HU184813B - Process for preparing diphosphonate derivatives - Google Patents
Process for preparing diphosphonate derivatives Download PDFInfo
- Publication number
- HU184813B HU184813B HU199880A HU199880A HU184813B HU 184813 B HU184813 B HU 184813B HU 199880 A HU199880 A HU 199880A HU 199880 A HU199880 A HU 199880A HU 184813 B HU184813 B HU 184813B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- phosphonate
- preparation
- dimethyl
- diphosphonate
- Prior art date
Links
- XQRLCLUYWUNEEH-UHFFFAOYSA-L diphosphonate(2-) Chemical class [O-]P(=O)OP([O-])=O XQRLCLUYWUNEEH-UHFFFAOYSA-L 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- 238000000034 method Methods 0.000 claims abstract description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 238000002360 preparation method Methods 0.000 claims abstract description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- -1 acyl phosphonate Chemical compound 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 claims description 10
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
- 239000007858 starting material Substances 0.000 claims description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 7
- 150000002431 hydrogen Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 229910052736 halogen Chemical group 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 6
- 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical group OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 claims description 3
- ZJXZSIYSNXKHEA-UHFFFAOYSA-N ethyl dihydrogen phosphate Chemical compound CCOP(O)(O)=O ZJXZSIYSNXKHEA-UHFFFAOYSA-N 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 3
- CBHVSJPJAISNNY-UHFFFAOYSA-N (4-chlorophenyl)methyl dihydrogen phosphate Chemical compound OP(O)(=O)OCC1=CC=C(Cl)C=C1 CBHVSJPJAISNNY-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- TUKCAVDKGXMEKW-UHFFFAOYSA-N (4-chlorophenyl)-dimethoxyphosphorylmethanone Chemical compound COP(=O)(OC)C(=O)C1=CC=C(Cl)C=C1 TUKCAVDKGXMEKW-UHFFFAOYSA-N 0.000 claims 2
- XMZQWZJMTBCUFT-UHFFFAOYSA-N 3-bromopropylbenzene Chemical compound BrCCCC1=CC=CC=C1 XMZQWZJMTBCUFT-UHFFFAOYSA-N 0.000 claims 1
- QUTJZXHYWIELGA-UHFFFAOYSA-N COP(=O)OP(O)=O Chemical compound COP(=O)OP(O)=O QUTJZXHYWIELGA-UHFFFAOYSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 76
- 235000012000 cholesterol Nutrition 0.000 abstract description 35
- 230000000694 effects Effects 0.000 abstract description 15
- 238000011282 treatment Methods 0.000 abstract description 13
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 5
- 210000004369 blood Anatomy 0.000 abstract description 5
- 239000008280 blood Substances 0.000 abstract description 5
- 230000000144 pharmacologic effect Effects 0.000 abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 239000002253 acid Substances 0.000 description 19
- 239000000203 mixture Substances 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 241000700159 Rattus Species 0.000 description 15
- 125000003118 aryl group Chemical group 0.000 description 15
- 210000002966 serum Anatomy 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 13
- 150000002632 lipids Chemical class 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 12
- 238000002329 infrared spectrum Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 108010010234 HDL Lipoproteins Proteins 0.000 description 11
- 102000015779 HDL Lipoproteins Human genes 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 201000001320 Atherosclerosis Diseases 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000004060 metabolic process Effects 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000009102 absorption Effects 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 125000001931 aliphatic group Chemical group 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 235000019197 fats Nutrition 0.000 description 7
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical group [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 239000012062 aqueous buffer Substances 0.000 description 5
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000011835 investigation Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 150000003626 triacylglycerols Chemical class 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 229960001214 clofibrate Drugs 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 235000021588 free fatty acids Nutrition 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 4
- 150000003904 phospholipids Chemical class 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 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 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- DMMRXPDQKOIOEA-UHFFFAOYSA-N OOP(=O)OP(O)=O Chemical class OOP(=O)OP(O)=O DMMRXPDQKOIOEA-UHFFFAOYSA-N 0.000 description 3
- VNQABZCSYCTZMS-UHFFFAOYSA-N Orthoform Chemical compound COC(=O)C1=CC=C(O)C(N)=C1 VNQABZCSYCTZMS-UHFFFAOYSA-N 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000489 anti-atherogenic effect Effects 0.000 description 3
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- 210000000709 aorta Anatomy 0.000 description 3
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- 230000015572 biosynthetic process Effects 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
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- 230000000668 effect on calcium Effects 0.000 description 3
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- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- OODRWLGKUBMFLZ-UHFFFAOYSA-N 2-(4-chlorophenoxy)-2-methylpropanoyl chloride Chemical compound ClC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 OODRWLGKUBMFLZ-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
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- 150000001793 charged compounds Chemical class 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
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- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
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- 235000019359 magnesium stearate Nutrition 0.000 description 2
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
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- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
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- INKXYFUMUBZQKV-UHFFFAOYSA-N (2,3,4-triethylphenyl) dihydrogen phosphate Chemical compound CCC1=CC=C(OP(O)(O)=O)C(CC)=C1CC INKXYFUMUBZQKV-UHFFFAOYSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- HVYWMOMLDIMFJA-VEIPTCAHSA-N (3r,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-ol Chemical compound C1C=C2C[C@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-VEIPTCAHSA-N 0.000 description 1
- DGXVNNDLAIJHRC-UHFFFAOYSA-N (4-chlorobenzoyl)phosphonic acid Chemical compound OP(O)(=O)C(=O)C1=CC=C(Cl)C=C1 DGXVNNDLAIJHRC-UHFFFAOYSA-N 0.000 description 1
- GXZVJBYYRGAQQV-UHFFFAOYSA-N (4-chlorophenyl)-(4-dimethoxyphosphorylcarbonylphenyl)methanone Chemical compound C1=CC(C(=O)P(=O)(OC)OC)=CC=C1C(=O)C1=CC=C(Cl)C=C1 GXZVJBYYRGAQQV-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- DNKCHGSCDQXXLE-UHFFFAOYSA-N 2-(4-chlorophenoxy)-1-dimethoxyphosphoryl-2-methylpropan-1-one Chemical compound COP(=O)(OC)C(=O)C(C)(C)OC1=CC=C(Cl)C=C1 DNKCHGSCDQXXLE-UHFFFAOYSA-N 0.000 description 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7933157A GB2043072B (en) | 1979-02-13 | 1979-09-25 | Diphosphonate compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU184813B true HU184813B (en) | 1984-10-29 |
Family
ID=10508049
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU199880A HU184813B (en) | 1979-09-25 | 1980-08-11 | Process for preparing diphosphonate derivatives |
Country Status (8)
| Country | Link |
|---|---|
| DD (1) | DD154490A5 (cg-RX-API-DMAC10.html) |
| FI (1) | FI68243C (cg-RX-API-DMAC10.html) |
| GR (1) | GR69713B (cg-RX-API-DMAC10.html) |
| HU (1) | HU184813B (cg-RX-API-DMAC10.html) |
| NO (1) | NO158257C (cg-RX-API-DMAC10.html) |
| NZ (1) | NZ194383A (cg-RX-API-DMAC10.html) |
| PL (1) | PL123831B1 (cg-RX-API-DMAC10.html) |
| SU (1) | SU1207397A3 (cg-RX-API-DMAC10.html) |
-
1980
- 1980-07-18 NZ NZ19438380A patent/NZ194383A/xx unknown
- 1980-07-19 GR GR62502A patent/GR69713B/el unknown
- 1980-07-30 NO NO802285A patent/NO158257C/no unknown
- 1980-08-06 FI FI802472A patent/FI68243C/fi not_active IP Right Cessation
- 1980-08-11 SU SU802962255A patent/SU1207397A3/ru active
- 1980-08-11 HU HU199880A patent/HU184813B/hu unknown
- 1980-08-11 DD DD22324680A patent/DD154490A5/de unknown
- 1980-08-12 PL PL22619680A patent/PL123831B1/pl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL226196A1 (cg-RX-API-DMAC10.html) | 1981-05-08 |
| NO158257C (no) | 1988-08-10 |
| GR69713B (cg-RX-API-DMAC10.html) | 1982-07-09 |
| NZ194383A (en) | 1982-05-31 |
| SU1207397A3 (ru) | 1986-01-23 |
| DD154490A5 (de) | 1982-03-24 |
| FI68243C (fi) | 1985-08-12 |
| NO802285L (no) | 1981-03-26 |
| FI802472A7 (fi) | 1981-03-26 |
| PL123831B1 (en) | 1982-11-30 |
| NO158257B (no) | 1988-05-02 |
| FI68243B (fi) | 1985-04-30 |
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