CA2673598A1 - Macrocyclic factor viia inhibitors useful as anticoagulants - Google Patents
Macrocyclic factor viia inhibitors useful as anticoagulants Download PDFInfo
- Publication number
- CA2673598A1 CA2673598A1 CA002673598A CA2673598A CA2673598A1 CA 2673598 A1 CA2673598 A1 CA 2673598A1 CA 002673598 A CA002673598 A CA 002673598A CA 2673598 A CA2673598 A CA 2673598A CA 2673598 A1 CA2673598 A1 CA 2673598A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- alkyl
- mmol
- heterocycle
- phenyl
- 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.)
- Abandoned
Links
- 239000003146 anticoagulant agent Substances 0.000 title description 32
- 229940082863 Factor VIIa inhibitor Drugs 0.000 title description 13
- 229940127219 anticoagulant drug Drugs 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 181
- 150000003839 salts Chemical class 0.000 claims abstract description 59
- 239000012453 solvate Substances 0.000 claims abstract description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 162
- -1 methoxy, ethoxy, cyclopropyl Chemical group 0.000 claims description 103
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 125000004432 carbon atom Chemical group C* 0.000 claims description 88
- 238000000034 method Methods 0.000 claims description 87
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 81
- 229910052801 chlorine Inorganic materials 0.000 claims description 76
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 76
- 229910052731 fluorine Inorganic materials 0.000 claims description 72
- 125000005842 heteroatom Chemical group 0.000 claims description 65
- 229910052794 bromium Inorganic materials 0.000 claims description 64
- 208000035475 disorder Diseases 0.000 claims description 63
- 230000009424 thromboembolic effect Effects 0.000 claims description 60
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 53
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 46
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- 229910052760 oxygen Inorganic materials 0.000 claims description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 35
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 35
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- 125000000217 alkyl group Chemical group 0.000 claims description 25
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- 125000004429 atom Chemical group 0.000 claims description 22
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 17
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- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 7
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
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- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
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- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 206010042434 Sudden death Diseases 0.000 claims description 4
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 4
- 210000002216 heart Anatomy 0.000 claims description 4
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
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- 238000011324 primary prophylaxis Methods 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
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- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
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- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000005403 thiohaloalkoxy group Chemical group 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
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- 208000005057 thyrotoxicosis Diseases 0.000 description 1
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- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
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- 230000032258 transport Effects 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- AVCVDUDESCZFHJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound [Cl-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 AVCVDUDESCZFHJ-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 229960005044 vorapaxar Drugs 0.000 description 1
- 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 1
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- 238000010626 work up procedure Methods 0.000 description 1
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- 235000010493 xanthan gum Nutrition 0.000 description 1
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- 229940082509 xanthan gum Drugs 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229960001522 ximelagatran Drugs 0.000 description 1
- ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
- A61P9/06—Antiarrhythmics
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- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
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- 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
- C07D255/00—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00
- C07D255/04—Heterocyclic compounds containing rings having three nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D249/00 - C07D253/00 condensed with carbocyclic rings or ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
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- Vascular Medicine (AREA)
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- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
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| US87086406P | 2006-12-20 | 2006-12-20 | |
| US60/870,864 | 2006-12-20 | ||
| US98446007P | 2007-11-01 | 2007-11-01 | |
| US60/984,460 | 2007-11-01 | ||
| PCT/US2007/088032 WO2008079836A2 (en) | 2006-12-20 | 2007-12-19 | Macrocyclic factor viia inhibitors useful as anticoagulants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2673598A1 true CA2673598A1 (en) | 2008-07-03 |
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Family Applications (1)
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|---|---|---|---|
| CA002673598A Abandoned CA2673598A1 (en) | 2006-12-20 | 2007-12-19 | Macrocyclic factor viia inhibitors useful as anticoagulants |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8420830B2 (enExample) |
| EP (1) | EP2102176A2 (enExample) |
| JP (1) | JP2010514681A (enExample) |
| AR (1) | AR064471A1 (enExample) |
| AU (1) | AU2007337025A1 (enExample) |
| CA (1) | CA2673598A1 (enExample) |
| CL (1) | CL2007003718A1 (enExample) |
| MX (1) | MX2009006689A (enExample) |
| NO (1) | NO20092279L (enExample) |
| PE (1) | PE20081775A1 (enExample) |
| TW (1) | TW200836735A (enExample) |
| WO (1) | WO2008079836A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2099783A1 (en) | 2006-12-20 | 2009-09-16 | Brystol-Myers Squibb Company | Bicyclic lactam factor viia inhibitors useful as anticoagulants |
| WO2011071730A1 (en) * | 2009-12-08 | 2011-06-16 | Boehringer Ingelheim International Gmbh | Process for synthesis of intermediates useful for making substituted indazole and azaindazole compounds |
| NZ602266A (en) * | 2010-02-11 | 2014-05-30 | Bristol Myers Squibb Co | Macrocycles as factor xia inhibitors |
| CN102993065B (zh) * | 2011-09-13 | 2015-07-29 | 中国科学院上海药物研究所 | 含手性叔丁基亚磺酰基的α-芳基氨基酸酯类化合物、其制备方法及用途 |
| JP6033319B2 (ja) | 2011-10-14 | 2016-11-30 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物 |
| EP2797880B1 (en) * | 2011-12-27 | 2017-03-01 | Bio-Pharm Solutions Co., Ltd. | Phenyl carbamate compounds for use in preventing or treating epilepsy |
| US9174974B2 (en) | 2012-06-08 | 2015-11-03 | Bristol-Myers Squibb Company | Macrocyclic factor VIIa inhibitors |
| AU2013296259A1 (en) * | 2012-08-03 | 2015-03-19 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| US9376444B2 (en) * | 2012-08-03 | 2016-06-28 | Bristol-Myers Squibb Company | Dihydropyridone P1 as factor XIa inhibitors |
| EP2906552B1 (en) | 2012-10-12 | 2017-11-22 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| TR201807316T4 (tr) | 2012-10-12 | 2018-06-21 | Bristol Myers Squibb Co | Bir faktör XIa inhibitörünün kristalli formları. |
| US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| WO2014160668A1 (en) | 2013-03-25 | 2014-10-02 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors |
| EP3008052A1 (en) * | 2013-06-13 | 2016-04-20 | Bristol-Myers Squibb Company | Macrocyclic factor viia inhibitors |
| SG10201908467RA (en) | 2014-01-31 | 2019-10-30 | Bristol Myers Squibb Co | Macrocycles with hetrocyclic p2' groups as factor xia inhibitors |
| NO2760821T3 (enExample) | 2014-01-31 | 2018-03-10 | ||
| ES2714283T3 (es) | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| EP3072943B1 (en) | 2015-03-26 | 2018-05-02 | Idemitsu Kosan Co., Ltd. | Dibenzofuran/carbazole-substituted benzonitriles |
| CN114874222B (zh) * | 2015-07-29 | 2025-06-06 | 百时美施贵宝公司 | 携带非芳族p2,基团的因子xia新大环 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0028489B1 (en) | 1979-11-05 | 1983-10-05 | Beecham Group Plc | Enzyme derivatives, and their preparation |
| US5023236A (en) | 1988-04-07 | 1991-06-11 | Corvas, Inc. | Factor VII/VIIA active site inhibitors |
| US5843442A (en) | 1990-10-22 | 1998-12-01 | Corvas International, Inc. | Blood coagulation protein antagonists and uses therefor |
| US5866542A (en) | 1994-10-18 | 1999-02-02 | Corvas International, Inc. | Nematode-extracted anticoagulant protein |
| PE121699A1 (es) | 1997-02-18 | 1999-12-08 | Boehringer Ingelheim Pharma | Heterociclos biciclicos disustituidos como inhibidores de la trombina |
| ZA985247B (en) | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Guanidine mimics as factor Xa inhibitors. |
| WO2000077027A2 (en) | 1999-06-14 | 2000-12-21 | Tularik Limited | Serine protease inhibitors |
| DE19962924A1 (de) | 1999-12-24 | 2001-07-05 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
| EP1332131A2 (en) | 2000-11-07 | 2003-08-06 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
| AR035216A1 (es) | 2000-12-01 | 2004-05-05 | Astrazeneca Ab | Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios |
| AU2002322802A1 (en) | 2001-07-27 | 2003-02-17 | Merck And Co., Inc. | Thrombin inhibitors |
| CN104744461A (zh) | 2001-09-21 | 2015-07-01 | 百时美施贵宝公司 | 含有内酰胺的化合物及其衍生物作为Xa因子的抑制剂 |
| US7144895B2 (en) | 2003-02-11 | 2006-12-05 | Bristol-Myers Squibb Co. | Benzene acetamide compounds useful as serine protease inhibitors |
| EP1594505A4 (en) | 2003-02-11 | 2008-08-13 | Bristol Myers Squibb Co | PHENYLGLYCIN DERIVATIVES USEFUL AS SERINE PROTEASE INHIBITORS |
| DE602006016566D1 (de) | 2005-01-10 | 2010-10-14 | Bristol Myers Squibb Co | Als antikoagulanzien verwendbare phenylglycinamid-derivate |
| CA2600745A1 (en) * | 2005-03-03 | 2006-09-08 | The Burnham Institute For Medical Research | Screening methods for protein kinase b inhibitors employing virtual docking approaches and compounds and compositions discovered thereby |
| US7456195B2 (en) | 2005-06-24 | 2008-11-25 | Bristol-Myers Squibb Company | Phenylglycinamide and pyridylglycinamide derivatives useful as anticoagulants |
| PE20071132A1 (es) | 2005-12-23 | 2007-12-14 | Bristol Myers Squibb Co | Compuestos macrociclicos como inhibidores del factor viia |
| US8044242B2 (en) | 2006-03-09 | 2011-10-25 | Bristol-Myers Squibb Company | 2-(aryloxy) acetamide factor VIIa inhibitors useful as anticoagulants |
| EP2099783A1 (en) | 2006-12-20 | 2009-09-16 | Brystol-Myers Squibb Company | Bicyclic lactam factor viia inhibitors useful as anticoagulants |
-
2007
- 2007-12-14 PE PE2007001814A patent/PE20081775A1/es not_active Application Discontinuation
- 2007-12-19 CL CL200703718A patent/CL2007003718A1/es unknown
- 2007-12-19 EP EP07869479A patent/EP2102176A2/en not_active Withdrawn
- 2007-12-19 MX MX2009006689A patent/MX2009006689A/es not_active Application Discontinuation
- 2007-12-19 AU AU2007337025A patent/AU2007337025A1/en not_active Abandoned
- 2007-12-19 TW TW096148731A patent/TW200836735A/zh unknown
- 2007-12-19 US US12/519,376 patent/US8420830B2/en active Active
- 2007-12-19 JP JP2009543158A patent/JP2010514681A/ja not_active Withdrawn
- 2007-12-19 WO PCT/US2007/088032 patent/WO2008079836A2/en not_active Ceased
- 2007-12-19 AR ARP070105750A patent/AR064471A1/es not_active Application Discontinuation
- 2007-12-19 CA CA002673598A patent/CA2673598A1/en not_active Abandoned
-
2009
- 2009-06-12 NO NO20092279A patent/NO20092279L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008079836A3 (en) | 2009-01-15 |
| WO2008079836A4 (en) | 2009-03-12 |
| US20100113488A1 (en) | 2010-05-06 |
| WO2008079836A2 (en) | 2008-07-03 |
| AR064471A1 (es) | 2009-04-01 |
| EP2102176A2 (en) | 2009-09-23 |
| PE20081775A1 (es) | 2008-12-18 |
| AU2007337025A1 (en) | 2008-07-03 |
| JP2010514681A (ja) | 2010-05-06 |
| NO20092279L (no) | 2009-08-31 |
| TW200836735A (en) | 2008-09-16 |
| CL2007003718A1 (es) | 2008-07-11 |
| MX2009006689A (es) | 2009-06-30 |
| US8420830B2 (en) | 2013-04-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20121219 |