SE463239B - Farmaceutiskt aktiva bifosfonater samt farmaceutiska kompositioner innehaallande desamma - Google Patents
Farmaceutiskt aktiva bifosfonater samt farmaceutiska kompositioner innehaallande desammaInfo
- Publication number
- SE463239B SE463239B SE8302130A SE8302130A SE463239B SE 463239 B SE463239 B SE 463239B SE 8302130 A SE8302130 A SE 8302130A SE 8302130 A SE8302130 A SE 8302130A SE 463239 B SE463239 B SE 463239B
- Authority
- SE
- Sweden
- Prior art keywords
- acid
- amino
- group
- pharmaceutical
- compound
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 16
- 210000000988 bone and bone Anatomy 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 230000009103 reabsorption Effects 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- DXGBLRMRXHGUFX-UHFFFAOYSA-N (5-amino-1-hydroxy-1-phosphonopentyl)phosphonic acid Chemical compound NCCCCC(O)(P(O)(O)=O)P(O)(O)=O DXGBLRMRXHGUFX-UHFFFAOYSA-N 0.000 claims description 4
- 208000009911 Urinary Calculi Diseases 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 208000008281 urolithiasis Diseases 0.000 claims description 4
- -1 4-amino-1-hydroxybutane-1,2-diphosphonic acid Chemical compound 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 2
- 229910018828 PO3H2 Inorganic materials 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 description 29
- 230000000694 effects Effects 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 229940122361 Bisphosphonate Drugs 0.000 description 9
- 150000004663 bisphosphonates Chemical class 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 230000033558 biomineral tissue development Effects 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 235000011007 phosphoric acid Nutrition 0.000 description 7
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- JJMDCOVWQOJGCB-UHFFFAOYSA-N 5-aminopentanoic acid Chemical compound [NH3+]CCCCC([O-])=O JJMDCOVWQOJGCB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 4
- 230000009102 absorption Effects 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 4
- 235000011180 diphosphates Nutrition 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000018678 bone mineralization Effects 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000004679 31P NMR spectroscopy Methods 0.000 description 2
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical group NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052586 apatite Inorganic materials 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 238000003926 complexometric titration Methods 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
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- 231100000517 death Toxicity 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- 238000003918 potentiometric titration Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 208000013220 shortness of breath Diseases 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
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- 238000004448 titration Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VCDRAONLIPOEFL-UHFFFAOYSA-N 4-n-[4-(4-anilinoanilino)phenyl]benzene-1,4-diamine Chemical class C1=CC(N)=CC=C1NC(C=C1)=CC=C1NC(C=C1)=CC=C1NC1=CC=CC=C1 VCDRAONLIPOEFL-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 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
- 208000020084 Bone disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 229920000084 Gum arabic Polymers 0.000 description 1
- 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 1
- 208000000913 Kidney Calculi Diseases 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 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
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 241001460678 Napo <wasp> Species 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229910004856 P—O—P Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 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
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- ZCDUVNFZBOKDQT-UHFFFAOYSA-N [bromo(difluoro)methyl]phosphonic acid Chemical compound OP(O)(=O)C(F)(F)Br ZCDUVNFZBOKDQT-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000002479 acid--base titration Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- DAZLBCIMRZNCRV-UHFFFAOYSA-N aniline;sodium Chemical compound [Na].NC1=CC=CC=C1 DAZLBCIMRZNCRV-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 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
- 230000000903 blocking effect Effects 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- AZSZCFSOHXEJQE-UHFFFAOYSA-N dibromodifluoromethane Chemical compound FC(F)(Br)Br AZSZCFSOHXEJQE-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- NCEMUOYFYLEORV-UHFFFAOYSA-N difluoromethylphosphonic acid Chemical compound OP(O)(=O)C(F)F NCEMUOYFYLEORV-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
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- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004821 effect on bone Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 239000012894 fetal calf serum Substances 0.000 description 1
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- 125000000524 functional group Chemical group 0.000 description 1
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- 230000001969 hypertrophic effect Effects 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- MTKUWDYQPVIKLB-UHFFFAOYSA-N sodium;dipropan-2-yl phosphite Chemical compound [Na+].CC(C)OP([O-])OC(C)C MTKUWDYQPVIKLB-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- VGBPIHVLVSGJGR-UHFFFAOYSA-N thorium(4+);tetranitrate Chemical compound [Th+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VGBPIHVLVSGJGR-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
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- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
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- 239000011782 vitamin Substances 0.000 description 1
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- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/3856—Polyphosphonic acids containing halogen or nitro(so) substituents
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8220781A IT1201087B (it) | 1982-04-15 | 1982-04-15 | Bifosfonati farmacologicamente attivi,procedimento per la loro preparazione e relative composizioni farmaceutiche |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| SE8302130D0 SE8302130D0 (sv) | 1983-04-15 |
| SE8302130L SE8302130L (sv) | 1983-10-16 |
| SE463239B true SE463239B (sv) | 1990-10-29 |
Family
ID=11171970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8302130A SE463239B (sv) | 1982-04-15 | 1983-04-15 | Farmaceutiskt aktiva bifosfonater samt farmaceutiska kompositioner innehaallande desamma |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4621077A (fr) |
| JP (1) | JPS58189193A (fr) |
| BE (1) | BE896453A (fr) |
| CH (1) | CH661437A5 (fr) |
| FR (1) | FR2525223B1 (fr) |
| GB (1) | GB2118042B (fr) |
| HK (1) | HK79390A (fr) |
| IT (1) | IT1201087B (fr) |
| LU (2) | LU84746A1 (fr) |
| MX (1) | MX9203428A (fr) |
| NL (5) | NL192562C (fr) |
| SE (1) | SE463239B (fr) |
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| DE3623397A1 (de) * | 1986-07-11 | 1988-01-14 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
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| US4216211A (en) * | 1977-10-31 | 1980-08-05 | The Procter & Gamble Company | Therapeutic composition |
| US4230700A (en) * | 1977-12-07 | 1980-10-28 | The Procter & Gamble Company | Methods for inhibiting mobilization of calcium phosphate in animal tissue |
| US4330537A (en) * | 1977-12-07 | 1982-05-18 | The Procter & Gamble Company | Compositions for inhibiting mobilization of calcium phosphate in animal tissue |
| US4216212A (en) * | 1978-06-08 | 1980-08-05 | The Procter & Gamble Company | Pyrazolidine anti-inflammatory composition and methods of use |
| IT1097292B (it) * | 1978-06-27 | 1985-08-31 | Gentili Ist Spa | Composizione farmaceutica per la terapia dell'ittero ostruttivo non neoplastico |
| US4264582A (en) * | 1978-07-31 | 1981-04-28 | The Procter & Gamble Company | Isobutylphenylacetate anti-inflammatory composition |
| US4282214A (en) * | 1978-07-31 | 1981-08-04 | The Procter & Gamble Company | Phenylacetate anti-inflammatory composition |
| US4254114A (en) * | 1979-01-02 | 1981-03-03 | The Proctor & Gamble Company | Control of pyrophosphate microorganisms with organophosphonates |
| GB2043072B (en) * | 1979-02-13 | 1983-11-23 | Symphar Sa | Diphosphonate compounds |
| GB2076889B (en) * | 1980-03-12 | 1983-10-26 | Cadbury Schweppes Transport | Feeding fuel and water emulsion i c engines |
| DE3016289A1 (de) * | 1980-04-28 | 1981-10-29 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur herstellung von omega -amino-1-hydroxyalkyliden-1,1-bis-phosphonsaeuren |
| GB2079285B (en) * | 1980-07-09 | 1984-05-23 | Symphar Sa | Dipthosphonate derivatives and pahrmaceutical compositions containing them |
| GB2082585A (en) * | 1980-08-27 | 1982-03-10 | Vysoka Skola Chem Tech | 6-amino-1-hydroxyhexylidene diphosphonic acid, salts thereof and a method of producing the acid and salts. |
| JPS5759900A (en) * | 1980-09-29 | 1982-04-10 | Vysoka Skola Chem Tech | 6-amino-1-hydroxyhexylidene diphosphonic acid |
| BE890453A (fr) * | 1980-10-07 | 1982-03-22 | Procter & Gamble | Procede d'inhibition des metastases de cellules tumorales |
| US4330530A (en) * | 1980-12-22 | 1982-05-18 | The Procter & Gamble Company | Anti-arthritic compositions and method using gold salts and organophosphonates |
| IT1194748B (it) * | 1981-02-12 | 1988-09-28 | Gentili Ist Spa | Composizioni farmaceutiche per il trattamento di osteopatie |
-
1982
- 1982-04-15 IT IT8220781A patent/IT1201087B/it active Protection Beyond IP Right Term
-
1983
- 1983-03-25 CH CH1654/83A patent/CH661437A5/it not_active IP Right Cessation
- 1983-03-30 GB GB08308791A patent/GB2118042B/en not_active Expired
- 1983-04-11 FR FR8305858A patent/FR2525223B1/fr not_active Expired
- 1983-04-13 JP JP58065160A patent/JPS58189193A/ja active Granted
- 1983-04-13 LU LU84746A patent/LU84746A1/fr active Protection Beyond IP Right Term
- 1983-04-13 LU LU88714C patent/LU88714I2/fr unknown
- 1983-04-14 BE BE2/60071A patent/BE896453A/fr not_active IP Right Cessation
- 1983-04-15 NL NL8301324A patent/NL192562C/nl active Protection Beyond IP Right Term
- 1983-04-15 SE SE8302130A patent/SE463239B/sv not_active IP Right Cessation
-
1984
- 1984-06-08 US US06/618,578 patent/US4621077A/en not_active Expired - Lifetime
-
1990
- 1990-10-03 HK HK793/90A patent/HK79390A/xx not_active IP Right Cessation
-
1992
- 1992-06-25 MX MX9203428A patent/MX9203428A/es unknown
-
1997
- 1997-11-07 NL NL970038C patent/NL970038I2/nl unknown
-
1998
- 1998-01-09 NL NL980004C patent/NL980004I1/nl unknown
- 1998-01-26 NL NL980005C patent/NL980005I1/nl unknown
- 1998-03-03 NL NL980010C patent/NL980010I1/nl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB8308791D0 (en) | 1983-05-11 |
| LU88714I2 (fr) | 1996-08-23 |
| SE8302130L (sv) | 1983-10-16 |
| NL970038I2 (nl) | 2000-11-01 |
| NL970038I1 (nl) | 1998-01-05 |
| NL192562B (nl) | 1997-06-02 |
| NL980010I1 (nl) | 1998-05-06 |
| NL192562C (nl) | 1997-10-03 |
| FR2525223B1 (fr) | 1986-04-25 |
| US4621077A (en) | 1986-11-04 |
| GB2118042A (en) | 1983-10-26 |
| MX9203428A (es) | 1992-07-01 |
| SE8302130D0 (sv) | 1983-04-15 |
| BE896453A (fr) | 1983-08-01 |
| GB2118042B (en) | 1986-01-15 |
| JPS58189193A (ja) | 1983-11-04 |
| NL980005I1 (nl) | 1998-04-01 |
| FR2525223A1 (fr) | 1983-10-21 |
| IT1201087B (it) | 1989-01-27 |
| LU84746A1 (fr) | 1983-11-17 |
| HK79390A (en) | 1990-10-12 |
| CH661437A5 (it) | 1987-07-31 |
| NL980004I1 (nl) | 1998-04-01 |
| IT8220781A0 (it) | 1982-04-15 |
| NL8301324A (nl) | 1983-11-01 |
| JPH0213645B2 (fr) | 1990-04-04 |
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