CA1202635A - Diphosphonic acid derivatives, process for their preparation and pharmaceutical preparations containing them - Google Patents
Diphosphonic acid derivatives, process for their preparation and pharmaceutical preparations containing themInfo
- Publication number
- CA1202635A CA1202635A CA000420239A CA420239A CA1202635A CA 1202635 A CA1202635 A CA 1202635A CA 000420239 A CA000420239 A CA 000420239A CA 420239 A CA420239 A CA 420239A CA 1202635 A CA1202635 A CA 1202635A
- Authority
- CA
- Canada
- Prior art keywords
- phosphonic acid
- hydroxyethane
- hydrogen
- bis
- whenever prepared
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 126
- 230000008569 process Effects 0.000 title claims abstract description 125
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical class OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000000825 pharmaceutical preparation Substances 0.000 title abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 32
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 8
- 239000004305 biphenyl Substances 0.000 claims abstract description 7
- 235000010290 biphenyl Nutrition 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 100
- 239000002253 acid Substances 0.000 claims description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
- 239000000126 substance Substances 0.000 claims description 42
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 24
- YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 229950005499 carbon tetrachloride Drugs 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 18
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- -1 acyl phos-phonate Chemical compound 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- HZCDANOFLILNSA-UHFFFAOYSA-N Dimethyl hydrogen phosphite Chemical compound COP(=O)OC HZCDANOFLILNSA-UHFFFAOYSA-N 0.000 claims description 11
- 239000002585 base Substances 0.000 claims description 10
- 229940116254 phosphonic acid Drugs 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 claims description 8
- 159000000007 calcium salts Chemical class 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 3
- 239000001639 calcium acetate Substances 0.000 claims description 3
- 229960005147 calcium acetate Drugs 0.000 claims description 3
- 235000011092 calcium acetate Nutrition 0.000 claims description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 13
- DLQDGVZAEYZNTG-UHFFFAOYSA-N dimethyl hydrogen phosphite Chemical compound COP(O)OC DLQDGVZAEYZNTG-UHFFFAOYSA-N 0.000 claims 9
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 8
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 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 claims 2
- 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 claims 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- 229960000443 hydrochloric acid Drugs 0.000 claims 2
- 235000011167 hydrochloric acid Nutrition 0.000 claims 2
- 150000002431 hydrogen Chemical group 0.000 claims 2
- CTLLRTPCDLQWPE-UHFFFAOYSA-N (1-hydroxy-1-phosphono-2-thiophen-2-ylethyl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CS1 CTLLRTPCDLQWPE-UHFFFAOYSA-N 0.000 claims 1
- BNXBJUGVJRQKSF-UHFFFAOYSA-N (1-hydroxy-2-naphthalen-1-yl-1-phosphonoethyl)phosphonic acid Chemical compound C1=CC=C2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CC=CC2=C1 BNXBJUGVJRQKSF-UHFFFAOYSA-N 0.000 claims 1
- VUVZZRAADNOYTF-UHFFFAOYSA-N (1-hydroxy-2-naphthalen-2-yl-1-phosphonoethyl)phosphonic acid Chemical compound C1=CC=CC2=CC(CC(O)(P(O)(O)=O)P(O)(O)=O)=CC=C21 VUVZZRAADNOYTF-UHFFFAOYSA-N 0.000 claims 1
- OGIGBBNRQUWLMU-UHFFFAOYSA-N 1-dimethoxyphosphoryl-2-(2-fluorophenyl)ethenol Chemical compound COP(=O)(OC)C(O)=CC1=CC=CC=C1F OGIGBBNRQUWLMU-UHFFFAOYSA-N 0.000 claims 1
- VRBNEBYEXFPIQO-UHFFFAOYSA-N 1-dimethoxyphosphoryl-2-(4-fluorophenyl)ethenol Chemical compound COP(=O)(OC)C(O)=CC1=CC=C(F)C=C1 VRBNEBYEXFPIQO-UHFFFAOYSA-N 0.000 claims 1
- JBXFUJZCHHNJNQ-UHFFFAOYSA-N 1-dimethoxyphosphoryl-2-(4-methylphenyl)ethenol Chemical compound COP(=O)(OC)C(O)=CC1=CC=C(C)C=C1 JBXFUJZCHHNJNQ-UHFFFAOYSA-N 0.000 claims 1
- PMNPDRKGHARORY-UHFFFAOYSA-N 1-dimethoxyphosphoryl-2-naphthalen-1-ylethenol Chemical compound C1=CC=C2C(C=C(O)P(=O)(OC)OC)=CC=CC2=C1 PMNPDRKGHARORY-UHFFFAOYSA-N 0.000 claims 1
- OBGSVDWJBCQTRN-UHFFFAOYSA-N 1-dimethoxyphosphoryl-2-naphthalen-2-ylethenol Chemical compound C1=CC=CC2=CC(C=C(O)P(=O)(OC)OC)=CC=C21 OBGSVDWJBCQTRN-UHFFFAOYSA-N 0.000 claims 1
- JPMWHPDYNXEZSU-UHFFFAOYSA-N 1-dimethoxyphosphoryl-2-thiophen-2-ylethenol Chemical compound COP(=O)(OC)C(O)=CC1=CC=CS1 JPMWHPDYNXEZSU-UHFFFAOYSA-N 0.000 claims 1
- KMVJBOHBQYMWAS-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-(4-propan-2-ylphenyl)propan-1-one Chemical compound COP(=O)(OC)C(=O)CCC1=CC=C(C(C)C)C=C1 KMVJBOHBQYMWAS-UHFFFAOYSA-N 0.000 claims 1
- GGAQGBGZFHCLJQ-UHFFFAOYSA-N 2-(3-chlorophenyl)-1-dimethoxyphosphorylethenol Chemical compound COP(=O)(OC)C(O)=CC1=CC=CC(Cl)=C1 GGAQGBGZFHCLJQ-UHFFFAOYSA-N 0.000 claims 1
- DKZMJIBTEIBRKZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-1-dimethoxyphosphorylethenol Chemical compound COP(=O)(OC)C(O)=CC1=CC=C(Cl)C=C1 DKZMJIBTEIBRKZ-UHFFFAOYSA-N 0.000 claims 1
- KKVLDMDZAHKCPS-UHFFFAOYSA-N 2-(4-chlorophenyl)-1-dimethoxyphosphorylprop-1-en-1-ol Chemical compound COP(=O)(OC)C(O)=C(C)C1=CC=C(Cl)C=C1 KKVLDMDZAHKCPS-UHFFFAOYSA-N 0.000 claims 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 claims 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 claims 1
- MWUVGXCUHWKQJE-UHFFFAOYSA-N 4-fluorophenethyl alcohol Chemical compound OCCC1=CC=C(F)C=C1 MWUVGXCUHWKQJE-UHFFFAOYSA-N 0.000 claims 1
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- USJSYBDDVFBFFO-UHFFFAOYSA-N COC1=CC=C(C=C(O)P(=O)(OC)OC)C=C1 Chemical compound COC1=CC=C(C=C(O)P(=O)(OC)OC)C=C1 USJSYBDDVFBFFO-UHFFFAOYSA-N 0.000 claims 1
- CDPSYELKJIKCRK-UHFFFAOYSA-N COP(=O)(OC)C(O)=CC1=C(Cl)C=CC=C1Cl Chemical compound COP(=O)(OC)C(O)=CC1=C(Cl)C=CC=C1Cl CDPSYELKJIKCRK-UHFFFAOYSA-N 0.000 claims 1
- ZSYHGAPUPQNZAC-UHFFFAOYSA-N [1-hydroxy-1-phosphono-3-(4-propan-2-ylphenyl)propyl]phosphonic acid Chemical compound CC(C)C1=CC=C(CCC(O)(P(O)(O)=O)P(O)(O)=O)C=C1 ZSYHGAPUPQNZAC-UHFFFAOYSA-N 0.000 claims 1
- BQUYKOLPMHLHRB-UHFFFAOYSA-N [1-hydroxy-2-(4-methylphenyl)-1-phosphonoethyl]phosphonic acid Chemical compound CC1=CC=C(CC(O)(P(O)(O)=O)P(O)(O)=O)C=C1 BQUYKOLPMHLHRB-UHFFFAOYSA-N 0.000 claims 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 claims 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 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 3
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 3
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 2
- 229940124346 antiarthritic agent Drugs 0.000 abstract description 2
- 239000003435 antirheumatic agent Substances 0.000 abstract description 2
- 125000001544 thienyl group Chemical group 0.000 abstract description 2
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 25
- 239000000047 product Substances 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 6
- 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 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 229960003887 dichlorophen Drugs 0.000 description 5
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 2
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-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
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002456 anti-arthritic effect Effects 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
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- 125000004185 ester group Chemical group 0.000 description 2
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- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HNIGZVZDWCTFPR-UHFFFAOYSA-N 2-(2-fluorophenyl)ethanol Chemical compound OCCC1=CC=CC=C1F HNIGZVZDWCTFPR-UHFFFAOYSA-N 0.000 description 1
- QDZAWVLWIMOXJT-UHFFFAOYSA-N 2-(4-methylphenyl)acetyl chloride Chemical compound CC1=CC=C(CC(Cl)=O)C=C1 QDZAWVLWIMOXJT-UHFFFAOYSA-N 0.000 description 1
- QKSGIGXOKHZCQZ-UHFFFAOYSA-N 2-chloro-2-phenylacetic acid Chemical compound OC(=O)C(Cl)C1=CC=CC=C1 QKSGIGXOKHZCQZ-UHFFFAOYSA-N 0.000 description 1
- QEJGMKHQXSZCOS-UHFFFAOYSA-N 2-naphthalen-2-ylacetyl chloride Chemical compound C1=CC=CC2=CC(CC(=O)Cl)=CC=C21 QEJGMKHQXSZCOS-UHFFFAOYSA-N 0.000 description 1
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 206010002556 Ankylosing Spondylitis 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- IVHVNMLJNASKHW-UHFFFAOYSA-M Chlorphonium chloride Chemical compound [Cl-].CCCC[P+](CCCC)(CCCC)CC1=CC=C(Cl)C=C1Cl IVHVNMLJNASKHW-UHFFFAOYSA-M 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- MDNWOSOZYLHTCG-UHFFFAOYSA-N Dichlorophen Chemical compound OC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1O MDNWOSOZYLHTCG-UHFFFAOYSA-N 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
- 241000700159 Rattus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 206010003246 arthritis Diseases 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
- 230000003913 calcium metabolism Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000006731 degradation 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
- SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000011707 mineral Substances 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
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—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 |
| DEP3203309.5 | 1982-01-27 | ||
| DEP3225468.7 | 1982-07-05 | ||
| DE19823225468 DE3225468A1 (de) | 1982-07-05 | 1982-07-05 | Diphosphonsaeure-derivate und diese enthaltende pharmazeutische praeparate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1202635A true CA1202635A (en) | 1986-04-01 |
Family
ID=25799266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000420239A Expired CA1202635A (en) | 1982-01-27 | 1983-01-26 | Diphosphonic acid derivatives, process for their preparation and pharmaceutical preparations containing them |
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 |
| FI77041C (fi) | 1989-01-10 |
| EP0085321B1 (de) | 1986-08-27 |
| FI830299L (fi) | 1983-07-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |