AU652064B2 - Heterocyclic compounds - Google Patents
Heterocyclic compounds Download PDFInfo
- Publication number
- AU652064B2 AU652064B2 AU20569/92A AU2056992A AU652064B2 AU 652064 B2 AU652064 B2 AU 652064B2 AU 20569/92 A AU20569/92 A AU 20569/92A AU 2056992 A AU2056992 A AU 2056992A AU 652064 B2 AU652064 B2 AU 652064B2
- Authority
- AU
- Australia
- Prior art keywords
- group
- groups
- phenyl
- formula
- denotes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 5
- -1 amincalkyl Chemical group 0.000 claims description 234
- 150000001875 compounds Chemical class 0.000 claims description 157
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 129
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 120
- 229910052757 nitrogen Inorganic materials 0.000 claims description 89
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 65
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 125000003545 alkoxy group Chemical group 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- 125000003118 aryl group Chemical group 0.000 claims description 48
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 47
- 229910052801 chlorine Inorganic materials 0.000 claims description 41
- 239000000460 chlorine Substances 0.000 claims description 40
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 37
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 239000002253 acid Substances 0.000 claims description 32
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 32
- 125000003277 amino group Chemical group 0.000 claims description 32
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 32
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 32
- 239000001301 oxygen Substances 0.000 claims description 32
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 32
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 29
- 229910052731 fluorine Inorganic materials 0.000 claims description 27
- 239000011737 fluorine Substances 0.000 claims description 26
- 150000001721 carbon Chemical group 0.000 claims description 25
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 24
- 125000004429 atom Chemical group 0.000 claims description 24
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 23
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 23
- 125000002947 alkylene group Chemical group 0.000 claims description 22
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 20
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 20
- 239000005864 Sulphur Substances 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 19
- 125000005576 pyrimidinylene group Chemical group 0.000 claims description 19
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- 125000004450 alkenylene group Chemical group 0.000 claims description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 17
- 125000005550 pyrazinylene group Chemical group 0.000 claims description 17
- 125000005551 pyridylene group Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 16
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 16
- 125000001246 bromo group Chemical group Br* 0.000 claims description 16
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 12
- NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical compound N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
- 230000000269 nucleophilic effect Effects 0.000 claims description 11
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000011541 reaction mixture Substances 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- HMXQIFUGFZEJEO-UHFFFAOYSA-N 1,2-dihydropyrrol-3-one Chemical compound O=C1CNC=C1 HMXQIFUGFZEJEO-UHFFFAOYSA-N 0.000 claims description 8
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 8
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 8
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 8
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 7
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 7
- 238000004220 aggregation Methods 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 150000007522 mineralic acids Chemical class 0.000 claims description 7
- 150000007524 organic acids Chemical class 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 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 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 230000003480 fibrinolytic effect Effects 0.000 claims description 6
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000005835 indanylene group Chemical group 0.000 claims description 6
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 6
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 5
- 206010061216 Infarction Diseases 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
- 208000037919 acquired disease Diseases 0.000 claims description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 230000008619 cell matrix interaction Effects 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 230000007574 infarction Effects 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- 230000035939 shock Effects 0.000 claims description 5
- 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 claims description 5
- 150000003536 tetrazoles Chemical class 0.000 claims description 5
- 238000001149 thermolysis Methods 0.000 claims description 5
- 230000002537 thrombolytic effect Effects 0.000 claims description 5
- 125000005558 triazinylene group Chemical group 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical group C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 claims description 4
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 4
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 206010047249 Venous thrombosis Diseases 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000003435 aroyl group Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 230000000747 cardiac effect Effects 0.000 claims description 4
- 230000008614 cellular interaction Effects 0.000 claims description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
- 208000005189 Embolism Diseases 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 230000000144 pharmacologic effect Effects 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
- MUZIZEZCKKMZRT-UHFFFAOYSA-N 1,2-dithiolane Chemical compound C1CSSC1 MUZIZEZCKKMZRT-UHFFFAOYSA-N 0.000 claims description 2
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical class C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims description 2
- DQLOTKZORORBPO-UHFFFAOYSA-N 1,3-dithiolane 1,1,3,3-tetraoxide Chemical compound O=S1(=O)CCS(=O)(=O)C1 DQLOTKZORORBPO-UHFFFAOYSA-N 0.000 claims description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical class C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 claims description 2
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims description 2
- MPTKDOQUXZAHPJ-UHFFFAOYSA-N 2,3-dihydroindazole Chemical compound C1=CC=C2CN[N]C2=C1 MPTKDOQUXZAHPJ-UHFFFAOYSA-N 0.000 claims description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 2
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 2
- KPUNZOASCONSFC-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-1h-1,2,4-triazol-5-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=NNC(C=2C=CC(CCC(O)=O)=CC=2)=N1 KPUNZOASCONSFC-UHFFFAOYSA-N 0.000 claims description 2
- 150000000565 5-membered heterocyclic compounds Chemical class 0.000 claims description 2
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 2
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003713 acetylimino group Chemical group [H]C([H])([H])C(=O)N=[*] 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 2
- MXMZCLLIUQEKSN-UHFFFAOYSA-N benzimidazoline Chemical compound C1=CC=C2NCNC2=C1 MXMZCLLIUQEKSN-UHFFFAOYSA-N 0.000 claims description 2
- 125000006630 butoxycarbonylamino group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 2
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 2
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 2
- ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 claims description 2
- 150000003557 thiazoles Chemical class 0.000 claims description 2
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- HGMJGJDBRCZPNN-UHFFFAOYSA-N 3-[1-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]imidazol-4-yl]-2-(dibenzylamino)propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C=C(CC(N(CC=3C=CC=CC=3)CC=3C=CC=CC=3)C(O)=O)N=C2)N=N1 HGMJGJDBRCZPNN-UHFFFAOYSA-N 0.000 claims 1
- GTMHMJIGXWJKNJ-UHFFFAOYSA-N 3-[5-[4-(4-carbamimidoylphenyl)phenyl]-1,3,4-thiadiazol-2-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C=2SC(CCC(O)=O)=NN=2)C=C1 GTMHMJIGXWJKNJ-UHFFFAOYSA-N 0.000 claims 1
- 101100515517 Arabidopsis thaliana XI-I gene Proteins 0.000 claims 1
- 241000237518 Arion Species 0.000 claims 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims 1
- PWWSSIYVTQUJQQ-UHFFFAOYSA-N distearyl thiodipropionate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCCCCCCCC PWWSSIYVTQUJQQ-UHFFFAOYSA-N 0.000 claims 1
- 230000003993 interaction Effects 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- BZOMNTZBGVHJKL-UHFFFAOYSA-N methyl 3-[5-[4-(4-carbamimidoylphenyl)phenyl]tetrazol-2-yl]propanoate Chemical compound COC(=O)CCN1N=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=N1 BZOMNTZBGVHJKL-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 324
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 288
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 75
- 239000000741 silica gel Substances 0.000 description 75
- 229910002027 silica gel Inorganic materials 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- 235000002639 sodium chloride Nutrition 0.000 description 38
- 239000000243 solution Substances 0.000 description 38
- 229910021529 ammonia Inorganic materials 0.000 description 29
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- 238000002844 melting Methods 0.000 description 24
- 230000008018 melting Effects 0.000 description 24
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 229960000583 acetic acid Drugs 0.000 description 19
- 239000002585 base Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000012362 glacial acetic acid Substances 0.000 description 17
- 239000013543 active substance Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000012071 phase Substances 0.000 description 13
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 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 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 239000001117 sulphuric acid Substances 0.000 description 11
- 235000011149 sulphuric acid Nutrition 0.000 description 11
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 10
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 239000002775 capsule Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 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
- 238000009835 boiling Methods 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 150000002460 imidazoles Chemical class 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 6
- SYOANZBNGDEJFH-UHFFFAOYSA-N 2,5-dihydro-1h-triazole Chemical compound C1NNN=C1 SYOANZBNGDEJFH-UHFFFAOYSA-N 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- 108010049003 Fibrinogen Proteins 0.000 description 5
- 102000008946 Fibrinogen Human genes 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 5
- 229940012952 fibrinogen Drugs 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 4
- LOESLMDNPQYFOG-UHFFFAOYSA-N 3-(1h-imidazol-2-yl)propanoic acid Chemical compound OC(=O)CCC1=NC=CN1 LOESLMDNPQYFOG-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
- 229930195725 Mannitol Natural products 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 239000003708 ampul Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- KVEPOCMZETWSML-UHFFFAOYSA-N cyclopentyl 3-[4-[5-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]-3-methyl-4h-imidazol-5-yl]phenyl]propanoate Chemical compound C1=CC(C(=N)NC(=O)OC)=CC=C1C1(C=2C=CC(CCC(=O)OC3CCCC3)=CC=2)N=CN(C)C1 KVEPOCMZETWSML-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 229940093915 gynecological organic acid Drugs 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- WLCUXJVURVNUEX-UHFFFAOYSA-N methyl 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-1,3-thiazol-2-yl]propanoate Chemical compound S1C(CCC(=O)OC)=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=C1 WLCUXJVURVNUEX-UHFFFAOYSA-N 0.000 description 4
- FRPLAZNUFADXJC-UHFFFAOYSA-N methyl 3-[5-[4-(4-carbamimidoylphenyl)phenyl]furan-2-yl]propanoate Chemical compound O1C(CCC(=O)OC)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 FRPLAZNUFADXJC-UHFFFAOYSA-N 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 235000005985 organic acids Nutrition 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000008215 water for injection Substances 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 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-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
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 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
- 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 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- IFTJINFRUTYBHB-UHFFFAOYSA-N cyclohexyl 3-[4-[5-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]-3-methyl-4h-imidazol-5-yl]phenyl]propanoate Chemical compound C1=CC(C(N)=NC(=O)OC)=CC=C1C1(C=2C=CC(CCC(=O)OC3CCCCC3)=CC=2)N=CN(C)C1 IFTJINFRUTYBHB-UHFFFAOYSA-N 0.000 description 3
- 239000012024 dehydrating agents Substances 0.000 description 3
- ZCKYOWGFRHAZIQ-UHFFFAOYSA-N dihydrourocanic acid Chemical compound OC(=O)CCC1=CNC=N1 ZCKYOWGFRHAZIQ-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- DUQPKSWXRALGJX-UHFFFAOYSA-N methyl 3-(1h-imidazol-2-yl)propanoate Chemical compound COC(=O)CCC1=NC=CN1 DUQPKSWXRALGJX-UHFFFAOYSA-N 0.000 description 3
- MKSDBHPZYTZLRM-UHFFFAOYSA-N methyl 3-[1-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]-2-pyridin-3-ylimidazol-4-yl]propanoate Chemical compound N=1C(CCC(=O)OC)=CN(C=2N=NC(=CC=2)C=2C=CC(=CC=2)C(N)=N)C=1C1=CC=CN=C1 MKSDBHPZYTZLRM-UHFFFAOYSA-N 0.000 description 3
- BHGDICNLDQLIAJ-UHFFFAOYSA-N methyl 3-[1-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]imidazol-4-yl]-2-methoxypropanoate Chemical compound C1=NC(CC(OC)C(=O)OC)=CN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)N=N1 BHGDICNLDQLIAJ-UHFFFAOYSA-N 0.000 description 3
- MSYQAFYLEIYAPM-UHFFFAOYSA-N methyl 3-[4-[5-(4-carbamimidoylphenyl)furan-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)O1 MSYQAFYLEIYAPM-UHFFFAOYSA-N 0.000 description 3
- QSQJMQCABJKPAS-UHFFFAOYSA-N methyl 3-[5-[4-(4-carbamimidoylphenyl)phenyl]-1,3-oxazol-2-yl]propanoate Chemical compound O1C(CCC(=O)OC)=NC=C1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 QSQJMQCABJKPAS-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 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
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 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
- BODVSESPBZOELC-UHFFFAOYSA-N 2-(2-phenylethyl)-1h-imidazole Chemical compound N=1C=CNC=1CCC1=CC=CC=C1 BODVSESPBZOELC-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- OJGIBFZKRHTWHU-UHFFFAOYSA-N 2-[(4-cyanophenyl)methyl]propanedioic acid Chemical compound OC(=O)C(C(O)=O)CC1=CC=C(C#N)C=C1 OJGIBFZKRHTWHU-UHFFFAOYSA-N 0.000 description 2
