RU2394038C2 - Органические соединения - Google Patents
Органические соединения Download PDFInfo
- Publication number
- RU2394038C2 RU2394038C2 RU2007120695/04A RU2007120695A RU2394038C2 RU 2394038 C2 RU2394038 C2 RU 2394038C2 RU 2007120695/04 A RU2007120695/04 A RU 2007120695/04A RU 2007120695 A RU2007120695 A RU 2007120695A RU 2394038 C2 RU2394038 C2 RU 2394038C2
- Authority
- RU
- Russia
- Prior art keywords
- crystalline form
- ethanol
- benzoyl
- solvent
- solution
- Prior art date
Links
- 150000002894 organic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 102000003923 Protein Kinase C Human genes 0.000 claims abstract description 7
- 108090000315 Protein Kinase C Proteins 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 131
- BMGQWWVMWDBQGC-IIFHNQTCSA-N midostaurin Chemical compound CN([C@H]1[C@H]([C@]2(C)O[C@@H](N3C4=CC=CC=C4C4=C5C(=O)NCC5=C5C6=CC=CC=C6N2C5=C43)C1)OC)C(=O)C1=CC=CC=C1 BMGQWWVMWDBQGC-IIFHNQTCSA-N 0.000 claims description 98
- 239000000203 mixture Substances 0.000 claims description 48
- 239000000243 solution Substances 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 37
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 26
- 239000000047 product Substances 0.000 claims description 26
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 claims description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 18
- 239000007787 solid Substances 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000001694 spray drying Methods 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 239000003826 tablet Substances 0.000 claims description 7
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 claims description 6
- 238000010521 absorption reaction Methods 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000001556 precipitation Methods 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 2
- 239000002831 pharmacologic agent Substances 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims 1
- 238000000862 absorption spectrum Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 239000000126 substance Substances 0.000 abstract description 8
- 239000013078 crystal Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 230000001613 neoplastic effect Effects 0.000 abstract 1
- 239000000725 suspension Substances 0.000 description 30
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 12
- 239000000463 material Substances 0.000 description 11
- 229950010895 midostaurin Drugs 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000013543 active substance Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000004566 IR spectroscopy Methods 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 239000000010 aprotic solvent Substances 0.000 description 6
- 235000019445 benzyl alcohol Nutrition 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000003586 protic polar solvent Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 239000012065 filter cake Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- -1 pyrrolo [3,4-j] [1,7] benzodiazonin-11-yl Chemical group 0.000 description 4
- 239000013557 residual solvent Substances 0.000 description 4
- 229910002012 Aerosil® Inorganic materials 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000012296 anti-solvent Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012527 feed solution Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 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 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 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 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000005574 benzylation reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000036457 multidrug resistance Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 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 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 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 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- HZVVJJIYJKGMFL-UHFFFAOYSA-N almasilate Chemical compound O.[Mg+2].[Al+3].[Al+3].O[Si](O)=O.O[Si](O)=O HZVVJJIYJKGMFL-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- LBOVMDOAMWYGHK-UHFFFAOYSA-N ethanol;methylsulfinylmethane Chemical compound CCO.CS(C)=O LBOVMDOAMWYGHK-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000005426 pharmaceutical component Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Extraction Or Liquid Replacement (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62534304P | 2004-11-05 | 2004-11-05 | |
| US60/625,343 | 2004-11-05 | ||
| US64213105P | 2005-01-07 | 2005-01-07 | |
| US60/642,131 | 2005-01-07 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2009137788/04A Division RU2467012C2 (ru) | 2004-11-05 | 2009-10-13 | Способ очистки стауроспорина и способ получения n-бензоилстауроспорина |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2007120695A RU2007120695A (ru) | 2008-12-10 |
| RU2394038C2 true RU2394038C2 (ru) | 2010-07-10 |
Family
ID=35501294
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007120695/04A RU2394038C2 (ru) | 2004-11-05 | 2005-11-03 | Органические соединения |
| RU2009137788/04A RU2467012C2 (ru) | 2004-11-05 | 2009-10-13 | Способ очистки стауроспорина и способ получения n-бензоилстауроспорина |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2009137788/04A RU2467012C2 (ru) | 2004-11-05 | 2009-10-13 | Способ очистки стауроспорина и способ получения n-бензоилстауроспорина |
Country Status (31)
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008021347A2 (en) * | 2006-08-16 | 2008-02-21 | Novartis Ag | Method for making solid dispersions of highly crystalline therapeutic compounds |
| EP2327706A1 (en) * | 2009-11-30 | 2011-06-01 | Novartis AG | Polymorphous forms III and IV of N-benzoyl-staurosporine |
| KR20160008267A (ko) | 2014-07-14 | 2016-01-22 | 주식회사 윈스 | 네트워크 기반 영상감시체계에서의 사용자 행위 분석 시스템 |
| US20200010481A1 (en) | 2017-03-06 | 2020-01-09 | Teva Pharmaceutical Works Ltd. | Solid state forms of midostaurin |
| WO2019215759A1 (en) * | 2018-05-09 | 2019-11-14 | Alaparthi Lakshmi Prasad | An improved process for preparation of midostaurin |
| IT201900004729A1 (it) | 2019-03-29 | 2020-09-29 | Procos Spa | Processo per la preparazione di midostaurina ad elevato grado di purezza |
| WO2020261293A1 (en) * | 2019-06-24 | 2020-12-30 | Dr. Reddy's Laboratories Limited | Process for preparation of midostaurin |
| IT201900014346A1 (it) | 2019-08-08 | 2021-02-08 | Procos Spa | Processo per la preparazione di midostaurina amorfa con un basso contenuto di solvente organico residuo |
| IT202000004291A1 (it) | 2020-03-02 | 2021-09-02 | Indena Spa | Processo per la purificazione di alcaloidi indolo carbazolici |
| CN111393454A (zh) * | 2020-05-07 | 2020-07-10 | 奥锐特药业(天津)有限公司 | 米哚妥林的新晶型及其制备方法 |
| CN115124551B (zh) * | 2021-03-24 | 2024-04-30 | 奥锐特药业(天津)有限公司 | 一种高纯度米哚妥林的制备方法 |
| WO2023205504A1 (en) * | 2022-04-22 | 2023-10-26 | Rutgers, The State University Of New Jersey | Formulations and methods for treating epidermolysis bullosa simplex and related conditions |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0296110A2 (de) * | 1987-06-15 | 1988-12-21 | Ciba-Geigy Ag | An Methylamino-Stickstoff substituierte Derivate von Staurosporin |
| US5093330A (en) * | 1987-06-15 | 1992-03-03 | Ciba-Geigy Corporation | Staurosporine derivatives substituted at methylamino nitrogen |
| RU2191175C2 (ru) * | 1995-12-11 | 2002-10-20 | Сефалон, Инкорпорейтед | Конденсированные изоиндолоны в качестве ингибиторов протеинкиназы с |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5373501A (en) | 1976-12-11 | 1978-06-30 | Kitasato Inst | Novel antibiotics amm2282 and process for preparing same |
| JPS60185719A (ja) | 1984-03-06 | 1985-09-21 | Ajinomoto Co Inc | 抗腫瘍剤 |
| US5073633A (en) | 1989-03-23 | 1991-12-17 | Bristol-Myers Company | BMY-41950 antitumor antibiotic |
| US5096330A (en) * | 1990-06-21 | 1992-03-17 | M-B-W Inc. | Pitch control mechanism for a surface finishing machine |
| JPH05247055A (ja) * | 1992-03-03 | 1993-09-24 | Meiji Seika Kaisha Ltd | スタウロスポリン誘導体及びそれを含有する抗腫瘍効果増強剤 |
| JPH05247955A (ja) | 1992-03-06 | 1993-09-24 | Taisei Corp | 擁壁の施工方法 |
| EP0575955B1 (en) | 1992-06-22 | 1999-09-15 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing staurosporine derivatives |
| WO1995032975A1 (en) * | 1994-06-01 | 1995-12-07 | Ciba-Geigy Ag | Indolocarbazole derivatives for sensitizing multidrug-resistant cells to antitumor agents |
| US6878804B1 (en) * | 1999-08-30 | 2005-04-12 | University Of Zurich | Synthesis of template-fixed β-hairpin loop mimetics |
| WO2002076432A2 (en) | 2001-03-26 | 2002-10-03 | Novartis Ag | Pharmaceutical composition comprising a poorly water-soluble active ingredient, a surfactant and a water-soluble polymer |
| KR100407758B1 (ko) * | 2001-08-27 | 2003-12-01 | 씨제이 주식회사 | 스타틴의 제조에 있어서 락톤화 방법 |
| US7608420B2 (en) * | 2003-04-22 | 2009-10-27 | Lonza Ag | Process for the recovery of staurosporine from a fermentation broth |
-
2005
- 2005-10-26 JO JO2005162A patent/JO2897B1/en active
- 2005-10-28 MY MYPI20055091A patent/MY147404A/en unknown
- 2005-10-28 GT GT200500311A patent/GT200500311A/es unknown
- 2005-10-28 MY MYPI20091911A patent/MY154878A/en unknown
- 2005-11-03 SI SI200531555T patent/SI1812448T1/sl unknown
- 2005-11-03 PL PL05803350T patent/PL1812448T3/pl unknown
- 2005-11-03 ES ES05803350T patent/ES2388142T3/es not_active Expired - Lifetime
- 2005-11-03 CN CN2012101018747A patent/CN102627658A/zh active Pending
- 2005-11-03 WO PCT/EP2005/011789 patent/WO2006048296A1/en not_active Ceased
- 2005-11-03 PT PT05803350T patent/PT1812448E/pt unknown
- 2005-11-03 BR BRPI0517689-1A patent/BRPI0517689A/pt not_active IP Right Cessation
- 2005-11-03 HR HRP20120652TT patent/HRP20120652T1/hr unknown
- 2005-11-03 NZ NZ599033A patent/NZ599033A/xx not_active IP Right Cessation
- 2005-11-03 JP JP2007539535A patent/JP5057986B2/ja not_active Expired - Lifetime
- 2005-11-03 CA CA2584911A patent/CA2584911C/en not_active Expired - Lifetime
- 2005-11-03 EP EP15171908.5A patent/EP2955186A1/en not_active Withdrawn
- 2005-11-03 RU RU2007120695/04A patent/RU2394038C2/ru active
- 2005-11-03 DK DK05803350.7T patent/DK1812448T3/da active
- 2005-11-03 AU AU2005300693A patent/AU2005300693B2/en not_active Expired
- 2005-11-03 EP EP10173464.8A patent/EP2272850B1/en not_active Expired - Lifetime
- 2005-11-03 EP EP05803350A patent/EP1812448B1/en not_active Expired - Lifetime
- 2005-11-03 US US11/718,029 patent/US8198435B2/en active Active
- 2005-11-03 KR KR1020127022582A patent/KR101265850B1/ko not_active Expired - Lifetime
- 2005-11-03 NZ NZ588025A patent/NZ588025A/en not_active IP Right Cessation
- 2005-11-03 KR KR1020127022584A patent/KR101289998B1/ko not_active Expired - Lifetime
- 2005-11-03 MX MX2011007303A patent/MX346525B/es unknown
- 2005-11-03 KR KR1020077010191A patent/KR101333851B1/ko not_active Expired - Lifetime
- 2005-11-03 MX MX2007005429A patent/MX2007005429A/es active IP Right Grant
- 2005-11-03 NZ NZ554653A patent/NZ554653A/en not_active IP Right Cessation
- 2005-11-03 CN CN2012104320940A patent/CN102993213A/zh active Pending
- 2005-11-04 PE PE2009000199A patent/PE20090433A1/es not_active Application Discontinuation
- 2005-11-04 AR ARP050104637A patent/AR052322A1/es not_active Application Discontinuation
- 2005-11-04 TW TW103130302A patent/TWI530501B/zh not_active IP Right Cessation
- 2005-11-04 PE PE2012002519A patent/PE20130377A1/es not_active Application Discontinuation
- 2005-11-04 TW TW094138677A patent/TWI433852B/zh not_active IP Right Cessation
- 2005-11-04 TW TW101122880A patent/TWI530500B/zh not_active IP Right Cessation
- 2005-11-04 TW TW101122882A patent/TWI455941B/zh not_active IP Right Cessation
- 2005-11-04 PE PE2005001297A patent/PE20060947A1/es not_active Application Discontinuation
-
2007
- 2007-04-19 IL IL182691A patent/IL182691A/en active IP Right Grant
- 2007-05-02 NO NO20072290A patent/NO338960B1/no unknown
- 2007-05-04 TN TNP2007000165A patent/TNSN07165A1/fr unknown
- 2007-05-22 MA MA29924A patent/MA29033B1/fr unknown
- 2007-12-19 HK HK15112508.3A patent/HK1211587A1/en unknown
-
2009
- 2009-10-13 RU RU2009137788/04A patent/RU2467012C2/ru active
- 2009-12-07 AU AU2009245817A patent/AU2009245817B2/en not_active Expired
-
2010
- 2010-08-19 IL IL207702A patent/IL207702A/en active IP Right Grant
-
2012
- 2012-01-16 IL IL217571A patent/IL217571A/en active IP Right Grant
- 2012-03-12 EC ECSP12007431 patent/ECSP12007431A/es unknown
- 2012-05-11 JP JP2012109447A patent/JP5701246B2/ja not_active Expired - Lifetime
- 2012-05-15 US US13/472,130 patent/US8710216B2/en not_active Expired - Lifetime
- 2012-08-21 CY CY20121100747T patent/CY1113059T1/el unknown
-
2015
- 2015-01-09 JP JP2015003634A patent/JP2015063569A/ja not_active Withdrawn
-
2016
- 2016-07-12 NO NO20161152A patent/NO340404B1/no unknown
-
2017
- 2017-01-13 JP JP2017004320A patent/JP2017061578A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0296110A2 (de) * | 1987-06-15 | 1988-12-21 | Ciba-Geigy Ag | An Methylamino-Stickstoff substituierte Derivate von Staurosporin |
| US5093330A (en) * | 1987-06-15 | 1992-03-03 | Ciba-Geigy Corporation | Staurosporine derivatives substituted at methylamino nitrogen |
| RU2191175C2 (ru) * | 1995-12-11 | 2002-10-20 | Сефалон, Инкорпорейтед | Конденсированные изоиндолоны в качестве ингибиторов протеинкиназы с |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2467012C2 (ru) | Способ очистки стауроспорина и способ получения n-бензоилстауроспорина | |
| HK1108881B (en) | Organic compounds | |
| HK1149754A (en) | Process for purifying staurosporine | |
| CN109721558A (zh) | 来曲唑晶iii型固体物质及制备方法和其药物组合物与用途 |