FI104901B - Uudet metyleenibisfosfonihappojohdannaiset - Google Patents
Uudet metyleenibisfosfonihappojohdannaiset Download PDFInfo
- Publication number
- FI104901B FI104901B FI974001A FI974001A FI104901B FI 104901 B FI104901 B FI 104901B FI 974001 A FI974001 A FI 974001A FI 974001 A FI974001 A FI 974001A FI 104901 B FI104901 B FI 104901B
- Authority
- FI
- Finland
- Prior art keywords
- dichloromethylene
- ppm
- acid
- bisphosphonate
- salt
- Prior art date
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- MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical class OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 title description 14
- 229910052698 phosphorus Inorganic materials 0.000 claims description 135
- -1 (isobutyroyl) (dichloromethylene) bisphosphonic acid sodium salt Chemical compound 0.000 claims description 61
- 239000002253 acid Substances 0.000 claims description 55
- 150000001875 compounds Chemical class 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 26
- 150000008064 anhydrides Chemical class 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 229910052751 metal Inorganic materials 0.000 claims description 11
- 239000002184 metal Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 150000007513 acids Chemical class 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- ZEKKCKJNBVLJIO-UHFFFAOYSA-L [Na+].[Na+].[O-]P(=O)OC(Cl)(Cl)OP([O-])=O Chemical compound [Na+].[Na+].[O-]P(=O)OC(Cl)(Cl)OP([O-])=O ZEKKCKJNBVLJIO-UHFFFAOYSA-L 0.000 claims description 3
- 239000004480 active ingredient Substances 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
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- FALZCNWTEGSSCS-UHFFFAOYSA-N ClC([Na])([Na])Cl Chemical class ClC([Na])([Na])Cl FALZCNWTEGSSCS-UHFFFAOYSA-N 0.000 claims 2
- SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 238000005481 NMR spectroscopy Methods 0.000 description 63
- 239000000651 prodrug Substances 0.000 description 26
- 229940002612 prodrug Drugs 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 22
- 229940122361 Bisphosphonate Drugs 0.000 description 17
- 229960002286 clodronic acid Drugs 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 150000004663 bisphosphonates Chemical class 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- PFBUKDPBVNJDEW-UHFFFAOYSA-N dichlorocarbene Chemical group Cl[C]Cl PFBUKDPBVNJDEW-UHFFFAOYSA-N 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- YQZICAIMXIOFOI-UHFFFAOYSA-L [O-]P(=O)OC(Cl)(Cl)OP([O-])=O.CCCC[N+](C)(CCCC)CCCC.CCCC[N+](C)(CCCC)CCCC Chemical compound [O-]P(=O)OC(Cl)(Cl)OP([O-])=O.CCCC[N+](C)(CCCC)CCCC.CCCC[N+](C)(CCCC)CCCC YQZICAIMXIOFOI-UHFFFAOYSA-L 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
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- 238000010306 acid treatment Methods 0.000 description 7
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- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- HJHUXWBTVVFLQI-UHFFFAOYSA-N tributyl(methyl)azanium Chemical class CCCC[N+](C)(CCCC)CCCC HJHUXWBTVVFLQI-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 102100036893 Parathyroid hormone Human genes 0.000 description 5
- 238000005192 partition Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 208000006386 Bone Resorption Diseases 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- GTDPSWPPOUPBNX-UHFFFAOYSA-N ac1mqpva Chemical compound CC12C(=O)OC(=O)C1(C)C1(C)C2(C)C(=O)OC1=O GTDPSWPPOUPBNX-UHFFFAOYSA-N 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 230000024279 bone resorption Effects 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- FPDNKWSQWXOPSC-UHFFFAOYSA-N 1-(methylamino)ethanol Chemical compound CNC(C)O FPDNKWSQWXOPSC-UHFFFAOYSA-N 0.000 description 3
