JP5268897B2 - フェニルペンタジエノイル誘導体およびｐａｒ１拮抗薬としてのそれらの使用 - Google Patents
フェニルペンタジエノイル誘導体およびｐａｒ１拮抗薬としてのそれらの使用 Download PDFInfo
- Publication number
- JP5268897B2 JP5268897B2 JP2009515858A JP2009515858A JP5268897B2 JP 5268897 B2 JP5268897 B2 JP 5268897B2 JP 2009515858 A JP2009515858 A JP 2009515858A JP 2009515858 A JP2009515858 A JP 2009515858A JP 5268897 B2 JP5268897 B2 JP 5268897B2
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- penta
- piperazin
- dien
- general formula
- 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.)
- Expired - Fee Related
Links
- -1 Phenylpentadienoyl Chemical class 0.000 title claims description 10
- 229940098892 Protease-activated receptor-1 antagonist Drugs 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims description 75
- 238000000034 method Methods 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 30
- 150000001412 amines Chemical class 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 239000002327 cardiovascular agent Substances 0.000 claims description 5
- 229940125692 cardiovascular agent Drugs 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- FIHTUEXLBGQJPI-UHFFFAOYSA-N 1-(4-cyclopentylpiperazin-1-yl)-5-(2-fluorophenyl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC=C1C=CC=CC(=O)N1CCN(C2CCCC2)CC1 FIHTUEXLBGQJPI-UHFFFAOYSA-N 0.000 claims description 3
- RWAGJRSRCSOWHV-UHFFFAOYSA-N 5-(2,6-difluorophenyl)-1-(4-phenylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC(F)=C1C=CC=CC(=O)N1CCN(C=2C=CC=CC=2)CC1 RWAGJRSRCSOWHV-UHFFFAOYSA-N 0.000 claims description 3
- LWOVQLFJUFSKKR-UHFFFAOYSA-N 5-(2-chlorophenyl)-1-(4-cyclopentylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound ClC1=CC=CC=C1C=CC=CC(=O)N1CCN(C2CCCC2)CC1 LWOVQLFJUFSKKR-UHFFFAOYSA-N 0.000 claims description 3
- DRSBEGHOVKMDFR-UHFFFAOYSA-N 5-(2-nitrophenyl)-1-(4-phenylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(C=2C=CC=CC=2)CC1 DRSBEGHOVKMDFR-UHFFFAOYSA-N 0.000 claims description 3
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 3
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- 229940127218 antiplatelet drug Drugs 0.000 claims description 3
- 238000011161 development Methods 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 230000004761 fibrosis Effects 0.000 claims description 3
- 208000019423 liver disease Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 2
- GDMFQEYMRVQWAD-UHFFFAOYSA-N 2-[5-oxo-5-(4-pyridin-2-ylpiperazin-1-yl)penta-1,3-dienyl]benzonitrile Chemical compound C1CN(C=2N=CC=CC=2)CCN1C(=O)C=CC=CC1=CC=CC=C1C#N GDMFQEYMRVQWAD-UHFFFAOYSA-N 0.000 claims description 2
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 claims description 2
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 claims description 2
- 108010056764 Eptifibatide Proteins 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000019693 Lung disease Diseases 0.000 claims description 2
- 208000007718 Stable Angina Diseases 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 206010047249 Venous thrombosis Diseases 0.000 claims description 2
- 229960000446 abciximab Drugs 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims description 2
- 229960003009 clopidogrel Drugs 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 229960004468 eptifibatide Drugs 0.000 claims description 2
- GLGOPUHVAZCPRB-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CN=C2[C]1C=CC=C2 GLGOPUHVAZCPRB-LROMGURASA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- KAVSMINTEBGDTI-UHFFFAOYSA-N pyridine;thiophene Chemical group C=1C=CSC=1.C1=CC=NC=C1 KAVSMINTEBGDTI-UHFFFAOYSA-N 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 claims description 2
- 229960005001 ticlopidine Drugs 0.000 claims description 2
- 229960003425 tirofiban Drugs 0.000 claims description 2
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims 6
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 claims 2
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 claims 2
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims 2
- VIYJOYNKGXZRKW-UHFFFAOYSA-N 1-(4-butylpiperazin-1-yl)-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound C1CN(CCCC)CCN1C(=O)C=CC=CC1=CC=CC=C1[N+]([O-])=O VIYJOYNKGXZRKW-UHFFFAOYSA-N 0.000 claims 1
- MULCNWFWOQIAOK-UHFFFAOYSA-N 1-(4-cyclohexylpiperazin-1-yl)-5-(2,6-difluorophenyl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC(F)=C1C=CC=CC(=O)N1CCN(C2CCCCC2)CC1 MULCNWFWOQIAOK-UHFFFAOYSA-N 0.000 claims 1
- XCKKENKKNBFFSM-UHFFFAOYSA-N 1-(4-cyclohexylpiperazin-1-yl)-5-(2-fluorophenyl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC=C1C=CC=CC(=O)N1CCN(C2CCCCC2)CC1 XCKKENKKNBFFSM-UHFFFAOYSA-N 0.000 claims 1
- SAJBTFAPFJTUMT-UHFFFAOYSA-N 1-(4-cyclohexylpiperazin-1-yl)-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(C2CCCCC2)CC1 SAJBTFAPFJTUMT-UHFFFAOYSA-N 0.000 claims 1
- BSUOPQDAPWBOFZ-UHFFFAOYSA-N 1-(4-cyclopentylpiperazin-1-yl)-5-(2,6-difluorophenyl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC(F)=C1C=CC=CC(=O)N1CCN(C2CCCC2)CC1 BSUOPQDAPWBOFZ-UHFFFAOYSA-N 0.000 claims 1
- NHJKEXDXBUKOIQ-UHFFFAOYSA-N 1-(4-cyclopentylpiperazin-1-yl)-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(C2CCCC2)CC1 NHJKEXDXBUKOIQ-UHFFFAOYSA-N 0.000 claims 1
- ILNSDBAEPQSNFQ-UHFFFAOYSA-N 1-[4-(3-chlorophenyl)piperazin-1-yl]-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(C=2C=C(Cl)C=CC=2)CC1 ILNSDBAEPQSNFQ-UHFFFAOYSA-N 0.000 claims 1
- SSCCADCLSFMOBL-UHFFFAOYSA-N 1-[4-(3-chloropropyl)piperazin-1-yl]-5-(2,6-difluorophenyl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC(F)=C1C=CC=CC(=O)N1CCN(CCCCl)CC1 SSCCADCLSFMOBL-UHFFFAOYSA-N 0.000 claims 1
- JJUWYPRAUGXXGP-UHFFFAOYSA-N 1-[4-(3-chloropropyl)piperazin-1-yl]-5-(2-fluorophenyl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC=C1C=CC=CC(=O)N1CCN(CCCCl)CC1 JJUWYPRAUGXXGP-UHFFFAOYSA-N 0.000 claims 1
- QXBUOOFTTYVKTJ-UHFFFAOYSA-N 1-[4-(3-chloropropyl)piperazin-1-yl]-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(CCCCl)CC1 QXBUOOFTTYVKTJ-UHFFFAOYSA-N 0.000 claims 1
- KLKOJWGACZECEJ-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)piperazin-1-yl]-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(C=2C=CC(F)=CC=2)CC1 KLKOJWGACZECEJ-UHFFFAOYSA-N 0.000 claims 1
- ILVIRTJZAPSIDO-UHFFFAOYSA-N 1-[4-(cyclopentylmethyl)piperazin-1-yl]-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(CC2CCCC2)CC1 ILVIRTJZAPSIDO-UHFFFAOYSA-N 0.000 claims 1
- AUTMYWIQROXELN-UHFFFAOYSA-N 1-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]-5-(2-nitrophenyl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(CC=2C=CC(F)=CC=2)CC1 AUTMYWIQROXELN-UHFFFAOYSA-N 0.000 claims 1
- LASVNPWDTRSLEG-UHFFFAOYSA-N 2-[5-(4-cyclohexylpiperazin-1-yl)-5-oxopenta-1,3-dienyl]benzonitrile Chemical compound C1CN(C2CCCCC2)CCN1C(=O)C=CC=CC1=CC=CC=C1C#N LASVNPWDTRSLEG-UHFFFAOYSA-N 0.000 claims 1
- MCHVJUNYNVRDFT-UHFFFAOYSA-N 2-[5-(4-cyclopentylpiperazin-1-yl)-5-oxopenta-1,3-dienyl]benzonitrile Chemical compound C1CN(C2CCCC2)CCN1C(=O)C=CC=CC1=CC=CC=C1C#N MCHVJUNYNVRDFT-UHFFFAOYSA-N 0.000 claims 1
- JDVJPBLMTAKTOG-UHFFFAOYSA-N 2-[5-[4-(2-hydroxyphenyl)piperazin-1-yl]-5-oxopenta-1,3-dienyl]benzonitrile Chemical compound OC1=CC=CC=C1N1CCN(C(=O)C=CC=CC=2C(=CC=CC=2)C#N)CC1 JDVJPBLMTAKTOG-UHFFFAOYSA-N 0.000 claims 1
- FWAVEOMITGRLGC-UHFFFAOYSA-N 2-[5-[4-(3-chlorophenyl)piperazin-1-yl]-5-oxopenta-1,3-dienyl]benzonitrile Chemical compound ClC1=CC=CC(N2CCN(CC2)C(=O)C=CC=CC=2C(=CC=CC=2)C#N)=C1 FWAVEOMITGRLGC-UHFFFAOYSA-N 0.000 claims 1
- CVWSGUBYHIQXGZ-UHFFFAOYSA-N 2-[5-[4-(3-chloropropyl)piperazin-1-yl]-5-oxopenta-1,3-dienyl]benzonitrile Chemical compound C1CN(CCCCl)CCN1C(=O)C=CC=CC1=CC=CC=C1C#N CVWSGUBYHIQXGZ-UHFFFAOYSA-N 0.000 claims 1
- VAMKKNAYGYORQD-UHFFFAOYSA-N 2-[5-[4-[(2,4-dimethylphenyl)methyl]-1,4-diazepan-1-yl]-5-oxopenta-1,3-dienyl]benzonitrile Chemical compound CC1=CC(C)=CC=C1CN1CCN(C(=O)C=CC=CC=2C(=CC=CC=2)C#N)CCC1 VAMKKNAYGYORQD-UHFFFAOYSA-N 0.000 claims 1
- RFKPLCHFTCIBTH-UHFFFAOYSA-N 2-[5-[4-[(2-methylphenyl)methyl]-1,4-diazepan-1-yl]-5-oxopenta-1,3-dienyl]benzonitrile Chemical compound CC1=CC=CC=C1CN1CCN(C(=O)C=CC=CC=2C(=CC=CC=2)C#N)CCC1 RFKPLCHFTCIBTH-UHFFFAOYSA-N 0.000 claims 1
- IKTYNORQZZVTKQ-UHFFFAOYSA-N 5-(2,6-difluorophenyl)-1-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]penta-2,4-dien-1-one Chemical compound C1=CC(F)=CC=C1CN1CCN(C(=O)C=CC=CC=2C(=CC=CC=2F)F)CC1 IKTYNORQZZVTKQ-UHFFFAOYSA-N 0.000 claims 1
- BFXVHPFWZWBLBR-UHFFFAOYSA-N 5-(2-chlorophenyl)-1-(4-cycloheptylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound ClC1=CC=CC=C1C=CC=CC(=O)N1CCN(C2CCCCCC2)CC1 BFXVHPFWZWBLBR-UHFFFAOYSA-N 0.000 claims 1
- XEIHWWFJWFDMTH-UHFFFAOYSA-N 5-(2-chlorophenyl)-1-(4-cyclohexylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound ClC1=CC=CC=C1C=CC=CC(=O)N1CCN(C2CCCCC2)CC1 XEIHWWFJWFDMTH-UHFFFAOYSA-N 0.000 claims 1
- PNADLAXDYOSOMG-UHFFFAOYSA-N 5-(2-chlorophenyl)-1-(4-pyridin-2-ylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound ClC1=CC=CC=C1C=CC=CC(=O)N1CCN(C=2N=CC=CC=2)CC1 PNADLAXDYOSOMG-UHFFFAOYSA-N 0.000 claims 1
- DOWFQZLUHHBSOY-UHFFFAOYSA-N 5-(2-chlorophenyl)-1-[4-(3-chloropropyl)piperazin-1-yl]penta-2,4-dien-1-one Chemical compound C1CN(CCCCl)CCN1C(=O)C=CC=CC1=CC=CC=C1Cl DOWFQZLUHHBSOY-UHFFFAOYSA-N 0.000 claims 1
- VTQYCILIROXFPL-UHFFFAOYSA-N 5-(2-chlorophenyl)-1-[4-[(2-fluorophenyl)methyl]-1,4-diazepan-1-yl]penta-2,4-dien-1-one Chemical compound FC1=CC=CC=C1CN1CCN(C(=O)C=CC=CC=2C(=CC=CC=2)Cl)CCC1 VTQYCILIROXFPL-UHFFFAOYSA-N 0.000 claims 1
- PYGISMBXLOJPHL-UHFFFAOYSA-N 5-(2-chlorophenyl)-1-[4-[(2-methylphenyl)methyl]-1,4-diazepan-1-yl]penta-2,4-dien-1-one Chemical compound CC1=CC=CC=C1CN1CCN(C(=O)C=CC=CC=2C(=CC=CC=2)Cl)CCC1 PYGISMBXLOJPHL-UHFFFAOYSA-N 0.000 claims 1
- SRVLVCKOIHOCRT-UHFFFAOYSA-N 5-(2-fluorophenyl)-1-(4-phenylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC=C1C=CC=CC(=O)N1CCN(C=2C=CC=CC=2)CC1 SRVLVCKOIHOCRT-UHFFFAOYSA-N 0.000 claims 1
- SPAAPLUKKOCJCE-UHFFFAOYSA-N 5-(2-fluorophenyl)-1-(4-pyridin-2-ylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound FC1=CC=CC=C1C=CC=CC(=O)N1CCN(C=2N=CC=CC=2)CC1 SPAAPLUKKOCJCE-UHFFFAOYSA-N 0.000 claims 1
- APHUBFYHUBPJKO-UHFFFAOYSA-N 5-(2-nitrophenyl)-1-(4-pyridin-2-ylpiperazin-1-yl)penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(C=2N=CC=CC=2)CC1 APHUBFYHUBPJKO-UHFFFAOYSA-N 0.000 claims 1
- OVSDRQWOOCDUEI-UHFFFAOYSA-N 5-(2-nitrophenyl)-1-[4-(thiophen-3-ylmethyl)piperazin-1-yl]penta-2,4-dien-1-one Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=CC(=O)N1CCN(CC2=CSC=C2)CC1 OVSDRQWOOCDUEI-UHFFFAOYSA-N 0.000 claims 1
- 208000032845 Atrial Remodeling Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 208000026106 cerebrovascular disease Diseases 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 125000000168 pyrrolyl group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 102000032626 PAR-1 Receptor Human genes 0.000 description 18
- 108010070519 PAR-1 Receptor Proteins 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 13
- 238000001819 mass spectrum Methods 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 235000002639 sodium chloride Nutrition 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 208000007536 Thrombosis Diseases 0.000 description 8
- 229940125904 compound 1 Drugs 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 7
- 108090000190 Thrombin Proteins 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 229910052791 calcium Inorganic materials 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 150000007529 inorganic bases Chemical class 0.000 description 7
- 229960004072 thrombin Drugs 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000002798 polar solvent Substances 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000006188 syrup Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 210000001008 atrial appendage Anatomy 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 210000001715 carotid artery Anatomy 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000011630 iodine Chemical group 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 229940044551 receptor antagonist Drugs 0.000 description 4
- 239000002464 receptor antagonist Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010061216 Infarction Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000002785 anti-thrombosis Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002592 echocardiography Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 0 *C(C=CC=Cc1c(*)cccc1*)=* Chemical compound *C(C=CC=Cc1c(*)cccc1*)=* 0.000 description 2
- PVMCQBPJKPMOKM-UHFFFAOYSA-N 1-cyclopentylpiperazine Chemical compound C1CCCC1N1CCNCC1 PVMCQBPJKPMOKM-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- HJBLUNHMOKFZQX-UHFFFAOYSA-N 3-hydroxy-1,2,3-benzotriazin-4-one Chemical compound C1=CC=C2C(=O)N(O)N=NC2=C1 HJBLUNHMOKFZQX-UHFFFAOYSA-N 0.000 description 2
- IICCLYANAQEHCI-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 IICCLYANAQEHCI-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-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
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- PTPUOMXKXCCSEN-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-dichloro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(Cl)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(Cl)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O PTPUOMXKXCCSEN-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000010339 dilation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- SDGAEBKMHIPSAC-ONEGZZNKSA-N ethyl (e)-4-oxobut-2-enoate Chemical compound CCOC(=O)\C=C\C=O SDGAEBKMHIPSAC-ONEGZZNKSA-N 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 2
- 150000004714 phosphonium salts Chemical class 0.000 description 2
- 239000003880 polar aprotic solvent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229930187593 rose bengal Natural products 0.000 description 2
- 229940081623 rose bengal Drugs 0.000 description 2
- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-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
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- QGXNHCXKWFNKCG-UHFFFAOYSA-N 2-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC=C1C#N QGXNHCXKWFNKCG-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- ABQCTYYKKNJKPK-UHFFFAOYSA-N 3-(2,6-difluorophenyl)prop-2-enal Chemical compound FC1=CC=CC(F)=C1C=CC=O ABQCTYYKKNJKPK-UHFFFAOYSA-N 0.000 description 1
- VMSMELHEXDVEDE-UHFFFAOYSA-N 3-(2-nitrophenyl)prop-2-enal Chemical compound [O-][N+](=O)C1=CC=CC=C1C=CC=O VMSMELHEXDVEDE-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
- HTAGCJYTFLDEMJ-UHFFFAOYSA-N 5-(2,6-difluorophenyl)penta-2,4-dienoic acid Chemical compound OC(=O)C=CC=CC1=C(F)C=CC=C1F HTAGCJYTFLDEMJ-UHFFFAOYSA-N 0.000 description 1
- RDEPRHUXLADLAG-UHFFFAOYSA-N 5-(2-cyanophenyl)penta-2,4-dienoic acid Chemical compound OC(=O)C=CC=CC1=CC=CC=C1C#N RDEPRHUXLADLAG-UHFFFAOYSA-N 0.000 description 1
- XXZHAMVSMPBWRE-UHFFFAOYSA-N 5-(2-fluorophenyl)penta-2,4-dienoic acid Chemical compound OC(=O)C=CC=CC1=CC=CC=C1F XXZHAMVSMPBWRE-UHFFFAOYSA-N 0.000 description 1
- IJXZQTLMGOOIAI-UHFFFAOYSA-N 5-(2-nitrophenyl)penta-2,4-dienoic acid Chemical compound OC(=O)C=CC=CC1=CC=CC=C1[N+]([O-])=O IJXZQTLMGOOIAI-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
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- VLBHSXGYPUVRNW-RVCHVYMYSA-N C(C)(=O)OCC.C(#N)C1=C(C=CC=C1)/C=C/C=C/C(=O)O Chemical compound C(C)(=O)OCC.C(#N)C1=C(C=CC=C1)/C=C/C=C/C(=O)O VLBHSXGYPUVRNW-RVCHVYMYSA-N 0.000 description 1
- RSDSIRCCAWVZCS-UHFFFAOYSA-N C(C)(=O)OCCP(=O)(OCC)OCC.FC1=C(C(=CC=C1)F)C=CC=CC(=O)OCC Chemical compound C(C)(=O)OCCP(=O)(OCC)OCC.FC1=C(C(=CC=C1)F)C=CC=CC(=O)OCC RSDSIRCCAWVZCS-UHFFFAOYSA-N 0.000 description 1
