WO2016010178A1 - 5-클로로-n-({(5s)-2-옥소-3-[4-(5,6-디하이드로-4h-[1,2,4]트리아진-1-일)페닐]-1,3-옥사졸리딘-5-일}메틸)티오펜-2-카르복사미드 메탄설폰산염의 신규 결정형 및 이를 포함하는 약학 조성물 - Google Patents
5-클로로-n-({(5s)-2-옥소-3-[4-(5,6-디하이드로-4h-[1,2,4]트리아진-1-일)페닐]-1,3-옥사졸리딘-5-일}메틸)티오펜-2-카르복사미드 메탄설폰산염의 신규 결정형 및 이를 포함하는 약학 조성물 Download PDFInfo
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- WO2016010178A1 WO2016010178A1 PCT/KR2014/006555 KR2014006555W WO2016010178A1 WO 2016010178 A1 WO2016010178 A1 WO 2016010178A1 KR 2014006555 W KR2014006555 W KR 2014006555W WO 2016010178 A1 WO2016010178 A1 WO 2016010178A1
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- WIPO (PCT)
- Prior art keywords
- dihydro
- chloro
- thiophene
- oxo
- methyl
- Prior art date
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- YSNDMQDQQLSJMR-UQKRIMTDSA-N 5-chloro-n-[[(5s)-3-[4-(5,6-dihydro-2h-1,2,4-triazin-1-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]thiophene-2-carboxamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2NC=NCC2)C1 YSNDMQDQQLSJMR-UQKRIMTDSA-N 0.000 claims abstract description 12
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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
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Definitions
- the present invention is supported by a national research and development project (Detailed Project Number: KDDF-201210-04; Assigned Project Number: 1345193908; Research Project Name: Development of a new anti-auretic Factor Xa inhibitory treatment).
- 5 -Chloro N-( ⁇ (5S) — 2-oxo-3 '[4- (5,6-dihydro ⁇ 4H— [1, 2, 4] triazin-1-yl) Phenyl] -1,3-oxazolidin-5-ylyl ⁇ methyl) thiophene-2-carboxamide methanesulfonate is known as an inhibitor of hemoglobin factor Xa and is a thrombosis, myocardial infarction, atherosclerosis, inflammation, stroke, angina. And has been used for the treatment and prevention of thromboembolism, such as restenosis after angioplasty, and intermittent claudication (US Pat. No. 817825).
- Another object of the present invention is any one or more diseases or symptoms selected from the group consisting of thromboembolism, such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, stroke, angina pectoris, restenosis after angioplasty, and intermittent claudication including the crystalline form It is to provide a pharmaceutical composition for the prophylaxis or treatment of.
- the present invention provides a diffraction angle of 2 ⁇ in the X-ray powder diffraction spectrum using Cu- ⁇ radiation of 4.302, 8.621, 9.606, 12.103, 12.879,
- the diffraction angle of 2 ⁇ is 12.022, 15.721, 15.971, 18.125, 18.928, 19.979, 20.311,
- Anhydrous crystalline 5-chloro-N-( ⁇ (5S) -25oxo-3-, characterized by being 29.753 [4- (5,6-Dihydro-4H- [1,2,4] triazin-1-yl) phenyl] -1,3-oxazolidin-5-yl ⁇ methyl) thiophene-2-carbox Provides radiamide midmethanesulfonate.
- the present invention provides the anhydrous crystalline 5-chloro-N-( ⁇ (5S) -2-oxo-3- [4- (5,6-dihydro-4H- [1] as an active ingredient. , 2,4] triazine-1-yl) phenal] -1,3-oxazoladine-5-al ⁇ methyl) thiotene-2-carboxamide methanesulfonate.
- novel crystalline compounds according to the present invention are stable in high temperature and humid environment and have excellent dissolution rate, therefore, the group consisting of thromboembolism such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, stroke, angina, restenosis after angioplasty, and intermittent claudication. It can be usefully used for the prevention or treatment of any one or more diseases or symptoms selected from.
- TGA Thermogravimetric Analysis
- FIG. 6 shows polarization micrographs of crystalline forms 1 and 5.
- GCO4401C triazine-1-yl) phenyl] -1, 3-oxazolidin-5-yl ⁇ methyl) thiophene-2-carboxamide methanesulfonate
- the new crystalline form of has excellent solubility and stability in high silver and humid environments.
- the novel crystalline form of GCC-4401C according to the present invention can be easily obtained by an organic solvent cooling crystallization method or a solvent-antisolvent crystallization method.
- GCC-4401C which is used as a reaction raw material, could be prepared according to the method disclosed in PCT Publication No. W02011 / 005029, and the resulting crystals were dissolved in an organic solvent, added with anti-solvent and then cooled, and the resulting crystals were filtered. And by drying it is possible to obtain novel crystalline compounds according to the invention.
- the organic solvent that can be used may be selected from the group consisting of methanol, dimethylacetamide (DMA), dimethyl sulfoxide (DMS0) and combinations thereof, and preferably methanol.
- the usable anti-solvent can be selected from the group consisting of isopropyl alcohol (IPA), n'butanol, ethyl acetate, toluene and combinations thereof, preferably n-butane can be used.
- the anti-solvent may be used in an amount of 1 to 10 times by volume, preferably 2 to 3 times by volume, based on the organic solvent.
- the crystals precipitated through the addition of the anti-solvent and then cooled are filtered according to a conventional filtration method, and then dried at 55 to 65 ° C. for 3 to 4 hours to remove residual solvents.
- Compounds can be prepared.
- the novel of the invention referred to as Form 1
- the crystalline compound is dissolved by dissolving GCC-4401C in an organic solvent (eg methanol) followed by the addition of a semi-solvent (eg n-butanol). Crystals produced in the above process can be obtained by filtration and drying for 3 to 4 hours at 60 ⁇ 5 ° C.
- the novel crystalline compound of the present invention referred to as Form 5.
- Crystals produced in the above process can be obtained by filtration and drying at 60 ⁇ 5 ° C for 3 to 4 hours.
- Form 1 according to the present invention has a diffraction angle of 2 ⁇ in the X-ray powder diffraction spectrum using Cu- ⁇ radiation is 4.302, 8.621, 9.606, 12.103, 12.879, 15.648, 17.353, 17.949, 19.26, 19.577, 20.252, 21.792, 23.108 , 23.356, 25.76 and 27.463 have crystal structures showing peaks characteristic.
- the diffraction angle of 2 ⁇ has a relative intensity of 10% or more.
- the peak of 178 ⁇ 2t: is shown by an additive differential scanning calorimeter (DSC) analysis (see Example 1).
- Form 5 according to the present invention has a diffraction angle of 2 ⁇ in the X-ray powder diffraction spectrum using Cu— ⁇ radiation of 12.022, 15.721, 15.971, 18.125, 18.928, 19.979, 20.311, 20.726, 21.66, 22.805, 23.18, 23.985 , 25.857, 27.25, 27.829, 28, 28.189 and 29.753.
- the diffraction angle of 2 ⁇ has a relative intensity of 103 ⁇ 4 or more.
- the quaternary scanning calorimetry analysis shows a peak of 186 ⁇ 2 ° C. (see Example 2).
- Crystal forms 1 and 5 according to the present invention show an anhydrous crystalline form, as can be seen from the X-ray powder diffraction spectrum results, and show a stable state without changing the form even when polished or exposed to humidification conditions (see Test Example 1).
- pharmaceutical formulations such as tablets and capsules can be found within 10 minutes without significant difference in foot solubility.
- New crystalline forms 1 and 5 of GCC-4401C are thrombosis, myocardial infarction, atherosclerosis, inflammation, stroke, It is useful for the treatment of angina pectoris, restenosis after angioplasty, or thromboembolism such as intermittent claudication.
- the present invention provides 5-chloro-N-( ⁇ (5S) -2-oxo-3- [4- (5,6—dihydro-4H- [1, 2, 4] triazine as an active ingredient.
- the pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier or excipient.
- a pharmaceutically acceptable carrier or excipient may depend on the mode of administration used to treat the particular patient, or on the type of medical condition or disease state.
- Examples of the pharmaceutically acceptable carrier or excipient include starch, sugar, lactose dextrin, manny, solbi, crystalline salulose, low-substituted hydroxypropyl cellulose, sodium carboxymethyl salolose, gum arabic.
- Excipients such as amylopectin, hard silicic anhydride, and synthetic aluminum silicate; Fillers and extenders such as calcium phosphate and silicic acid derivatives; Starch, sugar, manny, trehalose, dextrin, amylopectin, sucrose, glutin, gum arabic, methyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, crystalline cellulose, hydroxy Binders such as cellulose derivatives such as propyl cellulose or hardoxypropylmethyl cellulose, querlatin, alginate, and polyvinyl parolidon; Lubricating agents such as talc, stearic acid stag or magnesium, hydrogenated castor oil, talcum powder, and solid polyethylene glycols; Disintegrants such as povidone, sodium croscarmellose and crospovidone; surfactants such as polysorbate, cetyl alcohol, glycerol monostearate and the like. '
- composition of the present invention can be prepared according to known common methods. Conventional formulation techniques are described in Remington: The Science and Practice of Pharmacy, 20 th Edition, Lippincott Williams & White, Baltimore, Maryland (2000); and
- the pharmaceutical composition according to the present invention is 5-chloro-N-( ⁇ (5S) -2-oxo-3- [4- (5, 6-dihydro-4H- [1, 2, 4] tree) as an active ingredient.
- the pharmaceutical compositions of the present invention may be formulated as oral or parenteral preparations and administered to a patient in a suitable route of administration. Preferably, it may be formulated into a preparation such as capsules, tablets, dispersions, suspensions and the like and orally administered.
- the pharmaceutical composition according to the present invention may be administered alone or in divided doses, and the total daily dosage range in humans ranges from 5-chloro-N-( ⁇ (5S) -2-oxo-3- [4- ( 5, 6-dihydro-4H- [1,2,4] triazin-1-yl) phenyl] -1,3-oxazolidin-5-yl ⁇ methyl) thiophene-2-carboxamide methanesulfone Form 1 or Form 5 of the acid salt may be 2.5 mg to 80 mg.
- DSC Differential Scanning Calorie
- IR (KBr, cm “1 ): 3301, 3453, 3066, 2939, 2357, 2124, 2018, 1962, 1742, 1670, 1644, 1552, 1509, I486, 1429, 1411, 1361, 1344, 1323, 1301, 1287 , 1217, 1196, 1160, 1146, 1105, 1085, 1032, 991, 930, 882, 839, 821, 803, 776, 751, 729, 707, 683, 667.
- IR (KBr, cm “1 ): 3315, 3236, 3050, 2963, 2439, 2144, 2167, 2135, 2055, 2015, 1892, 1708, 1656, 1572, 1550, 1514, 1479, 1438, 1419, 1429, 1322 , 1303, 1273, 1236, 1226, 1202, 1169, 1150, 1082, 1058, 1038, 1018, 996, 943, 882, 821, 807, 777, 757, 723, 685, 671, 655.
- Test Example 1 Confirmation of Stability of New Crystalline Form In order to confirm the stability of the novel crystalline form obtained in Examples 1 and 2, the following experiments were carried out.
- the solvents described in Table 3 below were layered at room temperature (30 ⁇ 5 ° C.), respectively, in an automated polyblock reactor.
- the crystal form 1 30 ⁇ 5 ° C placed in a reactor, and then heated for mekmi transparent quality is obtained, and then stirred to, to the anti-solvent (the n- butane or IPA) shown in Table 330 in half unggi
- the half agitation was stirred for 30 ⁇ 15 minutes to add ⁇ 15 minutes to obtain a clear solution. After that, After cooling to 0 ⁇ 5 ° C. and stirring for 2-3 hours, it was filtered at 0 ⁇ 5 ° C.
- Form 1 was stirred for 24 hours. While there was a tendency to be converted to the form of Form 5, Form 5 was found to be in a stable state by maintaining the form of Form 5 without being converted to another form even after stirring in a combination of different solvents for 24 hours.
- Multi-milling was milled with crystals 1 and 5 at 3, 000 rpm using a prototype multimill machine (Sreenex) and manual grinding was gradually drawn using a Pest le and mortar machine.
- Humidification experiments stored Forms 1 and 5 for 24 hours at 30 ° C. and 90% relative humidity conditions.
- crystalline form 1 of the present invention 175.5 mg of lactosulfone, 7 mg of Primojel (Pr imojel), 5 mg of hydroxypropylmethylcellose (HPMC), and 1.5 mg of Aerosil 200 were prepared in a pharmaceutical preparation.
- the mixture was mixed at 20 rpm for 20 minutes.
- magnesium stearate 1 mg to this was further mixed for 5 minutes at 20 rpm.
- the mixture was compressed into tablets using a tablet press to prepare a tablet including Form 1.
- the tablet obtained above was coated with about 10 mg of Opadry to prepare a film coated tablet.
- crystalline Form 5 was used instead of crystalline Form 1, it was carried out in the same manner as above to prepare a film coated tablet containing Form 5.
- the capsule does not need a large amount of excipients and has a simple manufacturing process, but the capsule itself is weak to moisture, and since the components in the capsule are not compressed, the surface area is large and easily affected by the external environment. Has a vulnerability in.
- tablets can compensate for the shortcomings of the capsules, there is an advantage that the production efficiency is excellent and the production price can be lowered.
- a polymorph has the same structure as a crystal but has a different arrangement, which may affect solubility depending on the arrangement.
- both the tablet and the capsulicide of the present invention showed an excellent dissolution rate of 80% or more within 10 minutes.
- the crystalline forms according to the present invention showed a dissolution rate similar to that of tablets even when prepared with a capsule, so that the solubility between capsules and tablets was dynamic.
- the dissolution pattern was similar, and it was confirmed that Forms 1 and 5 according to the present invention had similar effects in terms of solubility as well as pharmacological effects.
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Abstract
Description
Claims
Priority Applications (19)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2014400894A AU2014400894B2 (en) | 2014-07-18 | 2014-07-18 | Novel crystalline form of 5-chloro-N-({(5S)-2-oxo-3-[4-(5,6-dihydro-4H-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition containing same |
IL297649A IL297649A (en) | 2014-07-18 | 2014-07-18 | Crystalline form of 5-chloro-m ({5)-2-oxo-3-[4-(6,5-dihydro-4-[1,2,4]triazin-1yl)phenyl}-1,3- Oxazolidine-5-yl} methyl) thiophene-2-an innovative carboxamide and pharmaceutical preparations containing it |
CA2955397A CA2955397C (en) | 2014-07-18 | 2014-07-18 | Novel crystalline form of 5-chloro-n-({(5s)-2-oxo-3-[4-(5,6-dihydro-4h-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition comprising same |
CN201480080661.8A CN106661011B (zh) | 2014-07-18 | 2014-07-18 | Gcc-4401c的晶形和包含所述晶形的药物组合物 |
US15/325,521 US9988372B2 (en) | 2014-07-18 | 2014-07-18 | Crystalline form of 5-chloro-N-({(5S)-2-oxo-3-[4-(5,6-dihydro-4H-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition comprising same |
RU2017105147A RU2663617C1 (ru) | 2014-07-18 | 2014-07-18 | Новая кристаллическая форма метансульфонат 5-хлор-n-({ (5s)-2-оксо-3-[4-(5,6-дигидро-4h-[1,2,4]триазин-1-ил)фенил]-1,3-оксазолидин-5-ил} метил)тиофен-2-карбоксамида и содержащая его фармацевтическая композиция |
KR1020167035812A KR102100357B1 (ko) | 2014-07-18 | 2014-07-18 | 5-클로로-n-({(5s)-2-옥소-3-[4-(5,6-디하이드로-4h-[1,2,4]트리아진-1-일)페닐]-1,3-옥사졸리딘-5-일}메틸)티오펜-2-카르복사미드 메탄설폰산염의 신규 결정형 및 이를 포함하는 약학 조성물 |
JP2017523744A JP6450840B2 (ja) | 2014-07-18 | 2014-07-18 | 5−クロロ−n−({(5s)−2−オキソ−3−[4−(5,6−ジヒドロ−4h−[1,2,4]トリアジン−1−イル)フェニル]−1,3−オキサゾリジン−5−イル}メチル)チオフェン−2−カルボキシアミド メタンスルホネートの新規結晶形態および前記結晶形態を含む医薬組成物 |
BR112017000351-1A BR112017000351B1 (pt) | 2014-07-18 | 2014-07-18 | Anidro cristalino de metanossulfonato de 5-cloro-n-({(5s)-2-oxo-3-[4-(5,6-diidro-4h-[1,2,4] triazin-1-il)f enil]-1,3-oxazolidin-5-il}metil)tiofeno-2-carboxamida, composição farmacêutica compreendendo dito anidrido e uso terapêutico da mesma |
NZ727829A NZ727829B2 (en) | 2014-07-18 | Novel crystalline form of 5-chloro-n-({(5s)-2-oxo-3-[4-(5,6-dihydro-4h-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition containing same | |
UAA201701494A UA116182C2 (uk) | 2014-07-18 | 2014-07-18 | Кристалічна форма метансульфонату 5-хлор-n-({(5s)-2-оксо-3-[4-(5,6-дигідро-4h-[1,2,4]триазин-1-іл)феніл]-1,3-оксазолідин-5-іл}метил)тіофен-2-карбоксаміду та фармацевтична композиція, що його містить |
MYPI2016704816A MY190477A (en) | 2014-07-18 | 2014-07-18 | Novel crystalline form of 5-chloro-n-({(5s)-2-oxo-3-[4-(5,6-dihydro-4h-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition containing same |
MX2017000409A MX2017000409A (es) | 2014-07-18 | 2014-07-18 | Forma cristalina novedosa de metansulfonato de 5-cloro-n-({(5s)-2-oxo-3-[4-(5,6-dihidro-4h-[1,2,4]triazin-1-il)f enil]-1,3-oxazolidin-5-il}metil)tiofen-2-carboxamida y composicion farmaceutica que contiene la misma. |
CN201910687566.9A CN110407827B (zh) | 2014-07-18 | 2014-07-18 | Gcc-4401c的晶形和包含所述晶形的药物组合物 |
PCT/KR2014/006555 WO2016010178A1 (ko) | 2014-07-18 | 2014-07-18 | 5-클로로-n-({(5s)-2-옥소-3-[4-(5,6-디하이드로-4h-[1,2,4]트리아진-1-일)페닐]-1,3-옥사졸리딘-5-일}메틸)티오펜-2-카르복사미드 메탄설폰산염의 신규 결정형 및 이를 포함하는 약학 조성물 |
SG11201700066TA SG11201700066TA (en) | 2014-07-18 | 2014-07-18 | Novel crystalline form of 5-chloro-n-({(5s)-2-oxo-3-[4-(5,6-dihydro-4h-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition containing same |
EP14897871.1A EP3170819B1 (en) | 2014-07-18 | 2014-07-18 | Novel crystalline form of 5-chloro-n-({(5s)-2-oxo-3-[4-(5,6-dihydro-4h-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition containing same |
PH12017500093A PH12017500093A1 (en) | 2014-07-18 | 2017-01-13 | Novel crystalline form of 5-chloro-n-({(5s)-2-oxo-3-[4-(5,6-dihydro-4h-[1,2,4]triazin-1-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide methanesulfonate and pharmaceutical composition containing same |
IL250168A IL250168A0 (en) | 2014-07-18 | 2017-01-17 | Crystalline form of 5 – chloro –n ( { (5s) – 2 – oxo – 3 – [ 4 – ( 5,6 – dihydro – 4h – [ 1,2,4 ] triazin-1-yl) phenyl] – 1, 3-oxazolidine-5-yl}methyl)thiophene-2-an innovative carboxamide and pharmaceutical preparations containing it |
Applications Claiming Priority (1)
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PCT/KR2014/006555 WO2016010178A1 (ko) | 2014-07-18 | 2014-07-18 | 5-클로로-n-({(5s)-2-옥소-3-[4-(5,6-디하이드로-4h-[1,2,4]트리아진-1-일)페닐]-1,3-옥사졸리딘-5-일}메틸)티오펜-2-카르복사미드 메탄설폰산염의 신규 결정형 및 이를 포함하는 약학 조성물 |
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PCT/KR2014/006555 WO2016010178A1 (ko) | 2014-07-18 | 2014-07-18 | 5-클로로-n-({(5s)-2-옥소-3-[4-(5,6-디하이드로-4h-[1,2,4]트리아진-1-일)페닐]-1,3-옥사졸리딘-5-일}메틸)티오펜-2-카르복사미드 메탄설폰산염의 신규 결정형 및 이를 포함하는 약학 조성물 |
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US (1) | US9988372B2 (ko) |
EP (1) | EP3170819B1 (ko) |
JP (1) | JP6450840B2 (ko) |
KR (1) | KR102100357B1 (ko) |
CN (2) | CN106661011B (ko) |
AU (1) | AU2014400894B2 (ko) |
BR (1) | BR112017000351B1 (ko) |
CA (1) | CA2955397C (ko) |
IL (2) | IL297649A (ko) |
MX (1) | MX2017000409A (ko) |
MY (1) | MY190477A (ko) |
PH (1) | PH12017500093A1 (ko) |
RU (1) | RU2663617C1 (ko) |
SG (1) | SG11201700066TA (ko) |
UA (1) | UA116182C2 (ko) |
WO (1) | WO2016010178A1 (ko) |
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KR100898361B1 (ko) * | 2008-07-03 | 2009-05-20 | 주식회사 레고켐 바이오사이언스 | P4 위치에 사이클릭 아미독심 또는 사이클릭 아미드라존기를 가지는 FXa 저해제, 이의 유도체, 제조방법 및이를 함유하는 의약 조성물 |
KR20110004590A (ko) * | 2009-07-08 | 2011-01-14 | 주식회사 레고켐 바이오사이언스 | 5-클로로-n-(((5s)-2-옥소-3-(4-(5,6-디하이드로-1,2,4-트리아진-1(4h)-일)페닐)-1,3-옥사졸리딘-5-일)메틸)티오펜-2-카르복사미드 유도체의 제조방법 및 그 제조중간체 |
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- 2014-07-18 US US15/325,521 patent/US9988372B2/en active Active
- 2014-07-18 WO PCT/KR2014/006555 patent/WO2016010178A1/ko active Application Filing
- 2014-07-18 BR BR112017000351-1A patent/BR112017000351B1/pt active IP Right Grant
- 2014-07-18 KR KR1020167035812A patent/KR102100357B1/ko active IP Right Grant
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- 2014-07-18 CA CA2955397A patent/CA2955397C/en active Active
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- 2014-07-18 EP EP14897871.1A patent/EP3170819B1/en active Active
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Patent Citations (2)
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PH12017500093A1 (en) | 2017-05-22 |
CA2955397C (en) | 2019-01-08 |
UA116182C2 (uk) | 2018-02-12 |
US9988372B2 (en) | 2018-06-05 |
SG11201700066TA (en) | 2017-02-27 |
AU2014400894B2 (en) | 2018-04-19 |
EP3170819A1 (en) | 2017-05-24 |
KR20170023003A (ko) | 2017-03-02 |
CN106661011B (zh) | 2020-01-10 |
RU2663617C1 (ru) | 2018-08-07 |
MX2017000409A (es) | 2017-05-01 |
BR112017000351A2 (pt) | 2017-11-07 |
AU2014400894A1 (en) | 2017-02-02 |
JP2017521500A (ja) | 2017-08-03 |
EP3170819A4 (en) | 2018-05-16 |
MY190477A (en) | 2022-04-22 |
EP3170819B1 (en) | 2019-07-10 |
CN110407827A (zh) | 2019-11-05 |
US20170152251A1 (en) | 2017-06-01 |
IL297649A (en) | 2022-12-01 |
BR112017000351B1 (pt) | 2022-10-25 |
CA2955397A1 (en) | 2016-01-21 |
CN106661011A (zh) | 2017-05-10 |
JP6450840B2 (ja) | 2019-01-09 |
NZ727829A (en) | 2021-01-29 |
IL250168A0 (en) | 2017-03-30 |
KR102100357B1 (ko) | 2020-04-13 |
CN110407827B (zh) | 2023-05-23 |
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