- DWRVKCFZZJZSJX-UHFFFAOYSA-N 1-propan-2-ylpyridin-1-ium Chemical class CC(C)[N+]1=CC=CC=C1 DWRVKCFZZJZSJX-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
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- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 2
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- YVMMMLLMHCGYCE-UHFFFAOYSA-L C[N+](CCCC)(CCCC)CCCC.P(OC(Br)(Br)OP([O-])=O)([O-])=O.C[N+](CCCC)(CCCC)CCCC Chemical compound C[N+](CCCC)(CCCC)CCCC.P(OC(Br)(Br)OP([O-])=O)([O-])=O.C[N+](CCCC)(CCCC)CCCC YVMMMLLMHCGYCE-UHFFFAOYSA-L 0.000 description 2
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- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
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- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
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- 125000005624 silicic acid group Chemical class 0.000 description 1
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- YPPQYORGOMWNMX-UHFFFAOYSA-L sodium phosphonate pentahydrate Chemical compound [Na+].[Na+].[O-]P([O-])=O YPPQYORGOMWNMX-UHFFFAOYSA-L 0.000 description 1
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- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LPWCRLGKYWVLHQ-UHFFFAOYSA-N tetradecanoyl chloride Chemical compound CCCCCCCCCCCCCC(Cl)=O LPWCRLGKYWVLHQ-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- LQHJDMDQUHOTFV-UHFFFAOYSA-J tetrasodium;[dichloro(phosphonato)methyl]-dioxido-oxo-$l^{5}-phosphane Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)C(Cl)(Cl)P([O-])([O-])=O LQHJDMDQUHOTFV-UHFFFAOYSA-J 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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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)]
-
- 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)]
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/409—Compounds containing the structure P(=X)-X-acyl, P(=X) -X-heteroatom, P(=X)-X-CN (X = O, S, Se)
-
- 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
-
- 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
-
- 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
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- 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)]
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/409—Compounds containing the structure P(=X)-X-acyl, P(=X) -X-heteroatom, P(=X)-X-CN (X = O, S, Se)
- C07F9/4093—Compounds containing the structure P(=X)-X-C(=X)- (X = O, S, Se)
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Animal Behavior & Ethology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (19)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI974001A FI104901B (fi) | 1997-10-20 | 1997-10-20 | Uudet metyleenibisfosfonihappojohdannaiset |
| IL13563998A IL135639A0 (en) | 1997-10-20 | 1998-10-20 | Novel methylenebisphosphonic acid derivatives |
| EP98949022A EP1032578A1 (en) | 1997-10-20 | 1998-10-20 | Novel methylenebisphosphonic acid derivatives |
| BR9813102-8A BR9813102A (pt) | 1997-10-20 | 1998-10-20 | Derivados de ácido metilenobisfosfÈnico novos |
| HU0004386A HUP0004386A3 (en) | 1997-10-20 | 1998-10-20 | Methylenebisphosphonic acid derivatives, process for producing them and medicaments containing the same as active agent |
| CA002306080A CA2306080A1 (en) | 1997-10-20 | 1998-10-20 | Novel methylenebisphosphonic acid derivatives |
| PL98340055A PL340055A1 (en) | 1997-10-20 | 1998-10-20 | Novel derivatives of methylene biphosphonic acid |
| CNB988103710A CN1147497C (zh) | 1997-10-20 | 1998-10-20 | 亚甲基双膦酸类衍生物 |