- LDLAZNMEBLZTCT-UHFFFAOYSA-N 2-[4-[5-(4-carbamimidoylphenyl)-1h-imidazol-2-yl]phenyl]sulfanylacetic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CNC(C=2C=CC(SCC(O)=O)=CC=2)=N1 LDLAZNMEBLZTCT-UHFFFAOYSA-N 0.000 description 2
- PNAIMMQUKRSNNU-UHFFFAOYSA-N 2-[4-[5-(4-carbamimidoylphenyl)-1h-imidazol-2-yl]phenyl]sulfinylacetic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CNC(C=2C=CC(=CC=2)S(=O)CC(O)=O)=N1 PNAIMMQUKRSNNU-UHFFFAOYSA-N 0.000 description 2
- UIJKOEKKSJBAGR-UHFFFAOYSA-N 2-[4-[5-(4-carbamimidoylphenyl)-1h-imidazol-2-yl]phenyl]sulfonylacetic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CNC(C=2C=CC(=CC=2)S(=O)(=O)CC(O)=O)=N1 UIJKOEKKSJBAGR-UHFFFAOYSA-N 0.000 description 2
- BSUOLXPXYABSLP-UHFFFAOYSA-N 2-amino-3-[1-[4-[4-(aminomethyl)-2-oxopiperidin-1-yl]phenyl]imidazol-4-yl]propanoic acid Chemical compound O=C1CC(CN)CCN1C1=CC=C(N2C=C(CC(N)C(O)=O)N=C2)C=C1 BSUOLXPXYABSLP-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
- RHIGOXBTMPLABF-UHFFFAOYSA-N 3-(4-cyanophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=C(C#N)C=C1 RHIGOXBTMPLABF-UHFFFAOYSA-N 0.000 description 2
- DNQZNXFNAQDDTF-UHFFFAOYSA-N 3-[1-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]imidazol-4-yl]-2-methoxypropanoic acid Chemical compound C1=NC(CC(OC)C(O)=O)=CN1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)N=N1 DNQZNXFNAQDDTF-UHFFFAOYSA-N 0.000 description 2
- CZHFEFRBVOJTAU-UHFFFAOYSA-N 3-[1-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]imidazol-4-yl]prop-2-enoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C=C(C=CC(O)=O)N=C2)N=N1 CZHFEFRBVOJTAU-UHFFFAOYSA-N 0.000 description 2
- XORMFGPBEWPRHN-UHFFFAOYSA-N 3-[1-[6-[4-(n'-butylcarbamimidoyl)phenyl]pyridazin-3-yl]imidazol-4-yl]propanoic acid Chemical compound C1=CC(C(=N)NCCCC)=CC=C1C1=CC=C(N2C=C(CCC(O)=O)N=C2)N=N1 XORMFGPBEWPRHN-UHFFFAOYSA-N 0.000 description 2
- RTXFWVAVIPEVPT-UHFFFAOYSA-N 3-[2-amino-4-[5-(4-carbamimidoylphenyl)-1h-imidazol-2-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CNC(C=2C=C(N)C(CCC(O)=O)=CC=2)=N1 RTXFWVAVIPEVPT-UHFFFAOYSA-N 0.000 description 2
- MOUGSBZHPVASDB-UHFFFAOYSA-N 3-[3-[4-(4-carbamimidoylphenyl)phenyl]-1h-pyrazol-5-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C2=NNC(CCC(O)=O)=C2)C=C1 MOUGSBZHPVASDB-UHFFFAOYSA-N 0.000 description 2
- BAVQXXDICFGCHX-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-2-phenylimidazol-4-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1N1C(C=2C=CC=CC=2)=NC(C=2C=CC(CCC(O)=O)=CC=2)=C1 BAVQXXDICFGCHX-UHFFFAOYSA-N 0.000 description 2
- KRHDIDPQNMNQSH-UHFFFAOYSA-N 3-[4-[4-(1-carbamimidoylpiperidin-4-yl)phenyl]-1,3-thiazol-2-yl]propanoic acid Chemical compound C1CN(C(=N)N)CCC1C1=CC=C(C=2N=C(CCC(O)=O)SC=2)C=C1 KRHDIDPQNMNQSH-UHFFFAOYSA-N 0.000 description 2
- VATNVYAPNZLNBG-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-1-methylimidazol-2-yl]phenyl]pentanedioic acid Chemical compound CN1C=C(C=2C=CC(=CC=2)C(N)=N)N=C1C1=CC=C(C(CC(O)=O)CC(O)=O)C=C1 VATNVYAPNZLNBG-UHFFFAOYSA-N 0.000 description 2
- BMKFDJXBQWVCOB-UHFFFAOYSA-N 3-[4-[4-[4-(1-aminocyclopentyl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoic acid Chemical compound CN1C=C(C=2C=CC(=CC=2)C2(N)CCCC2)N=C1C1=CC=C(CCC(O)=O)C=C1 BMKFDJXBQWVCOB-UHFFFAOYSA-N 0.000 description 2
- XZKYCBMFNJZSKO-UHFFFAOYSA-N 3-[4-[4-[4-(2-aminopropan-2-yl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoic acid Chemical compound CN1C=C(C=2C=CC(=CC=2)C(C)(C)N)N=C1C1=CC=C(CCC(O)=O)C=C1 XZKYCBMFNJZSKO-UHFFFAOYSA-N 0.000 description 2
- PGUIEQCWXWOJBM-UHFFFAOYSA-N 3-[4-[5-(4-carbamimidoylphenyl)thiophen-2-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C=2C=CC(CCC(O)=O)=CC=2)S1 PGUIEQCWXWOJBM-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
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 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
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000002785 anti-thrombosis Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 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
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000007891 compressed tablet Substances 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- WBSYPRDYSHXXJR-UHFFFAOYSA-N ethyl 3-[4-(4-cyanophenyl)phenyl]-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)c1ccc(cc1)-c1ccc(cc1)C#N WBSYPRDYSHXXJR-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000001914 filtration 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
- 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
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 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
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- QXUAFCKBYYPTPQ-ZWKAXHIPSA-L magnesium (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(2R,3S,4R,5R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol octadecanoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O QXUAFCKBYYPTPQ-ZWKAXHIPSA-L 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- GJIWULOPNOPSIP-UHFFFAOYSA-N methyl 2-amino-3-[1-[6-(4-cyanophenyl)pyridazin-3-yl]imidazol-4-yl]propanoate Chemical compound C1=NC(CC(N)C(=O)OC)=CN1C1=CC=C(C=2C=CC(=CC=2)C#N)N=N1 GJIWULOPNOPSIP-UHFFFAOYSA-N 0.000 description 2
- YFEPBWKUBQUBKL-UHFFFAOYSA-N methyl 3-(1h-imidazol-5-yl)propanoate Chemical compound COC(=O)CCC1=CN=CN1 YFEPBWKUBQUBKL-UHFFFAOYSA-N 0.000 description 2
- GNFUDRKNTMIIDX-UHFFFAOYSA-N methyl 3-(4-carbamimidoylphenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)CCC1=CC=C(C(N)=N)C=C1 GNFUDRKNTMIIDX-UHFFFAOYSA-N 0.000 description 2
- NCDZIRVHIXURJT-UHFFFAOYSA-N methyl 3-(4-carbamothioylphenyl)propanoate Chemical compound COC(=O)CCC1=CC=C(C(N)=S)C=C1 NCDZIRVHIXURJT-UHFFFAOYSA-N 0.000 description 2
- JPRNCCUCPOZUDK-UHFFFAOYSA-N methyl 3-(4-cyanophenyl)propanoate Chemical compound COC(=O)CCC1=CC=C(C#N)C=C1 JPRNCCUCPOZUDK-UHFFFAOYSA-N 0.000 description 2
- JWENNAYCOQMQMG-UHFFFAOYSA-N methyl 3-[2-[1-(5-carbamimidoylpyridin-2-yl)piperidin-4-yl]-1,3-thiazol-4-yl]propanoate Chemical compound COC(=O)CCC1=CSC(C2CCN(CC2)C=2N=CC(=CC=2)C(N)=N)=N1 JWENNAYCOQMQMG-UHFFFAOYSA-N 0.000 description 2
- WJJGSDJSRUTBTH-UHFFFAOYSA-N methyl 3-[2-[4-(4-carbamimidoylphenyl)phenyl]-1,3-thiazol-4-yl]propanoate Chemical compound COC(=O)CCC1=CSC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=N1 WJJGSDJSRUTBTH-UHFFFAOYSA-N 0.000 description 2
- VFBXSNNRZAGJDU-UHFFFAOYSA-N methyl 3-[4-[1-(4-carbamimidoylphenyl)-2-methylimidazol-4-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=CN(C=2C=CC(=CC=2)C(N)=N)C(C)=N1 VFBXSNNRZAGJDU-UHFFFAOYSA-N 0.000 description 2
- XMDPGROZTHLZRF-UHFFFAOYSA-N methyl 3-[4-[3-(4-carbamimidoylphenyl)-1,2-oxazol-5-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=CC(C=2C=CC(=CC=2)C(N)=N)=NO1 XMDPGROZTHLZRF-UHFFFAOYSA-N 0.000 description 2
- LXPFETZMQVYZQY-UHFFFAOYSA-N methyl 3-[4-[4-[4-(aminomethyl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(CN)=CC=2)=CN1C LXPFETZMQVYZQY-UHFFFAOYSA-N 0.000 description 2
- ASZVXKAPTCWCPT-UHFFFAOYSA-N methyl 3-[4-[[(4-cyanobenzoyl)amino]carbamoyl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(=O)NNC(=O)C1=CC=C(C#N)C=C1 ASZVXKAPTCWCPT-UHFFFAOYSA-N 0.000 description 2
- JYPAYQKQOTYKAG-UHFFFAOYSA-N methyl 3-[5-[1-(5-carbamimidoylpyridin-2-yl)piperidin-4-yl]tetrazol-2-yl]propanoate Chemical compound COC(=O)CCN1N=NC(C2CCN(CC2)C=2N=CC(=CC=2)C(N)=N)=N1 JYPAYQKQOTYKAG-UHFFFAOYSA-N 0.000 description 2
- HVSYOBVZIMDLEZ-UHFFFAOYSA-N methyl 3-[5-[4-(4-carbamimidoylphenyl)phenyl]-1h-imidazol-2-yl]propanoate Chemical compound N1C(CCC(=O)OC)=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=C1 HVSYOBVZIMDLEZ-UHFFFAOYSA-N 0.000 description 2
- PZVQTMIVLMROHX-UHFFFAOYSA-N methyl 3-[6-[4-(4-carbamimidoylphenyl)imidazol-1-yl]pyridazin-3-yl]propanoate Chemical compound N1=NC(CCC(=O)OC)=CC=C1N1C=C(C=2C=CC(=CC=2)C(N)=N)N=C1 PZVQTMIVLMROHX-UHFFFAOYSA-N 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
- XCAOVNOHVSHZTL-UHFFFAOYSA-N triethyl 2-(4-cyanophenyl)ethane-1,1,1-tricarboxylate Chemical compound CCOC(=O)C(C(=O)OCC)(C(=O)OCC)CC1=CC=C(C#N)C=C1 XCAOVNOHVSHZTL-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
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-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
- 125000003161 (C1-C6) alkylene group Chemical group 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
- KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-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
- FBAOVPVVMDOHPK-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinyl)-1h-imidazole Chemical compound N=1C=CNC=1S(=O)C1=NC=CN1 FBAOVPVVMDOHPK-UHFFFAOYSA-N 0.000 description 1
- NQIBQILAMKZKFE-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)-3-fluoropyridine Chemical compound FC1=CC=C(Br)C=C1C1=NC=CC=C1F NQIBQILAMKZKFE-UHFFFAOYSA-N 0.000 description 1
- LLSQTKHEAIUEDP-UHFFFAOYSA-N 2-amino-3-[1-[6-[4-(aminomethyl)phenyl]pyridazin-3-yl]imidazol-4-yl]propanoic acid;dihydrochloride Chemical compound Cl.Cl.C1=CC(CN)=CC=C1C1=CC=C(N2C=C(CC(N)C(O)=O)N=C2)N=N1 LLSQTKHEAIUEDP-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
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- ILHUVWVIEVFDPX-UHFFFAOYSA-N 2-phenylethyl 3-[4-[4-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(C(=N)NC(=O)OC)=CC=C1C1=CN(C)C(C=2C=CC(CCC(=O)OCCC=3C=CC=CC=3)=CC=2)=N1 ILHUVWVIEVFDPX-UHFFFAOYSA-N 0.000 description 1
- ZXKOENSQFURTSZ-UHFFFAOYSA-N 3-(1H-imidazol-5-yl)-2-propenoic acid methyl ester Chemical compound COC(=O)C=CC1=CN=CN1 ZXKOENSQFURTSZ-UHFFFAOYSA-N 0.000 description 1
- ZQZJULZPQACTES-UHFFFAOYSA-N 3-(1h-imidazol-2-yl)pyridine Chemical compound C1=CNC(C=2C=NC=CC=2)=N1 ZQZJULZPQACTES-UHFFFAOYSA-N 0.000 description 1
- ZFJXQZDHZQNHNA-UHFFFAOYSA-N 3-[1-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]imidazol-4-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(N2C=C(CCC(O)=O)N=C2)N=N1 ZFJXQZDHZQNHNA-UHFFFAOYSA-N 0.000 description 1
- AMPHFGGQZXPSFA-UHFFFAOYSA-N 3-[4-[1-(4-carbamimidoylphenyl)-2-methylimidazol-4-yl]phenyl]propanoic acid Chemical compound CC1=NC(C=2C=CC(CCC(O)=O)=CC=2)=CN1C1=CC=C(C(N)=N)C=C1 AMPHFGGQZXPSFA-UHFFFAOYSA-N 0.000 description 1
- VUZZFPNYQZASEM-UHFFFAOYSA-N 3-[4-[1-methyl-4-[4-[(e)-n'-phenylmethoxycarbonylcarbamimidoyl]phenyl]imidazol-2-yl]phenyl]propanoic acid Chemical compound CN1C=C(C=2C=CC(=CC=2)C(N)=NC(=O)OCC=2C=CC=CC=2)N=C1C1=CC=C(CCC(O)=O)C=C1 VUZZFPNYQZASEM-UHFFFAOYSA-N 0.000 description 1
- JFUSTGAFTFDZDX-UHFFFAOYSA-N 3-[4-[2-(4-aminocyclohexyl)-1h-imidazol-5-yl]phenyl]propanoic acid Chemical compound C1CC(N)CCC1C1=NC(C=2C=CC(CCC(O)=O)=CC=2)=CN1 JFUSTGAFTFDZDX-UHFFFAOYSA-N 0.000 description 1
- DOZWPFRWERPYBW-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)-1,2,4-triazol-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=NN(C=2C=CC(CCC(O)=O)=CC=2)C=N1 DOZWPFRWERPYBW-UHFFFAOYSA-N 0.000 description 1
- MCXVLTYCCPSFDZ-UHFFFAOYSA-N 3-[4-[3-(4-carbamimidoylphenyl)pyrazol-1-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=NN(C=2C=CC(CCC(O)=O)=CC=2)C=C1 MCXVLTYCCPSFDZ-UHFFFAOYSA-N 0.000 description 1
- RFSXIEAYLUHQNY-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-1,3-thiazol-2-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CSC(C=2C=CC(CCC(O)=O)=CC=2)=N1 RFSXIEAYLUHQNY-UHFFFAOYSA-N 0.000 description 1
- NGWOGPJKZVPROF-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)-1-methylimidazol-2-yl]phenyl]propanoic acid Chemical compound CN1C=C(C=2C=CC(=CC=2)C(N)=N)N=C1C1=CC=C(CCC(O)=O)C=C1 NGWOGPJKZVPROF-UHFFFAOYSA-N 0.000 description 1
- KVAYYHUNSCWCKP-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-1,3-thiazol-2-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C=2N=C(CCC(O)=O)SC=2)C=C1 KVAYYHUNSCWCKP-UHFFFAOYSA-N 0.000 description 1
- FGGZWSWNWFEZFY-UHFFFAOYSA-N 3-[4-[4-(4-carbamimidoylphenyl)phenyl]-1-methylimidazol-2-yl]propanoic acid Chemical compound N1=C(CCC(O)=O)N(C)C=C1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 FGGZWSWNWFEZFY-UHFFFAOYSA-N 0.000 description 1
- JSVWSYDTSJLQSV-UHFFFAOYSA-N 3-[4-[4-[4-(1-aminocyclopropyl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoic acid Chemical compound CN1C=C(C=2C=CC(=CC=2)C2(N)CC2)N=C1C1=CC=C(CCC(O)=O)C=C1 JSVWSYDTSJLQSV-UHFFFAOYSA-N 0.000 description 1
- FZEPOLLBQTYLDV-UHFFFAOYSA-N 3-[4-[5-(4-carbamimidoylphenyl)-1h-imidazol-2-yl]phenyl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CNC(C=2C=CC(CCC(O)=O)=CC=2)=N1 FZEPOLLBQTYLDV-UHFFFAOYSA-N 0.000 description 1
- KEVZIGFKACJMMG-UHFFFAOYSA-N 3-[5-[4-(4-carbamimidoylphenyl)phenyl]-1,3-oxazol-2-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C=2OC(CCC(O)=O)=NC=2)C=C1 KEVZIGFKACJMMG-UHFFFAOYSA-N 0.000 description 1
- CJPFYMPKJYWIAA-UHFFFAOYSA-N 3-[5-[4-(4-carbamimidoylphenyl)phenyl]tetrazol-2-yl]propanoic acid Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(C2=NN(CCC(O)=O)N=N2)C=C1 CJPFYMPKJYWIAA-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
- HGINADPHJQTSKN-UHFFFAOYSA-M 3-ethoxy-3-oxopropanoate Chemical compound CCOC(=O)CC([O-])=O HGINADPHJQTSKN-UHFFFAOYSA-M 0.000 description 1
- FGNFUUPUNGZEDY-UHFFFAOYSA-N 4-(1h-imidazol-2-yl)benzenecarboximidamide Chemical compound C1=CC(C(=N)N)=CC=C1C1=NC=CN1 FGNFUUPUNGZEDY-UHFFFAOYSA-N 0.000 description 1
- LJANCPRIUMHGJE-UHFFFAOYSA-N 4-(2-bromoacetyl)benzonitrile Chemical compound BrCC(=O)C1=CC=C(C#N)C=C1 LJANCPRIUMHGJE-UHFFFAOYSA-N 0.000 description 1
- KAXYYLCSSXFXKR-UHFFFAOYSA-N 4-(4-cyanophenyl)benzonitrile Chemical group C1=CC(C#N)=CC=C1C1=CC=C(C#N)C=C1 KAXYYLCSSXFXKR-UHFFFAOYSA-N 0.000 description 1
- STZOTSLZVGSAKO-UHFFFAOYSA-N 4-(4-cyanophenyl)benzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C1=CC=C(C#N)C=C1 STZOTSLZVGSAKO-UHFFFAOYSA-N 0.000 description 1
- LSANLKRTTRMYRC-UHFFFAOYSA-N 4-(6-chloropyridazin-3-yl)benzenecarboximidamide Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC=C(Cl)N=N1 LSANLKRTTRMYRC-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
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
- XBKNBDLMVSHZGY-UHFFFAOYSA-N 4-[4-(2h-tetrazol-5-yl)phenyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1=CC=C(C=2NN=NN=2)C=C1 XBKNBDLMVSHZGY-UHFFFAOYSA-N 0.000 description 1
- PJWRZYGGTHXGQO-UHFFFAOYSA-N 4-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=C(C#N)C=C1 PJWRZYGGTHXGQO-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 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
- XTIKIVWSYBVJJK-UHFFFAOYSA-N 5-bromo-4-oxopentanoic acid Chemical compound OC(=O)CCC(=O)CBr XTIKIVWSYBVJJK-UHFFFAOYSA-N 0.000 description 1
- QBQOOUMQVKQIQH-UHFFFAOYSA-N 5-methylsulfanyl-1h-1,2,4-triazole Chemical compound CSC=1N=CNN=1 QBQOOUMQVKQIQH-UHFFFAOYSA-N 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
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 241000518994 Conta Species 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
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-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
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 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
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 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
