DK172832B1 - Analogifremgangsmåde til fremstilling af diphosphonsyrederivater - Google Patents
Analogifremgangsmåde til fremstilling af diphosphonsyrederivater Download PDFInfo
- Publication number
- DK172832B1 DK172832B1 DK198300299A DK29983A DK172832B1 DK 172832 B1 DK172832 B1 DK 172832B1 DK 198300299 A DK198300299 A DK 198300299A DK 29983 A DK29983 A DK 29983A DK 172832 B1 DK172832 B1 DK 172832B1
- Authority
- DK
- Denmark
- Prior art keywords
- chlorophenyl
- pyrazolyl
- diphosphonic acid
- general formula
- fluorophenyl
- Prior art date
Links
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical class OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 3
- 150000001340 alkali metals Chemical group 0.000 claims abstract description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims abstract description 3
- 150000001342 alkaline earth metals Chemical group 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 13
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 claims description 5
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- MJUJXFBTEFXVKU-UHFFFAOYSA-N diethyl phosphonate Chemical compound CCOP(=O)OCC MJUJXFBTEFXVKU-UHFFFAOYSA-N 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- -1 acyl phosphonate Chemical compound 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- VIRXTVKQSONSCM-UHFFFAOYSA-N [2-[5-(4-chlorophenyl)-2-phenyl-1h-pyrazol-5-yl]-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound C1=CC(CC(O)(P(O)(O)=O)P(O)(O)=O)(C=2C=CC(Cl)=CC=2)NN1C1=CC=CC=C1 VIRXTVKQSONSCM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 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
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 12
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 2
- 230000001741 anti-phlogistic effect Effects 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
- 229950005499 carbon tetrachloride Drugs 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KAZRLJCDXRMZTJ-UHFFFAOYSA-N [2-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 KAZRLJCDXRMZTJ-UHFFFAOYSA-N 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
- 239000011541 reaction mixture 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
- AARQGXJHRQOCAU-UHFFFAOYSA-N 2-[[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]methyl]propanedioic acid Chemical compound OC(=O)C(C(O)=O)CC1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 AARQGXJHRQOCAU-UHFFFAOYSA-N 0.000 description 2
- NZSPDFOEZDCBHS-UHFFFAOYSA-N 3-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]-1-dimethoxyphosphorylpropan-1-one Chemical compound COP(=O)(OC)C(=O)CCC1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 NZSPDFOEZDCBHS-UHFFFAOYSA-N 0.000 description 2
- YFYVMFUJSMVRCS-UHFFFAOYSA-N 3-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 YFYVMFUJSMVRCS-UHFFFAOYSA-N 0.000 description 2
- OGIQUTOPUAREKB-UHFFFAOYSA-N 3-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]propanoyl chloride Chemical compound C1=CC(F)=CC=C1N1N=C(CCC(Cl)=O)C(C=2C=CC(Cl)=CC=2)=C1 OGIQUTOPUAREKB-UHFFFAOYSA-N 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
- 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002456 anti-arthritic effect Effects 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 2
- 229940042400 direct acting antivirals phosphonic acid derivative Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000003007 phosphonic acid derivatives Chemical class 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 2
