CA2624533A1 - Phosphoantigen salts of organic bases and methods for their crystallization - Google Patents

Info

Publication number

CA2624533A1

CA2624533A1 CA002624533A CA2624533A CA2624533A1 CA 2624533 A1 CA2624533 A1 CA 2624533A1 CA 002624533 A CA002624533 A CA 002624533A CA 2624533 A CA2624533 A CA 2624533A CA 2624533 A1 CA2624533 A1 CA 2624533A1

Authority

CA

Canada

Prior art keywords

phosphoantigen

salt

organic base

group

crystalline

Prior art date

2005-10-06

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000003839 salts Chemical class 0.000 title claims abstract description 220
• 238000000034 method Methods 0.000 title claims abstract description 164
• 150000007530 organic bases Chemical class 0.000 title claims description 70
• 238000002425 crystallisation Methods 0.000 title description 28
• 230000008025 crystallization Effects 0.000 title description 25
• 239000000203 mixture Substances 0.000 claims abstract description 160
• 239000012453 solvate Substances 0.000 claims abstract description 36
• 239000013078 crystal Substances 0.000 claims abstract description 14
• 150000001875 compounds Chemical class 0.000 claims description 175
• -1 benzathin Chemical compound 0.000 claims description 146
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 97
• YKAYCWPQDPILSA-UHFFFAOYSA-N bromohydrin pyrophosphate Chemical compound BrCC(O)(C)CCOP(O)(=O)OP(O)(O)=O YKAYCWPQDPILSA-UHFFFAOYSA-N 0.000 claims description 84
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 79
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 75
• KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 claims description 63
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 61
• 239000002552 dosage form Substances 0.000 claims description 59
• KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 claims description 49
• LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 claims description 42
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 38
• 239000007787 solid Substances 0.000 claims description 38
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 36
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 36
• 235000001258 Cinchona calisaya Nutrition 0.000 claims description 35
• 229960000948 quinine Drugs 0.000 claims description 35
• 239000002904 solvent Substances 0.000 claims description 31
• 239000005725 8-Hydroxyquinoline Substances 0.000 claims description 27
• 229960003540 oxyquinoline Drugs 0.000 claims description 27
• MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 claims description 27
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 22
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 22
• 239000000725 suspension Substances 0.000 claims description 22
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 21
• CTQMJYWDVABFRZ-UHFFFAOYSA-N cloxiquine Chemical compound C1=CN=C2C(O)=CC=C(Cl)C2=C1 CTQMJYWDVABFRZ-UHFFFAOYSA-N 0.000 claims description 21
• 239000004475 Arginine Substances 0.000 claims description 20
• 150000001413 amino acids Chemical class 0.000 claims description 20
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 20
• 238000001704 evaporation Methods 0.000 claims description 20
• 229960004919 procaine Drugs 0.000 claims description 20
• 229960001404 quinidine Drugs 0.000 claims description 20
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 19
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 19
• 239000004472 Lysine Substances 0.000 claims description 19
• VFOSDIOKPAJPOS-UHFFFAOYSA-N hydroxysulfanylmethanamine Chemical compound NCSO VFOSDIOKPAJPOS-UHFFFAOYSA-N 0.000 claims description 19
• 125000000129 anionic group Chemical group 0.000 claims description 18
• 230000008020 evaporation Effects 0.000 claims description 18
• 229960003237 betaine Drugs 0.000 claims description 17
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 17
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 16
• 239000011347 resin Substances 0.000 claims description 14
• 229920005989 resin Polymers 0.000 claims description 14
• 239000007858 starting material Substances 0.000 claims description 14
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 13
• 125000002091 cationic group Chemical group 0.000 claims description 13
• 230000020477 pH reduction Effects 0.000 claims description 12
• 239000002002 slurry Substances 0.000 claims description 12
• 239000007884 disintegrant Substances 0.000 claims description 10
• 229930013930 alkaloid Natural products 0.000 claims description 9
• 238000001816 cooling Methods 0.000 claims description 9
• 238000004821 distillation Methods 0.000 claims description 9
• 239000002775 capsule Substances 0.000 claims description 8
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 7
• 238000001035 drying Methods 0.000 claims description 6
• 230000035800 maturation Effects 0.000 claims description 6
• 230000007423 decrease Effects 0.000 claims description 5
• 229940126534 drug product Drugs 0.000 claims description 5
• 238000002955 isolation Methods 0.000 claims description 5
• 239000007921 spray Substances 0.000 claims description 5
• 150000003797 alkaloid derivatives Chemical class 0.000 claims description 4
• 239000012296 anti-solvent Substances 0.000 claims description 4
• 238000004320 controlled atmosphere Methods 0.000 claims description 4
• 230000008859 change Effects 0.000 claims description 3
• 238000004090 dissolution Methods 0.000 claims description 3
• 238000005406 washing Methods 0.000 claims description 3
• 239000007795 chemical reaction product Substances 0.000 claims description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
• 125000003410 quininyl group Chemical group 0.000 claims 4
• JREYOWJEWZVAOR-UHFFFAOYSA-N triazanium;[3-methylbut-3-enoxy(oxido)phosphoryl] phosphate Chemical compound [NH4+].[NH4+].[NH4+].CC(=C)CCOP([O-])(=O)OP([O-])([O-])=O JREYOWJEWZVAOR-UHFFFAOYSA-N 0.000 claims 2
• 239000003814 drug Substances 0.000 abstract description 58
• 238000011282 treatment Methods 0.000 abstract description 56
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 39
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 25
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• 230000028993 immune response Effects 0.000 abstract description 3
• 239000012071 phase Substances 0.000 description 140
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 93
• 239000001177 diphosphate Substances 0.000 description 81
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 55
• 238000004458 analytical method Methods 0.000 description 52
• 206010028980 Neoplasm Diseases 0.000 description 51
• 229910001868 water Inorganic materials 0.000 description 44
• 239000000243 solution Substances 0.000 description 42
• 235000019441 ethanol Nutrition 0.000 description 41
• 239000002585 base Substances 0.000 description 40
• 125000000217 alkyl group Chemical group 0.000 description 37
• 229940079593 drug Drugs 0.000 description 34
• 239000008186 active pharmaceutical agent Substances 0.000 description 33
• 238000002360 preparation method Methods 0.000 description 31
• 238000004519 manufacturing process Methods 0.000 description 30
• YYYUHBYKZCBOPY-ZZXKWVIFSA-N [(e)-5-hydroxy-4-methylpent-3-enyl]-phosphonooxyphosphinic acid Chemical compound OCC(/C)=C/CCP(O)(=O)OP(O)(O)=O YYYUHBYKZCBOPY-ZZXKWVIFSA-N 0.000 description 27
• 230000000694 effects Effects 0.000 description 27
• 238000003756 stirring Methods 0.000 description 27
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
• 239000002777 nucleoside Substances 0.000 description 24
• NUHSROFQTUXZQQ-UHFFFAOYSA-N isopentenyl diphosphate Chemical compound CC(=C)CCO[P@](O)(=O)OP(O)(O)=O NUHSROFQTUXZQQ-UHFFFAOYSA-N 0.000 description 23
• 150000003833 nucleoside derivatives Chemical class 0.000 description 23
• 229940126530 T cell activator Drugs 0.000 description 22
• 239000004480 active ingredient Substances 0.000 description 22
• 125000003729 nucleotide group Chemical group 0.000 description 22
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• 229940122361 Bisphosphonate Drugs 0.000 description 15
• 125000005466 alkylenyl group Chemical group 0.000 description 15
• 238000013270 controlled release Methods 0.000 description 15
• 150000002148 esters Chemical class 0.000 description 15
• 238000001914 filtration Methods 0.000 description 15
• 239000002773 nucleotide Substances 0.000 description 15
• 125000002252 acyl group Chemical group 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 14
• 150000001768 cations Chemical class 0.000 description 14
• 238000001179 sorption measurement Methods 0.000 description 14
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 13
• 230000002829 reductive effect Effects 0.000 description 13
• 239000003826 tablet Substances 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• 239000007864 aqueous solution Substances 0.000 description 12
• XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical group OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 12
• 150000002430 hydrocarbons Chemical class 0.000 description 12
• 230000001965 increasing effect Effects 0.000 description 12
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• 239000001226 triphosphate Substances 0.000 description 12
• 150000004325 8-hydroxyquinolines Chemical class 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 11
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