2)C=N1 SIGWQHYLVMKNLH-UHFFFAOYSA-N 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- RJMNOISSPINOCP-UHFFFAOYSA-N 3-(4-cyanophenyl)-1-[4-(2-dimethoxyphosphorylethyl)phenyl]-1-(2-hydroxyethyl)urea Chemical compound C1=CC(CCP(=O)(OC)OC)=CC=C1N(CCO)C(=O)NC1=CC=C(C#N)C=C1 RJMNOISSPINOCP-UHFFFAOYSA-N 0.000 description 4
- CXEYRFKHXXBDQC-UHFFFAOYSA-N 3-[3-[2-acetamido-4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CC(=O)NC1=CC(C=2C=CC(=CC=2)C(N)=N)=CC=C1N1CCN(CCC(O)=O)C1=O CXEYRFKHXXBDQC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 239000012448 Lithium borohydride Substances 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 150000004703 alkoxides Chemical class 0.000 description 4
- 239000001099 ammonium carbonate Substances 0.000 description 4
- 239000012024 dehydrating agents Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- JNYVPQWTJZBEQJ-UHFFFAOYSA-N methyl 3-[4-[1-(4-cyanophenyl)-3,5-dimethyl-2-oxoimidazol-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(N(C1=O)C)=C(C)N1C1=CC=C(C#N)C=C1 JNYVPQWTJZBEQJ-UHFFFAOYSA-N 0.000 description 4
- RDFKLKWHVHIAJD-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)phenyl]-3-methyl-2-sulfanylideneimidazol-1-yl]propanoate Chemical compound CN1C(=S)N(CCC(=O)OC)C=C1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 RDFKLKWHVHIAJD-UHFFFAOYSA-N 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 238000006902 nitrogenation reaction Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- DKWYVJQOCFGPRS-UHFFFAOYSA-N propan-2-yl 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC(C)C)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 DKWYVJQOCFGPRS-UHFFFAOYSA-N 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- SNFCBUZALCFEBG-UHFFFAOYSA-N 2-(4-cyano-n-methoxycarbonylanilino)acetic acid Chemical compound COC(=O)N(CC(O)=O)C1=CC=C(C#N)C=C1 SNFCBUZALCFEBG-UHFFFAOYSA-N 0.000 description 3
- BDHPVJZDNMHBPS-UHFFFAOYSA-N 2-[acetyl-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethyl]amino]acetic acid Chemical compound O=C1N(CCN(C(=O)C)CC(O)=O)CCN1C1=CC=C(C(N)=N)C=C1 BDHPVJZDNMHBPS-UHFFFAOYSA-N 0.000 description 3
- YBBQAQGDWVNCHQ-UHFFFAOYSA-N 3-[3-[2-bromo-4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1Br)=CC=C1N1C(=O)N(CCC(O)=O)CC1 YBBQAQGDWVNCHQ-UHFFFAOYSA-N 0.000 description 3
- JAPUVEKHTCDCLN-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)-2-nitrophenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1[N+]([O-])=O)=CC=C1N1C(=O)N(CCC(O)=O)CC1 JAPUVEKHTCDCLN-UHFFFAOYSA-N 0.000 description 3
- HFCCFHOTXYAHLX-UHFFFAOYSA-N 3-[3-[4-(5-carbamimidoylpyridin-2-yl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound N1=CC(C(=N)N)=CC=C1C1=CC=C(N2C(N(CCC(O)=O)CC2)=O)C=C1 HFCCFHOTXYAHLX-UHFFFAOYSA-N 0.000 description 3
- BUBFONZGBIXNCP-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoyl-2-methylsulfinylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound CS(=O)C1=CC(C(N)=N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 BUBFONZGBIXNCP-UHFFFAOYSA-N 0.000 description 3
- ZLEQHYKPOLGQTN-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoyl-3-chlorophenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=C(Cl)C(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 ZLEQHYKPOLGQTN-UHFFFAOYSA-N 0.000 description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 description 3
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 235000012501 ammonium carbonate Nutrition 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- DJYXKDBQFYFUSM-UHFFFAOYSA-N methyl 3-[4-[(5-cyanopyridin-2-yl)carbamoyl-(2-methylsulfonyloxyethyl)amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N(CCOS(C)(=O)=O)C(=O)NC1=CC=C(C#N)C=N1 DJYXKDBQFYFUSM-UHFFFAOYSA-N 0.000 description 3
- HCPNUJAVJWOLBX-UHFFFAOYSA-N methyl 3-[6-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]pyridin-3-yl]propanoate Chemical compound N1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 HCPNUJAVJWOLBX-UHFFFAOYSA-N 0.000 description 3
- WPHGSKGZRAQSGP-UHFFFAOYSA-N methylenecyclohexane Natural products C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 229960005235 piperonyl butoxide Drugs 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000005245 sintering Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- 239000005051 trimethylchlorosilane Substances 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
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DZNLZVZTSOKEDG-UHFFFAOYSA-N 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethylsulfanyl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCSCC(O)=O)CC1 DZNLZVZTSOKEDG-UHFFFAOYSA-N 0.000 description 2
- XLEOAXRZRBAHKY-UHFFFAOYSA-N 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethylsulfinyl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCS(=O)CC(O)=O)CC1 XLEOAXRZRBAHKY-UHFFFAOYSA-N 0.000 description 2
- DXEAAUJSFGRKDN-UHFFFAOYSA-N 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethylsulfonyl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCS(=O)(=O)CC(O)=O)CC1 DXEAAUJSFGRKDN-UHFFFAOYSA-N 0.000 description 2
- QRILOGPEHSTCRD-UHFFFAOYSA-N 2-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]ethyl methanesulfonate Chemical compound O=C1N(CCOS(=O)(=O)C)CCN1C1=CC=C(C#N)C=C1 QRILOGPEHSTCRD-UHFFFAOYSA-N 0.000 description 2
- KZTOTBUSEOGKKX-UHFFFAOYSA-N 2-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenoxy]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(OCC(O)=O)=CC=2)CC1 KZTOTBUSEOGKKX-UHFFFAOYSA-N 0.000 description 2
- PSVVASFNEDNZMW-UHFFFAOYSA-N 2-[benzoyl-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethyl]amino]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCN(CC(O)=O)C(=O)C=2C=CC=CC=2)CC1 PSVVASFNEDNZMW-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
- STECXIGQOCCZPC-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)-2-(methanesulfonamido)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CS(=O)(=O)NC1=CC(C=2C=CC(=CC=2)C(N)=N)=CC=C1N1CCN(CCC(O)=O)C1=O STECXIGQOCCZPC-UHFFFAOYSA-N 0.000 description 2
- BONWACGCGZDWMR-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-2-oxo-3-phenylimidazol-4-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC=CC=2)C(C=2C=CC(CCC(O)=O)=CC=2)=C1 BONWACGCGZDWMR-UHFFFAOYSA-N 0.000 description 2
- PVXWLLGQDSPQFC-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-2-oxo-3-phenylimidazolidin-4-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC=CC=2)C(C=2C=CC(CCC(O)=O)=CC=2)C1 PVXWLLGQDSPQFC-UHFFFAOYSA-N 0.000 description 2
- IOFPNEBFSXZWGN-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-2-oxoimidazolidin-4-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)NC(C=2C=CC(CCC(O)=O)=CC=2)C1 IOFPNEBFSXZWGN-UHFFFAOYSA-N 0.000 description 2
- RFXSFSOIKZJABZ-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-3-methyl-2-oxoimidazol-4-yl]phenyl]propanoic acid Chemical compound O=C1N(C)C(C=2C=CC(CCC(O)=O)=CC=2)=CN1C1=CC=C(C(N)=N)C=C1 RFXSFSOIKZJABZ-UHFFFAOYSA-N 0.000 description 2
- QDANGTMEICYVDP-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-3-methyl-2-oxoimidazolidin-4-yl]phenyl]propanoic acid Chemical compound O=C1N(C)C(C=2C=CC(CCC(O)=O)=CC=2)CN1C1=CC=C(C(N)=N)C=C1 QDANGTMEICYVDP-UHFFFAOYSA-N 0.000 description 2
- GGFRJWGAQRFBJO-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-5-methyl-2-oxo-3-phenylimidazol-4-yl]phenyl]propanoic acid Chemical compound C=1C=CC=CC=1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)C(C)=C1C1=CC=C(CCC(O)=O)C=C1 GGFRJWGAQRFBJO-UHFFFAOYSA-N 0.000 description 2
- CDOYVPDJNZZBMS-UHFFFAOYSA-N 3-[4-[2-(4-carbamimidoylphenyl)-3-oxo-1h-1,2,4-triazol-5-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)NC(C=2C=CC(CCC(O)=O)=CC=2)=N1 CDOYVPDJNZZBMS-UHFFFAOYSA-N 0.000 description 2
- ITGYVNGHUADVAD-UHFFFAOYSA-N 3-[4-[3-(1-carbamimidoylpiperidin-4-yl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1CN(C(=N)N)CCC1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 ITGYVNGHUADVAD-UHFFFAOYSA-N 0.000 description 2
- VRIAMZCUNRIGJK-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2,4-dioxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1=O VRIAMZCUNRIGJK-UHFFFAOYSA-N 0.000 description 2
- XTLQKMXCEGEUDQ-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-iminoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=N)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 XTLQKMXCEGEUDQ-UHFFFAOYSA-N 0.000 description 2
- QBAARFLHVUSVRX-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-methyliminoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound CN=C1N(C=2C=CC(CCC(O)=O)=CC=2)CCN1C1=CC=C(C(N)=N)C=C1 QBAARFLHVUSVRX-UHFFFAOYSA-N 0.000 description 2
- MBDYNNGTFPFDFD-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxo-1h-imidazol-5-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)NC(C=2C=CC(CCC(O)=O)=CC=2)=C1 MBDYNNGTFPFDFD-UHFFFAOYSA-N 0.000 description 2
- ZCLXGAIVAZSGDX-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxo-4-(trifluoromethyl)imidazol-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C=C1C(F)(F)F ZCLXGAIVAZSGDX-UHFFFAOYSA-N 0.000 description 2
- CGJWJMXUMZNSIH-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxo-5-phenylimidazol-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C(C=2C=CC=CC=2)=C1 CGJWJMXUMZNSIH-UHFFFAOYSA-N 0.000 description 2
- HKVKFPKEYOXJCV-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxo-5-phenylimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C(C=2C=CC=CC=2)C1 HKVKFPKEYOXJCV-UHFFFAOYSA-N 0.000 description 2
- CZSIVXODQZZTTC-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]-2-oxopyridin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C2=CC(=O)N(CCC(O)=O)C=C2)CC1 CZSIVXODQZZTTC-UHFFFAOYSA-N 0.000 description 2
- IDZKPBMVEZYJPN-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]-3-chlorophenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C(=CC(CCC(O)=O)=CC=2)Cl)CC1 IDZKPBMVEZYJPN-UHFFFAOYSA-N 0.000 description 2
- QMOSTXWRALZHJI-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]-3-fluorophenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C(=CC(CCC(O)=O)=CC=2)F)CC1 QMOSTXWRALZHJI-UHFFFAOYSA-N 0.000 description 2
- BCIZXOMJMWICQR-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]-3-methoxyphenyl]propanoic acid Chemical compound COC1=CC(CCC(O)=O)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 BCIZXOMJMWICQR-UHFFFAOYSA-N 0.000 description 2
- QMCUGRNSDYYFPU-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]-3-methylsulfonylphenyl]propanoic acid Chemical compound CS(=O)(=O)C1=CC(CCC(O)=O)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 QMCUGRNSDYYFPU-UHFFFAOYSA-N 0.000 description 2
- WBQIYTPUVFZLLT-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]-2,2-dimethylpropanoic acid Chemical compound C1=CC(CC(C)(C)C(O)=O)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 WBQIYTPUVFZLLT-UHFFFAOYSA-N 0.000 description 2
- BQPGVMXLYITRBM-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-phenyliminoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N(CCN1C=2C=CC(CCC(O)=O)=CC=2)C1=NC1=CC=CC=C1 BQPGVMXLYITRBM-UHFFFAOYSA-N 0.000 description 2
- UFEVDDFDESWTIF-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-pyridin-3-yliminoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N(CCN1C=2C=CC(CCC(O)=O)=CC=2)C1=NC1=CC=CN=C1 UFEVDDFDESWTIF-UHFFFAOYSA-N 0.000 description 2
- BUZNKLFJGURPEN-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-sulfanylideneimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=S)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 BUZNKLFJGURPEN-UHFFFAOYSA-N 0.000 description 2
- FJKIWRJKEPUNPX-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound O=C1C(C)(C)N(C=2C=CC(=CC=2)C(N)=N)C(=O)N1C1=CC=C(CCC(O)=O)C=C1 FJKIWRJKEPUNPX-UHFFFAOYSA-N 0.000 description 2
- HOZBELZNHIRGLZ-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-4-methyl-2-oxo-1h-imidazol-5-yl]phenyl]propanoic acid Chemical compound CC1=C(C=2C=CC(CCC(O)=O)=CC=2)NC(=O)N1C1=CC=C(C(N)=N)C=C1 HOZBELZNHIRGLZ-UHFFFAOYSA-N 0.000 description 2
- LKGDMTHQSMITLQ-UHFFFAOYSA-N 3-[4-[3-(5-carbamimidoylpyridin-2-yl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound N1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 LKGDMTHQSMITLQ-UHFFFAOYSA-N 0.000 description 2
- JJYXFCHWVJXFBB-UHFFFAOYSA-N 3-[4-[3-[4-(aminomethyl)cyclohexyl]-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1CC(CN)CCC1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 JJYXFCHWVJXFBB-UHFFFAOYSA-N 0.000 description 2
- CPWMKWRHLWSELV-UHFFFAOYSA-N 3-[4-[3-[4-[(dimethylamino)methyl]phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(CN(C)C)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 CPWMKWRHLWSELV-UHFFFAOYSA-N 0.000 description 2
- IHOMRKAXSBDXMM-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-2-oxo-3-phenylimidazol-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(N(C1=O)C=2C=CC=CC=2)=CN1C1=CC=C(CCC(O)=O)C=C1 IHOMRKAXSBDXMM-UHFFFAOYSA-N 0.000 description 2
- HSXAEFGYRCNJHZ-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-2-oxo-3-phenylimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1N(C=2C=CC=CC=2)C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C1 HSXAEFGYRCNJHZ-UHFFFAOYSA-N 0.000 description 2
- GUDPYXSPJWWYOC-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-3,5-dimethyl-2-oxoimidazol-1-yl]phenyl]propanoic acid Chemical compound CN1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C(C)=C1C1=CC=C(C(N)=N)C=C1 GUDPYXSPJWWYOC-UHFFFAOYSA-N 0.000 description 2
- XNQCYVBOZALHDD-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-3-methyl-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound O=C1N(C)C(C=2C=CC(=CC=2)C(N)=N)CN1C1=CC=C(CCC(O)=O)C=C1 XNQCYVBOZALHDD-UHFFFAOYSA-N 0.000 description 2
- HBHZSTRSRQPCRI-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-3-phenyl-2-sulfanylideneimidazol-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(N(C1=S)C=2C=CC=CC=2)=CN1C1=CC=C(CCC(O)=O)C=C1 HBHZSTRSRQPCRI-UHFFFAOYSA-N 0.000 description 2
- BIPFZCCXGGMBOJ-UHFFFAOYSA-N 3-[4-[5-(4-carbamimidoylphenyl)-3-oxo-1h-1,2,4-triazol-2-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(NC1=O)=NN1C1=CC=C(CCC(O)=O)C=C1 BIPFZCCXGGMBOJ-UHFFFAOYSA-N 0.000 description 2
- LRBHQTXYPOCNJG-UHFFFAOYSA-N 3-[4-[5-(4-carbamimidoylphenyl)-4-methyl-2-oxo-1h-imidazol-3-yl]phenyl]propanoic acid Chemical compound CC1=C(C=2C=CC(=CC=2)C(N)=N)NC(=O)N1C1=CC=C(CCC(O)=O)C=C1 LRBHQTXYPOCNJG-UHFFFAOYSA-N 0.000 description 2
- YDDLSBUSWGIOGN-UHFFFAOYSA-N 3-[6-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]pyridin-3-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2N=CC(CCC(O)=O)=CC=2)CC1 YDDLSBUSWGIOGN-UHFFFAOYSA-N 0.000 description 2
- NCNBHVKGCQEGFD-UHFFFAOYSA-N 3-[[4-[3-(4-aminocyclohexyl)-2-oxoimidazolidin-1-yl]benzoyl]amino]propanoic acid Chemical compound C1CC(N)CCC1N1C(=O)N(C=2C=CC(=CC=2)C(=O)NCCC(O)=O)CC1 NCNBHVKGCQEGFD-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- RJWQDPGTDSRETR-UHFFFAOYSA-N 4-(4-oxopiperidin-1-yl)benzonitrile Chemical compound C1CC(=O)CCN1C1=CC=C(C#N)C=C1 RJWQDPGTDSRETR-UHFFFAOYSA-N 0.000 description 2
- NJXZSDVOMVDTOT-UHFFFAOYSA-N 4-[(3-aminopyridin-2-yl)amino]benzonitrile Chemical compound NC1=CC=CN=C1NC1=CC=C(C#N)C=C1 NJXZSDVOMVDTOT-UHFFFAOYSA-N 0.000 description 2
- SMULFOYOQULSQB-UHFFFAOYSA-N 4-[4-(2-oxoimidazolidin-1-yl)phenyl]benzonitrile Chemical compound O=C1NCCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 SMULFOYOQULSQB-UHFFFAOYSA-N 0.000 description 2
- LJBJHVIDLZQPLW-UHFFFAOYSA-N 4-[4-(3-but-3-enyl-2-oxoimidazolidin-1-yl)phenyl]benzonitrile Chemical compound O=C1N(CCC=C)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 LJBJHVIDLZQPLW-UHFFFAOYSA-N 0.000 description 2
- ZMVGSRYMTFGKLT-UHFFFAOYSA-N 4-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]butanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCCC(O)=O)=CC=2)CC1 ZMVGSRYMTFGKLT-UHFFFAOYSA-N 0.000 description 2
- PDOJOAVAHLKMGN-UHFFFAOYSA-N 4-[6-(2-oxoimidazolidin-1-yl)pyridazin-3-yl]benzonitrile Chemical compound O=C1NCCN1C1=CC=C(C=2C=CC(=CC=2)C#N)N=N1 PDOJOAVAHLKMGN-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 2
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000002785 anti-thrombosis Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- 239000007891 compressed tablet Substances 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- KRUWIBCYLAIRAX-UHFFFAOYSA-N ethyl 2-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]acetate Chemical compound O=C1N(CC(=O)OCC)CCN1C1=CC=C(C#N)C=C1 KRUWIBCYLAIRAX-UHFFFAOYSA-N 0.000 description 2
- NQRBHBDYLUZLKR-UHFFFAOYSA-N ethyl 3-[3-[4-(4-carbamimidoylphenyl)phenyl]-2,5-dioxoimidazolidin-1-yl]propanoate;hydrochloride Chemical compound Cl.O=C1N(CCC(=O)OCC)C(=O)CN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 NQRBHBDYLUZLKR-UHFFFAOYSA-N 0.000 description 2
- ROPBETLLYDPIRM-UHFFFAOYSA-N ethyl 3-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazol-1-yl]propanoate;hydrochloride Chemical compound Cl.O=C1N(CCC(=O)OCC)C=CN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 ROPBETLLYDPIRM-UHFFFAOYSA-N 0.000 description 2
- JAVYBWZGOLVQFU-UHFFFAOYSA-N ethyl 3-[4-[acetamido-[(4-cyanophenyl)carbamoyl]amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1N(NC(C)=O)C(=O)NC1=CC=C(C#N)C=C1 JAVYBWZGOLVQFU-UHFFFAOYSA-N 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- RTPQLMKGNUUQCC-UHFFFAOYSA-N methyl 2-(dibenzylamino)-3-(4-nitrophenyl)propanoate Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)C(C(=O)OC)CC1=CC=C([N+]([O-])=O)C=C1 RTPQLMKGNUUQCC-UHFFFAOYSA-N 0.000 description 2
- NPJCOZWBVULHIP-UHFFFAOYSA-N methyl 2-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]acetate;hydrochloride Chemical compound Cl.O=C1N(CC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 NPJCOZWBVULHIP-UHFFFAOYSA-N 0.000 description 2
- AEPDYDDYISFPDG-UHFFFAOYSA-N methyl 2-[4-(2-hydroxyethylamino)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(NCCO)C=C1 AEPDYDDYISFPDG-UHFFFAOYSA-N 0.000 description 2
- JAHRVKKDPYFQOO-UHFFFAOYSA-N methyl 2-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 JAHRVKKDPYFQOO-UHFFFAOYSA-N 0.000 description 2
- NFFOXPLOXZDPPD-UHFFFAOYSA-N methyl 3-(4-aminophenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)CCC1=CC=C(N)C=C1 NFFOXPLOXZDPPD-UHFFFAOYSA-N 0.000 description 2
- KBZHGACXRMAMHR-UHFFFAOYSA-N methyl 3-[3-[4-(4-cyanophenyl)-2-nitrophenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1[N+]([O-])=O KBZHGACXRMAMHR-UHFFFAOYSA-N 0.000 description 2
- WEUZQXHXLACKJP-UHFFFAOYSA-N methyl 3-[3-[4-(4-cyanophenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 WEUZQXHXLACKJP-UHFFFAOYSA-N 0.000 description 2
- UAKRCOKZUUSVHK-UHFFFAOYSA-N methyl 3-[3-[6-(4-cyanophenyl)pyridazin-3-yl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)N=N1 UAKRCOKZUUSVHK-UHFFFAOYSA-N 0.000 description 2
- UWTVTWIXUYDNLT-UHFFFAOYSA-N methyl 3-[4-(2-oxoimidazolidin-1-yl)cyclohexyl]propanoate Chemical compound C1CC(CCC(=O)OC)CCC1N1C(=O)NCC1 UWTVTWIXUYDNLT-UHFFFAOYSA-N 0.000 description 2
- QBSQHNAOQRCCRM-UHFFFAOYSA-N methyl 3-[4-(carbamoylamino)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(NC(N)=O)C=C1 QBSQHNAOQRCCRM-UHFFFAOYSA-N 0.000 description 2
- AGWAOUVPBHFQOP-UHFFFAOYSA-N methyl 3-[4-[(4-cyanophenyl)carbamoyl-(2-hydroxypropyl)amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N(CC(C)O)C(=O)NC1=CC=C(C#N)C=C1 AGWAOUVPBHFQOP-UHFFFAOYSA-N 0.000 description 2
- KOMMTHLOMGQEBV-UHFFFAOYSA-N methyl 3-[4-[3-(4-acetylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(C)=O)CC1 KOMMTHLOMGQEBV-UHFFFAOYSA-N 0.000 description 2
- NFBQBHMGHCCKQA-UHFFFAOYSA-N methyl 3-[4-[3-(4-carbamimidoylphenyl)-5-methyl-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)C=C1C NFBQBHMGHCCKQA-UHFFFAOYSA-N 0.000 description 2
- IJGLXHXHOULJBJ-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyano-2-methylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C(=CC(=CC=2)C#N)C)CC1 IJGLXHXHOULJBJ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 229910001927 ruthenium tetroxide Inorganic materials 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- 229940038773 trisodium citrate Drugs 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 229940075966 (+)- menthol Drugs 0.000 description 1
- NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- YLFRZTMXDWOXIO-UHFFFAOYSA-N (4-cyanophenyl)urea Chemical compound NC(=O)NC1=CC=C(C#N)C=C1 YLFRZTMXDWOXIO-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 1
- SWXXKWPYNMZFTE-UHFFFAOYSA-N (c-ethylsulfanylcarbonimidoyl)azanium;bromide Chemical compound Br.CCSC(N)=N SWXXKWPYNMZFTE-UHFFFAOYSA-N 0.000 description 1
- UFFNNHYFJAVGTB-UHFFFAOYSA-N 1,3-dihydroimidazol-2-one;hydrochloride Chemical compound Cl.O=C1NC=CN1 UFFNNHYFJAVGTB-UHFFFAOYSA-N 0.000 description 1
- DSDAVQGUIXPZAU-UHFFFAOYSA-N 1-(2-chloroethyl)-1-[4-(4-cyanophenyl)phenyl]urea Chemical compound ClCCN(C(=O)N)C1=CC=C(C=C1)C1=CC=C(C=C1)C#N DSDAVQGUIXPZAU-UHFFFAOYSA-N 0.000 description 1
- PLJBBPTVAIKZJY-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[4-(4-cyanophenyl)-2-methoxyphenyl]urea Chemical compound C1=C(NC(=O)NCCCl)C(OC)=CC(C=2C=CC(=CC=2)C#N)=C1 PLJBBPTVAIKZJY-UHFFFAOYSA-N 0.000 description 1
- OZEUCMJLXMJQPL-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[4-(4-cyanophenyl)-2-methylsulfanylphenyl]urea Chemical compound C1=C(NC(=O)NCCCl)C(SC)=CC(C=2C=CC(=CC=2)C#N)=C1 OZEUCMJLXMJQPL-UHFFFAOYSA-N 0.000 description 1
- BLSKAHSUNNPIFE-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[4-(4-cyanophenyl)phenyl]urea Chemical compound C1=CC(NC(=O)NCCCl)=CC=C1C1=CC=C(C#N)C=C1 BLSKAHSUNNPIFE-UHFFFAOYSA-N 0.000 description 1
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 description 1
- UGHQIUXYKYLWLS-UHFFFAOYSA-N 1-[4-(aminomethyl)phenyl]-3-[4-[2-(2h-tetrazol-5-yl)ethyl]phenyl]imidazolidin-2-one Chemical compound C1=CC(CN)=CC=C1N1C(=O)N(C=2C=CC(CCC=3NN=NN=3)=CC=2)CC1 UGHQIUXYKYLWLS-UHFFFAOYSA-N 0.000 description 1
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
- BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 1
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
- LNSCNEJNLACZPA-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylphenyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=CC=C1C LNSCNEJNLACZPA-UHFFFAOYSA-N 0.000 description 1
- LILXUZCFFQKRIH-UHFFFAOYSA-N 2,5-dihydro-1,2,5-thiadiazole 1,1-dioxide Chemical compound O=S1(=O)NC=CN1 LILXUZCFFQKRIH-UHFFFAOYSA-N 0.000 description 1
- XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical compound NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 1
- YKJNHYVVPMEEQJ-UHFFFAOYSA-N 2-(4-aminophenyl)pyrimidine-5-carbonitrile Chemical compound C1=CC(N)=CC=C1C1=NC=C(C#N)C=N1 YKJNHYVVPMEEQJ-UHFFFAOYSA-N 0.000 description 1
- ILVKBBGIGNSVDO-UHFFFAOYSA-N 2-(4-nitrophenyl)-2-oxoacetaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C(=O)C=O)C=C1 ILVKBBGIGNSVDO-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ADKXGOSFCPLXGR-UHFFFAOYSA-N 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethoxy]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCOCC(O)=O)CC1 ADKXGOSFCPLXGR-UHFFFAOYSA-N 0.000 description 1
- WYTROMNIZDPDKQ-UHFFFAOYSA-N 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethylamino]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCNCC(O)=O)CC1 WYTROMNIZDPDKQ-UHFFFAOYSA-N 0.000 description 1
- ISROCMMZZPIUCB-UHFFFAOYSA-N 2-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxo-1,3-diazinan-1-yl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C(N(CC(O)=O)CCC2)=O)C=C1 ISROCMMZZPIUCB-UHFFFAOYSA-N 0.000 description 1
- OAYSRKBDWFACMT-UHFFFAOYSA-N 2-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C(N(CC(O)=O)CC2)=O)C=C1 OAYSRKBDWFACMT-UHFFFAOYSA-N 0.000 description 1
- SSUJWAMFNLCVMH-UHFFFAOYSA-N 2-[4-(2-oxoimidazolidin-1-yl)phenyl]pyrimidine-5-carbonitrile Chemical compound O=C1NCCN1C1=CC=C(C=2N=CC(=CN=2)C#N)C=C1 SSUJWAMFNLCVMH-UHFFFAOYSA-N 0.000 description 1
- SVNDJVYWFDUMBU-UHFFFAOYSA-N 2-[4-(3-but-3-enyl-2-oxoimidazolidin-1-yl)phenyl]pyrimidine-5-carbonitrile Chemical compound O=C1N(CCC=C)CCN1C1=CC=C(C=2N=CC(=CN=2)C#N)C=C1 SVNDJVYWFDUMBU-UHFFFAOYSA-N 0.000 description 1
- DTUSDLYIMJSUQB-UHFFFAOYSA-N 2-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]sulfanylacetic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(SCC(O)=O)=CC=2)CC1 DTUSDLYIMJSUQB-UHFFFAOYSA-N 0.000 description 1
- DRMUGTPJXZNUPE-UHFFFAOYSA-N 2-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]phenyl]ethylphosphonic acid Chemical compound C1=CC(CCP(O)(=O)O)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 DRMUGTPJXZNUPE-UHFFFAOYSA-N 0.000 description 1
- GFLUGCGBUCBEQM-UHFFFAOYSA-N 2-amino-3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(CC(N)C(O)=O)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 GFLUGCGBUCBEQM-UHFFFAOYSA-N 0.000 description 1
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical class C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- MMWFMFZFCKADEL-UHFFFAOYSA-N 2-fluoro-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1F MMWFMFZFCKADEL-UHFFFAOYSA-N 0.000 description 1
- VFUDDKHMYGQRAP-UHFFFAOYSA-N 2-methylbenzenesulfonate;pyridin-1-ium Chemical compound C1=CC=NC=C1.CC1=CC=CC=C1S(O)(=O)=O VFUDDKHMYGQRAP-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- NRMIRFMJAIIFJY-UHFFFAOYSA-N 3-(4-amino-3-methylsulfanylphenyl)propanoic acid Chemical compound CSC1=CC(CCC(O)=O)=CC=C1N NRMIRFMJAIIFJY-UHFFFAOYSA-N 0.000 description 1
- BJJQJLOZWBZEGA-UHFFFAOYSA-N 3-Methoxybenzenepropanoic acid Chemical compound COC1=CC=CC(CCC(O)=O)=C1 BJJQJLOZWBZEGA-UHFFFAOYSA-N 0.000 description 1
- WXBFVCXTKSQVEJ-UHFFFAOYSA-N 3-[3-[1-(4-carbamimidoylphenyl)piperidin-4-yl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1CCC(N2C(N(CCC(O)=O)CC2)=O)CC1 WXBFVCXTKSQVEJ-UHFFFAOYSA-N 0.000 description 1
- MOYSWCQKNBHOBF-UHFFFAOYSA-N 3-[3-[2-(4-cyanophenyl)pyrimidin-5-yl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound O=C1N(CCC(=O)O)CCN1C1=CN=C(C=2C=CC(=CC=2)C#N)N=C1 MOYSWCQKNBHOBF-UHFFFAOYSA-N 0.000 description 1
- KMUHXQCKWKUYNL-UHFFFAOYSA-N 3-[3-[2-amino-4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1N)=CC=C1N1C(=O)N(CCC(O)=O)CC1 KMUHXQCKWKUYNL-UHFFFAOYSA-N 0.000 description 1
- IOQQWIUEJCBWJK-UHFFFAOYSA-N 3-[3-[2-benzamido-4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1NC(=O)C=2C=CC=CC=2)=CC=C1N1C(=O)N(CCC(O)=O)CC1 IOQQWIUEJCBWJK-UHFFFAOYSA-N 0.000 description 1
- YUULPMHXFGEJHE-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)-2,3-dimethylphenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CC1=C(C)C(C=2C=CC(=CC=2)C(N)=N)=CC=C1N1CCN(CCC(O)=O)C1=O YUULPMHXFGEJHE-UHFFFAOYSA-N 0.000 description 1
- LHPSEFTXEMJYFD-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)-2-methoxyphenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound COC1=CC(C=2C=CC(=CC=2)C(N)=N)=CC=C1N1CCN(CCC(O)=O)C1=O LHPSEFTXEMJYFD-UHFFFAOYSA-N 0.000 description 1
- GIGIIHLKWFVREH-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)-2-methylsulfinylphenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CS(=O)C1=CC(C=2C=CC(=CC=2)C(N)=N)=CC=C1N1CCN(CCC(O)=O)C1=O GIGIIHLKWFVREH-UHFFFAOYSA-N 0.000 description 1
- IQTUFNQPDHSNCX-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)-2-methylsulfonylphenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CS(=O)(=O)C1=CC(C=2C=CC(=CC=2)C(N)=N)=CC=C1N1CCN(CCC(O)=O)C1=O IQTUFNQPDHSNCX-UHFFFAOYSA-N 0.000 description 1
- IQWFBMNDTDOQMN-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)cyclohexyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1CCC(N2C(N(CCC(O)=O)CC2)=O)CC1 IQWFBMNDTDOQMN-UHFFFAOYSA-N 0.000 description 1
- FSEAVYZAJOUYKT-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxo-1,3-diazinan-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C(N(CCC(O)=O)CCC2)=O)C=C1 FSEAVYZAJOUYKT-UHFFFAOYSA-N 0.000 description 1
- NLMVYYDATJTZTN-UHFFFAOYSA-N 3-[3-[4-(4-cyanophenyl)-2,3-dimethylphenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CC1=C(C)C(C=2C=CC(=CC=2)C#N)=CC=C1N1CCN(CCC(O)=O)C1=O NLMVYYDATJTZTN-UHFFFAOYSA-N 0.000 description 1
- QXIZTXPTLFMJEA-UHFFFAOYSA-N 3-[3-[4-(4-cyanophenyl)-2-methylsulfanylphenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CSC1=CC(C=2C=CC(=CC=2)C#N)=CC=C1N1CCN(CCC(O)=O)C1=O QXIZTXPTLFMJEA-UHFFFAOYSA-N 0.000 description 1
- DYYFATXTKZBOMT-UHFFFAOYSA-N 3-[3-[4-(4-cyanophenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound O=C1N(CCC(=O)O)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 DYYFATXTKZBOMT-UHFFFAOYSA-N 0.000 description 1
- QPWRAKUFIFKWNT-UHFFFAOYSA-N 3-[3-[4-(5-cyanopyrazin-2-yl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound O=C1N(CCC(=O)O)CCN1C1=CC=C(C=2N=CC(=NC=2)C#N)C=C1 QPWRAKUFIFKWNT-UHFFFAOYSA-N 0.000 description 1
- ADTBBIBEHBDZHL-UHFFFAOYSA-N 3-[3-[4-(5-cyanopyridin-2-yl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound O=C1N(CCC(=O)O)CCN1C1=CC=C(C=2N=CC(=CC=2)C#N)C=C1 ADTBBIBEHBDZHL-UHFFFAOYSA-N 0.000 description 1
- LOVKHTWJEHLKTJ-UHFFFAOYSA-N 3-[3-[4-(5-cyanopyrimidin-2-yl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound O=C1N(CCC(=O)O)CCN1C1=CC=C(C=2N=CC(=CN=2)C#N)C=C1 LOVKHTWJEHLKTJ-UHFFFAOYSA-N 0.000 description 1
- IQBOJLCJFIDBSP-UHFFFAOYSA-N 3-[3-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C(N(CCC(O)=O)CC2)=O)N=N1 IQBOJLCJFIDBSP-UHFFFAOYSA-N 0.000 description 1
- VPEOGJWQHBXCRJ-UHFFFAOYSA-N 3-[3-[6-(4-cyanophenyl)pyridazin-3-yl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound O=C1N(CCC(=O)O)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)N=N1 VPEOGJWQHBXCRJ-UHFFFAOYSA-N 0.000 description 1
- CSJCCFVGAIQRTF-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-5-oxo-1,2,4-triazol-4-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C=N1 CSJCCFVGAIQRTF-UHFFFAOYSA-N 0.000 description 1
- FFZRSTNJYSZGDI-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoyl-2-methylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound CC1=CC(C(N)=N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 FFZRSTNJYSZGDI-UHFFFAOYSA-N 0.000 description 1
- ACEZMYPTAGFJEC-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoyl-2-methylsulfanylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound CSC1=CC(C(N)=N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 ACEZMYPTAGFJEC-UHFFFAOYSA-N 0.000 description 1
- VMIRMCJXOWQZCH-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoyl-3-fluorophenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=C(F)C(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 VMIRMCJXOWQZCH-UHFFFAOYSA-N 0.000 description 1
- DBVHNOQCWSDVQC-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazol-1-yl]phenyl]-2-hydroxypropanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(C=2C=CC(CC(O)C(O)=O)=CC=2)C=C1 DBVHNOQCWSDVQC-UHFFFAOYSA-N 0.000 description 1
- QJXKTJYYXNQLGC-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]-3-methylsulfanylphenyl]propanoic acid Chemical compound CSC1=CC(CCC(O)=O)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 QJXKTJYYXNQLGC-UHFFFAOYSA-N 0.000 description 1
- LKXYIKHBNDWZRG-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-2-sulfanylidene-1h-imidazol-5-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=S)NC(C=2C=CC(CCC(O)=O)=CC=2)=C1 LKXYIKHBNDWZRG-UHFFFAOYSA-N 0.000 description 1
- AOVNDENJMLAVJH-UHFFFAOYSA-N 3-[4-[3-[4-(aminomethyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(CN)=CC=C1N1C(=O)N(C=2C=CC(CCC(O)=O)=CC=2)CC1 AOVNDENJMLAVJH-UHFFFAOYSA-N 0.000 description 1
- AZLSXRHSGMWKNV-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1NC(=O)N(C=2C=CC(CCC(O)=O)=CC=2)C1 AZLSXRHSGMWKNV-UHFFFAOYSA-N 0.000 description 1
- XJZZQWOAGFZFEO-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-3-methyl-2-oxoimidazolidin-1-yl]phenyl]propanoic acid;hydrochloride Chemical compound Cl.O=C1N(C)C(C=2C=CC(=CC=2)C(N)=N)CN1C1=CC=C(CCC(O)=O)C=C1 XJZZQWOAGFZFEO-UHFFFAOYSA-N 0.000 description 1
- GAPPCYHZCDPNHC-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-2-oxo-3-phenylimidazolidin-1-yl]propanoic acid;hydrochloride Chemical compound Cl.C1=CC(C(=N)N)=CC=C1C1=CC=C(C2N(C(=O)N(CCC(O)=O)C2)C=2C=CC=CC=2)C=C1 GAPPCYHZCDPNHC-UHFFFAOYSA-N 0.000 description 1
- JIPRMHWCRJGGTH-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoic acid;hydrochloride Chemical compound Cl.C1=CC(C(=N)N)=CC=C1C1=CC=C(C2NC(=O)N(CCC(O)=O)C2)C=C1 JIPRMHWCRJGGTH-UHFFFAOYSA-N 0.000 description 1
- WHZKUJHDRUTZTB-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-3-methyl-2-oxoimidazol-1-yl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCN1C(=O)N(C)C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=C1 WHZKUJHDRUTZTB-UHFFFAOYSA-N 0.000 description 1
- CUXSJKIGANYUSK-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-3-methyl-2-oxoimidazolidin-1-yl]propanoic acid;hydrochloride Chemical compound Cl.C1N(CCC(O)=O)C(=O)N(C)C1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 CUXSJKIGANYUSK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- PWURRRRGLCVBMX-UHFFFAOYSA-N 3-methoxy-4-nitrobenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1[N+]([O-])=O PWURRRRGLCVBMX-UHFFFAOYSA-N 0.000 description 1
- FGMYNGSWRAOYSV-UHFFFAOYSA-N 4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1N1CCC2(OCCO2)CC1 FGMYNGSWRAOYSV-UHFFFAOYSA-N 0.000 description 1
- WQYPNPPXRPOACM-UHFFFAOYSA-N 4-(2-hydroxypropylamino)benzonitrile Chemical compound CC(O)CNC1=CC=C(C#N)C=C1 WQYPNPPXRPOACM-UHFFFAOYSA-N 0.000 description 1
- GVHMWTGTAGUXGY-UHFFFAOYSA-N 4-(2-oxo-1h-imidazo[4,5-b]pyridin-3-yl)benzonitrile Chemical compound O=C1NC2=CC=CN=C2N1C1=CC=C(C#N)C=C1 GVHMWTGTAGUXGY-UHFFFAOYSA-N 0.000 description 1
- YYSBRUIQVXMYAF-UHFFFAOYSA-N 4-(4-amino-3-methylsulfanylphenyl)benzonitrile Chemical group C1=C(N)C(SC)=CC(C=2C=CC(=CC=2)C#N)=C1 YYSBRUIQVXMYAF-UHFFFAOYSA-N 0.000 description 1
- ZSFKODANZQVHCK-UHFFFAOYSA-N 4-(4-aminophenyl)benzoic acid Chemical compound C1=CC(N)=CC=C1C1=CC=C(C(O)=O)C=C1 ZSFKODANZQVHCK-UHFFFAOYSA-N 0.000 description 1
- XFRVACCGEKPJDI-UHFFFAOYSA-N 4-(4-oxocyclohexyl)benzonitrile Chemical compound C1CC(=O)CCC1C1=CC=C(C#N)C=C1 XFRVACCGEKPJDI-UHFFFAOYSA-N 0.000 description 1
- PXZYQWCHWCOZAL-UHFFFAOYSA-N 4-(6-chloropyridazin-3-yl)benzonitrile Chemical compound N1=NC(Cl)=CC=C1C1=CC=C(C#N)C=C1 PXZYQWCHWCOZAL-UHFFFAOYSA-N 0.000 description 1
- MSOSXHRMVRHNHF-UHFFFAOYSA-N 4-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethyl]benzoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCC=2C=CC(=CC=2)C(O)=O)CC1 MSOSXHRMVRHNHF-UHFFFAOYSA-N 0.000 description 1
- UTDINAXENJVEMO-UHFFFAOYSA-N 4-[3-(2-hydroxyethyl)-2-oxoimidazolidin-1-yl]benzonitrile Chemical compound O=C1N(CCO)CCN1C1=CC=C(C#N)C=C1 UTDINAXENJVEMO-UHFFFAOYSA-N 0.000 description 1
- CAEKSEURPVNMGX-UHFFFAOYSA-N 4-[3-[4-(2-dimethoxyphosphorylethyl)phenyl]-2-oxoimidazolidin-1-yl]benzonitrile Chemical compound C1=CC(CCP(=O)(OC)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 CAEKSEURPVNMGX-UHFFFAOYSA-N 0.000 description 1
- IBHQGVKJWQGDOD-UHFFFAOYSA-N 4-[3-methoxy-4-(2-oxoimidazolidin-1-yl)phenyl]benzonitrile Chemical compound COC1=CC(C=2C=CC(=CC=2)C#N)=CC=C1N1CCNC1=O IBHQGVKJWQGDOD-UHFFFAOYSA-N 0.000 description 1
- CRCRRCXIZSGZQU-UHFFFAOYSA-N 4-[4-(2,2-diethoxyethylamino)cyclohexyl]benzonitrile Chemical compound C1CC(NCC(OCC)OCC)CCC1C1=CC=C(C#N)C=C1 CRCRRCXIZSGZQU-UHFFFAOYSA-N 0.000 description 1
- DPISOHZEVUAHGQ-UHFFFAOYSA-N 4-[4-(2,2-dimethoxyethylamino)piperidin-1-yl]benzonitrile Chemical compound C1CC(NCC(OC)OC)CCN1C1=CC=C(C#N)C=C1 DPISOHZEVUAHGQ-UHFFFAOYSA-N 0.000 description 1
- DJAPJQUQSMQYGD-UHFFFAOYSA-N 4-[4-(2-aminoethyl)phenyl]benzonitrile Chemical compound C1=CC(CCN)=CC=C1C1=CC=C(C#N)C=C1 DJAPJQUQSMQYGD-UHFFFAOYSA-N 0.000 description 1
- ALDBBWCRZLGCPV-UHFFFAOYSA-N 4-[4-(2-bromoethyl)phenyl]benzonitrile Chemical group C1=CC(CCBr)=CC=C1C1=CC=C(C#N)C=C1 ALDBBWCRZLGCPV-UHFFFAOYSA-N 0.000 description 1
- XJBGJHXRWZJPDQ-UHFFFAOYSA-N 4-[4-(2-iodoethyl)phenyl]benzonitrile Chemical group C1=CC(CCI)=CC=C1C1=CC=C(C#N)C=C1 XJBGJHXRWZJPDQ-UHFFFAOYSA-N 0.000 description 1
- OWOIVEHVNCNJCS-UHFFFAOYSA-N 4-[4-(3-but-3-enyl-2-oxoimidazolidin-1-yl)-3-methoxyphenyl]benzonitrile Chemical compound COC1=CC(C=2C=CC(=CC=2)C#N)=CC=C1N1CCN(CCC=C)C1=O OWOIVEHVNCNJCS-UHFFFAOYSA-N 0.000 description 1
- GWMJNHQHHWIZTN-UHFFFAOYSA-N 4-[4-[(3-aminopyridin-2-yl)amino]phenyl]benzonitrile Chemical compound NC1=CC=CN=C1NC1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 GWMJNHQHHWIZTN-UHFFFAOYSA-N 0.000 description 1
- FDUGOYTWYJZNNP-UHFFFAOYSA-N 4-amino-2-fluorobenzonitrile Chemical compound NC1=CC=C(C#N)C(F)=C1 FDUGOYTWYJZNNP-UHFFFAOYSA-N 0.000 description 1
- SCXGWOFGMVEUGW-UHFFFAOYSA-N 4-amino-3-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC=C1N SCXGWOFGMVEUGW-UHFFFAOYSA-N 0.000 description 1
- ANLHIGVSXJXNFK-UHFFFAOYSA-N 4-amino-3-methylbenzenecarbothioic s-acid Chemical compound CC1=CC(C(S)=O)=CC=C1N ANLHIGVSXJXNFK-UHFFFAOYSA-N 0.000 description 1
- OVIFRHQONCVUTG-UHFFFAOYSA-N 4-amino-3-methylsulfanylbenzonitrile Chemical compound CSC1=CC(C#N)=CC=C1N OVIFRHQONCVUTG-UHFFFAOYSA-N 0.000 description 1
- WXOHKMNWMKZMND-UHFFFAOYSA-N 4-aminohydrocinnamic acid Chemical compound NC1=CC=C(CCC(O)=O)C=C1 WXOHKMNWMKZMND-UHFFFAOYSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- HGXWRDPQFZKOLZ-UHFFFAOYSA-N 4-bromo-2-fluorobenzonitrile Chemical compound FC1=CC(Br)=CC=C1C#N HGXWRDPQFZKOLZ-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 1
- MCSCIFLXNFLCDV-UHFFFAOYSA-N 4-methyl-1,3-dihydroimidazol-2-one Chemical compound CC1=CNC(=O)N1 MCSCIFLXNFLCDV-UHFFFAOYSA-N 0.000 description 1
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 1
- XDVLKYYNHCMBFI-UHFFFAOYSA-N 5-(4-aminophenyl)pyrazine-2-carbonitrile Chemical compound C1=CC(N)=CC=C1C1=CN=C(C#N)C=N1 XDVLKYYNHCMBFI-UHFFFAOYSA-N 0.000 description 1
- CQHLRHRBKOJSSA-UHFFFAOYSA-N 5-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]pentanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCCCC(O)=O)CC1 CQHLRHRBKOJSSA-UHFFFAOYSA-N 0.000 description 1
- KFWDKWZCJARQRB-UHFFFAOYSA-N 5-[4-(2-oxoimidazolidin-1-yl)phenyl]pyrazine-2-carbonitrile Chemical compound O=C1NCCN1C1=CC=C(C=2N=CC(=NC=2)C#N)C=C1 KFWDKWZCJARQRB-UHFFFAOYSA-N 0.000 description 1
- DTAFCRSPMRHSDU-UHFFFAOYSA-N 5-[4-(3-but-3-enyl-2-oxoimidazolidin-1-yl)phenyl]pyrazine-2-carbonitrile Chemical compound O=C1N(CCC=C)CCN1C1=CC=C(C=2N=CC(=NC=2)C#N)C=C1 DTAFCRSPMRHSDU-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- WPANFENVQVBRNO-UHFFFAOYSA-N 6-(4-aminophenyl)pyridine-3-carbonitrile Chemical compound C1=CC(N)=CC=C1C1=CC=C(C#N)C=N1 WPANFENVQVBRNO-UHFFFAOYSA-N 0.000 description 1
- STJBLYUFAIMUAV-UHFFFAOYSA-N 6-[4-(3-but-3-enyl-2-oxoimidazolidin-1-yl)phenyl]pyridine-3-carbonitrile Chemical compound O=C1N(CCC=C)CCN1C1=CC=C(C=2N=CC(=CC=2)C#N)C=C1 STJBLYUFAIMUAV-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- GTZWUWAFJLYGAF-UHFFFAOYSA-N COC(=O)CCC1=CC=C(NC(CN(C(=O)OC)C2=CC=C(C=C2)C#N)=O)C=C1 Chemical compound COC(=O)CCC1=CC=C(NC(CN(C(=O)OC)C2=CC=C(C=C2)C#N)=O)C=C1 GTZWUWAFJLYGAF-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- IVHVNMLJNASKHW-UHFFFAOYSA-M Chlorphonium chloride Chemical compound [Cl-].CCCC[P+](CCCC)(CCCC)CC1=CC=C(Cl)C=C1Cl IVHVNMLJNASKHW-UHFFFAOYSA-M 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- BYCFJYNUBNQNIY-UHFFFAOYSA-N Ethyl 3-(carbamoylamino)propanoate Chemical compound CCOC(=O)CCNC(N)=O BYCFJYNUBNQNIY-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- LYAVXWPXKIFHBU-UHFFFAOYSA-N N-{2-[(1,2-diphenylhydrazinyl)carbonyl]-2-hydroxyhexanoyl}-6-aminohexanoic acid Chemical compound C=1C=CC=CC=1N(C(=O)C(O)(C(=O)NCCCCCC(O)=O)CCCC)NC1=CC=CC=C1 LYAVXWPXKIFHBU-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 229920004482 WACKER® Polymers 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L Zinc chloride Inorganic materials [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
- YSVZGWAJIHWNQK-UHFFFAOYSA-N [3-(hydroxymethyl)-2-bicyclo[2.2.1]heptanyl]methanol Chemical compound C1CC2C(CO)C(CO)C1C2 YSVZGWAJIHWNQK-UHFFFAOYSA-N 0.000 description 1
- YEXZUKRYNMDNGU-UHFFFAOYSA-N [4-(2,2,5,5-tetramethyl-1,2,5-azadisilolidin-1-yl)phenyl]boronic acid Chemical compound C[Si]1(C)CC[Si](C)(C)N1C1=CC=C(B(O)O)C=C1 YEXZUKRYNMDNGU-UHFFFAOYSA-N 0.000 description 1
- NQMZOECBUXWNSB-UHFFFAOYSA-N [Li]c1ccc(cc1)N1[Si](C)(C)CC[Si]1(C)C Chemical compound [Li]c1ccc(cc1)N1[Si](C)(C)CC[Si]1(C)C NQMZOECBUXWNSB-UHFFFAOYSA-N 0.000 description 1
- DKUGIOKVZNGEQP-UHFFFAOYSA-M [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(C(C1)=O)C1=CC=C(C=C1)CCC(=O)O)=O Chemical compound [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(C(C1)=O)C1=CC=C(C=C1)CCC(=O)O)=O DKUGIOKVZNGEQP-UHFFFAOYSA-M 0.000 description 1
- CQDDVEPOTHNNOR-UHFFFAOYSA-M [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(CC1)C1=CC=C(C=C1)C(C)(CC(=O)O)C)=O Chemical compound [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(CC1)C1=CC=C(C=C1)C(C)(CC(=O)O)C)=O CQDDVEPOTHNNOR-UHFFFAOYSA-M 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 229940022682 acetone Drugs 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- PRKQVKDSMLBJBJ-UHFFFAOYSA-N ammonium carbonate Chemical class N.N.OC(O)=O PRKQVKDSMLBJBJ-UHFFFAOYSA-N 0.000 description 1
- 235000011162 ammonium carbonates Nutrition 0.000 description 1
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
- WKLQKWGBOCGFOP-UHFFFAOYSA-N benzyl 4-[3-[4-(3-methoxy-3-oxopropyl)phenyl]-2-oxoimidazolidin-1-yl]piperidine-1-carboxylate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C2CCN(CC2)C(=O)OCC=2C=CC=CC=2)CC1 WKLQKWGBOCGFOP-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 150000004650 carbonic acid diesters Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-AHCXROLUSA-N copper-60 Chemical compound [60Cu] RYGMFSIKBFXOCR-AHCXROLUSA-N 0.000 description 1
- 125000004966 cyanoalkyl group Chemical group 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 238000005661 deetherification reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- VUJGDEMTTYDVTB-UHFFFAOYSA-N diazanium;ethanol;carbonate Chemical compound [NH4+].[NH4+].CCO.[O-]C([O-])=O VUJGDEMTTYDVTB-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- DLUPAMLGCGRBJH-UHFFFAOYSA-L dipotassium;4-(2-oxoimidazolidin-1-yl)benzonitrile;carbonate Chemical compound [K+].[K+].[O-]C([O-])=O.O=C1NCCN1C1=CC=C(C#N)C=C1 DLUPAMLGCGRBJH-UHFFFAOYSA-L 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- OEJPEZNOJWYLID-UHFFFAOYSA-N ethyl 3-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxo-1,3-diazinan-1-yl]propanoate;hydrochloride Chemical compound Cl.O=C1N(CCC(=O)OCC)CCCN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 OEJPEZNOJWYLID-UHFFFAOYSA-N 0.000 description 1
- LNBHZFGRBLJZGV-UHFFFAOYSA-N ethyl 3-[3-[4-(4-cyanophenyl)phenyl]-2,5-dioxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OCC)C(=O)CN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 LNBHZFGRBLJZGV-UHFFFAOYSA-N 0.000 description 1
- MSFHDFKZJKYULT-UHFFFAOYSA-N ethyl 3-[3-[4-(4-cyanophenyl)phenyl]-2-oxo-1,3-diazinan-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OCC)CCCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 MSFHDFKZJKYULT-UHFFFAOYSA-N 0.000 description 1
- ILRWAIZWWRJGFX-UHFFFAOYSA-N ethyl 3-[3-[4-(4-cyanophenyl)phenyl]-2-oxoimidazol-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OCC)C=CN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 ILRWAIZWWRJGFX-UHFFFAOYSA-N 0.000 description 1
- XFXJSWVVQRSHKS-UHFFFAOYSA-N ethyl 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazol-1-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OCC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)C=C1 XFXJSWVVQRSHKS-UHFFFAOYSA-N 0.000 description 1
- OYBZRHQDUHVUCN-UHFFFAOYSA-N ethyl 3-[4-[3-[4-[(e)-n'-ethoxycarbonylcarbamimidoyl]phenyl]-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(=N)NC(=O)OCC)C=C1 OYBZRHQDUHVUCN-UHFFFAOYSA-N 0.000 description 1
- YSVPXXXTKKDQOE-UHFFFAOYSA-N ethyl 3-[4-[3-[4-[(e)-n'-ethoxycarbonylcarbamimidoyl]phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=NC(=O)OCC)CC1 YSVPXXXTKKDQOE-UHFFFAOYSA-N 0.000 description 1
- FPUOVKLBAIDSHC-UHFFFAOYSA-N ethyl 3-[[[4-(4-cyanophenyl)phenyl]-(2,2-diethoxyethyl)carbamoyl]amino]propanoate Chemical compound C1=CC(N(C(=O)NCCC(=O)OCC)CC(OCC)OCC)=CC=C1C1=CC=C(C#N)C=C1 FPUOVKLBAIDSHC-UHFFFAOYSA-N 0.000 description 1
- RJCGNNHKSNIUAT-UHFFFAOYSA-N ethyl 3-aminopropanoate;hydron;chloride Chemical compound Cl.CCOC(=O)CCN RJCGNNHKSNIUAT-UHFFFAOYSA-N 0.000 description 1
- XBSGYVHOINMTIM-UHFFFAOYSA-N ethyl 3-isocyanatopropanoate Chemical compound CCOC(=O)CCN=C=O XBSGYVHOINMTIM-UHFFFAOYSA-N 0.000 description 1
- YWUJTEAZVCZLDJ-UHFFFAOYSA-N ethyl 4-(5-aminopyrimidin-2-yl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=NC=C(N)C=N1 YWUJTEAZVCZLDJ-UHFFFAOYSA-N 0.000 description 1
- SEBINEYTXBJXOB-UHFFFAOYSA-N ethyl 4-carbamimidoylbenzoate Chemical compound CCOC(=O)C1=CC=C(C(N)=N)C=C1 SEBINEYTXBJXOB-UHFFFAOYSA-N 0.000 description 1
- VTFIQSOCWRSCSD-UHFFFAOYSA-N ethyl 5-[3-(4-cyanophenyl)-2-oxoimidazo[4,5-b]pyridin-1-yl]pentanoate Chemical compound O=C1N(CCCCC(=O)OCC)C2=CC=CN=C2N1C1=CC=C(C#N)C=C1 VTFIQSOCWRSCSD-UHFFFAOYSA-N 0.000 description 1
- PWONBHVEUJZUDU-UHFFFAOYSA-N ethyl 5-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]pentanoate Chemical compound O=C1N(CCCCC(=O)OCC)CCN1C1=CC=C(C#N)C=C1 PWONBHVEUJZUDU-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 150000002542 isoureas Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- LSCWGGQDWOBFAA-UHFFFAOYSA-M lithium 2-amino-3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid hydroxide Chemical compound [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(CC1)C1=CC=C(C=C1)CC(C(=O)O)N)=O LSCWGGQDWOBFAA-UHFFFAOYSA-M 0.000 description 1
- MEIXYAYVAXYBRJ-UHFFFAOYSA-M lithium 3-[4-[3-(4-carbamimidoylphenyl)-2-oxo-1,3-diazinan-1-yl]phenyl]propanoic acid hydroxide Chemical compound [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(CCC1)C1=CC=C(C=C1)CCC(=O)O)=O MEIXYAYVAXYBRJ-UHFFFAOYSA-M 0.000 description 1
- FGNWHGWSCXRAEB-UHFFFAOYSA-M lithium 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazol-1-yl]phenyl]propanoic acid hydroxide Chemical compound [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(C=C1)C1=CC=C(C=C1)CCC(=O)O)=O FGNWHGWSCXRAEB-UHFFFAOYSA-M 0.000 description 1
- AKTXSBSEYHWOEG-UHFFFAOYSA-M lithium 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid hydroxide Chemical compound [OH-].[Li+].C(N)(=N)C1=CC=C(C=C1)N1C(N(CC1)C1=CC=C(C=C1)CCC(=O)O)=O AKTXSBSEYHWOEG-UHFFFAOYSA-M 0.000 description 1
- LRUOSPIQPYPLCZ-UHFFFAOYSA-M lithium;2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethylamino]acetic acid;hydroxide Chemical compound [Li+].[OH-].C1=CC(C(=N)N)=CC=C1N1C(=O)N(CCNCC(O)=O)CC1 LRUOSPIQPYPLCZ-UHFFFAOYSA-M 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- OGBVCSMMCMIDJM-UHFFFAOYSA-N methyl 2-(dibenzylamino)-3-[4-(2,2-diethoxyethylamino)phenyl]propanoate Chemical compound C1=CC(NCC(OCC)OCC)=CC=C1CC(C(=O)OC)N(CC=1C=CC=CC=1)CC1=CC=CC=C1 OGBVCSMMCMIDJM-UHFFFAOYSA-N 0.000 description 1
- AORLHMUVNQLMKC-UHFFFAOYSA-N methyl 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]ethylsulfinyl]acetate Chemical compound O=C1N(CCS(=O)CC(=O)OC)CCN1C1=CC=C(C(N)=N)C=C1 AORLHMUVNQLMKC-UHFFFAOYSA-N 0.000 description 1
- ZJRZSRXGGPBEKD-UHFFFAOYSA-N methyl 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]sulfanylacetate Chemical compound COC(=O)CSC1=CC=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 ZJRZSRXGGPBEKD-UHFFFAOYSA-N 0.000 description 1
- IGYPJYGCODLPEK-UHFFFAOYSA-N methyl 2-[2-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]sulfonylacetate Chemical compound COC(=O)CS(=O)(=O)C1=CC=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 IGYPJYGCODLPEK-UHFFFAOYSA-N 0.000 description 1
- SILVNIICDSIRAL-UHFFFAOYSA-N methyl 2-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxo-1,3-diazinan-1-yl]acetate;hydrochloride Chemical compound Cl.O=C1N(CC(=O)OC)CCCN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 SILVNIICDSIRAL-UHFFFAOYSA-N 0.000 description 1
- WOJHDGZEVLOXOU-UHFFFAOYSA-N methyl 2-[3-[4-(4-cyanophenyl)phenyl]-2-oxo-1,3-diazinan-1-yl]acetate Chemical compound O=C1N(CC(=O)OC)CCCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 WOJHDGZEVLOXOU-UHFFFAOYSA-N 0.000 description 1
- LFUFABDEUSVBOE-UHFFFAOYSA-N methyl 2-[3-[4-(4-cyanophenyl)phenyl]-2-oxoimidazolidin-1-yl]acetate Chemical compound O=C1N(CC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 LFUFABDEUSVBOE-UHFFFAOYSA-N 0.000 description 1
- IORMLTWSESAVAQ-UHFFFAOYSA-N methyl 2-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]sulfinylacetate Chemical compound C1=CC(S(=O)CC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 IORMLTWSESAVAQ-UHFFFAOYSA-N 0.000 description 1
- VNIYZHUJGFTWIR-UHFFFAOYSA-N methyl 2-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]phenyl]sulfonylacetate Chemical compound C1=CC(S(=O)(=O)CC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 VNIYZHUJGFTWIR-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- FOYOOILINPEMPI-UHFFFAOYSA-N methyl 3-(4-amino-3-methoxyphenyl)propanoate Chemical compound COC(=O)CCC1=CC=C(N)C(OC)=C1 FOYOOILINPEMPI-UHFFFAOYSA-N 0.000 description 1
- IKYPMSPVXJQZIK-UHFFFAOYSA-N methyl 3-(4-aminophenyl)-2-(dibenzylamino)propanoate Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)C(C(=O)OC)CC1=CC=C(N)C=C1 IKYPMSPVXJQZIK-UHFFFAOYSA-N 0.000 description 1
- LXHNQRGWWMORLQ-UHFFFAOYSA-N methyl 3-(4-aminophenyl)propanoate Chemical compound COC(=O)CCC1=CC=C(N)C=C1 LXHNQRGWWMORLQ-UHFFFAOYSA-N 0.000 description 1
- KPVLDQQTTZSIBX-UHFFFAOYSA-N methyl 3-[3-[1-(4-carbamimidoylphenyl)piperidin-4-yl]-2-oxoimidazolidin-1-yl]propanoate;hydrochloride Chemical compound Cl.O=C1N(CCC(=O)OC)CCN1C1CCN(C=2C=CC(=CC=2)C(N)=N)CC1 KPVLDQQTTZSIBX-UHFFFAOYSA-N 0.000 description 1
- ODIZNVSQTXWDMZ-UHFFFAOYSA-N methyl 3-[3-[2-acetamido-4-(4-cyanophenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1NC(C)=O ODIZNVSQTXWDMZ-UHFFFAOYSA-N 0.000 description 1
- OJZWTBYOJCSJDT-UHFFFAOYSA-N methyl 3-[3-[2-amino-4-(4-cyanophenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1N OJZWTBYOJCSJDT-UHFFFAOYSA-N 0.000 description 1
- RKKAOCYFVRXVEB-UHFFFAOYSA-N methyl 3-[3-[2-bromo-4-(4-cyanophenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1Br RKKAOCYFVRXVEB-UHFFFAOYSA-N 0.000 description 1
- DKSIRFRLKHFQQL-UHFFFAOYSA-N methyl 3-[3-[4-(3-chloro-4-cyanophenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=C(Cl)C(C#N)=CC=2)C=C1 DKSIRFRLKHFQQL-UHFFFAOYSA-N 0.000 description 1
- CIWRSFQLGTYIEZ-UHFFFAOYSA-N methyl 3-[3-[4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoate;hydrochloride Chemical compound Cl.O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 CIWRSFQLGTYIEZ-UHFFFAOYSA-N 0.000 description 1
- KWSBBYGBQXHGKQ-UHFFFAOYSA-N methyl 3-[3-[4-(4-cyanophenyl)-2,3-dimethylphenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C(C)=C1C KWSBBYGBQXHGKQ-UHFFFAOYSA-N 0.000 description 1
- CPHOQQRKCZOWGO-UHFFFAOYSA-N methyl 3-[3-[4-(4-cyanophenyl)-2-(methanesulfonamido)phenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1NS(C)(=O)=O CPHOQQRKCZOWGO-UHFFFAOYSA-N 0.000 description 1
- SLQAOKGPQDPOKB-UHFFFAOYSA-N methyl 3-[3-[4-(4-cyanophenyl)-2-methylsulfanylphenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)CCN1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1SC SLQAOKGPQDPOKB-UHFFFAOYSA-N 0.000 description 1
- AOUNDPIBKFRTQO-UHFFFAOYSA-N methyl 3-[3-[4-(4-cyanophenyl)phenyl]-2-oxoimidazo[4,5-b]pyridin-1-yl]propanoate Chemical compound O=C1N(CCC(=O)OC)C2=CC=CN=C2N1C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 AOUNDPIBKFRTQO-UHFFFAOYSA-N 0.000 description 1
- YZLDMJITCCTEGZ-UHFFFAOYSA-N methyl 3-[3-chloro-4-[(4-cyanophenyl)carbamoyl-(2-methylsulfonyloxyethyl)amino]phenyl]propanoate Chemical compound ClC1=CC(CCC(=O)OC)=CC=C1N(CCOS(C)(=O)=O)C(=O)NC1=CC=C(C#N)C=C1 YZLDMJITCCTEGZ-UHFFFAOYSA-N 0.000 description 1
- CESWCVWPOKHNQQ-UHFFFAOYSA-N methyl 3-[3-chloro-4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound ClC1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 CESWCVWPOKHNQQ-UHFFFAOYSA-N 0.000 description 1
- LEYAWRSDCAPGPS-UHFFFAOYSA-N methyl 3-[3-fluoro-4-(2-hydroxyethylamino)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(NCCO)C(F)=C1 LEYAWRSDCAPGPS-UHFFFAOYSA-N 0.000 description 1
- UTYIRLXEDQIXAK-UHFFFAOYSA-N methyl 3-[3-fluoro-4-[2-(oxan-2-yloxy)ethyl-(2,2,2-trifluoroacetyl)amino]phenyl]propanoate Chemical compound FC1=CC(CCC(=O)OC)=CC=C1N(C(=O)C(F)(F)F)CCOC1OCCCC1 UTYIRLXEDQIXAK-UHFFFAOYSA-N 0.000 description 1
- QRDKKQXALVYUBO-UHFFFAOYSA-N methyl 3-[3-methoxy-4-[2-(oxan-2-yloxy)ethyl-(2,2,2-trifluoroacetyl)amino]phenyl]propanoate Chemical compound COC1=CC(CCC(=O)OC)=CC=C1N(C(=O)C(F)(F)F)CCOC1OCCCC1 QRDKKQXALVYUBO-UHFFFAOYSA-N 0.000 description 1
- NLXKJQFJJVTJNL-UHFFFAOYSA-N methyl 3-[3-methyl-4-[2-(oxan-2-yloxy)ethyl-(2,2,2-trifluoroacetyl)amino]phenyl]propanoate Chemical compound CC1=CC(CCC(=O)OC)=CC=C1N(C(=O)C(F)(F)F)CCOC1OCCCC1 NLXKJQFJJVTJNL-UHFFFAOYSA-N 0.000 description 1
- DBMXKTPCPRTRJI-UHFFFAOYSA-N methyl 3-[3-methylsulfanyl-4-[2-(oxan-2-yloxy)ethyl-(2,2,2-trifluoroacetyl)amino]phenyl]propanoate Chemical compound CSC1=CC(CCC(=O)OC)=CC=C1N(C(=O)C(F)(F)F)CCOC1OCCCC1 DBMXKTPCPRTRJI-UHFFFAOYSA-N 0.000 description 1
- AEGLMARUWCTKOJ-UHFFFAOYSA-N methyl 3-[4-(2,2-diethoxyethylamino)phenyl]prop-2-enoate Chemical compound CCOC(OCC)CNC1=CC=C(C=CC(=O)OC)C=C1 AEGLMARUWCTKOJ-UHFFFAOYSA-N 0.000 description 1
- MFUGAFAMXDNYLY-UHFFFAOYSA-N methyl 3-[4-(2-hydroxypropylamino)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(NCC(C)O)C=C1 MFUGAFAMXDNYLY-UHFFFAOYSA-N 0.000 description 1
- GIKHGSCSUVHWEA-UHFFFAOYSA-N methyl 3-[4-(2-oxo-3-piperidin-4-ylimidazolidin-1-yl)phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C2CCNCC2)CC1 GIKHGSCSUVHWEA-UHFFFAOYSA-N 0.000 description 1
- HUCVJRUQZSNFRC-UHFFFAOYSA-N methyl 3-[4-(2-oxoimidazolidin-1-yl)phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)NCC1 HUCVJRUQZSNFRC-UHFFFAOYSA-N 0.000 description 1
- YREHCFVQZXCQPU-UHFFFAOYSA-N methyl 3-[4-(3-hydroxypropylamino)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(NCCCO)C=C1 YREHCFVQZXCQPU-UHFFFAOYSA-N 0.000 description 1
- FFEQWVCAQZJOIJ-UHFFFAOYSA-N methyl 3-[4-[(3-chloro-4-cyanophenyl)carbamoyl-(2-hydroxyethyl)amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N(CCO)C(=O)NC1=CC=C(C#N)C(Cl)=C1 FFEQWVCAQZJOIJ-UHFFFAOYSA-N 0.000 description 1
- XLPFDUVPPKGGAV-UHFFFAOYSA-N methyl 3-[4-[(4-cyano-2-methylphenyl)carbamoyl-(2-hydroxyethyl)amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N(CCO)C(=O)NC1=CC=C(C#N)C=C1C XLPFDUVPPKGGAV-UHFFFAOYSA-N 0.000 description 1
- OPRZDLWVHSXNEY-UHFFFAOYSA-N methyl 3-[4-[(4-cyano-3-fluorophenyl)carbamoyl-(2-hydroxyethyl)amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N(CCO)C(=O)NC1=CC=C(C#N)C(F)=C1 OPRZDLWVHSXNEY-UHFFFAOYSA-N 0.000 description 1
- FUMVZFVBVSECEB-UHFFFAOYSA-N methyl 3-[4-[(4-cyanophenyl)carbamoyl-(2-methylsulfonyloxyethyl)amino]phenyl]-3-methylbutanoate Chemical compound C1=CC(C(C)(C)CC(=O)OC)=CC=C1N(CCOS(C)(=O)=O)C(=O)NC1=CC=C(C#N)C=C1 FUMVZFVBVSECEB-UHFFFAOYSA-N 0.000 description 1
- XKSOSODXYRKBFK-UHFFFAOYSA-N methyl 3-[4-[1-(4-carbamimidoylphenyl)-2-oxoimidazolidin-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1NC(=O)N(C=2C=CC(=CC=2)C(N)=N)C1 XKSOSODXYRKBFK-UHFFFAOYSA-N 0.000 description 1
- ZZFWUEICLGPEIY-UHFFFAOYSA-N methyl 3-[4-[1-(4-carbamimidoylphenyl)-3-methyl-2-oxoimidazolidin-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1N(C)C(=O)N(C=2C=CC(=CC=2)C(N)=N)C1 ZZFWUEICLGPEIY-UHFFFAOYSA-N 0.000 description 1
- BBHBJDHRIAGIEF-UHFFFAOYSA-N methyl 3-[4-[1-(4-cyanophenyl)-2-oxo-3-phenylimidazol-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(N(C1=O)C=2C=CC=CC=2)=CN1C1=CC=C(C#N)C=C1 BBHBJDHRIAGIEF-UHFFFAOYSA-N 0.000 description 1
- VXDMMIVCZBVZJW-UHFFFAOYSA-N methyl 3-[4-[2-(oxan-2-yloxy)ethyl-(2,2,2-trifluoroacetyl)amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N(C(=O)C(F)(F)F)CCOC1OCCCC1 VXDMMIVCZBVZJW-UHFFFAOYSA-N 0.000 description 1
- KLEMIKQDALEKIE-UHFFFAOYSA-N methyl 3-[4-[2-chloroethyl(sulfamoyl)amino]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(N(CCCl)S(N)(=O)=O)C=C1 KLEMIKQDALEKIE-UHFFFAOYSA-N 0.000 description 1
- DVHVAWIAFQIHHT-UHFFFAOYSA-N methyl 3-[4-[2-oxo-3-[4-(propylaminomethyl)phenyl]imidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CNCCC)=CC=C1N1C(=O)N(C=2C=CC(CCC(=O)OC)=CC=2)CC1 DVHVAWIAFQIHHT-UHFFFAOYSA-N 0.000 description 1
- MURBZYAPDVDFSX-UHFFFAOYSA-N methyl 3-[4-[2-oxo-3-[4-[(e)-n'-phenylmethoxycarbonylcarbamimidoyl]phenyl]imidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(=N)NC(=O)OCC=2C=CC=CC=2)CC1 MURBZYAPDVDFSX-UHFFFAOYSA-N 0.000 description 1
- OXOMNJGOACAAAW-UHFFFAOYSA-N methyl 3-[4-[3-(1-amino-2,3-dihydro-1h-inden-5-yl)-2-oxoimidazolidin-1-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=C3CCC(N)C3=CC=2)CC1 OXOMNJGOACAAAW-UHFFFAOYSA-N 0.000 description 1
- CNVQAJHCECCBPN-UHFFFAOYSA-N methyl 3-[4-[3-(3-aminophenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=C(N)C=CC=2)CC1 CNVQAJHCECCBPN-UHFFFAOYSA-N 0.000 description 1
- AAOVVPMYTXOIPF-UHFFFAOYSA-N methyl 3-[4-[3-(4-bromo-2-methylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C(=CC(Br)=CC=2)C)CC1 AAOVVPMYTXOIPF-UHFFFAOYSA-N 0.000 description 1
- MZKLYLQLIUVKSK-UHFFFAOYSA-N methyl 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1 MZKLYLQLIUVKSK-UHFFFAOYSA-N 0.000 description 1
- RJINQLOGVGVAFR-UHFFFAOYSA-N methyl 3-[4-[3-(4-carbamimidoylphenyl)-4-methyl-2-oxoimidazol-1-yl]phenyl]propanoate;hydrate;hydrochloride Chemical compound O.Cl.C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)C(C)=C1 RJINQLOGVGVAFR-UHFFFAOYSA-N 0.000 description 1
- BHSDEWKYRGQANZ-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyano-2-methylsulfanylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C(=CC(=CC=2)C#N)SC)CC1 BHSDEWKYRGQANZ-UHFFFAOYSA-N 0.000 description 1
- RIIWTMLZIUXXFW-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyano-2-methylsulfonylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)CC1 RIIWTMLZIUXXFW-UHFFFAOYSA-N 0.000 description 1
- BSNCVHWXOWVFIH-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyano-3-fluorophenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=C(F)C(C#N)=CC=2)CC1 BSNCVHWXOWVFIH-UHFFFAOYSA-N 0.000 description 1
- FHVANAKELHDARM-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2,5-dioxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1=O FHVANAKELHDARM-UHFFFAOYSA-N 0.000 description 1
- JMBKDBOJXOIYAQ-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-oxo-1,3-diazinan-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CCC1 JMBKDBOJXOIYAQ-UHFFFAOYSA-N 0.000 description 1
- YLDNSWRQSGSSCR-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-oxo-1h-imidazol-5-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(NC1=O)=CN1C1=CC=C(C#N)C=C1 YLDNSWRQSGSSCR-UHFFFAOYSA-N 0.000 description 1
- ZRCURHOYKZUOOC-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]-3-methylsulfonylphenyl]propanoate Chemical compound CS(=O)(=O)C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 ZRCURHOYKZUOOC-UHFFFAOYSA-N 0.000 description 1
- CIPWKSWMERFSPJ-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]cyclohexyl]propanoate Chemical compound C1CC(CCC(=O)OC)CCC1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 CIPWKSWMERFSPJ-UHFFFAOYSA-N 0.000 description 1
- ZJWZAHYOPACNEM-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)CC1 ZJWZAHYOPACNEM-UHFFFAOYSA-N 0.000 description 1
- QVWNXBDTWFXZGS-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-sulfanylidene-1h-imidazol-5-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(NC1=S)=CN1C1=CC=C(C#N)C=C1 QVWNXBDTWFXZGS-UHFFFAOYSA-N 0.000 description 1
- JESIWTBEAMFGEY-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-2-sulfanylideneimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=S)N(C=2C=CC(=CC=2)C#N)CC1 JESIWTBEAMFGEY-UHFFFAOYSA-N 0.000 description 1
- VMRPXWFNMVZXHC-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-4-methyl-2-oxo-1h-imidazol-5-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=C(C)N(C=2C=CC(=CC=2)C#N)C(=O)N1 VMRPXWFNMVZXHC-UHFFFAOYSA-N 0.000 description 1
- WPKGHCCZDRNTAR-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-4-methyl-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)C(C)=C1 WPKGHCCZDRNTAR-UHFFFAOYSA-N 0.000 description 1
- FQAKQDNARXFOAO-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-5-methyl-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)C=C1C FQAKQDNARXFOAO-UHFFFAOYSA-N 0.000 description 1
- OLOREBVVCPCAQQ-UHFFFAOYSA-N methyl 3-[4-[3-[3-(cyanomethyl)phenyl]-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=C(CC#N)C=CC=2)C=C1 OLOREBVVCPCAQQ-UHFFFAOYSA-N 0.000 description 1
- MQTSMTBTLRQOCO-UHFFFAOYSA-N methyl 3-[4-[3-[3-(diaminomethylideneamino)phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=C(NC(N)=N)C=CC=2)CC1 MQTSMTBTLRQOCO-UHFFFAOYSA-N 0.000 description 1
- VHXAFFGEUCEZDV-UHFFFAOYSA-N methyl 3-[4-[3-[4-(1-aminocyclopropyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C2(N)CC2)CC1 VHXAFFGEUCEZDV-UHFFFAOYSA-N 0.000 description 1
- XHODGKJEQDKZQV-UHFFFAOYSA-N methyl 3-[4-[3-[4-(1-aminoethyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(C)N)CC1 XHODGKJEQDKZQV-UHFFFAOYSA-N 0.000 description 1
- PBNZLNIACLPITF-UHFFFAOYSA-N methyl 3-[4-[3-[4-(aminomethyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(CN)=CC=2)CC1 PBNZLNIACLPITF-UHFFFAOYSA-N 0.000 description 1
- HJVAAHRGIXTWTK-UHFFFAOYSA-N methyl 3-[4-[3-[4-[(e)-n'-ethoxycarbonylcarbamimidoyl]phenyl]-5-methyl-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(C(=N)NC(=O)OCC)=CC=C1N1C(=O)N(C=2C=CC(CCC(=O)OC)=CC=2)C(C)=C1 HJVAAHRGIXTWTK-UHFFFAOYSA-N 0.000 description 1
- ZWOFCQDWOYMAFH-UHFFFAOYSA-N methyl 3-[4-[3-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]-2-oxoimidazolidin-1-yl]cyclohexyl]propanoate Chemical compound C1CC(CCC(=O)OC)CCC1N1C(=O)N(C=2C=CC(=CC=2)C(N)=NC(=O)OC)CC1 ZWOFCQDWOYMAFH-UHFFFAOYSA-N 0.000 description 1
- OCWBXGSPERBASN-UHFFFAOYSA-N methyl 3-[4-[4-(4-carbamimidoylphenyl)-2-oxo-3-phenylimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC=CC=2)C(C=2C=CC(=CC=2)C(N)=N)C1 OCWBXGSPERBASN-UHFFFAOYSA-N 0.000 description 1
- HONVZXGJXWAFTK-UHFFFAOYSA-N methyl 3-[4-[4-(4-carbamimidoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)NC(C=2C=CC(=CC=2)C(N)=N)C1 HONVZXGJXWAFTK-UHFFFAOYSA-N 0.000 description 1
- DVHJTUASDFOWQW-UHFFFAOYSA-N methyl 3-[4-[4-(4-carbamimidoylphenyl)-3-methyl-2-oxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C)C(C=2C=CC(=CC=2)C(N)=N)C1 DVHJTUASDFOWQW-UHFFFAOYSA-N 0.000 description 1
- ZFMVPWDBLKNBSQ-UHFFFAOYSA-N methyl 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-2-oxoimidazolidin-1-yl]propanoate Chemical compound N1C(=O)N(CCC(=O)OC)CC1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 ZFMVPWDBLKNBSQ-UHFFFAOYSA-N 0.000 description 1
- GKVKJMYDMUJEFO-UHFFFAOYSA-N methyl 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-3-methyl-2-oxoimidazolidin-1-yl]propanoate Chemical compound CN1C(=O)N(CCC(=O)OC)CC1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 GKVKJMYDMUJEFO-UHFFFAOYSA-N 0.000 description 1
- QMYFHCHEYWLBKP-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)-2-oxo-3-phenylimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC=CC=2)C(C=2C=CC(=CC=2)C#N)=C1 QMYFHCHEYWLBKP-UHFFFAOYSA-N 0.000 description 1
- VPARDLQVOZBBQZ-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)-3,5-dimethyl-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C)C(C=2C=CC(=CC=2)C#N)=C1C VPARDLQVOZBBQZ-UHFFFAOYSA-N 0.000 description 1
- UKJDANFIEYZQQN-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)-5-oxo-1,2,4-triazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C#N)C=N1 UKJDANFIEYZQQN-UHFFFAOYSA-N 0.000 description 1
- YKRSADAOSBQTFX-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)phenyl]-2-oxo-3-phenylimidazol-1-yl]propanoate Chemical compound C=1C=CC=CC=1N1C(=O)N(CCC(=O)OC)C=C1C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 YKRSADAOSBQTFX-UHFFFAOYSA-N 0.000 description 1
- JJZNNEFXNHNOOV-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)phenyl]-3,5-dimethyl-2-oxoimidazol-1-yl]propanoate Chemical compound CN1C(=O)N(CCC(=O)OC)C(C)=C1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 JJZNNEFXNHNOOV-UHFFFAOYSA-N 0.000 description 1
- QCHYEBNWSAAREK-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)phenyl]-3-phenyl-2-sulfanylideneimidazol-1-yl]propanoate Chemical compound C=1C=CC=CC=1N1C(=S)N(CCC(=O)OC)C=C1C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 QCHYEBNWSAAREK-UHFFFAOYSA-N 0.000 description 1
- WEDZLTNZRPDZKA-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)phenyl]-5-methyl-2-oxo-3-phenylimidazol-1-yl]propanoate Chemical compound C=1C=CC=CC=1N1C(=O)N(CCC(=O)OC)C(C)=C1C(C=C1)=CC=C1C1=CC=C(C#N)C=C1 WEDZLTNZRPDZKA-UHFFFAOYSA-N 0.000 description 1
- RYEIISYQAINVJW-UHFFFAOYSA-N methyl 3-[4-[4-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]-5-oxo-1,2,4-triazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(=N)NC(=O)OC)C=N1 RYEIISYQAINVJW-UHFFFAOYSA-N 0.000 description 1
- OHEIJWDPRISTCW-UHFFFAOYSA-N methyl 3-[4-[5-(4-cyanophenyl)-2-sulfanylidene-1h-imidazol-3-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=S)NC(C=2C=CC(=CC=2)C#N)=C1 OHEIJWDPRISTCW-UHFFFAOYSA-N 0.000 description 1
- VASILVDUWDWMBL-UHFFFAOYSA-N methyl 3-[4-[5-(4-cyanophenyl)-4-methyl-2-oxo-1h-imidazol-3-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1C(=O)NC(C=2C=CC(=CC=2)C#N)=C1C VASILVDUWDWMBL-UHFFFAOYSA-N 0.000 description 1
- WQXMROZTCVMXHJ-UHFFFAOYSA-N methyl 3-[4-[5-[4-[(e)-n'-ethoxycarbonylcarbamimidoyl]phenyl]-1,1-dioxo-1,2,5-thiadiazolidin-2-yl]phenyl]propanoate Chemical compound C1=CC(C(=N)NC(=O)OCC)=CC=C1N1S(=O)(=O)N(C=2C=CC(CCC(=O)OC)=CC=2)CC1 WQXMROZTCVMXHJ-UHFFFAOYSA-N 0.000 description 1
- KJUMFTGPSDIJNU-UHFFFAOYSA-N methyl 3-[4-[[(4-cyanophenyl)-formamidocarbamoyl]amino]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1NC(=O)N(NC=O)C1=CC=C(C#N)C=C1 KJUMFTGPSDIJNU-UHFFFAOYSA-N 0.000 description 1
- QLQQNCXSHOKPKN-UHFFFAOYSA-N methyl 3-[4-[[2-(4-cyanophenyl)-2-oxoethyl]amino]phenyl]prop-2-enoate Chemical compound C1=CC(C=CC(=O)OC)=CC=C1NCC(=O)C1=CC=C(C#N)C=C1 QLQQNCXSHOKPKN-UHFFFAOYSA-N 0.000 description 1
- QOKKGVKZSDXSBL-UHFFFAOYSA-N methyl 3-[5-[4-(4-cyanophenyl)phenyl]-2-sulfanylidene-1h-imidazol-3-yl]propanoate Chemical compound N1C(=S)N(CCC(=O)OC)C=C1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 QOKKGVKZSDXSBL-UHFFFAOYSA-N 0.000 description 1
- KOLIWBZDVYITNS-UHFFFAOYSA-N methyl 4-(2-chloroethyl)benzoate Chemical compound COC(=O)C1=CC=C(CCCl)C=C1 KOLIWBZDVYITNS-UHFFFAOYSA-N 0.000 description 1
- FCAAMTWLXPCNIV-UHFFFAOYSA-N methyl 4-[2-[3-(4-cyanophenyl)-2-oxoimidazol-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)N(C=2C=CC(=CC=2)C#N)C=C1 FCAAMTWLXPCNIV-UHFFFAOYSA-N 0.000 description 1
- PWGQCXXISMCRCA-UHFFFAOYSA-N methyl 4-[3-[2-(4-carbamimidoylphenyl)-2-hydroxyethyl]-2-oxoimidazolidin-1-yl]butanoate Chemical compound O=C1N(CCCC(=O)OC)CCN1CC(O)C1=CC=C(C(N)=N)C=C1 PWGQCXXISMCRCA-UHFFFAOYSA-N 0.000 description 1
- HOGNLOLTADBVKW-UHFFFAOYSA-N methyl 4-[3-[2-(4-carbamimidoylphenyl)-2-oxoethyl]-2-oxoimidazolidin-1-yl]butanoate;hydrochloride Chemical compound Cl.O=C1N(CCCC(=O)OC)CCN1CC(=O)C1=CC=C(C(N)=N)C=C1 HOGNLOLTADBVKW-UHFFFAOYSA-N 0.000 description 1
- GSKSWZSXFKBKIY-UHFFFAOYSA-N methyl 4-amino-5-[4-(4-cyanophenyl)phenyl]-5-oxopentanoate;hydrochloride Chemical compound Cl.C1=CC(C(=O)C(N)CCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 GSKSWZSXFKBKIY-UHFFFAOYSA-N 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 229940073584 methylene chloride Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- YKEZOKIPIIBNDN-UHFFFAOYSA-N n-(2-chloroethyl)sulfamoyl chloride Chemical compound ClCCNS(Cl)(=O)=O YKEZOKIPIIBNDN-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- XXYOYPMUIMJSRC-UHFFFAOYSA-N propan-2-yl 3-[4-[3-(4-carbamimidoylphenyl)-2,5-dioxoimidazolidin-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC(C)C)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)CC1=O XXYOYPMUIMJSRC-UHFFFAOYSA-N 0.000 description 1
- QETSJDXFTIVELG-UHFFFAOYSA-N propan-2-yl 3-[4-[3-(4-carbamimidoylphenyl)-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC(C)C)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)C=C1 QETSJDXFTIVELG-UHFFFAOYSA-N 0.000 description 1
- LPFXHRXAASUGID-UHFFFAOYSA-N propan-2-yl 3-[4-[3-(4-carbamimidoylphenyl)-5-methyl-2-oxoimidazol-1-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC(C)C)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(N)=N)C=C1C LPFXHRXAASUGID-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003303 ruthenium Chemical class 0.000 description 1
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-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
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003564 thiocarbonyl compounds Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- ZTWIEIFKPFJRLV-UHFFFAOYSA-K trichlororuthenium;trihydrate Chemical compound O.O.O.Cl[Ru](Cl)Cl ZTWIEIFKPFJRLV-UHFFFAOYSA-K 0.000 description 1
- 238000005583 trifluoroacetylation reaction Methods 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-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
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/30—Oxygen or sulfur atoms
- C07D233/32—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/70—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/10—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings 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
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Silicon Polymers (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4107857A DE4107857A1 (de) | 1991-03-12 | 1991-03-12 | Cyclische harnstoffderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
Publications (2)
Publication Number | Publication Date |
---|---|
IL101203A0 IL101203A0 (en) | 1992-11-15 |
IL101203A true IL101203A (en) | 1995-12-31 |
Family
ID=6427033
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL10120392A IL101203A (en) | 1991-03-12 | 1992-03-11 | History of cyclic urea, their preparation and pharmaceutical preparations containing them |
Country Status (23)
Country | Link |
---|---|
US (3) | US5276049A (fr) |
EP (1) | EP0503548B1 (fr) |
JP (1) | JPH04368372A (fr) |
KR (1) | KR920018031A (fr) |
AT (1) | ATE154013T1 (fr) |
AU (1) | AU654340B2 (fr) |
CA (1) | CA2062655A1 (fr) |
CZ (1) | CZ74592A3 (fr) |
DE (2) | DE4107857A1 (fr) |
DK (1) | DK0503548T3 (fr) |
ES (1) | ES2104754T3 (fr) |
FI (1) | FI921030A (fr) |
GR (1) | GR3024504T3 (fr) |
HU (1) | HUT60722A (fr) |
IE (1) | IE920781A1 (fr) |
IL (1) | IL101203A (fr) |
MX (1) | MX9201068A (fr) |
NO (1) | NO920957L (fr) |
NZ (1) | NZ241928A (fr) |
PL (1) | PL293795A1 (fr) |
SK (1) | SK74592A3 (fr) |
TW (1) | TW221811B (fr) |
ZA (1) | ZA921804B (fr) |
Families Citing this family (65)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
USRE37781E1 (en) | 1991-10-11 | 2002-07-02 | Dupont Pharmaceuticals Company | Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors |
WO1993018058A1 (fr) * | 1992-03-06 | 1993-09-16 | G.D. Searle & Co. | Imitateurs peptidiques utiles comme inhibiteurs de l'agregation plaquettaire |
ES2092170T3 (es) * | 1992-04-28 | 1996-11-16 | Thomae Gmbh Dr K | Antagonistas de receptores de fibrinogeno marcados con tritio, su utilizacion y procedimiento para su preparacion. |
DE4213931A1 (de) * | 1992-04-28 | 1993-11-04 | Thomae Gmbh Dr K | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
DE4213919A1 (de) * | 1992-04-28 | 1993-11-04 | Thomae Gmbh Dr K | Cyclische iminoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
SK94393A3 (en) * | 1992-09-11 | 1994-08-10 | Thomae Gmbh Dr K | Cyclic derivatives of urea, process for their production and their pharmaceutical agents with the content of those |
FR2700337B1 (fr) * | 1993-01-11 | 1995-04-14 | Lafon Labor | Dérivés d'imidazopyridine-2-one, leur procédé de préparation et leur utilisation en thérapeutique. |
DE4332168A1 (de) * | 1993-02-22 | 1995-03-23 | Thomae Gmbh Dr K | Cyclische Derivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
WO1994022834A1 (fr) * | 1993-03-29 | 1994-10-13 | Zeneca Limited | Derives heterocycliques utilises comme inhibiteurs d'agregation plaquettaire |
US5652242A (en) * | 1993-03-29 | 1997-07-29 | Zeneca Limited | Heterocyclic derivatives |
WO1994022835A2 (fr) * | 1993-03-29 | 1994-10-13 | Zeneca Limited | Composes heterocycliques en tant qu'inhibiteurs de l'agregation plaquettaire |
US5750754A (en) * | 1993-03-29 | 1998-05-12 | Zeneca Limited | Heterocyclic compounds |
US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
US5463011A (en) * | 1993-06-28 | 1995-10-31 | Zeneca Limited | Acid derivatives |
GB9313268D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Chemical compounds |
GB9313285D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Acid derivatives |
US5430043A (en) * | 1993-08-24 | 1995-07-04 | G. D. Searle & Co. | Platelet aggregation inhibitors |
US5849736A (en) * | 1993-11-24 | 1998-12-15 | The Dupont Merck Pharmaceutical Company | Isoxazoline and isoxazole fibrinogen receptor antagonists |
US5563158A (en) * | 1993-12-28 | 1996-10-08 | The Dupont Merck Pharmaceutical Company | Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists |
DE4407961A1 (de) * | 1994-03-10 | 1995-09-14 | Thomae Gmbh Dr K | Imidazolidin-2-one, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
DE4424974A1 (de) * | 1994-07-15 | 1996-01-18 | Thomae Gmbh Dr K | Harnstoff- und Carbaminsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
US5814636A (en) * | 1994-07-15 | 1998-09-29 | Meiji Seika Kabushiki Kaisha | Compounds with platelet aggregation inhibitor activity |
DE4427838A1 (de) * | 1994-08-05 | 1996-02-08 | Thomae Gmbh Dr K | Kondensierte Azepinderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
DE4429079A1 (de) * | 1994-08-17 | 1996-02-22 | Thomae Gmbh Dr K | Cyclische Harnstoffderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
ZA963391B (en) * | 1995-05-24 | 1997-10-29 | Du Pont Merck Pharma | Isoxazoline fibrinogen receptor antagonists. |
US5612363A (en) * | 1995-06-02 | 1997-03-18 | Berlex Laboratories, Inc. | N,N-di(aryl) cyclic urea derivatives as anti-coagulants |
WO1997002245A1 (fr) * | 1995-07-06 | 1997-01-23 | Japan Tobacco Inc. | Derives de benzamidoxime et leur utilisation a des fins medicinales |
ZA966885B (en) * | 1995-08-22 | 1998-02-16 | Du Pont Merck Pharma | Substituted cyclic ureas and derivatives thereof useful as retroviral protease inhibitors. |
US5925635A (en) * | 1996-04-17 | 1999-07-20 | Dupont Pharmaceuticals Company | N-(amidinophenyl) cyclourea analogs as factor XA inhibitors |
ATE269312T1 (de) * | 1996-04-17 | 2004-07-15 | Bristol Myers Squibb Pharma Co | N-(amidinophenyl)-n'-(subst.)-3h-2,4- benzodiazepin-3-on derivative als faktor xa inhibitoren |
WO1997048444A1 (fr) * | 1996-06-19 | 1997-12-24 | Becton Dickinson And Company | Administration iontophoretique d'inhibiteurs de l'adhesion cellulaire |
WO1999011630A1 (fr) * | 1997-09-03 | 1999-03-11 | American Home Products Corporation | Tetrahydro-pyrimidine-2(1h)-thione substitues elevateurs du hdl-c s'averant utiles comme agents antiatherosclereux |
US6340687B1 (en) | 1997-09-03 | 2002-01-22 | American Home Products Corporation | Substituted tetrahydro-pyrimidine-2(1H)-thione HDL-C elevators useful as antiatherosclerotic agents |
TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
US6313110B1 (en) | 1999-06-02 | 2001-11-06 | Dupont Pharmaceuticals Company | Substituted 2H-1,3-diazapin-2-one useful as an HIV protease inhibitor |
CA2413087C (fr) * | 2001-04-16 | 2008-03-11 | Taiho Pharmaceutical Co., Ltd. | Cristaux de tosilate de suplatast |
WO2003045918A1 (fr) | 2001-11-26 | 2003-06-05 | Schering Corporation | Antagonistes de la mch à base de pipéridine pour le traitement de l'obésité et des troubles liés au système nerveux central (cns) |
US7141561B2 (en) | 2002-07-25 | 2006-11-28 | Sanofi-Aventis Deutschland Gmbh | Substituted diaryl heterocycles, process for their preparation and their use as medicaments |
DE10233817A1 (de) * | 2002-07-25 | 2004-02-12 | Aventis Pharma Deutschland Gmbh | Substituierte Diarylheterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
JP2005538101A (ja) * | 2002-07-31 | 2005-12-15 | ユーロ−セルティーク エス.エイ. | アリール置換ヒダントイン化合物及びナトリウムチャネルブロッカーとしてのその使用 |
US7354933B2 (en) | 2003-01-31 | 2008-04-08 | Aventis Pharma Sa | Cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors |
US7141596B2 (en) * | 2003-10-08 | 2006-11-28 | Incyte Corporation | Inhibitors of proteins that bind phosphorylated molecules |
US7241787B2 (en) * | 2004-01-25 | 2007-07-10 | Sanofi-Aventis Deutschland Gmbh | Substituted N-cycloexylimidazolinones, process for their preparation and their use as medicaments |
US7794700B2 (en) | 2004-07-08 | 2010-09-14 | Elan Pharmaceuticals Inc. | Multimeric VLA-4 antagonists comprising polymer moieties |
BRPI0611285A2 (pt) * | 2005-05-20 | 2010-08-31 | Elan Pharm Inc | derivados de imidazolona fenilalanina |
JP5250967B2 (ja) * | 2005-11-30 | 2013-07-31 | 三菱化学株式会社 | 有機化合物、電荷輸送材料、電荷輸送材料用組成物および有機電界発光素子 |
KR101395615B1 (ko) * | 2005-11-30 | 2014-05-16 | 미쓰비시 가가꾸 가부시키가이샤 | 유기 화합물, 전하 수송 재료, 전하 수송 재료용 조성물 및유기 전계 발광 소자 |
KR101423898B1 (ko) * | 2005-12-14 | 2014-07-28 | 암브룩스, 인코포레이티드 | 비-천연 아미노산 및 폴리펩티드를 함유하는 조성물, 비-천연 아미노산 및 폴리펩티드를 포함하는 방법, 및 비-천연 아미노산 및 폴리펩티드의 용도 |
DE102006024024A1 (de) * | 2006-05-23 | 2007-11-29 | Bayer Healthcare Aktiengesellschaft | Substituierte Arylimidazolone und -triazolone sowie ihre Verwendung |
TW200831080A (en) * | 2006-12-15 | 2008-08-01 | Irm Llc | Compounds and compositions as inhibitors of cannabinoid receptor 1 activity |
DE102008060967A1 (de) | 2008-12-06 | 2010-06-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylsulfonyltriazolone und ihre Verwendung |
DE102010001064A1 (de) | 2009-03-18 | 2010-09-23 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung |
DE102009013642A1 (de) | 2009-03-18 | 2010-09-23 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylalaninderivate und deren Verwendung |
DE102009028929A1 (de) | 2009-08-27 | 2011-07-07 | Bayer Schering Pharma Aktiengesellschaft, 13353 | Heterocyclisch-substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung |
US9187466B2 (en) | 2010-02-27 | 2015-11-17 | Bayer Intellectual Property Gmbh | Bisaryl-bonded aryltriazolones and use thereof |
DE102010040187A1 (de) | 2010-09-02 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Substituierte N-Phenethyl-triazolonacetamide und ihre Verwendung |
DE102010040924A1 (de) | 2010-09-16 | 2012-03-22 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylacet- und Phenylpropanamide und ihre Verwendung |
SG11201608710TA (en) * | 2014-04-28 | 2016-11-29 | Jiangsu Kanion Parmaceutical Co Ltd | Anti-enterovirus 71 thiadiazolidine derivative |
EA032137B1 (ru) | 2014-11-03 | 2019-04-30 | Байер Фарма Акциенгезельшафт | Производные гидроксиалкил-замещенного фенилтриазола и их применение |
KR102486298B1 (ko) * | 2016-02-09 | 2023-01-06 | 인벤티스바이오 엘엘씨 | 인돌아민-2,3-디옥시게나아제(ido)의 억제제 |
US9988367B2 (en) | 2016-05-03 | 2018-06-05 | Bayer Pharma Aktiengesellschaft | Amide-substituted pyridinyltriazole derivatives and uses thereof |
AU2019387367A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Diarylhydantoin compounds and methods of use thereof |
WO2020113094A1 (fr) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Composés pyrrole et pyrazole et leurs procédés d'utilisation |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA697572A (en) * | 1964-11-10 | W. Luckenbaugh Raymond | Substituted imidazolinones | |
LU35567A1 (fr) * | 1956-11-21 | |||
US3989707A (en) * | 1974-06-21 | 1976-11-02 | Janssen Pharmaceutica N.V. | Benzimidazolinone derivatives |
US4055410A (en) * | 1976-03-15 | 1977-10-25 | E. I. Du Pont De Nemours And Company | Substituted bromo- or chloroacetamide herbicides |
DE2724819A1 (de) * | 1977-06-02 | 1978-12-07 | Hoechst Ag | Bis-phenyl-triazolone und verfahren zu ihrer herstellung |
US4677131A (en) * | 1985-11-01 | 1987-06-30 | Merck & Co., Inc. | Cyclic ureas as dermal penetration enhancers |
DE3604040A1 (de) * | 1986-02-08 | 1987-08-13 | Hoechst Ag | 1-aryl-imidazolin-2-thione, verfahren zu ihrer herstellung sowie ihre verwendung im pflanzenschutz |
US4724261A (en) * | 1986-11-24 | 1988-02-09 | Stauffer Chemical Company | Cyclic ureas |
FR2618779B1 (fr) * | 1987-07-31 | 1991-01-04 | Poudres & Explosifs Ste Nale | Nouveau procede de preparation des 1,2,4-triazol-3-ones |
-
1991
- 1991-03-12 DE DE4107857A patent/DE4107857A1/de not_active Withdrawn
-
1992
- 1992-03-10 FI FI921030A patent/FI921030A/fi unknown
- 1992-03-10 ES ES92104045T patent/ES2104754T3/es not_active Expired - Lifetime
- 1992-03-10 EP EP92104045A patent/EP0503548B1/fr not_active Expired - Lifetime
- 1992-03-10 DE DE59208559T patent/DE59208559D1/de not_active Expired - Fee Related
- 1992-03-10 DK DK92104045.7T patent/DK0503548T3/da active
- 1992-03-10 AT AT92104045T patent/ATE154013T1/de not_active IP Right Cessation
- 1992-03-11 ZA ZA921804A patent/ZA921804B/xx unknown
- 1992-03-11 KR KR1019920003953A patent/KR920018031A/ko not_active Application Discontinuation
- 1992-03-11 MX MX9201068A patent/MX9201068A/es unknown
- 1992-03-11 AU AU12803/92A patent/AU654340B2/en not_active Ceased
- 1992-03-11 NO NO92920957A patent/NO920957L/no unknown
- 1992-03-11 NZ NZ241928A patent/NZ241928A/en unknown
- 1992-03-11 PL PL29379592A patent/PL293795A1/xx unknown
- 1992-03-11 IL IL10120392A patent/IL101203A/en not_active IP Right Cessation
- 1992-03-11 US US07/849,557 patent/US5276049A/en not_active Expired - Fee Related
- 1992-03-11 IE IE078192A patent/IE920781A1/en not_active Application Discontinuation
- 1992-03-11 CA CA002062655A patent/CA2062655A1/fr not_active Abandoned
- 1992-03-11 HU HU9200823A patent/HUT60722A/hu unknown
- 1992-03-12 CZ CS92745A patent/CZ74592A3/cs unknown
- 1992-03-12 TW TW081101892A patent/TW221811B/zh active
- 1992-03-12 JP JP4053171A patent/JPH04368372A/ja active Pending
- 1992-03-12 SK SK745-92A patent/SK74592A3/sk unknown
-
1993
- 1993-10-28 US US08/144,909 patent/US5478942A/en not_active Expired - Fee Related
-
1995
- 1995-08-29 US US08/521,338 patent/US5650424A/en not_active Expired - Fee Related
-
1997
- 1997-08-21 GR GR970402143T patent/GR3024504T3/el unknown
Also Published As
Publication number | Publication date |
---|---|
DK0503548T3 (da) | 1997-11-03 |
AU1280392A (en) | 1992-09-17 |
ZA921804B (en) | 1993-09-13 |
NO920957D0 (no) | 1992-03-11 |
US5478942A (en) | 1995-12-26 |
FI921030A (fi) | 1992-09-13 |
HUT60722A (en) | 1992-10-28 |
IE920781A1 (en) | 1992-09-23 |
JPH04368372A (ja) | 1992-12-21 |
US5276049A (en) | 1994-01-04 |
KR920018031A (ko) | 1992-10-21 |
SK74592A3 (en) | 1993-12-08 |
ES2104754T3 (es) | 1997-10-16 |
NO920957L (no) | 1992-09-14 |
PL293795A1 (en) | 1993-03-08 |
HU9200823D0 (en) | 1992-05-28 |
AU654340B2 (en) | 1994-11-03 |
IL101203A0 (en) | 1992-11-15 |
FI921030A0 (fi) | 1992-03-10 |
ATE154013T1 (de) | 1997-06-15 |
EP0503548B1 (fr) | 1997-06-04 |
GR3024504T3 (en) | 1997-11-28 |
CZ74592A3 (en) | 1993-03-17 |
NZ241928A (en) | 1994-06-27 |
EP0503548A1 (fr) | 1992-09-16 |
DE4107857A1 (de) | 1992-09-17 |
US5650424A (en) | 1997-07-22 |
CA2062655A1 (fr) | 1992-09-13 |
DE59208559D1 (de) | 1997-07-10 |
TW221811B (fr) | 1994-03-21 |
MX9201068A (es) | 1992-09-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
IL101203A (en) | History of cyclic urea, their preparation and pharmaceutical preparations containing them | |
US5434150A (en) | Condensed 5-membered heterocyclic compounds, processes for preparing them and pharmaceutical preparations containing these compounds | |
US5519036A (en) | Cyclic derivatives pharmaceutical compositions containing these compounds and processes for preparing them | |
US5576444A (en) | Cyclic imino derivatives, processes for preparing them and pharmaceutical compositions containing these compounds | |
US5463071A (en) | 5-membered heterocyclic compounds, processes for preparing them and pharmaceutical compositions containing these compounds | |
AU654372B2 (en) | Cyclic imino derivatives | |
US5880284A (en) | Cyclic urea derivatives, pharmaceutical compositions containing these compounds and processes for preparing them | |
DE4302051A1 (de) | 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
CA2197789A1 (fr) | Derives cycliques d'uree; compositions pharmaceutiques renfermant ces coomposes et methodes de preparation | |
US5852192A (en) | Cyclic urea derivatives, pharmaceutical compositions containing these compounds and processes for preparing them | |
NZ247502A (en) | Cyclic imino derivatives and pharmaceutical compositions | |
CZ281314B6 (cs) | Amidtetrazoly inhibující cholesterolacyltransferasu | |
GB2093450A (en) | 2,1,3-benzothiadiazole derivatives | |
AU669736B2 (en) | Benzimidazoles | |
DE4309213A1 (de) | Cyclische Harnstoffderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
CZ289405B6 (cs) | Benzimidazolové deriváty, způsob jejich výroby, farmaceutický prostředek je obsahující a intermediáty pro jejich výrobu | |
DE4302052A1 (de) | Cyclische Harnstoffderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FF | Patent granted | ||
KB | Patent renewed | ||
MM9K | Patent not in force due to non-payment of renewal fees |