WO2014183667A1 - Solvate d'acide acétique de dérivé d'oxazolidinone, procédé de préparation dudit solvate, et application associée - Google Patents
Solvate d'acide acétique de dérivé d'oxazolidinone, procédé de préparation dudit solvate, et application associée Download PDFInfo
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- WO2014183667A1 WO2014183667A1 PCT/CN2014/077668 CN2014077668W WO2014183667A1 WO 2014183667 A1 WO2014183667 A1 WO 2014183667A1 CN 2014077668 W CN2014077668 W CN 2014077668W WO 2014183667 A1 WO2014183667 A1 WO 2014183667A1
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- Prior art keywords
- oxo
- methyl
- acetic acid
- carboxamide
- phenyl
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 title claims abstract description 128
- 239000012453 solvate Substances 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 title description 3
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 claims abstract description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 208000001435 Thromboembolism Diseases 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 11
- QAMZDDKPDSUSSX-UHFFFAOYSA-N 3-[4-(2-oxopyridin-1-yl)phenyl]-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1C1=CC=C(C=C1)N1C(C=CC=C1)=O QAMZDDKPDSUSSX-UHFFFAOYSA-N 0.000 claims description 10
- -1 1 ,3-oxazolidin-5-yl Chemical group 0.000 claims description 8
- 230000009424 thromboembolic effect Effects 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 7
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 7
- 230000008025 crystallization Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 5
- 238000010521 absorption reaction Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- MXWOUAQNXIUJIN-HNNXBMFYSA-N 5-chloro-n-[[(5s)-2-oxo-3-[4-(2-oxopyridin-1-yl)phenyl]-1,3-oxazolidin-5-yl]methyl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(C=CC=C2)=O)C1 MXWOUAQNXIUJIN-HNNXBMFYSA-N 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 238000001228 spectrum Methods 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 238000010586 diagram Methods 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 208000007536 Thrombosis Diseases 0.000 description 8
- 230000015271 coagulation Effects 0.000 description 8
- 238000005345 coagulation Methods 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000005189 Embolism Diseases 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- YPJDADRJERMKNY-UHFFFAOYSA-N 3-[4-(2-oxopyridin-1-yl)phenyl]-1,3-oxazol-2-one Chemical compound O=C1OC=CN1C1=CC=C(C=C1)N1C(C=CC=C1)=O YPJDADRJERMKNY-UHFFFAOYSA-N 0.000 description 6
- 239000003146 anticoagulant agent Substances 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 238000004455 differential thermal analysis Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 108010074860 Factor Xa Proteins 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 206010051055 Deep vein thrombosis Diseases 0.000 description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 206010047249 Venous thrombosis Diseases 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 230000002785 anti-thrombosis Effects 0.000 description 2
- 229940019700 blood coagulation factors Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 210000003709 heart valve Anatomy 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 206010002388 Angina unstable Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 229910016523 CuKa Inorganic materials 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010038548 Renal vein thrombosis Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 229940122388 Thrombin inhibitor Drugs 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000013194 cardioversion Methods 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 230000020971 positive regulation of blood coagulation Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- 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
- A61P9/06—Antiarrhythmics
-
- 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
Definitions
- the invention belongs to the technical field of medicine, and relates to an acetic acid solvate of an oxazolidinone derivative, a preparation method thereof and use thereof, in particular, the invention relates to (S)-5-chloro-N-((2- Acetic acid solvent of oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide And its preparation method and use. Background technique
- Thrombosis is an abnormal coagulation of blood in a flowing state due to activation of platelets and activation of blood coagulation factors.
- Blood coagulation is originally a protective mechanism of organisms. There are antagonistic coagulation systems and anticoagulant systems in the blood. Their dynamic balance ensures the potential coagulability of blood and always ensures the fluid state of blood. .
- thromboembolic disease is the most serious disease in cardiovascular disease and the first killer of human health. In China, with the improvement of living standards and the aging of the population, the incidence, mortality and disability of these diseases have increased year by year.
- antithrombotic diseases are classified into antiplatelet drugs, anticoagulant drugs, and fibrinolytic drugs.
- anticoagulant drugs are the main content of antithrombotic therapy.
- Xa is the best target for the development of new anticoagulant drugs.
- the coagulation process is usually divided into an endogenous coagulation pathway and an exogenous coagulation pathway.
- Many blood coagulation factors are involved in the coagulation process, and each inactive factor converts the next inactive coagulation factor precursor into an activated form.
- the final summary of the endogenous and exogenous pathways is the conversion of factor X to Xa. Therefore, in theory, direct inhibition of factor Xa activity should result in highly effective anticoagulant effects without the side effects of thrombin inhibitors.
- platelets Because it directly inhibits the activity of factor Xa, it has the least effect on the normal hemostatic reaction/regulation process. For example, platelets remain capable of responding to low levels of catalytically active thrombin and thus do not affect platelet thrombosis and minimize the risk of hemorrhagic syndrome.
- Patent CN201110337461.4 provides a novel compound having the structure of formula (A), which is a low molecular weight orally administrable inhibitor of factor Xa, which can be used for preventing/treating diseases, preferably thromboembolic diseases and/or thrombosis Embolism complications, especially deep vein thrombosis, pulmonary embolism, heart Muscle infarction and so on.
- diseases preferably thromboembolic diseases and/or thrombosis Embolism complications, especially deep vein thrombosis, pulmonary embolism, heart Muscle infarction and so on.
- An object of the present invention is to provide (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridyl)phenyl)-1,3-oxazole Acetic acid solvate of ⁇ -5-yl)methyl)thiophene-2-carboxamide, represented by the chemical formula (I): Wherein n is selected from the group consisting of 0.5 to 1.5, such as 0.5, 0.6, 07, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4 and 1.5; preferably 0.5 1.2, most preferably 0.8.
- the measurement conditions were as follows: CuKa, 40 KV, 100 mA, and the solvate X-ray powder diffraction characteristic absorption peak (2 ⁇ ) value was 3.60, 7.04, 10.50, 14.00, measured by D/Max-2500 X-ray diffractometer. 17.48, 20.12, 21.00, 23.86, 24.56, 26.42, 28.12; 2 ⁇ Measurement error is ⁇ 0.2.
- the crystal form X-ray powder diffraction has a diffraction angle (2 ⁇ ) and a crystal plane spacing (d value) as shown in Table 1, and the measurement error of 2 ⁇ is ⁇ 0.2.
- Table 1 Crystalline X-ray powder diffraction diffraction angle and interplanar spacing results
- the invention (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1)
- the differential thermal analysis of the acetic acid solvate of 3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide is shown in Figure 2.
- the test results show that the solvate has an endotherm at 155 °C. And with about 10% weight loss, it was proved that the solvate crystal form contained about 10% by weight of acetic acid.
- Another object of the present invention is to provide (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1, Process for the preparation of acetic acid solvates of 3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide.
- the present invention provides (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3-oxazole Process for the preparation of an acetic acid solvate of alk-5-yl)methyl)thiophene-2-carboxamide, which comprises (S)-5-chloro-N-((2-oxo-3-(4-) (2-oxo-2H-pyridin-1-yl)phenyl)-1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide crystallized in a crystallization solvent, wherein the crystallization The solvent is acetic acid.
- the preparation method may include: (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)) -1,3-oxazolidine-5-yl)methyl)thiophene-2-carboxamide is added to acetic acid, dissolved by heating, allowed to stand for crystallisation, filtered and dried to give (S)-5-chloro-N- ((2-Oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3-oxazolidine-5-yl)methyl)thiophene-2-methyl Acetate solvate of amide.
- the amount of the crystallization solvent is as follows:
- the volume of acetic acid is the corresponding (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridine-1-) 10) to 10 times, preferably 25 to 40 times the mass of the phenyl)-1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide, the multiple being a volume-to-mass ratio,
- the unit is mL/g.
- the heating and dissolving temperature may be from 80 ° C to reflux temperature, preferably from 80 to 110 ° C.
- Still another object of the present invention is to provide (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3 Use of an acetic acid solvate of oxazolidine-5-yl)methyl)thiophene-2-carboxamide for the preparation of a medicament for preventing/treating a thromboembolic disease and/or a thromboembolic complication and for preventing/treating a thrombus Use in embolic disease and/or thromboembolic complications.
- the present invention provides the (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3- Use of an acetic acid solvate of oxazolidine-5-yl)methyl)thiophene-2-carboxamide for the preparation of a medicament for the prevention/treatment of thromboembolic disorders and/or thromboembolic complications.
- the present invention also provides the (S)-5-chloro-N-((2-oxo-3-(4-(2-oxo-2H-pyridin-1-yl)phenyl)-1,3 Use of an acetic acid solvate of -oxazolidin-5-yl)methyl)thiophene-2-carboxamide for the prevention/treatment of thromboembolic diseases and/or thromboembolic complications.
- thromboembolic disease includes, inter alia, diseases such as myocardial infarction with ST-segment elevation (STEMI) and without ST-segment elevation (without STEMI), stable/unstable angina, coronary interventional therapy For example, re-occlusion and restenosis after angioplasty or aortic coronary artery bypass surgery, peripheral vascular occlusive disease, pulmonary embolism, deep vein thrombosis and renal vein thrombosis, transient ischemic attack, and thrombosis and thrombosis Embolism type stroke.
- diseases such as myocardial infarction with ST-segment elevation (STEMI) and without ST-segment elevation (without STEMI), stable/unstable angina, coronary interventional therapy
- re-occlusion and restenosis after angioplasty or aortic coronary artery bypass surgery peripheral vascular occlusive disease, pulmonary embolism, deep vein thrombosis and renal vein thro
- the thromboembolic disease also includes cardiac thromboembolism, such as stroke, cerebral ischemia, systemic thromboembolism, and ischemia, and also, for example, acute, intermittent or persistent cardiac arrhythmia, cardioversion, Heart valve disease or artificial heart valve.
- cardiac thromboembolism such as stroke, cerebral ischemia, systemic thromboembolism, and ischemia
- acute, intermittent or persistent cardiac arrhythmia such as cardioversion, Heart valve disease or artificial heart valve.
- the thromboembolic diseases also include atherosclerotic vascular diseases and inflammatory diseases (such as motor system rheumatic diseases), as well as other diseases (such as diabetes, tumor diseases, especially major surgical intervention or radiotherapy/chemotherapy).
- atherosclerotic vascular diseases and inflammatory diseases such as motor system rheumatic diseases
- other diseases such as diabetes, tumor diseases, especially major surgical intervention or radiotherapy/chemotherapy.
- the thromboembolic disease also includes diffuse invasive coagulation (DIC).
- DIC diffuse invasive coagulation
- the thromboembolic complications include microvascular hemolytic anemia, complications such as hemodialysis and heart valve repair in the context of extracorporeal blood circulation.
- Figure 1 is (S)-5-chloro-N-((2-oxo-3-(4-(2- ⁇ -2H-pyridine-1-yl)phenyl)-1,3-oxazolidine- Acetic acid solvated 4 X-ray powder diffraction pattern of 5-yl)methyl)thiophene-2-carboxamide;
- Figure 2 is (S)-5-chloro-indole-((2-oxo-3-(4-(2- ⁇ -2H-pyridin-1-yl)phenyl)-1,3-oxazolidine- Ei' differential thermal analysis of 5-yl)methyl)thiophene-2-carboxamide.
Abstract
L'invention concerne un solvate d'acide acétique de (S) 5-chloro-N-((2-oxo-3-(4-(2-oxo-2 H-pyridin-1-yl)phényl)-1,3-oxazolidine -5-yl) méthyl) thiophène -2-carboxamide, un procédé de préparation dudit solvate et une application correspondante. Le solvate d'acide acétique préparé de (S)-5-chloro-N-((2-oxo -3-(4-(2-oxo-2H-pyridin-1-yl)phényl)-1,3-oxazolidine -5-yl) méthyl) thiophène -2-carboxamide est caractérisé par un diagramme de diffraction de puissance X.
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CN201310185328.0 | 2013-05-17 |
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WO (1) | WO2014183667A1 (fr) |
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WO2008155069A2 (fr) * | 2007-06-20 | 2008-12-24 | Bayer Schering Pharma Aktiengesellschaft | Oxazolidinones substituées et leur utilisation |
CN101743244A (zh) * | 2007-06-20 | 2010-06-16 | 拜耳先灵制药股份公司 | 取代的*唑烷酮类及其用途 |
CN101772496A (zh) * | 2007-06-20 | 2010-07-07 | 拜耳先灵制药股份公司 | 取代的*唑烷酮类和其用途 |
CN101821259A (zh) * | 2007-06-20 | 2010-09-01 | 拜耳先灵制药股份公司 | 取代的(*唑烷酮-5-基-甲基)-2-噻吩-酰胺和其在血液凝固领域中的应用 |
CN102464658A (zh) * | 2010-11-03 | 2012-05-23 | 天津药物研究院 | 噁唑烷酮衍生物及其制备方法和用途 |
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US8288416B2 (en) * | 2006-09-25 | 2012-10-16 | Wockhardt Ltd. | Substituted piperidinophenyl oxazolidinones |
CN102050819B (zh) * | 2009-11-10 | 2012-05-23 | 天津药物研究院 | 噁唑烷酮衍生物及其制备方法和用途 |
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- 2014-05-16 WO PCT/CN2014/077668 patent/WO2014183667A1/fr active Application Filing
- 2014-05-16 CN CN201410209934.6A patent/CN104163819A/zh active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN1434822A (zh) * | 1999-12-24 | 2003-08-06 | 拜尔公司 | 取代的噁唑烷酮和其在血液凝固领域中的应用 |
WO2008155069A2 (fr) * | 2007-06-20 | 2008-12-24 | Bayer Schering Pharma Aktiengesellschaft | Oxazolidinones substituées et leur utilisation |
CN101743244A (zh) * | 2007-06-20 | 2010-06-16 | 拜耳先灵制药股份公司 | 取代的*唑烷酮类及其用途 |
CN101772496A (zh) * | 2007-06-20 | 2010-07-07 | 拜耳先灵制药股份公司 | 取代的*唑烷酮类和其用途 |
CN101821259A (zh) * | 2007-06-20 | 2010-09-01 | 拜耳先灵制药股份公司 | 取代的(*唑烷酮-5-基-甲基)-2-噻吩-酰胺和其在血液凝固领域中的应用 |
CN102464658A (zh) * | 2010-11-03 | 2012-05-23 | 天津药物研究院 | 噁唑烷酮衍生物及其制备方法和用途 |
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