SK10992002A3 - Postup na výrobu geminálnych bisfosfonátov - Google Patents
Postup na výrobu geminálnych bisfosfonátov Download PDFInfo
- Publication number
- SK10992002A3 SK10992002A3 SK1099-2002A SK10992002A SK10992002A3 SK 10992002 A3 SK10992002 A3 SK 10992002A3 SK 10992002 A SK10992002 A SK 10992002A SK 10992002 A3 SK10992002 A3 SK 10992002A3
- Authority
- SK
- Slovakia
- Prior art keywords
- substituted
- acid
- unsubstituted
- amino
- process according
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 28
- 229940122361 Bisphosphonate Drugs 0.000 title claims abstract description 27
- 150000004663 bisphosphonates Chemical group 0.000 title claims abstract description 21
- -1 -NR4- Substances 0.000 claims abstract description 32
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical class 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
- 125000001424 substituent group Chemical group 0.000 claims abstract description 11
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 9
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 9
- 239000011574 phosphorus Substances 0.000 claims abstract description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 9
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000003368 amide group Chemical group 0.000 claims abstract description 8
- 150000007942 carboxylates Chemical class 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims abstract description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 4
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002252 acyl group Chemical group 0.000 claims abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052711 selenium Inorganic materials 0.000 claims abstract description 4
- 239000011669 selenium Substances 0.000 claims abstract description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 239000011593 sulfur Substances 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 14
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 11
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims 2
- MXYOPVWZZKEAGX-UHFFFAOYSA-N 1-phosphonoethylphosphonic acid Chemical compound OP(=O)(O)C(C)P(O)(O)=O MXYOPVWZZKEAGX-UHFFFAOYSA-N 0.000 claims 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 claims 1
- 239000002904 solvent Substances 0.000 abstract description 16
- 239000000376 reactant Substances 0.000 abstract description 2
- 239000002585 base Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- 125000004429 atom Chemical group 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000003883 ointment base Substances 0.000 description 8
- 229940089617 risedronate Drugs 0.000 description 8
- 229920002125 Sokalan® Polymers 0.000 description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 239000011260 aqueous acid Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 229940046231 pamidronate Drugs 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 229960004793 sucrose Drugs 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920002907 Guar gum Polymers 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 229940000635 beta-alanine Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 2
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical compound OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000003974 emollient agent Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 239000000665 guar gum Substances 0.000 description 2
- 235000010417 guar gum Nutrition 0.000 description 2
- 229960002154 guar gum Drugs 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- JXYZHMPRERWTPM-UHFFFAOYSA-N hydron;morpholine;chloride Chemical compound Cl.C1COCCN1 JXYZHMPRERWTPM-UHFFFAOYSA-N 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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
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- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
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- 238000002560 therapeutic procedure Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
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- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
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Classifications
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- 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)]
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- C07F9/386—Polyphosphonic acids containing hydroxy substituents in the hydrocarbon radicals
-
- 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17950600P | 2000-02-01 | 2000-02-01 | |
| PCT/US2001/003309 WO2001057052A1 (en) | 2000-02-01 | 2001-02-01 | Process for making geminal bisphosphonates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK10992002A3 true SK10992002A3 (sk) | 2003-02-04 |
Family
ID=22656872
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1099-2002A SK10992002A3 (sk) | 2000-02-01 | 2001-02-01 | Postup na výrobu geminálnych bisfosfonátov |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6562974B2 (da) |
| EP (1) | EP1252169B1 (da) |
| JP (1) | JP4534185B2 (da) |
| KR (1) | KR100681740B1 (da) |
| CN (1) | CN1223598C (da) |
| AT (1) | ATE269343T1 (da) |
| AU (1) | AU784385B2 (da) |
| BR (1) | BRPI0107952B8 (da) |
| CA (1) | CA2399974C (da) |
| CO (1) | CO5430222A1 (da) |
| CZ (1) | CZ304038B6 (da) |
| DE (1) | DE60103851T2 (da) |
| DK (1) | DK1252169T3 (da) |
| ES (1) | ES2221887T3 (da) |
| HK (1) | HK1051045A1 (da) |
| HU (1) | HU228980B1 (da) |
| IL (2) | IL150512A0 (da) |
| MX (1) | MXPA02007418A (da) |
| NO (1) | NO330273B1 (da) |
| NZ (1) | NZ519967A (da) |
| PE (1) | PE20011065A1 (da) |
| PL (1) | PL207617B1 (da) |
| PT (1) | PT1252169E (da) |
| RU (1) | RU2002123362A (da) |
| SK (1) | SK10992002A3 (da) |
| TR (1) | TR200402317T4 (da) |
| WO (1) | WO2001057052A1 (da) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2347330C (en) * | 2001-05-10 | 2002-03-12 | Pharmaceutical Partners Of Canada Inc. | Liquid injectable formulation of disodium pamidronate |
| GB0115824D0 (en) * | 2001-06-28 | 2001-08-22 | Rhodia Cons Spec Ltd | Improved solvent systems |
| NZ552513A (en) * | 2001-12-24 | 2008-08-29 | Teva Pharma | Dosage form with a core tablet of active ingredient sheathed in a compressed annular body of powder or granular material, and process and tooling for producing it |
| US20040052843A1 (en) * | 2001-12-24 | 2004-03-18 | Lerner E. Itzhak | Controlled release dosage forms |
| ITMI20020908A1 (it) * | 2002-04-29 | 2003-10-29 | Chemi Spa | Processo di preparazione di sodio alendronato |
| CA2485443C (en) * | 2002-05-17 | 2010-04-06 | Teva Pharmaceutical Industries Ltd | Use of aromatic hydrocarbons and silicone fluids for making bisphosphonic acids |
| PT1656386E (pt) * | 2003-08-21 | 2010-03-05 | Sun Pharmaceuticals Ind Ltd | Processo para a preparação de compostos de ácido bifosfónico |
| US20050260272A1 (en) * | 2004-05-05 | 2005-11-24 | Alkermes Controlled Therapeutics, Inc. | Method of forming microparticles that include a bisphosphonate and a polymer |
| WO2006039721A2 (en) * | 2004-10-08 | 2006-04-13 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods for bone resorption diseases, cancer, bone pain, immune disorders, and infectious diseases |
| US8012949B2 (en) * | 2004-10-08 | 2011-09-06 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods with enhanced potency for multiple targets including FPPS, GGPPS, and DPPS |
| US7214818B2 (en) | 2004-10-29 | 2007-05-08 | Hoffmann-La Roche Inc. | Method for synthesizing bisphosphonate |
| PL199215B1 (pl) * | 2004-12-28 | 2008-08-29 | Politechnika Gdanska | Sposób wytwarzania kwasu [1-hydroksy-2-(3-pirydylo)etylidenobisfosfonowego] oraz jego soli monosodowej dwu i pół wodnej |
| EP1888606A2 (en) * | 2005-05-28 | 2008-02-20 | PLIVA HRVATSKA d.o.o. | Process and novel salt |
| WO2006134603A1 (en) | 2005-06-13 | 2006-12-21 | Jubilant Organosys Limited | Process for producing bisphosphonic acids and forms thereof |
| EP1775302A1 (en) | 2005-10-11 | 2007-04-18 | Sandoz A/S | Method for preparing crystalline sodium risedronate |
| US7768984B2 (en) | 2006-01-06 | 2010-08-03 | Samsung Electronics Co., Ltd | Apparatus and method for receiving a signal in a communication system |
| AU2007226964B2 (en) * | 2006-03-17 | 2012-03-22 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods |
| JP5354858B2 (ja) * | 2006-05-09 | 2013-11-27 | 株式会社Ａｄｅｋａ | スルホンアミド化合物の金属塩を含有するポリエステル樹脂組成物 |
| WO2007132478A2 (en) | 2006-05-11 | 2007-11-22 | Ind-Swift Laboratories Limited | Process for the preparation of pure risedronic acid or salts |
| PL2144919T3 (pl) | 2007-04-11 | 2016-05-31 | Hoffmann La Roche | Wieloetapowa synteza ibandronianu |
| WO2008152518A2 (en) * | 2007-05-16 | 2008-12-18 | Actavis Group Ptc Ehf | Process for the preparation of risedronic acid or risedronate sodium |
| WO2009050731A2 (en) * | 2007-06-20 | 2009-04-23 | Alkem Laboratories Ltd | Novel process for preparing risedronic acid |
| KR100877667B1 (ko) * | 2007-06-28 | 2009-01-08 | 보령제약 주식회사 | 리세드로네이트의 제조 방법 |
| CN101970586B (zh) * | 2008-03-17 | 2014-08-20 | 卡伯特公司 | 具有降低的磷酸根释放的改性颜料以及得自其的分散体和喷墨油墨组合物 |
| JP5258370B2 (ja) * | 2008-05-08 | 2013-08-07 | ダイト株式会社 | リセドロン酸の工業的製造方法 |
| EP2483283B1 (en) | 2009-10-02 | 2015-01-07 | Straitmark Holding AG | Method for the manufacture of aminohydroxy diphosphonic acids |
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| DE2534391C2 (de) | 1975-08-01 | 1983-01-13 | Henkel KGaA, 4000 Düsseldorf | 1-Hydroxy-3-aminoalkan-1,1-diphosphonsäuren |
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| DE2943498C2 (de) | 1979-10-27 | 1983-01-27 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur Herstellung von 3-Amino-1-hydroxypropan-1,1-diphosphonsäure |
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| US5317015A (en) | 1992-05-01 | 1994-05-31 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Azacyclic bisphosphonates as anticholesterolemic agents |
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| FR2694558B1 (fr) | 1992-08-05 | 1994-10-28 | Sanofi Elf | Monohydrate du sel disodique de l'acide 4-chlorophénylthiométhylène bisphosphonique, sa préparation, les compositions pharmaceutiques en contenant. |
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| US5580977A (en) | 1995-03-01 | 1996-12-03 | Eli Lilly And Company | Process for preparing loracarbef monohydrate |
| TW393488B (en) | 1995-04-20 | 2000-06-11 | Merck & Co Inc | Process for making 1-hydrox-ybisphosphonates |
| KR100192215B1 (ko) | 1996-09-03 | 1999-06-15 | 강재헌 | 3-아미노-1-히드록시프로판-1,1-디포스폰산의 제조방법 |
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-
2001
- 2001-01-29 US US09/771,899 patent/US6562974B2/en not_active Expired - Lifetime
- 2001-01-29 PE PE2001000095A patent/PE20011065A1/es not_active Application Discontinuation
- 2001-01-30 CO CO01006627A patent/CO5430222A1/es not_active Application Discontinuation
- 2001-02-01 NZ NZ519967A patent/NZ519967A/en not_active IP Right Cessation
- 2001-02-01 MX MXPA02007418A patent/MXPA02007418A/es active IP Right Grant
- 2001-02-01 PL PL357116A patent/PL207617B1/pl unknown
- 2001-02-01 DE DE60103851T patent/DE60103851T2/de not_active Expired - Lifetime
- 2001-02-01 CN CNB018043011A patent/CN1223598C/zh not_active Expired - Lifetime
- 2001-02-01 SK SK1099-2002A patent/SK10992002A3/sk unknown
- 2001-02-01 RU RU2002123362/04A patent/RU2002123362A/ru unknown
- 2001-02-01 CZ CZ20022515A patent/CZ304038B6/cs not_active IP Right Cessation
- 2001-02-01 KR KR1020027009032A patent/KR100681740B1/ko active IP Right Grant
- 2001-02-01 ES ES01908779T patent/ES2221887T3/es not_active Expired - Lifetime
- 2001-02-01 WO PCT/US2001/003309 patent/WO2001057052A1/en not_active Application Discontinuation
- 2001-02-01 AU AU36613/01A patent/AU784385B2/en not_active Expired
- 2001-02-01 AT AT01908779T patent/ATE269343T1/de active
- 2001-02-01 BR BRPI0107952A patent/BRPI0107952B8/pt not_active IP Right Cessation
- 2001-02-01 IL IL15051201A patent/IL150512A0/xx active IP Right Grant
- 2001-02-01 CA CA002399974A patent/CA2399974C/en not_active Expired - Lifetime
- 2001-02-01 HU HU0300890A patent/HU228980B1/hu active IP Right Revival
- 2001-02-01 PT PT01908779T patent/PT1252169E/pt unknown
- 2001-02-01 EP EP01908779A patent/EP1252169B1/en not_active Expired - Lifetime
- 2001-02-01 TR TR2004/02317T patent/TR200402317T4/xx unknown
- 2001-02-01 JP JP2001557883A patent/JP4534185B2/ja not_active Expired - Lifetime
- 2001-02-01 DK DK01908779T patent/DK1252169T3/da active
-
2002
- 2002-07-01 IL IL150512A patent/IL150512A/en unknown
- 2002-07-31 NO NO20023646A patent/NO330273B1/no not_active IP Right Cessation
-
2003
- 2003-03-13 HK HK03101831.8A patent/HK1051045A1/zh unknown
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| Date | Code | Title | Description |
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| FB9A | Suspension of patent application procedure |