FI77041C - Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara difosfonsyraderivat. - Google Patents
Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara difosfonsyraderivat. Download PDFInfo
- Publication number
- FI77041C FI77041C FI830299A FI830299A FI77041C FI 77041 C FI77041 C FI 77041C FI 830299 A FI830299 A FI 830299A FI 830299 A FI830299 A FI 830299A FI 77041 C FI77041 C FI 77041C
- Authority
- FI
- Finland
- Prior art keywords
- dimethyl ester
- phosphonic acid
- hydroxyethane
- formula
- acid dimethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 claims description 8
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical class OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 229910014033 C-OH Inorganic materials 0.000 claims description 4
- 229910014570 C—OH Inorganic materials 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- -1 2- (4-chlorophenyl) -1-hydroxyethylene phosphonic acid dimethyl ester Chemical compound 0.000 description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002456 anti-arthritic effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- AVIXBXVUOUVMSV-UHFFFAOYSA-N 3-(4-chlorophenyl)-1-dimethoxyphosphorylpropan-1-one Chemical compound COP(=O)(OC)C(=O)CCC1=CC=C(Cl)C=C1 AVIXBXVUOUVMSV-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 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
- XFFZSWGKGRSYOQ-UHFFFAOYSA-N [2-(2-fluorophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CC=C1F XFFZSWGKGRSYOQ-UHFFFAOYSA-N 0.000 description 2
- MLRLLSRGLQXHLC-UHFFFAOYSA-N [2-(4-chlorophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=C(Cl)C=C1 MLRLLSRGLQXHLC-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VFRDBQGBQYINBH-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=C(Cl)C=CC=C1Cl VFRDBQGBQYINBH-UHFFFAOYSA-N 0.000 description 1
- KUMKNGTWQNSAQW-UHFFFAOYSA-N 2-(2-fluorophenyl)acetyl chloride Chemical compound FC1=CC=CC=C1CC(Cl)=O KUMKNGTWQNSAQW-UHFFFAOYSA-N 0.000 description 1
- PYPMKORNJLTHGP-UHFFFAOYSA-N 2-(3-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=CC(Cl)=C1 PYPMKORNJLTHGP-UHFFFAOYSA-N 0.000 description 1
- UMQUIRYNOVNYPA-UHFFFAOYSA-N 2-(4-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C=C1 UMQUIRYNOVNYPA-UHFFFAOYSA-N 0.000 description 1
- SIOJFYRPBYGHOO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetyl chloride Chemical compound FC1=CC=C(CC(Cl)=O)C=C1 SIOJFYRPBYGHOO-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- SLXNVBFPCUGINW-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-1-dimethoxyphosphorylpropan-1-one Chemical compound COP(=O)(OC)C(=O)CCC1=CC=C(Cl)C(Cl)=C1 SLXNVBFPCUGINW-UHFFFAOYSA-N 0.000 description 1
- HDDDHVKZRWFIGT-UHFFFAOYSA-N 3-(4-chlorophenyl)propanoylphosphonic acid Chemical compound ClC1=CC=C(C=C1)CCC(P(O)(=O)O)=O HDDDHVKZRWFIGT-UHFFFAOYSA-N 0.000 description 1
- FVXXPEDMEKCYMB-UHFFFAOYSA-N 4-(4-chlorophenyl)-1-dimethoxyphosphorylbutan-1-one Chemical compound COP(=O)(OC)C(=O)CCCC1=CC=C(Cl)C=C1 FVXXPEDMEKCYMB-UHFFFAOYSA-N 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 208000004434 Calcinosis Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920008712 Copo Polymers 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000033678 Thelitis Diseases 0.000 description 1
- JMJWRODFUKUZFR-UHFFFAOYSA-N [2-(2,6-dichlorophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=C(Cl)C=CC=C1Cl JMJWRODFUKUZFR-UHFFFAOYSA-N 0.000 description 1
- JYWTZZZAMLTZOW-UHFFFAOYSA-N [2-(3-chlorophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CC(Cl)=C1 JYWTZZZAMLTZOW-UHFFFAOYSA-N 0.000 description 1
- HLAGEXGZBCAOLO-UHFFFAOYSA-N [2-(4-fluorophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=C(F)C=C1 HLAGEXGZBCAOLO-UHFFFAOYSA-N 0.000 description 1
- VEPLESMLRNYWFT-UHFFFAOYSA-N [3-(3,4-dichlorophenyl)-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CCC1=CC=C(Cl)C(Cl)=C1 VEPLESMLRNYWFT-UHFFFAOYSA-N 0.000 description 1
- REQZJYMWMIUNNV-UHFFFAOYSA-N [3-(4-chlorophenyl)-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CCC1=CC=C(Cl)C=C1 REQZJYMWMIUNNV-UHFFFAOYSA-N 0.000 description 1
- IQQGAVAKPLSHND-UHFFFAOYSA-N [4-(4-chlorophenyl)-1-hydroxy-1-phosphonobutyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CCCC1=CC=C(Cl)C=C1 IQQGAVAKPLSHND-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 208000015202 calcium metabolic disease Diseases 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 208000001413 spine osteoarthritis Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 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)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
- C07F9/404—Esters of poly(thio)phosphonic 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
- C07F9/28—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
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19823203309 DE3203309A1 (de) | 1982-01-27 | 1982-01-27 | Diphosphonsaeure-derivate und diese enthaltende pharmazeutische praeparate |
| DE3203309 | 1982-01-27 | ||
| DE19823225468 DE3225468A1 (de) | 1982-07-05 | 1982-07-05 | Diphosphonsaeure-derivate und diese enthaltende pharmazeutische praeparate |
| DE3225468 | 1982-07-05 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI830299A0 FI830299A0 (fi) | 1983-01-27 |
| FI830299L FI830299L (fi) | 1983-07-28 |
| FI77041B FI77041B (fi) | 1988-09-30 |
| FI77041C true FI77041C (fi) | 1989-01-10 |
Family
ID=25799266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI830299A FI77041C (fi) | 1982-01-27 | 1983-01-27 | Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara difosfonsyraderivat. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4473560A (enExample) |
| EP (1) | EP0085321B1 (enExample) |
| AU (1) | AU559513B2 (enExample) |
| CA (1) | CA1202635A (enExample) |
| DE (1) | DE3365492D1 (enExample) |
| DK (1) | DK30083A (enExample) |
| ES (1) | ES519322A0 (enExample) |
| FI (1) | FI77041C (enExample) |
| GR (1) | GR77145B (enExample) |
| IL (1) | IL67763A0 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3364638A (en) * | 1965-08-02 | 1968-01-23 | Johnson & Johnson | Composite plastic and corrugated panel |
| FR2531088B1 (fr) * | 1982-07-29 | 1987-08-28 | Sanofi Sa | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
| DE3334211A1 (de) * | 1983-09-22 | 1985-04-04 | Henkel KGaA, 4000 Düsseldorf | Dihydroxyalkandiphosphonsaeuren |
| DE3428524A1 (de) * | 1984-08-02 | 1986-02-13 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| IL77243A (en) * | 1984-12-21 | 1996-11-14 | Procter & Gamble | Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds |
| US4902679A (en) * | 1985-12-13 | 1990-02-20 | Norwich Eaton Pharmaceuticals, Inc. | Methods of treating diseases with certain geminal diphosphonates |
| DE3623397A1 (de) * | 1986-07-11 | 1988-01-14 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| DE3822650A1 (de) * | 1988-07-05 | 1990-02-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| JPH0377894A (ja) * | 1989-08-18 | 1991-04-03 | Toray Ind Inc | メチレンジホスホン酸化合物 |
| US5227506A (en) * | 1989-09-06 | 1993-07-13 | Merck & Co., Inc. | Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors |
| US5204334A (en) * | 1990-10-18 | 1993-04-20 | Ciba-Geigy Corporation | Benzoheterocyclylalkylaminoalkanediphosphonic acids, compositions thereof, and use thereof in the treatment of calcium metabolism disorders |
| EP0561948B1 (en) * | 1990-12-07 | 1995-04-05 | The Upjohn Company | Phosphonic acid derivatives useful as antiinflammatory agents |
| US5217994A (en) * | 1991-08-09 | 1993-06-08 | Merck & Co., Inc. | Method of inhibiting osteoclast-mediated bone resorption by administration of aminoalkyl-substituted phenyl derivatives |
| US5204350A (en) * | 1991-08-09 | 1993-04-20 | Merck & Co., Inc. | Method of inhibiting osteoclast-mediated bone resorption by administration of n-heterocyclicalkyl-substituted phenyl derivatives |
| DK0594857T3 (da) * | 1991-09-05 | 1998-10-07 | Toray Industries | Methandiphosphonsyrederivat, fremstilling deraf ogmedicinsk anvendelse deraf |
| FR2683528A1 (fr) * | 1991-11-12 | 1993-05-14 | Bretagne Occidentale Universit | Prodrogues et analogues gem-bisphosphoniques d'antiinflammatoires non-sterouidiens de type arylacetique ou arylpropionique. |
| KR100272907B1 (ko) * | 1992-07-10 | 2001-03-02 | 히라이 가쯔히꼬 | 메탄디포스폰산 유도체, 이의 제조방법 및 이의 의약 용도 |
| TW393488B (en) * | 1995-04-20 | 2000-06-11 | Merck & Co Inc | Process for making 1-hydrox-ybisphosphonates |
| RU2147299C1 (ru) * | 1998-01-05 | 2000-04-10 | Иркутский институт химии СО РАН | Гидроксиэтиленбифосфонат полигексаметиленгуанидина, обладающий антисептическими и антидотными свойствами |
| FR2784031B1 (fr) * | 1998-10-02 | 2002-02-01 | Sanofi Elf | Utilisation de derives de l'acide bisphosphonique pour la preparation d'un medicament destine au traitement des boiteries |
| CA2394650A1 (en) * | 1999-12-17 | 2001-06-21 | Chi B. Vu | Novel heterocycles |
| AU2583901A (en) * | 1999-12-17 | 2001-06-25 | Ariad Pharmaceuticals, Inc. | Proton pump inhibitors |
| IL150062A0 (en) | 1999-12-17 | 2002-12-01 | Ariad Pharma Inc | Proton pump inhibitors |
| US20030036537A1 (en) * | 2001-07-16 | 2003-02-20 | Marc Lecouvey | Bisphosphonate derivatives, their preparations and uses |
| EP1406910B1 (fr) | 2001-07-16 | 2010-01-13 | Universite Paris 13 | Procedes de preparation de derives de bisphosphonates |
| FR2827289B1 (fr) * | 2001-07-16 | 2004-07-23 | Univ Paris 13 | Nouveau derive d'acide diphosphonique, son application en therapeutique et procede de preparation |
| TW200413381A (en) | 2002-11-04 | 2004-08-01 | Hoffmann La Roche | Novel amino-substituted dihydropyrimido [4,5-d]pyrimidinone derivatives, their manufacture and use as pharmaceutical agents |
| WO2005009348A2 (en) * | 2003-06-25 | 2005-02-03 | Ariad Pharmaceuticals, Inc. | Substituted purine derivatives |
| WO2007109585A2 (en) * | 2006-03-17 | 2007-09-27 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3664975A (en) * | 1970-04-13 | 1972-05-23 | Monsanto Co | Flame resistant polyurethane prepared by adding an ethane diphosphonate into the urethane-forming mixture |
| US4069246A (en) * | 1971-12-31 | 1978-01-17 | Henkel Kommanditgesellschaft Auf Aktien | Production of 1-hydroxy-alkane-1,1-diphosphonic acids |
| GB2043072B (en) * | 1979-02-13 | 1983-11-23 | Symphar Sa | Diphosphonate compounds |
| EP0084822B1 (de) * | 1982-01-27 | 1986-01-08 | Schering Aktiengesellschaft | Diphosphonsäure-Derivate und diese enthaltende pharmazeutische Präparate |
-
1983
- 1983-01-14 DE DE8383100283T patent/DE3365492D1/de not_active Expired
- 1983-01-14 EP EP83100283A patent/EP0085321B1/de not_active Expired
- 1983-01-25 GR GR70330A patent/GR77145B/el unknown
- 1983-01-25 AU AU10743/83A patent/AU559513B2/en not_active Ceased
- 1983-01-26 DK DK30083A patent/DK30083A/da unknown
- 1983-01-26 CA CA000420239A patent/CA1202635A/en not_active Expired
- 1983-01-27 US US06/461,412 patent/US4473560A/en not_active Expired - Lifetime
- 1983-01-27 ES ES519322A patent/ES519322A0/es active Granted
- 1983-01-27 FI FI830299A patent/FI77041C/fi not_active IP Right Cessation
- 1983-01-27 IL IL67763A patent/IL67763A0/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU1074383A (en) | 1983-08-04 |
| DE3365492D1 (en) | 1986-10-02 |
| DK30083A (da) | 1983-07-28 |
| FI830299A0 (fi) | 1983-01-27 |
| FI77041B (fi) | 1988-09-30 |
| GR77145B (enExample) | 1984-09-07 |
| ES8400118A1 (es) | 1983-11-01 |
| AU559513B2 (en) | 1987-03-12 |
| ES519322A0 (es) | 1983-11-01 |
| IL67763A0 (en) | 1983-05-15 |
| DK30083D0 (da) | 1983-01-26 |
| EP0085321A2 (de) | 1983-08-10 |
| US4473560A (en) | 1984-09-25 |
| EP0085321A3 (en) | 1983-08-17 |
| EP0085321B1 (de) | 1986-08-27 |
| FI830299L (fi) | 1983-07-28 |
| CA1202635A (en) | 1986-04-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: SCHERING AKTIENGESELLSCHAFT |