| PCT/FI1998/000814 WO1999020634A1 (en) | 1997-10-20 | 1998-10-20 | Novel methylenebisphosphonic acid derivatives |
| NZ504390A NZ504390A (en) | 1997-10-20 | 1998-10-20 | Methylenebisphosphonic acid anhydride derivatives and pharmaceuticals thereof |
| KR1020007004256A KR20010031269A (ko) | 1997-10-20 | 1998-10-20 | 신규한 메틸렌비스포스폰산 유도체 |
| EEP200000239A EE04061B1 (et) | 1997-10-20 | 1998-10-20 | Metüleenbisfosfoonhappe derivaadid |
| JP2000516975A JP2001520232A (ja) | 1997-10-20 | 1998-10-20 | 新規なメチレンビスホスホン酸誘導体 |
| AU95437/98A AU740355B2 (en) | 1997-10-20 | 1998-10-20 | Novel Methylenebisphosphonic Acid Derivatives |
| RU2000112534/04A RU2205833C2 (ru) | 1997-10-20 | 1998-10-20 | Производные ангидрида метиленбисфосфоновой кислоты, способы их получения, фармацевтическая композиция |
| US09/529,826 US6326363B1 (en) | 1997-10-20 | 1998-10-20 | Methylenebisphosphonic acid derivatives |
| TR2000/01055T TR200001055T2 (tr) | 1997-10-20 | 1998-10-20 | Yeni metilenbifosfonik asit türevleri |
| NO20002006A NO20002006L (no) | 1997-10-20 | 2000-04-17 | Nye metylenbisfosfonsyrederivater |
| BG104452A BG104452A (en) | 1997-10-20 | 2000-05-17 | New derivatives of the methylenebisphosphonic acid |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FI974001 | 1997-10-20 | ||
| FI974001A FI104901B (fi) | 1997-10-20 | 1997-10-20 | Uudet metyleenibisfosfonihappojohdannaiset |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI974001A0 FI974001A0 (fi) | 1997-10-20 |
| FI974001A FI974001A (fi) | 1999-04-21 |
| FI104901B true FI104901B (fi) | 2000-04-28 |
Family
ID=8549759
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI974001A FI104901B (fi) | 1997-10-20 | 1997-10-20 | Uudet metyleenibisfosfonihappojohdannaiset |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US6326363B1 (xx) |
| EP (1) | EP1032578A1 (xx) |
| JP (1) | JP2001520232A (xx) |
| KR (1) | KR20010031269A (xx) |
| CN (1) | CN1147497C (xx) |
| AU (1) | AU740355B2 (xx) |
| BG (1) | BG104452A (xx) |
| BR (1) | BR9813102A (xx) |
| CA (1) | CA2306080A1 (xx) |
| EE (1) | EE04061B1 (xx) |
| FI (1) | FI104901B (xx) |
| HU (1) | HUP0004386A3 (xx) |
| IL (1) | IL135639A0 (xx) |
| NO (1) | NO20002006L (xx) |
| NZ (1) | NZ504390A (xx) |
| PL (1) | PL340055A1 (xx) |
| RU (1) | RU2205833C2 (xx) |
| TR (1) | TR200001055T2 (xx) |
| WO (1) | WO1999020634A1 (xx) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO313180B1 (no) * | 2000-07-04 | 2002-08-26 | Anticancer Therapeutic Inv Sa | Bensökende alfapartikkel emitterende radiofarmasöytika |
| US7862552B2 (en) | 2005-05-09 | 2011-01-04 | Boston Scientific Scimed, Inc. | Medical devices for treating urological and uterine conditions |
| WO2008024169A1 (en) * | 2006-07-21 | 2008-02-28 | Glsynthesis, Inc. | Reactive pyrophosphoric and bisphosphonic acid derivatives and methods of their use |
| CA2747188C (en) | 2008-11-20 | 2017-06-13 | Glsynthesis Inc. | Antithrombotic diadenosine tetraphosphates and related analogs |
| CN107011380A (zh) * | 2016-01-28 | 2017-08-04 | 臧伟 | 一种二膦酸衍生物及含二膦酸衍生物的组合物治疗骨折的应用 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4447256A (en) | 1977-07-20 | 1984-05-08 | Nissan Chemical Industries, Ltd. | N-(Unsubstituted or substituted pyridyl)aminomethylene-diphosphonic acids, herbicidal compositions containing same, their use for herbicides, and process for preparing same |
| DE2758580A1 (de) | 1977-12-29 | 1979-07-05 | Hoechst Ag | Verfahren zur herstellung von phosphin- und phosphonsaeure-anhydriden |
| US4973576A (en) | 1987-03-10 | 1990-11-27 | Yamanouchi Pharmaceutical Co., Ltd. | Bisphophonic acid derivatives and pharmaceutical compositions containing the same |
| US4933472A (en) | 1988-04-08 | 1990-06-12 | Yamanouchi Pharmaceutical Co., Ltd. | Substituted aminomethylenebis(phosphonic acid) derivatives |
| EP0356866A3 (en) | 1988-08-29 | 1991-03-27 | E.R. SQUIBB & SONS, INC. | Phosphorus-containing squalene synthetase inhibitors and method |
| FI83421C (fi) | 1989-06-21 | 1991-07-10 | Huhtamaeki Oy | Foerfarande foer framstaellning av farmakologiskt anvaendbara metylenbisfosfonsyraderivat. |
| DE69023844T2 (de) * | 1989-09-06 | 1996-06-20 | Merck & Co Inc | Acyloxymethylester der Bisphonsäuren als Knochenresorptions-Inhibitoren. |
| FI89366C (fi) | 1990-12-20 | 1993-09-27 | Leiras Oy | Foerfarande foer framstaellning av nya farmakologiskt anvaendbara metylenbisfosfonsyraderivat |
| FI89365C (fi) | 1990-12-20 | 1993-09-27 | Leiras Oy | Foerfarande foer framstaellning av nya farmakologiskt anvaendbara metylenbisfosfonsyraderivat |
| FI89364C (fi) | 1990-12-20 | 1993-09-27 | Leiras Oy | Foerfarande foer framstaellning av nya, farmakologiskt anvaendbara metylenbisfosfonsyraderivat |
| PL297372A1 (en) | 1991-04-06 | 1993-09-06 | Fisons Plc | Atp analogs |
| TW237386B (xx) | 1992-04-15 | 1995-01-01 | Ciba Geigy | |
| AU679721B2 (en) * | 1993-02-10 | 1997-07-10 | Astrazeneca Ab | N-alkyl-2-substituted ATP analogues |
| US5462932A (en) | 1994-05-17 | 1995-10-31 | Merck & Co., Inc. | Oral liquid alendronate formulations |
-
1997
- 1997-10-20 FI FI974001A patent/FI104901B/fi not_active IP Right Cessation
-
1998
- 1998-10-20 CA CA002306080A patent/CA2306080A1/en not_active Abandoned
- 1998-10-20 PL PL98340055A patent/PL340055A1/xx unknown
- 1998-10-20 WO PCT/FI1998/000814 patent/WO1999020634A1/en not_active Application Discontinuation
- 1998-10-20 IL IL13563998A patent/IL135639A0/xx unknown
- 1998-10-20 US US09/529,826 patent/US6326363B1/en not_active Expired - Lifetime
- 1998-10-20 JP JP2000516975A patent/JP2001520232A/ja not_active Withdrawn
- 1998-10-20 BR BR9813102-8A patent/BR9813102A/pt not_active IP Right Cessation
- 1998-10-20 TR TR2000/01055T patent/TR200001055T2/xx unknown
- 1998-10-20 EE EEP200000239A patent/EE04061B1/xx not_active IP Right Cessation
- 1998-10-20 NZ NZ504390A patent/NZ504390A/en unknown
- 1998-10-20 KR KR1020007004256A patent/KR20010031269A/ko not_active Application Discontinuation
- 1998-10-20 EP EP98949022A patent/EP1032578A1/en not_active Withdrawn
- 1998-10-20 CN CNB988103710A patent/CN1147497C/zh not_active Expired - Fee Related
- 1998-10-20 RU RU2000112534/04A patent/RU2205833C2/ru not_active IP Right Cessation
- 1998-10-20 AU AU95437/98A patent/AU740355B2/en not_active Ceased
- 1998-10-20 HU HU0004386A patent/HUP0004386A3/hu unknown
-
2000
- 2000-04-17 NO NO20002006A patent/NO20002006L/no not_active Application Discontinuation
- 2000-05-17 BG BG104452A patent/BG104452A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0004386A2 (hu) | 2001-04-28 |
| JP2001520232A (ja) | 2001-10-30 |
| FI974001A (fi) | 1999-04-21 |
| NO20002006D0 (no) | 2000-04-17 |
| CN1147497C (zh) | 2004-04-28 |
| EE04061B1 (et) | 2003-06-16 |
| WO1999020634A1 (en) | 1999-04-29 |
| AU740355B2 (en) | 2001-11-01 |
| HUP0004386A3 (en) | 2002-08-28 |
| EE200000239A (et) | 2001-08-15 |
| NZ504390A (en) | 2001-10-26 |
| US6326363B1 (en) | 2001-12-04 |
| BG104452A (en) | 2000-12-29 |
| EP1032578A1 (en) | 2000-09-06 |
| NO20002006L (no) | 2000-06-15 |
| IL135639A0 (en) | 2001-05-20 |
| CN1276793A (zh) | 2000-12-13 |
| RU2205833C2 (ru) | 2003-06-10 |
| CA2306080A1 (en) | 1999-04-29 |
| KR20010031269A (ko) | 2001-04-16 |
| TR200001055T2 (tr) | 2000-09-21 |
| BR9813102A (pt) | 2000-08-22 |
| FI974001A0 (fi) | 1997-10-20 |
| AU9543798A (en) | 1999-05-10 |
| PL340055A1 (en) | 2001-01-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |