FI75830C - Foerfarande foer framstaellning av terapeutiskt anvaendbara metylendifosfonsyraderivat. - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara metylendifosfonsyraderivat. Download PDFInfo
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- FI75830C FI75830C FI832758A FI832758A FI75830C FI 75830 C FI75830 C FI 75830C FI 832758 A FI832758 A FI 832758A FI 832758 A FI832758 A FI 832758A FI 75830 C FI75830 C FI 75830C
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- 150000001875 compounds Chemical class 0.000 claims description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 32
- 239000002904 solvent Substances 0.000 claims description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 23
- -1 allyl halide Chemical class 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical compound OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 claims description 7
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 150000003573 thiols Chemical class 0.000 claims 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 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 229910052717 sulfur Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000005907 alkyl ester group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl 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
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 150000003109 potassium Chemical class 0.000 claims 3
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 2
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- NGCRXXLKJAAUQQ-UHFFFAOYSA-N undec-5-ene Chemical compound CCCCCC=CCCCC NGCRXXLKJAAUQQ-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 239000000047 product Substances 0.000 description 54
- 239000002253 acid Substances 0.000 description 49
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- 150000002148 esters Chemical class 0.000 description 35
- 239000000203 mixture Substances 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 26
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 206010003246 arthritis Diseases 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- 210000003321 cartilage cell Anatomy 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- ODTQUKVFOLFLIQ-UHFFFAOYSA-N 2-[di(propan-2-yloxy)phosphorylmethyl-propan-2-yloxyphosphoryl]oxypropane Chemical compound CC(C)OP(=O)(OC(C)C)CP(=O)(OC(C)C)OC(C)C ODTQUKVFOLFLIQ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 101000693530 Staphylococcus aureus Staphylokinase Proteins 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 150000003385 sodium Chemical class 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000002683 foot Anatomy 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N CHCl3 Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000001612 chondrocyte Anatomy 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 210000003024 peritoneal macrophage Anatomy 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 2
- PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000010191 Osteitis Deformans Diseases 0.000 description 2
- 208000027868 Paget disease Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 206010036030 Polyarthritis Diseases 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003435 antirheumatic agent Substances 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- XAVFZUKFLWOSOS-UHFFFAOYSA-N bis(dimethoxyphosphoryl)methane Chemical compound COP(=O)(OC)CP(=O)(OC)OC XAVFZUKFLWOSOS-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000010908 decantation Methods 0.000 description 2
- WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 2
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical compound OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 150000002019 disulfides Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 208000027202 mammary Paget disease Diseases 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
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- 238000000926 separation method Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
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- 208000024891 symptom Diseases 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical class C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- FKKVLRBGDJBEKG-UHFFFAOYSA-N (4-phenylsulfanyl-1-phosphonobutyl)phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)CCCSC1=CC=CC=C1 FKKVLRBGDJBEKG-UHFFFAOYSA-N 0.000 description 1
- SSFWRALQHVKBRP-UHFFFAOYSA-N (diethylcarbamothioyltrisulfanyl) n,n-diethylcarbamodithioate Chemical compound CCN(CC)C(=S)SSSSC(=S)N(CC)CC SSFWRALQHVKBRP-UHFFFAOYSA-N 0.000 description 1
- BEDWVNVYPXSFLZ-UHFFFAOYSA-N 1,1,2,2,3,3,4,4,5,5,6,6,6-tridecafluorohexyl thiohypochlorite Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)SCl BEDWVNVYPXSFLZ-UHFFFAOYSA-N 0.000 description 1
- DRWUCXQPGUYPKG-UHFFFAOYSA-N 1,1-bis(diethoxyphosphoryl)pentane Chemical compound CCCCC(P(=O)(OCC)OCC)P(=O)(OCC)OCC DRWUCXQPGUYPKG-UHFFFAOYSA-N 0.000 description 1
- SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 1
- FKQYZCMBLDWDAR-UHFFFAOYSA-N 1-(6-bromohexylsulfanyl)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(SCCCCCCBr)C=C1 FKQYZCMBLDWDAR-UHFFFAOYSA-N 0.000 description 1
- AROCLDYPZXMJPW-UHFFFAOYSA-N 1-(octyldisulfanyl)octane Chemical compound CCCCCCCCSSCCCCCCCC AROCLDYPZXMJPW-UHFFFAOYSA-N 0.000 description 1
- AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 1
- YKJFIERCXKKVFD-UHFFFAOYSA-N 1-[bis[di(propan-2-yloxy)phosphoryl]methylsulfanyl]-3-(trifluoromethyl)benzene Chemical compound CC(C)OP(=O)(OC(C)C)C(P(=O)(OC(C)C)OC(C)C)SC1=CC=CC(C(F)(F)F)=C1 YKJFIERCXKKVFD-UHFFFAOYSA-N 0.000 description 1
- STJWVOQLJPNAQL-UHFFFAOYSA-N 1-[diethoxyphosphorylmethyl(ethoxy)phosphoryl]oxyethane Chemical compound CCOP(=O)(OCC)CP(=O)(OCC)OCC STJWVOQLJPNAQL-UHFFFAOYSA-N 0.000 description 1
- TZOVOULUMXXLOJ-UHFFFAOYSA-N 1-methyl-4-[(4-methylphenyl)disulfanyl]benzene Chemical compound C1=CC(C)=CC=C1SSC1=CC=C(C)C=C1 TZOVOULUMXXLOJ-UHFFFAOYSA-N 0.000 description 1
- CRQZWCLWENPKLS-UHFFFAOYSA-N 1-nitro-4-[[4-nitro-3-(trifluoromethyl)phenyl]disulfanyl]-2-(trifluoromethyl)benzene Chemical compound C1=C(C(F)(F)F)C([N+](=O)[O-])=CC=C1SSC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 CRQZWCLWENPKLS-UHFFFAOYSA-N 0.000 description 1
- IRYOZLKMXHUGKP-UHFFFAOYSA-N 1-phosphonopentylphosphonic acid Chemical compound CCCCC(P(O)(O)=O)P(O)(O)=O IRYOZLKMXHUGKP-UHFFFAOYSA-N 0.000 description 1
- KYNFOMQIXZUKRK-UHFFFAOYSA-N 2,2'-dithiodiethanol Chemical compound OCCSSCCO KYNFOMQIXZUKRK-UHFFFAOYSA-N 0.000 description 1
- RNFJDJUURJAICM-UHFFFAOYSA-N 2,2,4,4,6,6-hexaphenoxy-1,3,5-triaza-2$l^{5},4$l^{5},6$l^{5}-triphosphacyclohexa-1,3,5-triene Chemical compound N=1P(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP=1(OC=1C=CC=CC=1)OC1=CC=CC=C1 RNFJDJUURJAICM-UHFFFAOYSA-N 0.000 description 1
- DTBTTYFYSGBQRB-UHFFFAOYSA-N 2-(3,4-dihydro-2h-pyran-2-yloxy)-3,4-dihydro-2h-pyran Chemical compound O1C=CCCC1OC1OC=CCC1 DTBTTYFYSGBQRB-UHFFFAOYSA-N 0.000 description 1
- 229940054266 2-mercaptobenzothiazole Drugs 0.000 description 1
- YOLFWWMPGNMXFI-UHFFFAOYSA-N 2-thiophen-2-yldisulfanylthiophene Chemical compound C=1C=CSC=1SSC1=CC=CS1 YOLFWWMPGNMXFI-UHFFFAOYSA-N 0.000 description 1
- HJZSMSCYTCYQAZ-UHFFFAOYSA-N 3-(2h-1,3-benzothiazol-3-yldisulfanyl)-2h-1,3-benzothiazole Chemical compound C1SC2=CC=CC=C2N1SSN1C2=CC=CC=C2SC1 HJZSMSCYTCYQAZ-UHFFFAOYSA-N 0.000 description 1
- HKHSJOKVSIIXGU-UHFFFAOYSA-N 3-(3-phenylpropyldisulfanyl)propylbenzene Chemical compound C=1C=CC=CC=1CCCSSCCCC1=CC=CC=C1 HKHSJOKVSIIXGU-UHFFFAOYSA-N 0.000 description 1
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 1
- SFZPBSAOSSHPHM-UHFFFAOYSA-N 3-[bis[di(propan-2-yloxy)phosphoryl]methylsulfanyl]propylbenzene Chemical compound CC(C)OP(=O)(OC(C)C)C(P(=O)(OC(C)C)OC(C)C)SCCCC1=CC=CC=C1 SFZPBSAOSSHPHM-UHFFFAOYSA-N 0.000 description 1
- QKGLUZCZUKTKCC-UHFFFAOYSA-N 3-bromopropylsulfanylbenzene Chemical compound BrCCCSC1=CC=CC=C1 QKGLUZCZUKTKCC-UHFFFAOYSA-N 0.000 description 1
- KNJDGNKHTMJKOQ-UHFFFAOYSA-N 4-[bis[di(propan-2-yloxy)phosphoryl]methylsulfanyl]-1-nitro-2-(trifluoromethyl)benzene Chemical compound CC(C)OP(=O)(OC(C)C)C(P(=O)(OC(C)C)OC(C)C)SC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 KNJDGNKHTMJKOQ-UHFFFAOYSA-N 0.000 description 1
- CVTGMRBTTHIUIC-UHFFFAOYSA-N 5-(4-fluorophenyl)sulfanylpentanoyl chloride Chemical compound FC1=CC=C(SCCCCC(Cl)=O)C=C1 CVTGMRBTTHIUIC-UHFFFAOYSA-N 0.000 description 1
- OKRUMSWHDWKGHA-UHFFFAOYSA-N 5-bromopentanoyl chloride Chemical compound ClC(=O)CCCCBr OKRUMSWHDWKGHA-UHFFFAOYSA-N 0.000 description 1
- NKYDKCVZNMNZCM-UHFFFAOYSA-N 5-chloro-3h-1,3-benzothiazole-2-thione Chemical compound ClC1=CC=C2SC(S)=NC2=C1 NKYDKCVZNMNZCM-UHFFFAOYSA-N 0.000 description 1
- BZUZJVLPAKJIBP-UHFFFAOYSA-N 6-amino-1,2-dihydropyrazolo[3,4-d]pyrimidin-4-one Chemical compound O=C1N=C(N)N=C2NNC=C21 BZUZJVLPAKJIBP-UHFFFAOYSA-N 0.000 description 1
- HBPVGJGBRWIVSX-UHFFFAOYSA-N 6-bromohexanoyl chloride Chemical group ClC(=O)CCCCCBr HBPVGJGBRWIVSX-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- KNJBKTLHWDZJID-UHFFFAOYSA-N CC(C)OP(=O)(C(P(=O)(OC(C)C)OC(C)C)SC(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)OC(C)C Chemical compound CC(C)OP(=O)(C(P(=O)(OC(C)C)OC(C)C)SC(C(C(C(C(C(F)(F)F)(F)F)(F)F)(F)F)(F)F)(F)F)OC(C)C KNJBKTLHWDZJID-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NMQISEPYZAMNQY-UHFFFAOYSA-N [2-hydroxyethylsulfanyl(phosphono)methyl]phosphonic acid Chemical compound OCCSC(P(O)(O)=O)P(O)(O)=O NMQISEPYZAMNQY-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- 229940042400 direct acting antivirals phosphonic acid derivative Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000003063 flame retardant Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- OSZKBWPMEPEYFU-UHFFFAOYSA-N methyl 3-[(3-methoxy-3-oxopropyl)disulfanyl]propanoate Chemical compound COC(=O)CCSSCCC(=O)OC OSZKBWPMEPEYFU-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003007 phosphonic acid derivatives Chemical class 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- ABARMQVSPZAYRI-UHFFFAOYSA-N s-(4-bromobutyl) ethanethioate Chemical compound CC(=O)SCCCCBr ABARMQVSPZAYRI-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing 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)]
-
- 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
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
- C07F9/6539—Five-membered rings
- C07F9/6541—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]
-
- 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
- C07F9/3865—Polyphosphonic acids containing sulfur substituents
-
- 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
- C07F9/4043—Esters of poly(thio)phosphonic acids containing sulfur substituents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- 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
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
- C07F9/65068—Five-membered rings having the nitrogen atoms in positions 1 and 3 condensed with carbocyclic rings or carbocyclic ring systems
-
- 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
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Pain & Pain Management (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8213250A FR2531088B1 (fr) | 1982-07-29 | 1982-07-29 | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
| FR8213250 | 1982-07-29 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI832758A0 FI832758A0 (fi) | 1983-07-29 |
| FI832758L FI832758L (fi) | 1984-01-30 |
| FI75830B FI75830B (fi) | 1988-04-29 |
| FI75830C true FI75830C (fi) | 1988-08-08 |
Family
ID=9276447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI832758A FI75830C (fi) | 1982-07-29 | 1983-07-29 | Foerfarande foer framstaellning av terapeutiskt anvaendbara metylendifosfonsyraderivat. |
Country Status (35)
Families Citing this family (105)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2558837B1 (fr) * | 1984-01-26 | 1986-06-27 | Sanofi Sa | Derives de l'acide methylenediphosphonique, procede d'obtention et medicaments antirhumatismaux les contenant |
| IL77243A (en) * | 1984-12-21 | 1996-11-14 | Procter & Gamble | Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds |
| PH27078A (en) * | 1984-12-21 | 1993-02-01 | Procter & Gamble | Pharmaceutical compositions containing geminal diphosphonates |
| US5641762A (en) * | 1985-05-02 | 1997-06-24 | Research Corporation Technologies, Inc. | Bone targeted inhibitors of carbonic anhydrase |
| US4761406A (en) * | 1985-06-06 | 1988-08-02 | The Procter & Gamble Company | Regimen for treating osteoporosis |
| US4902679A (en) * | 1985-12-13 | 1990-02-20 | Norwich Eaton Pharmaceuticals, Inc. | Methods of treating diseases with certain geminal diphosphonates |
| ES2039237T3 (es) * | 1986-04-24 | 1993-09-16 | Fujisawa Pharmaceutical Co., Ltd. | Procedimiento para preparar nuevos compuestos de acido difosfonico. |
| IL84731A0 (en) * | 1986-12-19 | 1988-05-31 | Norwich Eaton Pharma | Heterocycle-substituted diphosphonic acids and salts and esters and pharmaceutical compositions containing them |
| KR880011136A (ko) * | 1987-03-11 | 1988-10-26 | 모리오까 시게오 | 아졸- 아미노메틸렌 비스포스폰산 유도체 |
| IL86951A (en) * | 1987-07-06 | 1996-07-23 | Procter & Gamble Pharma | Methylene phosphonoalkylphosphinates and pharmaceutical preparations containing them |
| DE3805663A1 (de) * | 1988-02-24 | 1989-09-07 | Henkel Kgaa | Oxaalkanpolyphosphonsaeuren, ihre verwendung als thresholder sowie diese verbindungen enthaltende, komplexierend wirkende zusammensetzungen |
| CH675422A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1988-03-31 | 1990-09-28 | Symphar Sa | |
| FR2629716B1 (fr) * | 1988-04-07 | 1991-07-19 | Sanofi Sa | Composition pharmaceutique pour administration orale a base d'un derive d'acide diphosphonique |
| DE3822650A1 (de) * | 1988-07-05 | 1990-02-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| RU2091311C1 (ru) * | 1988-11-01 | 1997-09-27 | Арч Дивелопмент Корпорейшн | Способ извлечения ионов металла |
| US5154843A (en) * | 1989-02-08 | 1992-10-13 | The Lubrizol Corporation | Hydroxyalkane phosphonic acids and derivatives thereof and lubricants containing the same |
| PH26923A (en) * | 1989-03-08 | 1992-12-03 | Ciba Geigy | N-substituted amino alkanediphosphonic acids |
| US5220021A (en) * | 1989-04-03 | 1993-06-15 | The Upjohn Company | Geminal bisphosphonic acids and derivatives as anti-arthritic agents |
| JPH0377894A (ja) * | 1989-08-18 | 1991-04-03 | Toray Ind Inc | メチレンジホスホン酸化合物 |
| EP0416689B1 (en) * | 1989-09-06 | 1995-11-29 | Merck & Co. Inc. | Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors |
| EP0438375B1 (de) * | 1990-01-18 | 1995-12-27 | Ciba-Geigy Ag | Phoshponsäure- und Thionophosphonsäure-Derivate |
| IE912115A1 (en) * | 1990-06-25 | 1992-01-01 | Takeda Chemical Industries Ltd | Bisphosphonic acid derivatives, their production and use |
| WO1992003451A1 (en) * | 1990-08-21 | 1992-03-05 | The Upjohn Company | Bisphosphonic acid derivatives as anti-arthritic agents |
| WO1992010504A2 (en) * | 1990-12-07 | 1992-06-25 | The Upjohn Company | Phosphonic acid derivatives useful as antiinflammatory agents |
| EP0491374B1 (en) * | 1990-12-19 | 1996-01-31 | Takeda Chemical Industries, Ltd. | Bisphosphonic acid derivatives, their production and use |
| 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 |
| EP0590009B1 (en) * | 1991-06-19 | 1998-03-18 | PHARMACIA & UPJOHN COMPANY | Dialkyl (dialkoxyphosphinyl)methyl phosphates as anti-inflammatory agents |
| EP0521622B1 (en) * | 1991-07-03 | 1997-08-13 | PHARMACIA & UPJOHN COMPANY | Pyrazolopyrimidine and pyrimidinyl bisphosphonic esters as anti-inflammatories |
| DK0594857T3 (da) * | 1991-09-05 | 1998-10-07 | Toray Industries | Methandiphosphonsyrederivat, fremstilling deraf ogmedicinsk anvendelse deraf |
| EP0541037A3 (en) * | 1991-11-06 | 1997-02-26 | Takeda Chemical Industries Ltd | Squalene synthetase inhibitory composition and use thereof |
| JPH06172372A (ja) * | 1991-11-06 | 1994-06-21 | Takeda Chem Ind Ltd | スクアレン合成酵素阻害剤およびその用途 |
| EP0642521A1 (en) * | 1992-05-29 | 1995-03-15 | Procter & Gamble Pharmaceuticals | Thio-substituted nitrogen-containing heterocyclic phosphonate compounds for treating abnormal calcium and phosphate metabolism |
| EP0646119B1 (en) * | 1992-05-29 | 1998-07-15 | PROCTER & GAMBLE PHARMACEUTICALS, INC. | Quaternary nitrogen-containing phosphonate compounds for treating abnormal calcium and phosphate metabolism as well as dental calculus and plaque |
| US5391743A (en) * | 1992-05-29 | 1995-02-21 | Procter & Gamble Pharmaceuticals, Inc. | Quaternary nitrogen-containing phosphonate compounds, pharmaceutical compositions, and methods of treating abnormal calcium and phosphate metabolism and methods of treating and preventing dental calculus and plaque |
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1982
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1983
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1984
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1985
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1986
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