- DHOGHHYRBNKVLV-UHFFFAOYSA-N C(C)(C)N(CC)C(C)C.O=C(C=CC=CC1=C(C#N)C=CC=C1)N1CCN(CC1)C1=NC=CC=C1 Chemical compound C(C)(C)N(CC)C(C)C.O=C(C=CC=CC1=C(C#N)C=CC=C1)N1CCN(CC1)C1=NC=CC=C1 DHOGHHYRBNKVLV-UHFFFAOYSA-N 0.000 description 1
- XAZGEVZVGVEYSD-UHFFFAOYSA-N C(C)OP(=O)(OCC)CC=CC(=O)OCC.ClC1=C(C=CC=C1)C=CC=CC(=O)OCC Chemical compound C(C)OP(=O)(OCC)CC=CC(=O)OCC.ClC1=C(C=CC=C1)C=CC=CC(=O)OCC XAZGEVZVGVEYSD-UHFFFAOYSA-N 0.000 description 1
- 108010091478 C186 65 Proteins 0.000 description 1
- JBISKJXFQRSCSC-UHFFFAOYSA-N CC(=O)OCCP(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound CC(=O)OCCP(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 JBISKJXFQRSCSC-UHFFFAOYSA-N 0.000 description 1
- SMMOIBIQBFCWEF-UHFFFAOYSA-N CC(C)N1C(C)(C)CCNCC1 Chemical compound CC(C)N1C(C)(C)CCNCC1 SMMOIBIQBFCWEF-UHFFFAOYSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 206010016803 Fluid overload Diseases 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
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 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 1
- 206010027476 Metastases Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 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 1
- 102000003790 Thrombin receptors Human genes 0.000 description 1
- 108090000166 Thrombin receptors Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- CPGKMLVTFNUAHL-UHFFFAOYSA-N [Ca].[Ca] Chemical compound [Ca].[Ca] CPGKMLVTFNUAHL-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000006502 antiplatelets effects Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 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
- 230000028956 calcium-mediated signaling Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000005242 cardiac chamber Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000009843 endothelial lesion Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- LXLODBXSCRTXFG-BQYQJAHWSA-N ethyl (e)-4-diethoxyphosphorylbut-2-enoate Chemical compound CCOC(=O)\C=C\CP(=O)(OCC)OCC LXLODBXSCRTXFG-BQYQJAHWSA-N 0.000 description 1
- CGYBTPXBQNJVNW-UHFFFAOYSA-N ethyl 5-(2-cyanophenyl)penta-2,4-dienoate Chemical compound CCOC(=O)C=CC=CC1=CC=CC=C1C#N CGYBTPXBQNJVNW-UHFFFAOYSA-N 0.000 description 1
- QNRSVZBNNZUZJL-UHFFFAOYSA-N ethyl 5-(2-fluorophenyl)penta-2,4-dienoate Chemical compound CCOC(=O)C=CC=CC1=CC=CC=C1F QNRSVZBNNZUZJL-UHFFFAOYSA-N 0.000 description 1
- XQHZCJABBFVTGA-UHFFFAOYSA-N ethyl 5-(2-nitrophenyl)penta-2,4-dienoate Chemical compound CCOC(=O)C=CC=CC1=CC=CC=C1[N+]([O-])=O XQHZCJABBFVTGA-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000011554 guinea pig model Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 238000011327 histological measurement Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000005248 left atrial appendage Anatomy 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 210000005247 right atrial appendage Anatomy 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0605418 | 2006-06-19 | ||
| FR0605418A FR2902427B1 (fr) | 2006-06-19 | 2006-06-19 | Derives de phenylpentadienoyle |
| PCT/EP2007/056078 WO2007147822A1 (en) | 2006-06-19 | 2007-06-19 | Phenylpentadienoyl derivatives and their use as par 1 antagonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2009541258A JP2009541258A (ja) | 2009-11-26 |
| JP2009541258A5 JP2009541258A5 (enExample) | 2010-07-22 |
| JP5268897B2 true JP5268897B2 (ja) | 2013-08-21 |
Family
ID=37622010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009515858A Expired - Fee Related JP5268897B2 (ja) | 2006-06-19 | 2007-06-19 | フェニルペンタジエノイル誘導体およびｐａｒ１拮抗薬としてのそれらの使用 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US8022064B2 (enExample) |
| EP (1) | EP2046748B1 (enExample) |
| JP (1) | JP5268897B2 (enExample) |
| KR (1) | KR20090031735A (enExample) |
| CN (1) | CN101472894B (enExample) |
| AR (1) | AR061519A1 (enExample) |
| AT (1) | ATE500223T1 (enExample) |
| AU (1) | AU2007263049B2 (enExample) |
| BR (1) | BRPI0713582A2 (enExample) |
| CA (1) | CA2655728A1 (enExample) |
| DE (1) | DE602007012888D1 (enExample) |
| ES (1) | ES2361061T3 (enExample) |
| FR (1) | FR2902427B1 (enExample) |
| IL (1) | IL195869A0 (enExample) |
| MA (1) | MA31131B1 (enExample) |
| MX (1) | MX2008016446A (enExample) |
| NO (1) | NO20090269L (enExample) |
| NZ (1) | NZ573591A (enExample) |
| RU (1) | RU2440985C2 (enExample) |
| TN (1) | TNSN08521A1 (enExample) |
| TW (1) | TW200815371A (enExample) |
| UA (1) | UA97370C2 (enExample) |
| WO (1) | WO2007147822A1 (enExample) |
| ZA (1) | ZA200810629B (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104496879A (zh) * | 2015-01-13 | 2015-04-08 | 佛山市赛维斯医药科技有限公司 | 一种含腈基苯和二烯氟代金刚烷结构的化合物和用途 |
| US20200157048A1 (en) * | 2018-03-27 | 2020-05-21 | Bioway., Inc | (2e,4e)-5-phenyl-penta-2,4-dien-1-one derivative |
| CN118852057B (zh) * | 2024-05-29 | 2025-09-26 | 赣南医科大学 | 胡椒碱或其衍生物的应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61106564A (ja) * | 1984-10-30 | 1986-05-24 | Terumo Corp | 不飽和脂肪酸アミド誘導体およびこれを含有する血小板凝集抑制剤 |
| JPS61137866A (ja) * | 1984-12-07 | 1986-06-25 | Terumo Corp | イミダゾ−ル誘導体およびこれを含有する血小板凝集抑制剤 |
| US4792553A (en) * | 1986-02-04 | 1988-12-20 | Terumo Kabushiki Kaisha | Diene derivatives and vasodilators containing the same |
| HK1049004A1 (en) * | 2000-01-20 | 2003-04-25 | Eisai Co., Ltd. | Nitrogenous cyclic compounds and pharmaceutical compositions containing the same |
| FR2917622B1 (fr) * | 2007-06-19 | 2009-10-23 | Pierre Fabre Medicament Sa | Utilisation d'un antagoniste par1 dans le traitement de la fibrillation atriale. |
-
2006
- 2006-06-19 FR FR0605418A patent/FR2902427B1/fr not_active Expired - Fee Related
-
2007
- 2007-06-19 CN CN2007800223489A patent/CN101472894B/zh not_active Expired - Fee Related
- 2007-06-19 WO PCT/EP2007/056078 patent/WO2007147822A1/en not_active Ceased
- 2007-06-19 BR BRPI0713582-3A patent/BRPI0713582A2/pt not_active Application Discontinuation
- 2007-06-19 JP JP2009515858A patent/JP5268897B2/ja not_active Expired - Fee Related
- 2007-06-19 ES ES07765492T patent/ES2361061T3/es active Active
- 2007-06-19 AT AT07765492T patent/ATE500223T1/de not_active IP Right Cessation
- 2007-06-19 EP EP07765492A patent/EP2046748B1/en active Active
- 2007-06-19 CA CA002655728A patent/CA2655728A1/en not_active Abandoned
- 2007-06-19 UA UAA200900375A patent/UA97370C2/ru unknown
- 2007-06-19 AU AU2007263049A patent/AU2007263049B2/en not_active Ceased
- 2007-06-19 AR ARP070102684A patent/AR061519A1/es not_active Application Discontinuation
- 2007-06-19 KR KR1020097000945A patent/KR20090031735A/ko not_active Ceased
- 2007-06-19 US US12/305,447 patent/US8022064B2/en not_active Expired - Fee Related
- 2007-06-19 MX MX2008016446A patent/MX2008016446A/es active IP Right Grant
- 2007-06-19 RU RU2008149917/04A patent/RU2440985C2/ru not_active IP Right Cessation
- 2007-06-19 NZ NZ573591A patent/NZ573591A/en not_active IP Right Cessation
- 2007-06-19 DE DE602007012888T patent/DE602007012888D1/de active Active
- 2007-06-20 TW TW096122075A patent/TW200815371A/zh unknown
-
2008
- 2008-12-11 IL IL195869A patent/IL195869A0/en unknown
- 2008-12-16 TN TNP2008000521A patent/TNSN08521A1/en unknown
- 2008-12-17 ZA ZA2008/10629A patent/ZA200810629B/en unknown
- 2008-12-18 MA MA31483A patent/MA31131B1/fr unknown
-
2009
- 2009-01-16 NO NO20090269A patent/NO20090269L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007263049A1 (en) | 2007-12-27 |
| CA2655728A1 (en) | 2007-12-27 |
| DE602007012888D1 (de) | 2011-04-14 |
| ES2361061T3 (es) | 2011-06-13 |
| IL195869A0 (en) | 2009-09-01 |
| FR2902427A1 (fr) | 2007-12-21 |
| EP2046748A1 (en) | 2009-04-15 |
| CN101472894B (zh) | 2012-09-05 |
| EP2046748B1 (en) | 2011-03-02 |
| AR061519A1 (es) | 2008-09-03 |
| UA97370C2 (ru) | 2012-02-10 |
| CN101472894A (zh) | 2009-07-01 |
| WO2007147822A1 (en) | 2007-12-27 |
| NZ573591A (en) | 2010-10-29 |
| TW200815371A (en) | 2008-04-01 |
| FR2902427B1 (fr) | 2008-08-22 |
| RU2440985C2 (ru) | 2012-01-27 |
| BRPI0713582A2 (pt) | 2012-10-23 |
| JP2009541258A (ja) | 2009-11-26 |
| MX2008016446A (es) | 2009-01-22 |
| US8022064B2 (en) | 2011-09-20 |
| ZA200810629B (en) | 2010-02-24 |
| RU2008149917A (ru) | 2010-07-27 |
| ATE500223T1 (de) | 2011-03-15 |
| MA31131B1 (fr) | 2010-02-01 |
| NO20090269L (no) | 2009-02-27 |
| TNSN08521A1 (en) | 2010-04-14 |
| KR20090031735A (ko) | 2009-03-27 |
| AU2007263049B2 (en) | 2011-10-27 |
| US20100003260A1 (en) | 2010-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5356222B2 (ja) | シンナモイル−ピペラジン誘導体およびｐａｒ−１拮抗薬としてのそれらの使用 | |
| JP5268897B2 (ja) | フェニルペンタジエノイル誘導体およびｐａｒ１拮抗薬としてのそれらの使用 | |
| HK1129385A (en) | Phenylpentadienoyl derivatives and their use as par 1 antagonists | |
| CN109879840B (zh) | 4-哌嗪甲基-7-羟基苯并呋喃类化合物及其医药用途 | |
| HK1127353B (en) | Cinnamoyl-piperazine derivatives and their use as par- i antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100603 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100603 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121016 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130116 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130123 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130306 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130405 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130507 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5268897 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |