DE60202958T2 - Stabiles polymorph von flibanserin, industrielles verfahren zu dessen herstellung und dessen verwendung zur herstellung von medikamenten - Google Patents
Stabiles polymorph von flibanserin, industrielles verfahren zu dessen herstellung und dessen verwendung zur herstellung von medikamenten Download PDFInfo
- Publication number
- DE60202958T2 DE60202958T2 DE60202958T DE60202958T DE60202958T2 DE 60202958 T2 DE60202958 T2 DE 60202958T2 DE 60202958 T DE60202958 T DE 60202958T DE 60202958 T DE60202958 T DE 60202958T DE 60202958 T2 DE60202958 T2 DE 60202958T2
- Authority
- DE
- Germany
- Prior art keywords
- flibanserin
- polymorph
- water
- production
- pharmaceutical
- 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.)
- Expired - Lifetime
Links
- PPRRDFIXUUSXRA-UHFFFAOYSA-N flibanserin Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CCN3C(NC4=CC=CC=C43)=O)CC2)=C1 PPRRDFIXUUSXRA-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229960002053 flibanserin Drugs 0.000 title claims abstract description 39
- 239000003814 drug Substances 0.000 title claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 title claims description 14
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 150000001298 alcohols Chemical class 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 230000008901 benefit Effects 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 208000000044 Amnesia Diseases 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 230000006984 memory degeneration Effects 0.000 claims description 3
- 208000023060 memory loss Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 208000020016 psychiatric disease Diseases 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 3
- 208000015891 sexual disease Diseases 0.000 claims description 3
- 230000001568 sexual effect Effects 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical compound C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- 239000003880 polar aprotic solvent Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- 238000002076 thermal analysis method Methods 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- -1 1,1-diphenylmethyl Chemical group 0.000 description 16
- 239000013543 active substance Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 230000035946 sexual desire Effects 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011877 solvent mixture Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010011953 Decreased activity Diseases 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- 238000003801 milling Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 0 O=C1Nc2ccccc2CC1*CCN(CC1)CCN1c1cccc(C(F)(F)F)c1 Chemical compound O=C1Nc2ccccc2CC1*CCN(CC1)CCN1c1cccc(C(F)(F)F)c1 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000000113 differential scanning calorimetry Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001107 psychogenic effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000021663 Female sexual arousal disease Diseases 0.000 description 1
- 206010057671 Female sexual dysfunction Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 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 1
- 208000030663 Libido disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/26—Radicals substituted by carbon atoms having three bonds to hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01118593 | 2001-08-02 | ||
| EP01118593 | 2001-08-02 | ||
| EP01130180 | 2001-12-19 | ||
| EP01130180 | 2001-12-19 | ||
| PCT/EP2002/008466 WO2003014079A1 (en) | 2001-08-02 | 2002-07-30 | Stable polymorph of flibanserin, technical process for its preparation and the use thereof for preparing medicaments |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60202958D1 DE60202958D1 (de) | 2005-03-17 |
| DE60202958T2 true DE60202958T2 (de) | 2006-04-06 |
Family
ID=26076670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60202958T Expired - Lifetime DE60202958T2 (de) | 2001-08-02 | 2002-07-30 | Stabiles polymorph von flibanserin, industrielles verfahren zu dessen herstellung und dessen verwendung zur herstellung von medikamenten |
Country Status (26)
| Country | Link |
|---|---|
| EP (2) | EP1518858A1 (enExample) |
| JP (1) | JP3822601B2 (enExample) |
| KR (1) | KR100899297B1 (enExample) |
| CN (1) | CN1288147C (enExample) |
| AR (2) | AR036208A1 (enExample) |
| AT (1) | ATE288911T1 (enExample) |
| AU (1) | AU2002331361B2 (enExample) |
| BR (1) | BR0211601A (enExample) |
| CA (1) | CA2450093C (enExample) |
| CO (1) | CO5560572A2 (enExample) |
| DE (1) | DE60202958T2 (enExample) |
| DK (1) | DK1414816T3 (enExample) |
| EA (1) | EA006400B1 (enExample) |
| ES (1) | ES2237694T3 (enExample) |
| HR (1) | HRP20040107B1 (enExample) |
| HU (1) | HU228666B1 (enExample) |
| IL (2) | IL159151A0 (enExample) |
| MX (1) | MXPA04000913A (enExample) |
| MY (1) | MY127294A (enExample) |
| NZ (1) | NZ530510A (enExample) |
| PL (1) | PL210224B1 (enExample) |
| PT (1) | PT1414816E (enExample) |
| RS (1) | RS50742B (enExample) |
| SI (1) | SI1414816T1 (enExample) |
| UA (1) | UA76767C2 (enExample) |
| WO (1) | WO2003014079A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7183410B2 (en) | 2001-08-02 | 2007-02-27 | Bidachem S.P.A. | Stable polymorph of flibanserin |
| DE10138273A1 (de) * | 2001-08-10 | 2003-02-27 | Boehringer Ingelheim Pharma | Arzneimittel mit neuroprotektiver Wirkung |
| US10675280B2 (en) | 2001-10-20 | 2020-06-09 | Sprout Pharmaceuticals, Inc. | Treating sexual desire disorders with flibanserin |
| UA78974C2 (en) | 2001-10-20 | 2007-05-10 | Boehringer Ingelheim Pharma | Use of flibanserin for treating disorders of sexual desire |
| CN101002780A (zh) * | 2002-05-22 | 2007-07-25 | 贝林格尔英格海姆法玛两合公司 | 新型含氟班色林多晶型物a的药物组合物 |
| JP2008540356A (ja) * | 2005-05-06 | 2008-11-20 | 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 | 薬物乱用の治療方法 |
| CA2617546C (en) | 2005-08-03 | 2014-07-15 | Boehringer Ingelheim International Gmbh | Use of flibanserin in the treatment of obesity |
| WO2007048803A1 (en) | 2005-10-29 | 2007-05-03 | Boehringer Ingelheim International Gmbh | Benzimidazolone derivatives for the treatment of premenstrual and other female sexual disorders |
| US20070105869A1 (en) * | 2005-11-08 | 2007-05-10 | Stephane Pollentier | Use of flibanserin for the treatment of pre-menopausal sexual desire disorders |
| WO2007099070A1 (en) * | 2006-02-28 | 2007-09-07 | Boehringer Ingelheim International Gmbh | Treatment of prevention of valvular heart disease with flibanserin |
| BRPI0712039A2 (pt) * | 2006-05-09 | 2011-12-20 | Boehringer Ingelheim Int | uso de flibanserina para o tratamento de distúrbios de desejo sexual pós-menopausa |
| WO2008000760A1 (en) | 2006-06-30 | 2008-01-03 | Boehringer Ingelheim International Gmbh | Flibanserin for the treatment of urinary incontinence and related diseases |
| CA2660476C (en) | 2006-08-14 | 2015-11-17 | Boehringer Ingelheim International Gmbh | Formulations of flibanserin and method for manufacturing the same |
| CL2007002214A1 (es) | 2006-08-14 | 2008-03-07 | Boehringer Ingelheim Int | Composicion farmaceutica en la forma de comprimido, donde al menos la longitud del comprimido en el estado anterior de la aplicacion es al menos 7/12 del diametro pilorico del paciente y despues de ingerirlo en estado alimentado, la longitud del comp |
| WO2008022932A2 (en) | 2006-08-25 | 2008-02-28 | Boehringer Ingelheim International Gmbh | Controlled release system and method for manufacturing the same |
| WO2008061966A2 (en) * | 2006-11-22 | 2008-05-29 | Boehringer Ingelheim International Gmbh | New use of flibanserin |
| EP2097389B1 (en) | 2006-12-20 | 2011-09-14 | Boehringer Ingelheim International GmbH | Sulfated benzimidazolone derivatives having mixed serotonine receptor affinity |
| EP1955699A1 (en) * | 2007-02-08 | 2008-08-13 | Boehringer Ingelheim Pharma GmbH & Co. KG | Use of flibanserin for the treatment of insomnia |
| PE20091188A1 (es) | 2007-09-12 | 2009-08-31 | Boehringer Ingelheim Int | Compuesto 1-[2-(4-(3-trifluorometil-fenil)piperazin-1-il)etil]-2,3-dihidro-1h-benzimidazol-2-ona (flibanserina), sus sales de adicion y composiciones farmaceuticas que los contienen |
| EP2090297A1 (en) | 2008-02-13 | 2009-08-19 | Boehringer Ingelheim International GmbH | Formulations of flibanserin |
| CA2686480A1 (en) | 2008-12-15 | 2010-06-15 | Boehringer Ingelheim International Gmbh | New salts |
| CN104926734B (zh) * | 2015-07-07 | 2017-04-05 | 苏州立新制药有限公司 | 氟班色林的制备方法 |
| WO2017076356A1 (zh) * | 2015-11-05 | 2017-05-11 | 苏州晶云药物科技有限公司 | 氟班色林的新晶型及其制备方法 |
| CN108699007A (zh) * | 2016-01-31 | 2018-10-23 | 孟晓明 | 氟班色林的新晶型及其制备方法及其用途 |
| CN111303043A (zh) * | 2019-04-19 | 2020-06-19 | 武汉万知化工医药有限公司 | 一种氟班色林盐酸盐的制备方法 |
| CN115919860B (zh) | 2022-12-05 | 2023-11-10 | 中国药科大学 | 氟班色林在制备治疗雄激素脱发药物中的用途 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1251144B (it) * | 1991-07-30 | 1995-05-04 | Boehringer Ingelheim Italia | Derivati del benzimidazolone |
-
2002
- 2002-07-30 HR HR20040107A patent/HRP20040107B1/xx not_active IP Right Cessation
- 2002-07-30 DE DE60202958T patent/DE60202958T2/de not_active Expired - Lifetime
- 2002-07-30 RS YUP-78/04A patent/RS50742B/sr unknown
- 2002-07-30 PT PT02767277T patent/PT1414816E/pt unknown
- 2002-07-30 WO PCT/EP2002/008466 patent/WO2003014079A1/en not_active Ceased
- 2002-07-30 ES ES02767277T patent/ES2237694T3/es not_active Expired - Lifetime
- 2002-07-30 PL PL364598A patent/PL210224B1/pl unknown
- 2002-07-30 CN CNB028152263A patent/CN1288147C/zh not_active Expired - Fee Related
- 2002-07-30 IL IL15915102A patent/IL159151A0/xx unknown
- 2002-07-30 HU HU0401201A patent/HU228666B1/hu unknown
- 2002-07-30 AT AT02767277T patent/ATE288911T1/de active
- 2002-07-30 MX MXPA04000913A patent/MXPA04000913A/es active IP Right Grant
- 2002-07-30 BR BR0211601-4A patent/BR0211601A/pt not_active Application Discontinuation
- 2002-07-30 SI SI200230104T patent/SI1414816T1/xx unknown
- 2002-07-30 EP EP04026410A patent/EP1518858A1/en not_active Withdrawn
- 2002-07-30 KR KR1020047001497A patent/KR100899297B1/ko not_active Expired - Fee Related
- 2002-07-30 EA EA200400252A patent/EA006400B1/ru not_active IP Right Cessation
- 2002-07-30 CA CA002450093A patent/CA2450093C/en not_active Expired - Fee Related
- 2002-07-30 DK DK02767277T patent/DK1414816T3/da active
- 2002-07-30 JP JP2003519029A patent/JP3822601B2/ja not_active Expired - Fee Related
- 2002-07-30 UA UA2004031505A patent/UA76767C2/uk unknown
- 2002-07-30 AU AU2002331361A patent/AU2002331361B2/en not_active Expired
- 2002-07-30 EP EP02767277A patent/EP1414816B1/en not_active Expired - Lifetime
- 2002-07-30 NZ NZ530510A patent/NZ530510A/en not_active IP Right Cessation
- 2002-07-31 MY MYPI20022876A patent/MY127294A/en unknown
- 2002-08-02 AR ARP020102942A patent/AR036208A1/es not_active Application Discontinuation
-
2003
- 2003-12-02 IL IL159151A patent/IL159151A/en active IP Right Grant
-
2004
- 2004-02-25 CO CO04016766A patent/CO5560572A2/es unknown
-
2010
- 2010-07-15 AR ARP100102577A patent/AR077416A2/es unknown
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Legal Events
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| 8364 | No opposition during term of opposition | ||
| 8381 | Inventor (new situation) |
Inventor name: BOMBARDA, CARLO, CHESTER, US Inventor name: DUBINI, ENRICA, I-ZIP 20135 MILANO, IT Inventor name: EZHAYA, ANTOINE, I-ZIP 20141 MILANO, IT Inventor name: SCHNEIDER, HEINRICH, DR., 55218 INGELHEIM, DE |