- GUHPRPJDBZHYCJ-SECBINFHSA-N (2s)-2-(5-benzoylthiophen-2-yl)propanoic acid Chemical compound S1C([C@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CC=C1 GUHPRPJDBZHYCJ-SECBINFHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YBPNJBYPFNTZIW-UHFFFAOYSA-N 2-(1,3,5-triphenylpyrazol-4-yl)acetic acid Chemical compound OC(=O)CC=1C(C=2C=CC=CC=2)=NN(C=2C=CC=CC=2)C=1C1=CC=CC=C1 YBPNJBYPFNTZIW-UHFFFAOYSA-N 0.000 description 1
- QNMZHGGKRXRREZ-UHFFFAOYSA-N 2-(1h-pyrazol-5-yl)acetyl chloride Chemical compound ClC(=O)CC1=CC=NN1 QNMZHGGKRXRREZ-UHFFFAOYSA-N 0.000 description 1
- JBJASTVVFKIZBG-UHFFFAOYSA-N 2-[2-(2-methylpropyl)-4,5-diphenylpyrazol-3-yl]acetic acid Chemical compound OC(=O)CC=1N(CC(C)C)N=C(C=2C=CC=CC=2)C=1C1=CC=CC=C1 JBJASTVVFKIZBG-UHFFFAOYSA-N 0.000 description 1
- OEOBIFMQBXSTEK-UHFFFAOYSA-N 2-[3-(4-chlorophenyl)-1-phenylpyrazol-4-yl]-1-dimethoxyphosphorylethenol Chemical compound COP(OC)(=O)C(=CC=1C(=NN(C1)C1=CC=CC=C1)C1=CC=C(C=C1)Cl)O OEOBIFMQBXSTEK-UHFFFAOYSA-N 0.000 description 1
- YAMFWQIVVMITPG-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]acetic acid Chemical compound OC(=O)CC1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 YAMFWQIVVMITPG-UHFFFAOYSA-N 0.000 description 1
- BCLXJQOHLUTWTC-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]acetyl chloride Chemical compound C1=CC(F)=CC=C1N1N=C(CC(Cl)=O)C(C=2C=CC(Cl)=CC=2)=C1 BCLXJQOHLUTWTC-UHFFFAOYSA-N 0.000 description 1
- JIEKMACRVQTPRC-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-2-phenyl-5-thiazolyl]acetic acid Chemical compound OC(=O)CC=1SC(C=2C=CC=CC=2)=NC=1C1=CC=C(Cl)C=C1 JIEKMACRVQTPRC-UHFFFAOYSA-N 0.000 description 1
- VPSXHKGJZJCWLV-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(1-ethylpiperidin-4-yl)oxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OC1CCN(CC1)CC VPSXHKGJZJCWLV-UHFFFAOYSA-N 0.000 description 1
- DHUACCWOJDEZAH-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)-2-phenyl-1H-pyrazol-5-yl]-1-dimethoxyphosphorylethenol Chemical compound COP(OC)(=O)C(=CC1(NN(C=C1)C1=CC=CC=C1)C1=CC=C(C=C1)Cl)O DHUACCWOJDEZAH-UHFFFAOYSA-N 0.000 description 1
- YMFDAYPDKZIZSE-UHFFFAOYSA-N 3-(bromomethyl)-4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazole Chemical compound C1=CC(F)=CC=C1N1N=C(CBr)C(C=2C=CC(Cl)=CC=2)=C1 YMFDAYPDKZIZSE-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 229910014033 C-OH Inorganic materials 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
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 241001245789 Goodea atripinnis Species 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical class [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- HXYBTTSVWXZKPL-UHFFFAOYSA-N [3-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CCC1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 HXYBTTSVWXZKPL-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 229950009075 bufezolac Drugs 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000003913 calcium metabolism Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229950009185 clopirac Drugs 0.000 description 1
- SJCRQMUYEQHNTC-UHFFFAOYSA-N clopirac Chemical compound CC1=CC(CC(O)=O)=C(C)N1C1=CC=C(Cl)C=C1 SJCRQMUYEQHNTC-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- MEIXERZSMCZBMI-UHFFFAOYSA-N dimethyl 2-[[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]methyl]propanedioate Chemical compound COC(=O)C(C(=O)OC)CC1=NN(C=2C=CC(F)=CC=2)C=C1C1=CC=C(Cl)C=C1 MEIXERZSMCZBMI-UHFFFAOYSA-N 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- IQRYPZXSRARLGV-UHFFFAOYSA-L disodium [1-[4-(4-chlorophenyl)-1-(4-fluorophenyl)pyrazol-3-yl]-2-hydroxy-2-phosphonatoethyl]phosphonic acid Chemical compound [Na+].[Na+].ClC1=CC=C(C=C1)C=1C(=NN(C=1)C1=CC=C(C=C1)F)C(C(P([O-])(=O)[O-])O)P(O)(=O)O IQRYPZXSRARLGV-UHFFFAOYSA-L 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229960002679 fentiazac Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 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
- LZRDDINFIHUVCX-UHFFFAOYSA-N isofezolac Chemical compound OC(=O)CC1=C(C=2C=CC=CC=2)C(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 LZRDDINFIHUVCX-UHFFFAOYSA-N 0.000 description 1
- 229950004425 isofezolac Drugs 0.000 description 1
- 229960003768 lonazolac Drugs 0.000 description 1
- XVUQHFRQHBLHQD-UHFFFAOYSA-N lonazolac Chemical compound OC(=O)CC1=CN(C=2C=CC=CC=2)N=C1C1=CC=C(Cl)C=C1 XVUQHFRQHBLHQD-UHFFFAOYSA-N 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000037361 pathway Effects 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
- 229950007914 pirazolac Drugs 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 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
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960001312 tiaprofenic acid Drugs 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 229950001411 trifezolac Drugs 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 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
- C07F9/547—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
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07F9/28—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
- C07F9/3882—Arylalkanephosphonic acids
-
- 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)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4056—Esters of arylalkanephosphonic acids
-
- 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
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
-
- 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
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65525—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a seven-(or more) membered ring
- C07F9/65527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a seven-(or more) membered ring condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19823203308 DE3203308A1 (de) | 1982-01-27 | 1982-01-27 | Diphosphonsaeure-derivate und diese enthaltende pharmazeutische praeparate |
| DE3203308 | 1982-01-27 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK29983D0 DK29983D0 (da) | 1983-01-26 |
| DK29983A DK29983A (da) | 1983-07-28 |
| DK172832B1 true DK172832B1 (da) | 1999-08-09 |
Family
ID=6154493
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK198300299A DK172832B1 (da) | 1982-01-27 | 1983-01-26 | Analogifremgangsmåde til fremstilling af diphosphonsyrederivater |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4503049A (ja) |
| JP (5) | JPS58174393A (ja) |
| AT (1) | ATE17356T1 (ja) |
| AU (1) | AU561542B2 (ja) |
| CA (1) | CA1224459A (ja) |
| DE (2) | DE3203308A1 (ja) |
| DK (1) | DK172832B1 (ja) |
| ES (1) | ES8400119A1 (ja) |
| FI (1) | FI76096C (ja) |
| GR (1) | GR77146B (ja) |
| ZA (1) | ZA83566B (ja) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3425812A1 (de) * | 1984-07-13 | 1986-01-16 | Deutsches Krebsforschungszentrum, 6900 Heidelberg | Neue 1-hydroxy-1,1-diphosphonsaeureverbindungen, verfahren zu ihrer herstellung und pharmakologische zubereitungen, insbesondere zur behandlung von knochentumoren |
| 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 |
| DE3512536A1 (de) * | 1985-04-06 | 1986-10-16 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue diphosphonsaeure-derivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| EP0243173B1 (en) * | 1986-04-24 | 1991-06-26 | Fujisawa Pharmaceutical Co., Ltd. | New diphosphonic acid compounds, processes for the preparation thereof and pharmaceutical composition comprising the same |
| DE3626058A1 (de) * | 1986-08-01 | 1988-02-11 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| ES2038692T4 (es) * | 1986-11-21 | 2012-02-10 | Novartis Ag | Procedimiento para la obtencion de acidos alcanodifosfonicos substituidos. |
| EP0317505A1 (de) * | 1987-11-13 | 1989-05-24 | Ciba-Geigy Ag | Neue Azacycloalkylalkandiphosphonsäuren |
| DE3822650A1 (de) * | 1988-07-05 | 1990-02-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| US4990503A (en) * | 1988-08-12 | 1991-02-05 | Yamanouchi Pharmaceutical Co., Ltd. | Heterocyclic bisphosphonic acid derivatives |
| US4950615A (en) * | 1989-02-06 | 1990-08-21 | International Solar Electric Technology, Inc. | Method and making group IIB metal - telluride films and solar cells |
| PH26923A (en) * | 1989-03-08 | 1992-12-03 | Ciba Geigy | N-substituted amino alkanediphosphonic acids |
| JPH0377894A (ja) * | 1989-08-18 | 1991-04-03 | Toray Ind Inc | メチレンジホスホン酸化合物 |
| 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 |
| IT1244698B (it) * | 1991-02-01 | 1994-08-08 | Gentili Ist Spa | Acidi aril-o arilalchil-acil ammino-alchil-idrossidifosfonici, procedimento per la loro preparazione e loro uso in terapia osteo-articolare e dei tessuti connettori in generale |
| US5128328A (en) * | 1991-10-25 | 1992-07-07 | American Home Products Corporation | Heterocyclic bisphosphonic acid derivatives |
| DE69330114T2 (de) * | 1992-07-10 | 2001-08-02 | Toray Industries, Inc. | Methandiphosphonat-derivat, dessen produktion und dessen verwendung als arzneimittel |
| IL150062A0 (en) | 1999-12-17 | 2002-12-01 | Ariad Pharma Inc | Proton pump inhibitors |
| EP1248790A1 (en) * | 1999-12-17 | 2002-10-16 | Ariad Pharmaceuticals, Inc. | Proton pump inhibitors |
| US6942262B2 (en) * | 2001-09-27 | 2005-09-13 | Shape Corporation | Tubular energy management system for absorbing impact energy |
| DE10152005A1 (de) * | 2001-10-22 | 2003-04-30 | Bayer Cropscience Ag | Pyrazolylsubstituierte Heterocyclen |
| 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 |
| US20050065171A1 (en) * | 2003-06-25 | 2005-03-24 | Shakespeare William C. | Substituted purine derivatives |
| FR2926081B1 (fr) * | 2008-01-03 | 2010-02-19 | Univ Nantes | Derives d'acide hydroxy-bisphosphonique comme vecteur ciblant le tissu osseux |
| JP5363045B2 (ja) * | 2008-07-24 | 2013-12-11 | 大八化学工業株式会社 | ホスホン酸の製造方法 |
| WO2010035664A1 (ja) * | 2008-09-24 | 2010-04-01 | 田辺三菱製薬株式会社 | ビスホスホン酸誘導体の製法 |
| WO2015120580A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Cathepsin cysteine protease inhibitors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2043073B (en) * | 1979-02-13 | 1983-05-11 | Symphar Sa | Mono-and diphosphonate compounds |
| GB2079285B (en) * | 1980-07-09 | 1984-05-23 | Symphar Sa | Dipthosphonate derivatives and pahrmaceutical compositions containing them |
-
1982
- 1982-01-27 DE DE19823203308 patent/DE3203308A1/de not_active Withdrawn
-
1983
- 1983-01-14 DE DE8383100282T patent/DE3361731D1/de not_active Expired
- 1983-01-14 AT AT83100282T patent/ATE17356T1/de not_active IP Right Cessation
- 1983-01-25 GR GR70331A patent/GR77146B/el unknown
- 1983-01-25 AU AU10742/83A patent/AU561542B2/en not_active Ceased
- 1983-01-26 CA CA000420298A patent/CA1224459A/en not_active Expired
- 1983-01-26 DK DK198300299A patent/DK172832B1/da not_active IP Right Cessation
- 1983-01-27 ES ES519323A patent/ES8400119A1/es not_active Expired
- 1983-01-27 FI FI830298A patent/FI76096C/fi not_active IP Right Cessation
- 1983-01-27 US US06/461,411 patent/US4503049A/en not_active Expired - Lifetime
- 1983-01-27 JP JP58010668A patent/JPS58174393A/ja active Granted
- 1983-01-27 ZA ZA83566A patent/ZA83566B/xx unknown
-
1991
- 1991-09-12 JP JP3232767A patent/JPH051087A/ja active Granted
- 1991-09-12 JP JP3232768A patent/JPH051088A/ja active Granted
- 1991-09-12 JP JP3232765A patent/JPH051085A/ja active Granted
- 1991-09-12 JP JP3232766A patent/JPH051086A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| DK29983A (da) | 1983-07-28 |
| GR77146B (ja) | 1984-09-07 |
| FI830298A0 (fi) | 1983-01-27 |
| ZA83566B (en) | 1983-10-26 |
| JPH0549676B2 (ja) | 1993-07-26 |
| DK29983D0 (da) | 1983-01-26 |
| JPH051274B2 (ja) | 1993-01-07 |
| JPH051088A (ja) | 1993-01-08 |
| AU561542B2 (en) | 1987-05-14 |
| ES519323A0 (es) | 1983-11-01 |
| DE3361731D1 (en) | 1986-02-20 |
| JPH051085A (ja) | 1993-01-08 |
| ES8400119A1 (es) | 1983-11-01 |
| FI76096C (fi) | 1988-09-09 |
| ATE17356T1 (de) | 1986-01-15 |
| JPH0549678B2 (ja) | 1993-07-26 |
| CA1224459A (en) | 1987-07-21 |
| JPH051086A (ja) | 1993-01-08 |
| US4503049A (en) | 1985-03-05 |
| JPH0549679B2 (ja) | 1993-07-26 |
| AU1074283A (en) | 1983-08-04 |
| JPH051087A (ja) | 1993-01-08 |
| JPS58174393A (ja) | 1983-10-13 |
| JPH0549677B2 (ja) | 1993-07-26 |
| FI830298L (fi) | 1983-07-28 |
| DE3203308A1 (de) | 1983-07-28 |
| FI76096B (fi) | 1988-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK172832B1 (da) | Analogifremgangsmåde til fremstilling af diphosphonsyrederivater | |
| FI77041C (fi) | Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara difosfonsyraderivat. | |
| TWI293304B (en) | Process for the preparation of bisphosphonates | |
| DK168630B1 (da) | Aromatiske substituerede azacycloalkyl-1-hydroxy-alkan-1,1-diphosphonsyrer og deres salte, fremgangsmåde til fremstilling deraf samt farmaceutisk præparat med indhold deraf | |
| SI9520067A (en) | Phosphinic acid derivates with metallopeptidase inhibitory activity. | |
| SK279601B6 (sk) | Deriváty kyseliny metylénbisfosfónovej, spôsob ich | |
| HU200465B (en) | Process for producing substituted alphaamino acids, derivatives thereof and pharmaceutical compositions comprising such compounds | |
| DK149609B (da) | Analogifremgangsmaade til fremstilling af hydroxyamino-alkan- eller -alkenphosphonsyrederivater eller estere eller salte deraf | |
| NO176569B (no) | Analogifremgangsmåte for fremstilling av nye, terapeutisk aktive, aromatisk substituerte alkylaminoalkandifosfonsyrer | |
| EP0084822A2 (de) | Diphosphonsäure-Derivate und diese enthaltende pharmazeutische Präparate | |
| FI92704B (fi) | Menetelmä terapeuttisesti käyttökelpoisten aromaattisesti substituoitujen alkyyliaminoalkaanidifosfonihappojen valmistamiseksi | |
| NO174152B (no) | Analogifremgangsm}te for fremstilling av N-substituerte aminoalkandifosfonsyrer | |
| AU2003230698B2 (en) | Plasma carboxypeptidase B inhibitors | |
| NO178030B (no) | Analogifremgangsmåte ved fremstilling av terapeutisk aktive metylenbisfosfonsyrederivater | |
| IL105834A (en) | Phosphate compounds containing sulfur and pharmaceutical preparations containing them | |
| JPH0329078B2 (ja) | ||
| DE3243917A1 (de) | Diphosphonsaeure-derivate und diese enthaltende pharmazeutische praeparate | |
| IE54135B1 (en) | Diphosphonic acid derivatives, and pharmaceutical preparations containing them | |
| US5210262A (en) | Method for preparing a phosphonic acid ester | |
| JPH0370715B2 (ja) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B1 | Patent granted (law 1993) | ||
| PBP | Patent lapsed |