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 101800001700 Saposin-D Proteins 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
- 108010023197 Streptokinase Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000003938 Thromboxane Receptors Human genes 0.000 description 1
- 108090000300 Thromboxane Receptors Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 229920004482 WACKER® Polymers 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 229940022682 acetone Drugs 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 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
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 235000011162 ammonium carbonates Nutrition 0.000 description 1
- CAMXVZOXBADHNJ-UHFFFAOYSA-N ammonium nitrite Chemical compound [NH4+].[O-]N=O CAMXVZOXBADHNJ-UHFFFAOYSA-N 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 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
- 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
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- INMYKEQIROXMPN-UHFFFAOYSA-N diethyl 2-[4-(4-cyanophenyl)benzoyl]-4-oxoheptanedioate Chemical compound C1=CC(C(=O)C(C(=O)OCC)CC(=O)CCC(=O)OCC)=CC=C1C1=CC=C(C#N)C=C1 INMYKEQIROXMPN-UHFFFAOYSA-N 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
- MYTMXVHNEWBFAL-UHFFFAOYSA-L dipotassium;carbonate;hydrate Chemical compound O.[K+].[K+].[O-]C([O-])=O MYTMXVHNEWBFAL-UHFFFAOYSA-L 0.000 description 1
- 230000004821 effect on bone Effects 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 229960001123 epoprostenol Drugs 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
- VFKWEKPXSSFRCK-UHFFFAOYSA-N ethyl 2-[4-(4-cyanophenyl)phenyl]-5-(3-ethoxy-3-oxopropyl)furan-3-carboxylate Chemical compound O1C(CCC(=O)OCC)=CC(C(=O)OCC)=C1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 VFKWEKPXSSFRCK-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 230000002718 inhibitory effect on inflammation Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 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
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002542 isoureas Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000011777 magnesium Substances 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- ONEXWXOXTBCATI-UHFFFAOYSA-N methyl 2-[4-(4-carbamimidoylphenyl)phenyl]-5-(3-methoxy-3-oxopropyl)furan-3-carboxylate;hydrochloride Chemical compound Cl.O1C(CCC(=O)OC)=CC(C(=O)OC)=C1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 ONEXWXOXTBCATI-UHFFFAOYSA-N 0.000 description 1
- IRRWMCLWJKKWOB-UHFFFAOYSA-N methyl 2-amino-3-[1-[6-[4-(aminomethyl)phenyl]pyridazin-3-yl]imidazol-4-yl]propanoate Chemical compound C1=NC(CC(N)C(=O)OC)=CN1C1=CC=C(C=2C=CC(CN)=CC=2)N=N1 IRRWMCLWJKKWOB-UHFFFAOYSA-N 0.000 description 1
- BAYIDMGOQRXHBC-UHFFFAOYSA-N methyl 3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(CCC(=O)OC)=CNC2=C1 BAYIDMGOQRXHBC-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
- IFMNEMPOJRAVSE-UHFFFAOYSA-N methyl 3-(4-carbamoylphenyl)propanoate Chemical compound COC(=O)CCC1=CC=C(C(N)=O)C=C1 IFMNEMPOJRAVSE-UHFFFAOYSA-N 0.000 description 1
- CIKIQYAEIGAWPF-UHFFFAOYSA-N methyl 3-(4-carbonochloridoylphenyl)propanoate Chemical compound COC(=O)CCC1=CC=C(C(Cl)=O)C=C1 CIKIQYAEIGAWPF-UHFFFAOYSA-N 0.000 description 1
- RGSBMOXJZUGVTG-UHFFFAOYSA-N methyl 3-[1-[6-(4-carbamimidoylphenyl)pyridazin-3-yl]indol-3-yl]propanoate Chemical compound C12=CC=CC=C2C(CCC(=O)OC)=CN1C(N=N1)=CC=C1C1=CC=C(C(N)=N)C=C1 RGSBMOXJZUGVTG-UHFFFAOYSA-N 0.000 description 1
- FERQJQWVMZAZDM-UHFFFAOYSA-N methyl 3-[1-[6-(4-cyanophenyl)pyridazin-3-yl]imidazol-4-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=NC(CC(C(=O)OC)NC(=O)OC(C)(C)C)=CN1C1=CC=C(C=2C=CC(=CC=2)C#N)N=N1 FERQJQWVMZAZDM-UHFFFAOYSA-N 0.000 description 1
- PBQVAXQYVKBAOZ-UHFFFAOYSA-N methyl 3-[1-[6-[4-(aminomethyl)phenyl]pyridazin-3-yl]imidazol-4-yl]propanoate;hydrochloride Chemical compound Cl.C1=NC(CCC(=O)OC)=CN1C1=CC=C(C=2C=CC(CN)=CC=2)N=N1 PBQVAXQYVKBAOZ-UHFFFAOYSA-N 0.000 description 1
- WCQSAHGERVPZGV-UHFFFAOYSA-N methyl 3-[3-[4-(4-carbamimidoylphenyl)phenyl]-1h-pyrazol-5-yl]propanoate Chemical compound N1C(CCC(=O)OC)=CC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=N1 WCQSAHGERVPZGV-UHFFFAOYSA-N 0.000 description 1
- MZPJYDWHHACVJL-UHFFFAOYSA-N methyl 3-[4-(1-methylimidazol-2-yl)phenyl]propanoate Chemical compound COC(=O)CCC1=CC=C(C=C1)C=1N(C=CN=1)C MZPJYDWHHACVJL-UHFFFAOYSA-N 0.000 description 1
- QMVVEEGSRCWWLT-UHFFFAOYSA-N methyl 3-[4-(4-piperidin-4-ylphenyl)-1,3-thiazol-2-yl]propanoate Chemical compound S1C(CCC(=O)OC)=NC(C=2C=CC(=CC=2)C2CCNCC2)=C1 QMVVEEGSRCWWLT-UHFFFAOYSA-N 0.000 description 1
- UVEYUWMSWYJADL-UHFFFAOYSA-N methyl 3-[4-[3-(4-cyanophenyl)-1h-1,2,4-triazol-5-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C#N)=NN1 UVEYUWMSWYJADL-UHFFFAOYSA-N 0.000 description 1
- SYQQYFHIJSNMDJ-UHFFFAOYSA-N methyl 3-[4-[4-(1-amino-2,3-dihydro-1h-inden-5-yl)-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=C3CCC(N)C3=CC=2)=CN1C SYQQYFHIJSNMDJ-UHFFFAOYSA-N 0.000 description 1
- BEOINUSYOWCGCM-UHFFFAOYSA-N methyl 3-[4-[4-(1-carbamimidoylpiperidin-4-yl)phenyl]-1,3-thiazol-2-yl]propanoate Chemical compound S1C(CCC(=O)OC)=NC(C=2C=CC(=CC=2)C2CCN(CC2)C(N)=N)=C1 BEOINUSYOWCGCM-UHFFFAOYSA-N 0.000 description 1
- PTYPXXNAELWJRX-UHFFFAOYSA-N methyl 3-[4-[4-(4-carbamimidoylphenyl)-1-(2-phenylethyl)imidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C(N)=N)=CN1CCC1=CC=CC=C1 PTYPXXNAELWJRX-UHFFFAOYSA-N 0.000 description 1
- XRTSYEDSVPUQQV-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)-1,3-thiazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C#N)=CS1 XRTSYEDSVPUQQV-UHFFFAOYSA-N 0.000 description 1
- PWUPFXAANFOLBQ-UHFFFAOYSA-N methyl 3-[4-[4-(4-cyanophenyl)-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C#N)=CN1C PWUPFXAANFOLBQ-UHFFFAOYSA-N 0.000 description 1
- GCNQWHZUHPTNQZ-UHFFFAOYSA-N methyl 3-[4-[4-[4-(1-aminocyclopropyl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C2(N)CC2)=CN1C GCNQWHZUHPTNQZ-UHFFFAOYSA-N 0.000 description 1
- HGGRFTSKCHRZJQ-UHFFFAOYSA-N methyl 3-[4-[4-[4-(1-aminoethyl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C(C)N)=CN1C HGGRFTSKCHRZJQ-UHFFFAOYSA-N 0.000 description 1
- JKBNGXHDWQOQDM-UHFFFAOYSA-N methyl 3-[4-[4-[4-(2-aminoethyl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(CCN)=CC=2)=CN1C JKBNGXHDWQOQDM-UHFFFAOYSA-N 0.000 description 1
- YMYPQNVHBHLJKE-UHFFFAOYSA-N methyl 3-[4-[4-[4-(2-aminopropan-2-yl)phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C(C)(C)N)=CN1C YMYPQNVHBHLJKE-UHFFFAOYSA-N 0.000 description 1
- CAFOODCWIXUPIM-UHFFFAOYSA-N methyl 3-[4-[4-[4-[(dimethylamino)methyl]phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(CN(C)C)=CC=2)=CN1C CAFOODCWIXUPIM-UHFFFAOYSA-N 0.000 description 1
- HAOIGRDDOYNSSU-UHFFFAOYSA-N methyl 3-[4-[4-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]-1-methylimidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C(=N)NC(=O)OC)=CN1C HAOIGRDDOYNSSU-UHFFFAOYSA-N 0.000 description 1
- DPMRPQRAEWNFNG-UHFFFAOYSA-N methyl 3-[4-[5-(4-carbamimidoylphenyl)-1h-imidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC=C(C=2C=CC(=CC=2)C(N)=N)N1 DPMRPQRAEWNFNG-UHFFFAOYSA-N 0.000 description 1
- HJASVRNQECERTF-UHFFFAOYSA-N methyl 3-[4-[5-(4-carbamimidoylphenyl)tetrazol-2-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OC)=CC=C1N1N=C(C=2C=CC(=CC=2)C(N)=N)N=N1 HJASVRNQECERTF-UHFFFAOYSA-N 0.000 description 1
- SAPNYWYUSOSYKA-UHFFFAOYSA-N methyl 3-[4-[5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NN=C(C=2C=CC(=CC=2)C#N)O1 SAPNYWYUSOSYKA-UHFFFAOYSA-N 0.000 description 1
- CTAIBRDTLFWJHK-UHFFFAOYSA-N methyl 3-[4-[5-(4-cyanophenyl)-1,3,4-thiadiazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NN=C(C=2C=CC(=CC=2)C#N)S1 CTAIBRDTLFWJHK-UHFFFAOYSA-N 0.000 description 1
- FGIXFUJXRLAKSP-UHFFFAOYSA-N methyl 3-[4-[5-(4-cyanophenyl)-1h-imidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C#N)=CN1 FGIXFUJXRLAKSP-UHFFFAOYSA-N 0.000 description 1
- BXQQIWFVCMDVEZ-UHFFFAOYSA-N methyl 3-[4-[5-(4-cyanophenyl)tetrazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1N=C(C=2C=CC(=CC=2)C#N)N=N1 BXQQIWFVCMDVEZ-UHFFFAOYSA-N 0.000 description 1
- DRSQZDRUAIXBKW-UHFFFAOYSA-N methyl 3-[4-[5-[3-(diaminomethylideneamino)phenyl]-1h-imidazol-2-yl]phenyl]propanoate;hydrochloride Chemical compound Cl.C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=C(NC(N)=N)C=CC=2)=CN1 DRSQZDRUAIXBKW-UHFFFAOYSA-N 0.000 description 1
- RVXJAMLNAPHQKI-UHFFFAOYSA-N methyl 3-[4-[5-[4-(n'-methoxycarbonylcarbamimidoyl)phenyl]-1h-imidazol-2-yl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C1=NC(C=2C=CC(=CC=2)C(=N)NC(=O)OC)=CN1 RVXJAMLNAPHQKI-UHFFFAOYSA-N 0.000 description 1
- GANFFMIXEPOAKR-UHFFFAOYSA-N methyl 3-[5-[4-(4-carbamimidoylphenyl)phenyl]tetrazol-2-yl]propanoate;hydrochloride Chemical compound Cl.COC(=O)CCN1N=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(N)=N)=N1 GANFFMIXEPOAKR-UHFFFAOYSA-N 0.000 description 1
- RYAYPTNCRHYWFZ-UHFFFAOYSA-N methyl 3-[5-[4-(4-cyanophenyl)phenyl]-1,3,4-thiadiazol-2-yl]propanoate Chemical compound S1C(CCC(=O)OC)=NN=C1C1=CC=C(C=2C=CC(=CC=2)C#N)C=C1 RYAYPTNCRHYWFZ-UHFFFAOYSA-N 0.000 description 1
- BZQDHGWARLNAOI-UHFFFAOYSA-N methyl 3-[5-[4-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]phenyl]phenyl]tetrazol-2-yl]propanoate Chemical compound COC(=O)CCN1N=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C(=N)NC(=O)OC)=N1 BZQDHGWARLNAOI-UHFFFAOYSA-N 0.000 description 1
- HJXVAPKPZLSZSV-UHFFFAOYSA-N methyl 3-[[4-[1-methyl-4-(1-methylpiperidin-4-yl)imidazol-2-yl]benzoyl]amino]propanoate Chemical compound C1=CC(C(=O)NCCC(=O)OC)=CC=C1C1=NC(C2CCN(C)CC2)=CN1C HJXVAPKPZLSZSV-UHFFFAOYSA-N 0.000 description 1
- KQEVIFKPZOGBMZ-UHFFFAOYSA-N methyl 3-bromopropanoate Chemical compound COC(=O)CCBr KQEVIFKPZOGBMZ-UHFFFAOYSA-N 0.000 description 1
- ZIFMKAOPLPWBMA-UHFFFAOYSA-N methyl 4-[2-[4-(4-cyanophenyl)benzoyl]hydrazinyl]-4-oxobutanoate Chemical compound C1=CC(C(=O)NNC(=O)CCC(=O)OC)=CC=C1C1=CC=C(C#N)C=C1 ZIFMKAOPLPWBMA-UHFFFAOYSA-N 0.000 description 1
- KKZMIDYKRKGJHG-UHFFFAOYSA-N methyl 4-cyanobenzoate Chemical compound COC(=O)C1=CC=C(C#N)C=C1 KKZMIDYKRKGJHG-UHFFFAOYSA-N 0.000 description 1
- ZSCLXSGTXOZOKF-UHFFFAOYSA-N methyl n-[amino-[4-(6-chloropyridazin-3-yl)phenyl]methylidene]carbamate Chemical compound C1=CC(C(=N)NC(=O)OC)=CC=C1C1=CC=C(Cl)N=N1 ZSCLXSGTXOZOKF-UHFFFAOYSA-N 0.000 description 1
- 229940073584 methylene chloride Drugs 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- FWANZNVPCBFZLT-UHFFFAOYSA-N n-[(4-cyanophenyl)methylideneamino]benzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)NN=CC1=CC=C(C#N)C=C1 FWANZNVPCBFZLT-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 class 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 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
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- KQFVEQPBKYBOSL-UHFFFAOYSA-N propan-2-yl 3-[5-[4-(4-carbamimidoylphenyl)phenyl]-1,3,4-thiadiazol-2-yl]propanoate Chemical compound S1C(CCC(=O)OC(C)C)=NN=C1C1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 KQFVEQPBKYBOSL-UHFFFAOYSA-N 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 108010073863 saruplase Proteins 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000005245 sintering Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 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
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- 150000007979 thiazole derivatives Chemical class 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- AGZPNUZBDCYTBB-UHFFFAOYSA-N triethyl methanetricarboxylate Chemical compound CCOC(=O)C(C(=O)OCC)C(=O)OCC AGZPNUZBDCYTBB-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229940019333 vitamin k antagonists Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
- C07D233/64—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 substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- 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)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4124942 | 1991-07-27 | ||
| DE4124942A DE4124942A1 (de) | 1991-07-27 | 1991-07-27 | 5-gliedrige heterocyclen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2056992A AU2056992A (en) | 1993-01-28 |
| AU652064B2 true AU652064B2 (en) | 1994-08-11 |
Family
ID=6437152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU20569/92A Ceased AU652064B2 (en) | 1991-07-27 | 1992-07-27 | Heterocyclic compounds |
Country Status (16)
Families Citing this family (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR940005271A (ko) * | 1992-04-28 | 1994-03-21 | 디터 라우딘, 게르하르트 후버 | 표지된 피브리노겐 수용체 길항제, 이의 용도 및 이의 제조방법 |
| DE4213919A1 (de) * | 1992-04-28 | 1993-11-04 | Thomae Gmbh Dr K | Cyclische iminoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE4213931A1 (de) * | 1992-04-28 | 1993-11-04 | Thomae Gmbh Dr K | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE4302051A1 (de) * | 1993-01-26 | 1994-07-28 | Thomae Gmbh Dr K | 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| DE4304650A1 (de) * | 1993-02-16 | 1994-08-18 | Thomae Gmbh Dr K | Kondensierte 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| PT825184E (pt) * | 1993-03-29 | 2001-11-30 | Astrazeneca Ab | Derivados heterociclicos como inibidores de agregacao de plaquetas |
| US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
| EP0690847A1 (en) * | 1993-03-29 | 1996-01-10 | Zeneca Limited | Heterocyclic compounds as platelet aggregation inhibitors |
| US5652242A (en) * | 1993-03-29 | 1997-07-29 | Zeneca Limited | Heterocyclic 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 |
| US5463011A (en) * | 1993-06-28 | 1995-10-31 | Zeneca Limited | Acid derivatives |
| US5523302A (en) * | 1993-11-24 | 1996-06-04 | The Du Pont Merck Pharmaceutical Company | Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists |
| ATE168106T1 (de) * | 1993-11-24 | 1998-07-15 | Du Pont Merck Pharma | Isoxazoline derivate anwendbar als fibrinogen rezeptor antagonisten |
| PT730590E (pt) * | 1993-11-24 | 2001-05-31 | Du Pont Pharm Co | Derivados de isoxazolina e isoxazole como antagonistas dos reciptores do fibrinogenio |
| US5446056A (en) * | 1993-11-24 | 1995-08-29 | The Du Pont Merck Pharmaceutical Company | Isoxazoline compounds useful as fibrinogen receptor antagonists |
| 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 |
| ZA963391B (en) * | 1995-05-24 | 1997-10-29 | Du Pont Merck Pharma | Isoxazoline fibrinogen receptor antagonists. |
| US5710159A (en) * | 1996-05-09 | 1998-01-20 | The Dupont Merck Pharmaceutical Company | Integrin receptor antagonists |
| IL118325A0 (en) * | 1995-05-25 | 1996-10-31 | Pont Merck And Pharmaceutical | Integrin receptor antagonists and pharmaceutical compositions containing them |
| US5668165A (en) * | 1995-06-07 | 1997-09-16 | Scriptgen Pharmaceuticals, Inc. | Small molecule inhibition of RNA/ligand binding |
| ZA966885B (en) * | 1995-08-22 | 1998-02-16 | Du Pont Merck Pharma | Substituted cyclic ureas and derivatives thereof useful as retroviral protease inhibitors. |
| WO1997015567A1 (de) * | 1995-10-20 | 1997-05-01 | Dr. Karl Thomae Gmbh | 5-gliedrige heterocyclen, diese verbindungen enthaltende arzneimittel und deren verwendung sowie verfahren zu ihrer herstellung |
| DE19605766A1 (de) * | 1996-02-16 | 1997-08-21 | Basf Ag | Substituierte 2-Phenylpyridine |
| US6011052A (en) * | 1996-04-30 | 2000-01-04 | Warner-Lambert Company | Pyrazolone derivatives as MCP-1 antagonists |
| WO1997049698A1 (en) * | 1996-06-21 | 1997-12-31 | Glaxo Group Limited | Piperidine acetic acid derivatives and their use in the treatment of thrombotic disorders |
| AR008245A1 (es) * | 1996-06-21 | 1999-12-29 | Glaxo Group Ltd | Derivados de acido acetico, uso de los mismos en la fabricacion de un agente terapeutico y proceso para preparar dichos derivados |
| US7094782B1 (en) | 1996-07-24 | 2006-08-22 | Bristol-Myers Squibb Company | Azolo triazines and pyrimidines |
| US6191131B1 (en) | 1997-07-23 | 2001-02-20 | Dupont Pharmaceuticals Company | Azolo triazines and pyrimidines |
| US6060478A (en) * | 1996-07-24 | 2000-05-09 | Dupont Pharmaceuticals | Azolo triazines and pyrimidines |
| US6124289A (en) * | 1996-07-24 | 2000-09-26 | Dupont Pharmaceuticals Co. | Azolo triazines and pyrimidines |
| US6313124B1 (en) | 1997-07-23 | 2001-11-06 | Dupont Pharmaceuticals Company | Tetrazine bicyclic compounds |
| CA2263311A1 (en) * | 1996-08-15 | 1998-02-19 | Pasquale Nicholas Confalone | Cyclic carbamates and isoxazolidines as iib/iiia antagonists |
| US6004955A (en) * | 1996-08-15 | 1999-12-21 | Dupont Pharmaceuticals Company | Cyclic carbamates and isoxazolidines as IIb/IIIa antagonists |
| WO1998006694A1 (en) * | 1996-08-16 | 1998-02-19 | Du Pont Pharmaceuticals Company | Amidinophenyl-pyrrolidines, -pyrrolines, and -isoxazolidines and derivatives thereof |
| US6057342A (en) * | 1996-08-16 | 2000-05-02 | Dupont Pharmaceutical Co. | Amidinophenyl-pyrrolidines, -pyrrolines, and -isoxazolidines and derivatives thereof |
| DE19647381A1 (de) * | 1996-11-15 | 1998-05-20 | Hoechst Ag | Neue Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten |
| US6187797B1 (en) * | 1996-12-23 | 2001-02-13 | Dupont Pharmaceuticals Company | Phenyl-isoxazoles as factor XA Inhibitors |
| US6548512B1 (en) | 1996-12-23 | 2003-04-15 | Bristol-Myers Squibb Pharma Company | Nitrogen containing heteroaromatics as factor Xa inhibitors |
| US6020357A (en) * | 1996-12-23 | 2000-02-01 | Dupont Pharmaceuticals Company | Nitrogen containing heteroaromatics as factor Xa inhibitors |
| ZA9711586B (en) | 1996-12-23 | 1999-07-01 | Du Pont Merck Pharma | Nitrogen containing heteroaromatics as factor Xa inhibitors. |
| AR012443A1 (es) * | 1997-04-16 | 2000-10-18 | Uriach & Cia Sa J | Nuevas carboxamidas como inhibidores de la agregacion plaquetaria, procedimiento para su preparacion, composiciones farmaceuticas que loscontienen y uso de los mismos en la manufactura de medicamentos |
| ZA985251B (en) | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Inhibitors of factor Xa with a neutral P1 specificity group. |
| AU8150398A (en) * | 1997-06-19 | 1999-01-04 | Du Pont Pharmaceuticals Company | Inhibitors of factor xa with a neutral p1 specificity group |
| US5998424A (en) | 1997-06-19 | 1999-12-07 | Dupont Pharmaceuticals Company | Inhibitors of factor Xa with a neutral P1 specificity group |
| US6339099B1 (en) | 1997-06-20 | 2002-01-15 | Dupont Pharmaceuticals Company | Guanidine mimics as factor Xa inhibitors |
| US5886191A (en) * | 1997-08-18 | 1999-03-23 | Dupont Pharmaceuticals Company | Amidinoindoles, amidinoazoles, and analogs thereof |
| JP2001524481A (ja) * | 1997-11-26 | 2001-12-04 | デュポン ファーマシューティカルズ カンパニー | αＶβ３アンタゴニストとしての１，３，４−チアジアゾール類および１，３，４−オキサジアゾール類 |
| US6271237B1 (en) | 1997-12-22 | 2001-08-07 | Dupont Pharmaceuticals Company | Nitrogen containing heteromatics with ortho-substituted P1s as factor Xa inhabitors |
| ES2230841T3 (es) | 1998-03-27 | 2005-05-01 | Bristol-Myers Squibb Pharma Company | Pirazolinas y triazolinas disustituidas como inhibidores del factor xa. |
| US6348504B1 (en) | 1999-03-30 | 2002-02-19 | Richard E. Olson | Oxime ethers as IIb/IIa antagonists |
| ES2197092T3 (es) | 1999-04-02 | 2004-01-01 | Bristol-Myers Squibb Pharma Company | Sulfonil arilos como inhibidores del factor xa. |
| EP1218376B1 (en) | 1999-09-10 | 2005-11-09 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| DE60208792T2 (de) | 2001-06-22 | 2006-08-31 | Merck & Co., Inc. | Tyrosin-kinase inhibitoren |
| CA2462000A1 (en) * | 2001-10-09 | 2003-04-17 | 3-Dimensional Pharmaceuticals, Inc. | Substituted diphenyloxazoles, the synthesis thereof, and the use thereof as fluorescence probes |
| MY151199A (en) * | 2001-11-02 | 2014-04-30 | Rigel Pharmaceuticals Inc | Substituted diphenyl heterocycles useful for treating hcv infection |
| US20050119251A1 (en) * | 2001-12-21 | 2005-06-02 | Jian-Min Fu | Nicotinamide derivatives and their use as therapeutic agents |
| MXPA04008901A (es) * | 2002-03-13 | 2004-11-26 | Euro Celtique Sa | Pirimidinas arilo sustituidas y el uso de las mismas. |
| US6872724B2 (en) * | 2002-07-24 | 2005-03-29 | Merck & Co., Inc. | Polymorphs with tyrosine kinase activity |
| US20040023978A1 (en) * | 2002-07-24 | 2004-02-05 | Yu Ren | Active salt forms with tyrosine kinase activity |
| US20040023981A1 (en) * | 2002-07-24 | 2004-02-05 | Yu Ren | Salt forms with tyrosine kinase activity |
| NZ537980A (en) * | 2002-08-23 | 2007-08-31 | Rigel Pharmaceuticals Inc | Pyridyl substituted heterocycles useful for treating or preventing HCV infection |
| US7326790B2 (en) * | 2003-05-02 | 2008-02-05 | Rigel Pharmaceuticals, Inc. | Diphenylisoxazole compounds and hydro isomers thereof |
| US7115642B2 (en) | 2003-05-02 | 2006-10-03 | Rigel Pharmaceuticals, Inc. | Substituted diphenyl isoxazoles, pyrazoles and oxadiazoles useful for treating HCV infection |
| US7220745B2 (en) * | 2003-05-15 | 2007-05-22 | Rigel Pharmaceuticals | Heterocyclic compounds useful to treat HCV |
| WO2005049065A2 (en) * | 2003-11-19 | 2005-06-02 | Rigel Pharmaceuticals, Inc. | Synergistic combinations of dihaloacetamide with interferon or ribavirin for treatment hcv infections |
| WO2005058848A1 (en) * | 2003-12-17 | 2005-06-30 | Merck & Co., Inc. | (3,4-disubstituted)propanoic carboxylates as s1p (edg) receptor agonists |
| US7514434B2 (en) | 2004-02-23 | 2009-04-07 | Rigel Pharmaceuticals, Inc. | Heterocyclic compounds having an oxadiazole moiety and hydro isomers thereof |
| WO2005097760A1 (en) * | 2004-03-26 | 2005-10-20 | Rigel Pharmaceuticals, Inc. | Heterocyclic anti-viral compounds comprising metabolizable moieties and their uses |
| MXPA06012130A (es) * | 2004-04-20 | 2007-01-31 | Transtech Pharma Inc | Derivados de tiazol y pirimidina substituidos como moduladores del receptor de melanocortina. |
| BRPI0515499A (pt) * | 2004-09-20 | 2008-07-29 | Xenon Pharmaceuticals Inc | derivados de piridina para a inibição de estearoil-coa-desaturase humana |
| AU2005286793A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-CoA desaturase enzymes |
| EP2266569A3 (en) | 2004-09-20 | 2011-03-09 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| AR051202A1 (es) * | 2004-09-20 | 2006-12-27 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
| EP2269610A3 (en) * | 2004-09-20 | 2011-03-09 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| TW200626148A (en) * | 2004-09-20 | 2006-08-01 | Xenon Pharmaceuticals Inc | Heterocyclic derivatives and their use as therapeutic agents |
| US7829712B2 (en) * | 2004-09-20 | 2010-11-09 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives for inhibiting human stearoyl-CoA-desaturase |
| WO2006034338A1 (en) * | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-coa desaturase |
| CN101084211A (zh) * | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 杂环衍生物及其作为治疗剂的用途 |
| AP2007004047A0 (en) * | 2005-01-20 | 2007-06-30 | Pfizer Ltd | Substituted triazole derivatives as oxtocin antagonists |
| CN101203498A (zh) * | 2005-05-02 | 2008-06-18 | 里格尔药品股份有限公司 | 包括可代谢部分的杂环抗病毒化合物及其用途 |
| JP2009513563A (ja) * | 2005-06-03 | 2009-04-02 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | ヒトのステアロイル−ＣｏＡデサチュラーゼ阻害剤としてのアミノチアゾール誘導体 |
| CA2731442A1 (en) * | 2008-08-29 | 2010-03-04 | Transtech Pharma, Inc. | Substituted aminothiazole derivatives, pharmaceutical compositions, and methods of use |
| US10252984B2 (en) * | 2011-10-27 | 2019-04-09 | Mayo Foundation For Medical Education And Research | Inhibiting G protein coupled receptor 6 kinase polypeptides |
| WO2013187496A1 (ja) | 2012-06-15 | 2013-12-19 | 田辺三菱製薬株式会社 | 芳香族複素環化合物 |
| HRP20220522T1 (hr) | 2014-08-04 | 2022-06-10 | Nuevolution A/S | Proizvoljno kondenzirani heterociklil-supstituirani derivati pirimidina koji su korisni za liječenje upalnih, metaboličkih, onkoloških i autoimunih bolesti |
| WO2017205459A1 (en) | 2016-05-26 | 2017-11-30 | Kalyra Pharmaceuticals, Inc. | Egfr inhibitor compounds |
| WO2020051424A1 (en) | 2018-09-07 | 2020-03-12 | Pic Therapeutics | Eif4e inhibitors and uses thereof |
| US11034669B2 (en) | 2018-11-30 | 2021-06-15 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| AU2020405446A1 (en) | 2019-12-20 | 2022-05-26 | Nuevolution A/S | Compounds active towards nuclear receptors |
| AR121506A1 (es) | 2020-03-03 | 2022-06-08 | Pic Therapeutics Inc | Inhibidores del eif4e y sus usos |
| AU2021245397A1 (en) | 2020-03-31 | 2022-10-20 | Nuevolution A/S | Compounds active towards nuclear receptors |
| US11613532B2 (en) | 2020-03-31 | 2023-03-28 | Nuevolution A/S | Compounds active towards nuclear receptors |
| EP4392422A1 (en) | 2021-08-25 | 2024-07-03 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
| WO2023028238A1 (en) | 2021-08-25 | 2023-03-02 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2096688A (en) * | 1987-08-14 | 1989-02-16 | Eli Lilly And Company | Improvements in or relating to leukotriene antagonists |
| AU2096788A (en) * | 1987-08-14 | 1989-02-16 | Eli Lilly And Company | Improvements in or relating to leukotriene antagonists |
| AU1040392A (en) * | 1991-01-24 | 1992-07-30 | Dr. Karl Thomae Gmbh | Biphenyl derivatives |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3792170A (en) * | 1972-03-14 | 1974-02-12 | Merck & Co Inc | Novel alkylsulfinyl derivatives for pain,fever and inflammation |
| DE3486009T2 (de) * | 1983-09-09 | 1993-04-15 | Takeda Chemical Industries Ltd | 5-pyridyl-1,3-thiazol-derivate, ihre herstellung und anwendung. |
| GB8725260D0 (en) * | 1987-10-28 | 1987-12-02 | Lilly Industries Ltd | Organic compounds |
| US5081127A (en) * | 1988-01-07 | 1992-01-14 | E. I. Du Pont De Nemours And Company | Substituted 1,2,3-triazole angiotensin II antagonists |
| EP0440183A1 (en) * | 1990-02-01 | 1991-08-07 | Takeda Chemical Industries, Ltd. | Oxazole compounds, their production and use |
| DE4107857A1 (de) * | 1991-03-12 | 1992-09-17 | Thomae Gmbh Dr K | Cyclische harnstoffderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
-
1991
- 1991-07-27 DE DE4124942A patent/DE4124942A1/de not_active Withdrawn
-
1992
- 1992-06-16 TW TW081104702A patent/TW225537B/zh active
- 1992-07-22 EP EP92112568A patent/EP0525629A3/de not_active Withdrawn
- 1992-07-24 NZ NZ243713A patent/NZ243713A/en unknown
- 1992-07-24 CA CA002074685A patent/CA2074685A1/en not_active Abandoned
- 1992-07-24 HU HU9202450A patent/HUT61747A/hu unknown
- 1992-07-24 IE IE242092A patent/IE922420A1/en not_active Application Discontinuation
- 1992-07-24 ZA ZA925573A patent/ZA925573B/xx unknown
- 1992-07-24 NO NO92922940A patent/NO922940L/no unknown
- 1992-07-24 IL IL10263892A patent/IL102638A/en not_active IP Right Cessation
- 1992-07-24 JP JP4198359A patent/JPH05221999A/ja active Pending
- 1992-07-24 MX MX9204354A patent/MX9204354A/es not_active IP Right Cessation
- 1992-07-24 FI FI923366A patent/FI923366L/fi not_active Application Discontinuation
- 1992-07-27 AU AU20569/92A patent/AU652064B2/en not_active Ceased
- 1992-07-27 KR KR1019920013494A patent/KR930002344A/ko not_active Withdrawn
-
1993
- 1993-11-08 US US08/148,724 patent/US5463071A/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2096688A (en) * | 1987-08-14 | 1989-02-16 | Eli Lilly And Company | Improvements in or relating to leukotriene antagonists |
| AU2096788A (en) * | 1987-08-14 | 1989-02-16 | Eli Lilly And Company | Improvements in or relating to leukotriene antagonists |
| AU1040392A (en) * | 1991-01-24 | 1992-07-30 | Dr. Karl Thomae Gmbh | Biphenyl derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| HUT61747A (en) | 1993-03-01 |
| FI923366A7 (fi) | 1993-01-28 |
| JPH05221999A (ja) | 1993-08-31 |
| EP0525629A3 (en) | 1997-03-19 |
| MX9204354A (es) | 1993-01-01 |
| NO922940L (no) | 1993-01-28 |
| FI923366A0 (fi) | 1992-07-24 |
| IL102638A0 (en) | 1993-01-14 |
| FI923366L (fi) | 1993-01-28 |
| CA2074685A1 (en) | 1993-01-28 |
| IL102638A (en) | 1996-10-16 |
| US5463071A (en) | 1995-10-31 |
| IE922420A1 (en) | 1993-01-27 |
| DE4124942A1 (de) | 1993-01-28 |
| EP0525629A2 (de) | 1993-02-03 |
| ZA925573B (en) | 1994-01-24 |
| NO922940D0 (no) | 1992-07-24 |
| HU9202450D0 (en) | 1992-10-28 |
| AU2056992A (en) | 1993-01-28 |
| NZ243713A (en) | 1995-06-27 |
| KR930002344A (ko) | 1993-02-23 |
| TW225537B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1994-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU652064B2 (en) | Heterocyclic compounds | |
| US5817677A (en) | 5-membered heterocycles, medicaments containing these compounds, their use and processes for their preparation | |
| US5650424A (en) | Cyclic urea derivatives, pharmaceutical compositions containing these compounds and processes for preparing them | |
| US5326776A (en) | Angiotensin II receptor antagonists | |
| US5434150A (en) | Condensed 5-membered heterocyclic compounds, processes for preparing them and pharmaceutical preparations containing these compounds | |
| EP1194425B1 (de) | Substituierte benzimidazole | |
| JPH072851A (ja) | ５員複素環化合物、それらの調製方法及びこれらの化合物を含む医薬組成物 | |
| AU2007211319B2 (en) | Substituted imidazole derivatives and their use as PTPase inhibitors | |
| JP4224215B2 (ja) | ベンゾイミダゾール、それらの調製及び医薬組成物としてのそれらの使用 | |
| CA2076311A1 (en) | Cyclic imino derivatives, pharmaceutical compositions containing these compounds and processes for preparing them | |
| SK94393A3 (en) | Cyclic derivatives of urea, process for their production and their pharmaceutical agents with the content of those | |
| DE19951360A1 (de) | Substituierte Indole | |
| CA2197789A1 (en) | Cyclic urea derivatives, pharmaceutical compositions comprising these compounds and processes for their preparation | |
| BRPI0215277B1 (pt) | dicetopiperazinas substituídas como antagonistas da ocitocina | |
| JPS6253976A (ja) | 複素環式カルボン酸誘導体 | |
| US5852192A (en) | Cyclic urea derivatives, pharmaceutical compositions containing these compounds and processes for preparing them | |
| AU729341B2 (en) | Hydantoin derivatives having an inhibitory activity for farnesyl transferase | |
| US20040073025A1 (en) | Thrombin inhibitors | |
| JPH0625159A (ja) | 環状イミノ誘導体、これらの化合物を含む医薬組成物及びそれらの調製法 | |
| DE19829964A1 (de) | Benzimidazole, deren Herstellung und deren Verwendung als Arzneimittel | |
| DE19857202A1 (de) | Benzimidazole, deren Herstellung und deren Verwendung als Arzneimittel | |
| CZ200147A3 (cs) | Benzimidazoly, jejich výroba a použití jako léčivo | |
| AU2002240389A1 (en) | Thrombin inhibitors | |
| MXPA98002988A (en) | Heterociclos of 5 members, cines containing these compounds, their use and processes to supreparate |