ES2625029T3 - Derivados del imidazotiadiazol como inhibidores del receptor 4 activado por proteasa (Par4) para el tratamiento de la agregación de plaquetas - Google Patents
Derivados del imidazotiadiazol como inhibidores del receptor 4 activado por proteasa (Par4) para el tratamiento de la agregación de plaquetas Download PDFInfo
- Publication number
- ES2625029T3 ES2625029T3 ES13719361.1T ES13719361T ES2625029T3 ES 2625029 T3 ES2625029 T3 ES 2625029T3 ES 13719361 T ES13719361 T ES 13719361T ES 2625029 T3 ES2625029 T3 ES 2625029T3
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- alkoxy
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- 238000011282 treatment Methods 0.000 title claims description 7
- 208000010110 spontaneous platelet aggregation Diseases 0.000 title description 14
- 239000003112 inhibitor Substances 0.000 title description 7
- BOXRDDIXJOUZLV-UHFFFAOYSA-N 2h-imidazo[4,5-d]thiadiazole Chemical class N1SC2=NC=NC2=N1 BOXRDDIXJOUZLV-UHFFFAOYSA-N 0.000 title description 5
- 102000004885 Protease-activated receptor 4 Human genes 0.000 title description 3
- 108090001010 Protease-activated receptor 4 Proteins 0.000 title description 3
- 101150101745 F2rl3 gene Proteins 0.000 title description 2
- 101150114311 PAWR gene Proteins 0.000 title description 2
- 102100040853 PRKC apoptosis WT1 regulator protein Human genes 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 52
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 49
- 125000005843 halogen group Chemical group 0.000 claims abstract description 47
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 40
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 39
- -1 carboxy, carbonyl Chemical group 0.000 claims abstract description 36
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 239000012453 solvate Substances 0.000 claims abstract description 24
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 23
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000011737 fluorine Substances 0.000 claims abstract description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 17
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 12
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 9
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 5
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
- 150000001721 carbon Chemical group 0.000 claims abstract description 3
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 48
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 230000009424 thromboembolic effect Effects 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 8
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 claims description 4
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 4
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical group F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 2
- 108010081348 HRT1 protein Hairy Chemical group 0.000 claims description 2
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 230000002776 aggregation Effects 0.000 claims 2
- 238000004220 aggregation Methods 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000003836 peripheral circulation Effects 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 description 6
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- 230000005764 inhibitory process Effects 0.000 description 5
- 229940127218 antiplatelet drug Drugs 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 229940126629 PAR4 antagonist Drugs 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000010118 platelet activation Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 2
- 101001098529 Homo sapiens Proteinase-activated receptor 1 Proteins 0.000 description 2
- 101000713169 Homo sapiens Solute carrier family 52, riboflavin transporter, member 2 Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 102000002020 Protease-activated receptors Human genes 0.000 description 2
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- 230000002785 anti-thrombosis Effects 0.000 description 2
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- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
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- ZBGXUVOIWDMMJE-QHNZEKIYSA-N vorapaxar Chemical compound C(/[C@@H]1[C@H]2[C@H](C(O[C@@H]2C)=O)C[C@H]2[C@H]1CC[C@H](C2)NC(=O)OCC)=C\C(N=C1)=CC=C1C1=CC=CC(F)=C1 ZBGXUVOIWDMMJE-QHNZEKIYSA-N 0.000 description 2
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 2
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- YLZBDEHOJSKJMY-UHFFFAOYSA-N 6-(1-benzofuran-2-yl)-2-bromoimidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=CC=C2OC(C3=CN4N=C(SC4=N3)Br)=CC2=C1 YLZBDEHOJSKJMY-UHFFFAOYSA-N 0.000 description 1
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- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- QWKAUGRRIXBIPO-UHFFFAOYSA-N Atopaxar Chemical compound N=C1C=2C(F)=C(OCC)C(OCC)=CC=2CN1CC(=O)C(C=C(C=1OC)C(C)(C)C)=CC=1N1CCOCC1 QWKAUGRRIXBIPO-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
- 241000282567 Macaca fascicularis Species 0.000 description 1
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- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
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- 208000001435 Thromboembolism Diseases 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- JAXYWRKRWWTUBX-UHFFFAOYSA-N [2-(1-benzylindazol-3-yl)furan-3-yl]methanol Chemical class C1=COC(C=2C3=CC=CC=C3N(CC=3C=CC=CC=3)N=2)=C1CO JAXYWRKRWWTUBX-UHFFFAOYSA-N 0.000 description 1
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- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
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- 229950007648 atopaxar Drugs 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 229940072645 coumadin Drugs 0.000 description 1
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229940020573 plavix Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- 230000002797 proteolythic effect Effects 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
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- 229960004072 thrombin Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4355—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261638591P | 2012-04-26 | 2012-04-26 | |
| US201261638591P | 2012-04-26 | ||
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| EP2855489B1 (en) | 2012-04-26 | 2017-01-04 | Bristol-Myers Squibb Company | Imidazothiadiazole and imidazopyridazine derivatives as protease activated receptor 4 (par4) inhibitors for treating platelet aggregation |
| SMT201700457T1 (it) | 2012-04-26 | 2017-11-15 | Bristol Myers Squibb Co | DERlVATI IMIDAZOTIADIAZOLICI E IMIDAZOPIRAZINICI COME INIBITORI DEL RECETTORE ATTIVATO DA PROTEASI 4 (PAR4) PER IL TRATTAMENTO DELL'AGGREGAZIONE PIASTRINICA |
| US9617279B1 (en) | 2014-06-24 | 2017-04-11 | Bristol-Myers Squibb Company | Imidazooxadiazole compounds |
| US9598419B1 (en) | 2014-06-24 | 2017-03-21 | Universite De Montreal | Imidazotriazine and imidazodiazine compounds |
| KR102586736B1 (ko) * | 2014-08-29 | 2023-10-11 | 씨에이치디아이 파운데이션, 인코포레이티드 | 헌팅틴을 단백질 영상화하기 위한 프로브 |
| WO2016125621A1 (ja) * | 2015-02-03 | 2016-08-11 | 住友化学株式会社 | ベンゾイミダゾール化合物及びその有害節足動物防除用途 |
| WO2016125622A1 (ja) * | 2015-02-03 | 2016-08-11 | 住友化学株式会社 | ベンゾオキサゾール化合物及びその有害節足動物防除用途 |
| WO2016138199A1 (en) | 2015-02-26 | 2016-09-01 | Bristol-Myers Squibb Company | Benzothiazole and benzothiophne compounds |
| ES2929208T3 (es) | 2015-02-26 | 2022-11-25 | Univ Montreal | Compuestos de imidazotiadiazol como inhibidores de PAR4 |
| US9789087B2 (en) | 2015-08-03 | 2017-10-17 | Thomas Jefferson University | PAR4 inhibitor therapy for patients with PAR4 polymorphism |
| KR102279993B1 (ko) | 2015-09-23 | 2021-07-21 | 엑스더블유파마 리미티드 | 감마-하이드록시부티르산의 전구체 및 이의 조성물 및 용도 |
| WO2017066863A1 (en) | 2015-10-19 | 2017-04-27 | Universite De Montreal | Heterocyclic compounds as inhibitors of platelet aggregation |
| WO2017184520A1 (en) * | 2016-04-18 | 2017-10-26 | Vanderbilt University | Substituted and fused 6-membered protease activated receptor 4 (par-4) antagonists |
| US10730868B2 (en) | 2016-07-14 | 2020-08-04 | Bristol-Myers Squibb Company | Bicyclic heteroaryl substituted compounds |
| WO2018013774A1 (en) | 2016-07-14 | 2018-01-18 | Bristol-Myers Squibb Company | Bicyclic heteroaryl substituted compounds |
| JP6903732B2 (ja) * | 2016-07-14 | 2021-07-14 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｐａｒ４阻害剤としての三環式ヘテロアリール置換のキノリンおよびアザキノリン化合物 |
| JP7102388B2 (ja) | 2016-07-14 | 2022-07-19 | ブリストル－マイヤーズ スクイブ カンパニー | 単環式ヘテロアリール置換化合物 |
| BR112019020464A2 (pt) | 2017-03-30 | 2020-04-28 | Xw Laboratories Inc. | compostos derivados de heteroarila bicíclica, composição farmacêutica compreendendo os ditos compostos, adesivo transdérmico compreendendo a dita composição e uso terapêutico dos compostos e composição |
| JP7733443B2 (ja) | 2017-09-11 | 2025-09-03 | モナシュ ユニバーシティー | ヒトトロンビン受容体ｐａｒ４に対する結合タンパク質 |
| CN111094300B (zh) * | 2018-01-31 | 2022-09-16 | 江苏恒瑞医药股份有限公司 | 苯并杂芳基类衍生物、其制备方法及其在医药上的应用 |
| CN110218218B (zh) * | 2018-03-01 | 2022-04-08 | 江苏恒瑞医药股份有限公司 | 苯并呋喃类衍生物、其制备方法及其在医药上的应用 |
| WO2019218956A1 (zh) * | 2018-05-16 | 2019-11-21 | 深圳信立泰药业股份有限公司 | 作为用于治疗血小板聚集的蛋白酶激活受体4(par4)抑制剂的化合物 |
| CN112074522B (zh) * | 2018-05-16 | 2022-08-26 | 深圳信立泰药业股份有限公司 | 作为用于治疗血小板聚集的蛋白酶激活受体4(par4)抑制剂的化合物 |
| WO2019218955A1 (zh) * | 2018-05-16 | 2019-11-21 | 深圳信立泰药业股份有限公司 | 作为用于治疗血小板聚集的蛋白酶激活受体4(par4)抑制剂的化合物 |
| CN110627817B (zh) * | 2018-06-25 | 2022-03-29 | 中国药科大学 | 咪唑并环类par4拮抗剂及其医药用途 |
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| CN111349105B (zh) * | 2018-12-24 | 2023-04-07 | 江苏恒瑞医药股份有限公司 | 苯并呋喃类衍生物、其制备方法及其在医药上的应用 |
| CN111362970A (zh) * | 2018-12-25 | 2020-07-03 | 天津药物研究院有限公司 | 苯并呋喃类衍生物及其制备方法和用途 |
| CN110407697A (zh) * | 2019-08-28 | 2019-11-05 | 上海毕得医药科技有限公司 | 一种4-甲酰基-3-羟基苯甲酸甲酯的合成方法 |
| TW202547822A (zh) | 2019-12-20 | 2025-12-16 | 香港商凱瑞康寧有限公司 | ４－纈胺醯氧基丁酸的合成方法 |
| EP4167971A1 (en) | 2020-06-18 | 2023-04-26 | XWPharma Ltd. | Controlled release granulations of water-soluble active pharmaceutical ingredients |
| EP4167966A1 (en) | 2020-06-18 | 2023-04-26 | XWPharma Ltd. | Pharmaceutical granulations of water-soluble active pharmaceutical ingredients |
| WO2022020621A1 (en) | 2020-07-24 | 2022-01-27 | XWPharma Ltd. | Pharmaceutical compositions and pharmacokinetics of a gamma-hydroxybutyric acid derivative |
| CN119970650A (zh) | 2020-10-05 | 2025-05-13 | 凯瑞康宁生物工程有限公司 | γ-羟基丁酸衍生物的修饰释放组合物 |
| EP4308086B1 (en) | 2021-03-19 | 2025-10-15 | XWPharma Ltd. | Pharmacokinetics of combined release formulations of a gamma-hydroxybutyric acid derivative |
| CN113150005B (zh) * | 2021-04-09 | 2022-08-30 | 中国药科大学 | 喹喔啉类化合物、制备方法及其在医药上的应用 |
| CN115521282B (zh) * | 2022-08-23 | 2023-10-27 | 大理大学 | 一种香豆素化合物E-Suberenol的合成工艺 |
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2013
- 2013-04-24 EA EA201491967A patent/EA201491967A1/ru unknown
- 2013-04-24 WO PCT/US2013/037892 patent/WO2013163244A1/en not_active Ceased
- 2013-04-24 SG SG11201406759YA patent/SG11201406759YA/en unknown
- 2013-04-24 CA CA2871637A patent/CA2871637A1/en not_active Abandoned
- 2013-04-24 BR BR112014026493A patent/BR112014026493A2/pt not_active IP Right Cessation
- 2013-04-24 AU AU2013251683A patent/AU2013251683A1/en not_active Abandoned
- 2013-04-24 CN CN201380033512.1A patent/CN104540835B/zh active Active
- 2013-04-24 EP EP13719361.1A patent/EP2847200B1/en active Active
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- 2013-04-24 KR KR20147030173A patent/KR20150003767A/ko not_active Withdrawn
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- 2014-10-19 IL IL235140A patent/IL235140A0/en unknown
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| US9862730B2 (en) | 2018-01-09 |
| SG11201406759YA (en) | 2014-11-27 |
| JP6181744B2 (ja) | 2017-08-16 |
| BR112014026493A2 (pt) | 2017-06-27 |
| AU2013251683A1 (en) | 2014-12-18 |
| EA201491967A1 (ru) | 2015-03-31 |
| EP2847200A1 (en) | 2015-03-18 |
| MX2014012454A (es) | 2015-03-13 |
| CA2871637A1 (en) | 2013-10-31 |
| CN104540835B (zh) | 2017-08-08 |
| JP2015518004A (ja) | 2015-06-25 |
| KR20150003767A (ko) | 2015-01-09 |
| IL235140A0 (en) | 2014-12-31 |
| CN104540835A (zh) | 2015-04-22 |
| EP2847200B1 (en) | 2017-03-29 |
| US20150133446A1 (en) | 2015-05-14 |
| WO2013163244A1 (en) | 2013-10-31 |
| WO2013163244A8 (en) | 2014-04-03 |
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