JP6851572B2 - Jakキナーゼ阻害剤の硫酸水素塩の結晶形およびその製造方法 - Google Patents
Jakキナーゼ阻害剤の硫酸水素塩の結晶形およびその製造方法 Download PDFInfo
- Publication number
- JP6851572B2 JP6851572B2 JP2017518183A JP2017518183A JP6851572B2 JP 6851572 B2 JP6851572 B2 JP 6851572B2 JP 2017518183 A JP2017518183 A JP 2017518183A JP 2017518183 A JP2017518183 A JP 2017518183A JP 6851572 B2 JP6851572 B2 JP 6851572B2
- Authority
- JP
- Japan
- Prior art keywords
- crystals
- pyrrole
- hexahydrocyclopenta
- methoxyl
- amino
- 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.)
- Active
Links
- 239000013078 crystal Substances 0.000 title claims description 81
- 238000004519 manufacturing process Methods 0.000 title claims description 16
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 title claims description 11
- 229940043355 kinase inhibitor Drugs 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 63
- 238000001228 spectrum Methods 0.000 claims description 35
- -1 methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino Chemical group 0.000 claims description 28
- 239000007787 solid Substances 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- 239000003960 organic solvent Substances 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 4
- 229910002483 Cu Ka Inorganic materials 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 229960001375 lactose Drugs 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 229940083542 sodium Drugs 0.000 claims description 2
- 235000015424 sodium Nutrition 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 3
- ZAEUOCGSFKFWHY-UHFFFAOYSA-N 3-methoxy-1,2,4-thiadiazole Chemical compound COC=1N=CSN=1 ZAEUOCGSFKFWHY-UHFFFAOYSA-N 0.000 claims 1
- 125000003158 alcohol group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000012265 solid product Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 33
- 238000000113 differential scanning calorimetry Methods 0.000 description 18
- 238000002441 X-ray diffraction Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 7
- 239000002198 insoluble material Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000013557 residual solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 102000015617 Janus Kinases Human genes 0.000 description 3
- 108010024121 Janus Kinases Proteins 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229940122245 Janus kinase inhibitor Drugs 0.000 description 2
- 239000004012 Tofacitinib Substances 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960001350 tofacitinib Drugs 0.000 description 2
- DNBCBAXDWNDRNO-FOSCPWQOSA-N (3aS,6aR)-N-(3-methoxy-1,2,4-thiadiazol-5-yl)-5-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2-carboxamide Chemical compound COC1=NSC(NC(=O)N2C[C@H]3CC(C[C@H]3C2)N(C)C=2C=3C=CNC=3N=CN=2)=N1 DNBCBAXDWNDRNO-FOSCPWQOSA-N 0.000 description 1
- 101100223811 Caenorhabditis elegans dsc-1 gene Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010060820 Joint injury Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940126397 ivarmacitinib Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
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)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
(1)(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル (7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミドを有機溶媒に溶解し、次いで濃硫酸を滴下し、溶液をろ過して結晶を沈殿させる;または式(I)の化合物の固形物を加熱下に適量の有機溶媒に溶解し、次いで溶液を冷却して結晶を沈殿させる;
(2)当該結晶をろ過し、次いでそれを洗浄して乾燥させる
のステップを含む式(I)の化合物のII型結晶の製造方法を提供する。
最も好ましくは、当該単一溶媒はメタノールである。
本発明を以下の実施例により詳細に説明するが、本発明の実施例は発明の技術的解決を記載することのみを意図するものであって、本発明の範囲を限定すると考えてはならない。
1.DSCスペクトル
装置タイプ:Mettler Toledo DSC 1 Staree System
パージガス:窒素
加熱速度:10.0℃/分
温度範囲:40-300℃
2.X線回折スペクトル
装置タイプ:D/Max-RA日本理学X線粉末回折計
光線:単色Cu- Ka線 (λ=1.5418Å)
スキャンモード:θ/2θ、角度範囲:2-40°
電圧:40KV 電流:40mA
Claims (11)
- 結晶が、Cu-Ka線を用いて得られ、2θ角と面間隔で表して、8.96 (9.87), 11.80 (7.50), 13.12 (6.74), 13.53 (6.54), 13.89 (6.37), 14.42 (6.14), 14.98 (5.91), 16.52 (5.36), 18.20 (4.87), 18.75 (4.73), 19.15 (4.63), 19.72 (4.50), 20.82 (4.26), 22.05 (4.03), 22.52 (3.95), 22.92 (3.88), 23.58 (3.77) および27.04 (3.30) に特徴的なピークがある、X線粉末回折スペクトルを有することを特徴とする、(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩のII型結晶。
- 結晶のD S Cスペクトルは218℃に融解吸熱ピークを示すことを特徴とする、請求項1に記載の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩のII型結晶。
- 以下:
1)いずれかの結晶形またはアモルファス形の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミドを適量の有機溶媒に溶解し、次いで濃硫酸を滴下し、結晶を沈殿させ、または逆溶剤を添加し、結晶を沈殿させ;またはいずれかの結晶形またはアモルファス形の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩の固体物を加熱下で適量の有機溶媒に溶解し、次いで溶液を冷却して結晶を沈殿させ、ここで有機溶媒は3つ以下の炭素原子を有するアルコール、ケトン、エステル、または前記1つ以上の溶媒の混合溶媒および3つ以下の炭素原子を有するハロゲン化炭化水素から選択され;
2)該結晶をろ過し、次いでそれを洗浄して乾燥する
のステップを含む、請求項1に記載の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩のII型結晶の製造方法。 - 以下:
1)いずれかの結晶形またはアモルファス形の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミドを適量の有機溶媒に溶解し、次いで濃硫酸を滴下し、結晶を沈殿させ、または逆溶剤を添加し、結晶を沈殿させ;またはいずれかの結晶形またはアモルファス形の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩の固体物を加熱下で適量の有機溶媒に溶解し、次いで溶液を冷却して結晶を沈殿させ、ここで有機溶媒はメタノール、エタノール、イソプロパノール、アセトン、酢酸エチル、ジクロロメタン/メタノール、ジクロロメタン/メタノール/エタノール、ジクロロメタン/メタノール/イソプロパノール、ジクロロメタン/メタノール/酢酸エチル、またはジクロロメタン/メタノール/アセトンであり;
2)該結晶をろ過し、次いでそれを洗浄して乾燥する
のステップを含む、請求項1に記載の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩のII型結晶の製造方法。 - ステップ1)における有機溶媒がメタノール、またはジクロロメタン/メタノール/エタノールであることを特徴とする、請求項4に記載の製造方法。
- ジクロロメタン/メタノール/エタノールの体積比が12:3:10であることを特徴とする、請求項5に記載の製造方法。
- 請求項1に記載の(3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩のII型結晶および薬学的に許容される少なくとも1つの担体を含有する医薬組成物。
- (3aR,5s,6aS)-N-(3-メトキシル-1,2,4-チアジアゾール-5-イル)-5-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)ヘキサヒドロシクロペンタ[c]ピロール-2(1H)-ホルムアミド硫酸水素塩のII型結晶の含有量が0.5mg〜200mgであることを特徴とする、請求項7に記載の医薬組成物。
- 薬学的に許容される担体が乳糖、マンニトール、微結晶セルロース、クロスカルメロースナトリウム、ナトリウムカルボキシメチルデンプン、ヒドロキシプロピルメチルセルロース、ポビドンおよびステアリン酸マグネシウムの少なくとも1つから選択されることを特徴とする、請求項7に記載の医薬組成物。
- JAK関連疾患の治療のための薬剤の製造における請求項1に記載のII型結晶または請求項7〜9のいずれに記載の医薬組成物の使用。
- リウマチ性関節炎および関節リウマチの治療のための薬剤の製造における請求項1に記載のII型結晶または請求項7〜9のいずれに記載の医薬組成物の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410617808 | 2014-11-05 | ||
CN201410617808.4 | 2014-11-05 | ||
PCT/CN2015/091527 WO2016070697A1 (zh) | 2014-11-05 | 2015-10-09 | 一种jak激酶抑制剂的硫酸氢盐的结晶形式及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017532327A JP2017532327A (ja) | 2017-11-02 |
JP6851572B2 true JP6851572B2 (ja) | 2021-03-31 |
Family
ID=55908546
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017518183A Active JP6851572B2 (ja) | 2014-11-05 | 2015-10-09 | Jakキナーゼ阻害剤の硫酸水素塩の結晶形およびその製造方法 |
Country Status (20)
Country | Link |
---|---|
US (1) | US10023577B2 (ja) |
EP (1) | EP3216790B1 (ja) |
JP (1) | JP6851572B2 (ja) |
KR (1) | KR102522895B1 (ja) |
CN (1) | CN105980390B (ja) |
AU (1) | AU2015342444B2 (ja) |
BR (1) | BR112017007953B1 (ja) |
CA (1) | CA2965716C (ja) |
CY (1) | CY1122468T1 (ja) |
DK (1) | DK3216790T3 (ja) |
ES (1) | ES2754548T3 (ja) |
HR (1) | HRP20192030T1 (ja) |
HU (1) | HUE047404T2 (ja) |
PL (1) | PL3216790T3 (ja) |
PT (1) | PT3216790T (ja) |
RS (1) | RS59669B1 (ja) |
RU (1) | RU2716260C2 (ja) |
SI (1) | SI3216790T1 (ja) |
TW (1) | TWI672305B (ja) |
WO (1) | WO2016070697A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6875407B2 (ja) | 2016-02-19 | 2021-05-26 | ジエンス ヘンルイ メデイシンカンパニー リミテッドJiangsu Hengrui Medicine Co.,Ltd. | Jakキナーゼ阻害剤またはその薬剤的に許容される塩を含有する医薬組成物 |
TW201827436A (zh) * | 2017-01-20 | 2018-08-01 | 大陸商江蘇恆瑞醫藥股份有限公司 | 一種jak激酶抑制劑的硫酸氫鹽的晶型及其製備方法 |
CN111205290B (zh) * | 2018-11-22 | 2021-10-08 | 江苏恒瑞医药股份有限公司 | 一种jak激酶抑制剂的结晶形式及其制备方法 |
EP4188333A1 (en) | 2020-07-28 | 2023-06-07 | Arcutis Biotherapeutics, Inc. | Topical formulation containing jak inhibitor and laureth-4 |
WO2022108911A1 (en) | 2020-11-17 | 2022-05-27 | Arcutis Biotherapeutics, Inc. | Compositions and methods for deep dermal drug delivery |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUP0301114A3 (en) | 2000-06-26 | 2004-11-29 | Pfizer Prod Inc | Pyrrolo[2,3-d]pyrimidine compounds as immunosuppressive agents and pharmaceutical compositions containing them |
ATE421322T1 (de) | 2003-04-04 | 2009-02-15 | Novartis Pharma Gmbh | Chinolin-2-on-derivate zur behandlung von erkankungen der atemwege |
WO2006096270A1 (en) * | 2005-02-03 | 2006-09-14 | Vertex Pharmaceuticals Incorporated | Pyrrolopyrimidines useful as inhibitors of protein kinase |
JP5786257B2 (ja) | 2011-06-16 | 2015-09-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規の選択的ccr2拮抗薬 |
ES2682755T3 (es) * | 2011-12-21 | 2018-09-21 | Jiangsu Hengrui Medicine Co. Ltd. | Derivado del anillo heteroarilo de seis miembros de pirrol, método de preparación del mismo y sus usos medicinales |
AU2014277506B2 (en) * | 2013-06-07 | 2017-08-31 | Jiangsu Hengrui Medicine Co., Ltd. | Bisulfate of Janus kinase (JAK) inhibitor and preparation method therefor |
CN105566327A (zh) | 2014-10-09 | 2016-05-11 | 江苏恒瑞医药股份有限公司 | 一种jak激酶抑制剂的硫酸氢盐的i型结晶及其制备方法 |
-
2015
- 2015-10-09 JP JP2017518183A patent/JP6851572B2/ja active Active
- 2015-10-09 EP EP15857844.3A patent/EP3216790B1/en active Active
- 2015-10-09 AU AU2015342444A patent/AU2015342444B2/en active Active
- 2015-10-09 HU HUE15857844A patent/HUE047404T2/hu unknown
- 2015-10-09 KR KR1020177013839A patent/KR102522895B1/ko active IP Right Grant
- 2015-10-09 RS RS20191420A patent/RS59669B1/sr unknown
- 2015-10-09 SI SI201530982T patent/SI3216790T1/sl unknown
- 2015-10-09 ES ES15857844T patent/ES2754548T3/es active Active
- 2015-10-09 PT PT158578443T patent/PT3216790T/pt unknown
- 2015-10-09 RU RU2017118193A patent/RU2716260C2/ru active
- 2015-10-09 WO PCT/CN2015/091527 patent/WO2016070697A1/zh active Application Filing
- 2015-10-09 CN CN201580008169.4A patent/CN105980390B/zh active Active
- 2015-10-09 CA CA2965716A patent/CA2965716C/en active Active
- 2015-10-09 BR BR112017007953-4A patent/BR112017007953B1/pt active IP Right Grant
- 2015-10-09 PL PL15857844T patent/PL3216790T3/pl unknown
- 2015-10-09 DK DK15857844T patent/DK3216790T3/da active
- 2015-10-09 US US15/522,991 patent/US10023577B2/en active Active
- 2015-10-22 TW TW104134655A patent/TWI672305B/zh active
-
2019
- 2019-11-04 CY CY20191101146T patent/CY1122468T1/el unknown
- 2019-11-08 HR HRP20192030TT patent/HRP20192030T1/hr unknown
Also Published As
Publication number | Publication date |
---|---|
JP2017532327A (ja) | 2017-11-02 |
EP3216790A4 (en) | 2018-04-25 |
RU2017118193A (ru) | 2018-12-05 |
ES2754548T3 (es) | 2020-04-20 |
RU2017118193A3 (ja) | 2019-05-08 |
US10023577B2 (en) | 2018-07-17 |
EP3216790A1 (en) | 2017-09-13 |
BR112017007953B1 (pt) | 2023-12-05 |
BR112017007953A2 (pt) | 2017-12-19 |
KR20170078710A (ko) | 2017-07-07 |
KR102522895B1 (ko) | 2023-04-17 |
US20170313709A1 (en) | 2017-11-02 |
CA2965716C (en) | 2023-03-21 |
SI3216790T1 (sl) | 2020-02-28 |
CY1122468T1 (el) | 2021-01-27 |
DK3216790T3 (da) | 2019-11-25 |
WO2016070697A1 (zh) | 2016-05-12 |
CN105980390B (zh) | 2017-07-07 |
CN105980390A (zh) | 2016-09-28 |
TWI672305B (zh) | 2019-09-21 |
PL3216790T3 (pl) | 2020-05-18 |
RU2716260C2 (ru) | 2020-03-11 |
CA2965716A1 (en) | 2016-05-12 |
AU2015342444A1 (en) | 2017-05-18 |
AU2015342444B2 (en) | 2019-12-12 |
HUE047404T2 (hu) | 2020-04-28 |
TW201617347A (zh) | 2016-05-16 |
HRP20192030T1 (hr) | 2020-02-07 |
EP3216790B1 (en) | 2019-10-02 |
PT3216790T (pt) | 2019-11-19 |
RS59669B1 (sr) | 2020-01-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6830888B2 (ja) | Jak阻害剤の硫酸水素塩の結晶形およびその製造方法 | |
JP6851572B2 (ja) | Jakキナーゼ阻害剤の硫酸水素塩の結晶形およびその製造方法 | |
CA2635834C (en) | Trihydrochloride forms of a dihydropteridinone derivative and processes for preparation | |
JP5261487B2 (ja) | ジヒドロプテリジノン誘導体の結晶形 | |
JP2021167327A (ja) | フリー体のクリサボロールの結晶形ならびにそれらの調製方法および使用 | |
WO2018148961A1 (zh) | Acp-196盐的晶型、其制备方法、药物组合物和用途 | |
AU2017373784B2 (en) | Compositions and methods related to pyridinoylpiperidine 5-HT1F agonists | |
JP6761564B2 (ja) | ナトリウム・グルコース共輸送体2阻害薬のl−プロリン化合物、およびl−プロリン化合物の一水和物および結晶 | |
WO2018054359A1 (zh) | 一种喹唑啉衍生物的盐、其制备方法及应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181005 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190522 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190523 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190801 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20190902 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191113 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20191113 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20191122 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20191125 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20191227 |
|
C211 | Notice of termination of reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C211 Effective date: 20200108 |
|
C22 | Notice of designation (change) of administrative judge |
Free format text: JAPANESE INTERMEDIATE CODE: C22 Effective date: 20200812 |
|
C13 | Notice of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: C13 Effective date: 20200901 |
|
C22 | Notice of designation (change) of administrative judge |
Free format text: JAPANESE INTERMEDIATE CODE: C22 Effective date: 20201012 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201128 |
|
C302 | Record of communication |
Free format text: JAPANESE INTERMEDIATE CODE: C302 Effective date: 20201211 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20201201 |
|
C23 | Notice of termination of proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C23 Effective date: 20210106 |
|
C03 | Trial/appeal decision taken |
Free format text: JAPANESE INTERMEDIATE CODE: C03 Effective date: 20210208 |
|
C30A | Notification sent |
Free format text: JAPANESE INTERMEDIATE CODE: C3012 Effective date: 20210208 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210209 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6851572 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |