IL87037A - History of 3-dimethyl-4-fluoromvolonic acid, process for making and using pharmaceutical preparations based on these - Google Patents

History of 3-dimethyl-4-fluoromvolonic acid, process for making and using pharmaceutical preparations based on these

Info

Publication number: IL87037A
Authority: IL; Israel
Prior art keywords: formula; alkyl; carbon atoms; halogen; phenyl
Prior art date: 1987-07-10

Application number

IL8703788A

Other languages

English (en)

Hebrew (he)

Other versions

IL87037A0 (en

Original Assignee

Hoechst Ag

Priority date (The priority date 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 date listed.)

1987-07-10

Filing date

1988-07-08

Publication date

1995-03-30

1988-07-08 Application filed by Hoechst Ag filed Critical Hoechst Ag

1988-12-30 Publication of IL87037A0 publication Critical patent/IL87037A0/xx

1995-03-30 Publication of IL87037A publication Critical patent/IL87037A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 105
238000000034 method Methods 0.000 title claims abstract description 44
239000002253 acid Substances 0.000 title claims abstract description 31
238000002360 preparation method Methods 0.000 title claims abstract description 23
230000008569 process Effects 0.000 title claims abstract description 23
239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 6
229940127557 pharmaceutical product Drugs 0.000 title claims abstract description 6
MMCOUVMKNAHQOY-UHFFFAOYSA-N carbonoperoxoic acid Chemical class OOC(O)=O MMCOUVMKNAHQOY-UHFFFAOYSA-N 0.000 claims abstract description 5
-1 phenoxy, benzyloxy Chemical group 0.000 claims description 74
125000004432 carbon atom Chemical group C* 0.000 claims description 70
229910052736 halogen Inorganic materials 0.000 claims description 48
150000002367 halogens Chemical class 0.000 claims description 48
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
125000000217 alkyl group Chemical group 0.000 claims description 37
229910052739 hydrogen Inorganic materials 0.000 claims description 30
150000002596 lactones Chemical class 0.000 claims description 29
125000003545 alkoxy group Chemical group 0.000 claims description 24
239000001257 hydrogen Substances 0.000 claims description 22
150000002148 esters Chemical class 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 18
125000000753 cycloalkyl group Chemical group 0.000 claims description 17
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 12
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 11
125000006239 protecting group Chemical group 0.000 claims description 11
229910052731 fluorine Inorganic materials 0.000 claims description 10
125000001153 fluoro group Chemical group F* 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
150000004714 phosphonium salts Chemical class 0.000 claims description 9
150000007513 acids Chemical class 0.000 claims description 8
150000002373 hemiacetals Chemical class 0.000 claims description 8
JCYWCSGERIELPG-UHFFFAOYSA-N imes Chemical class CC1=CC(C)=CC(C)=C1N1C=CN(C=2C(=CC(C)=CC=2C)C)[C]1 JCYWCSGERIELPG-UHFFFAOYSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
230000003647 oxidation Effects 0.000 claims description 7
238000007254 oxidation reaction Methods 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 6
239000011593 sulfur Substances 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
238000007239 Wittig reaction Methods 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
150000002170 ethers Chemical class 0.000 claims description 5
238000005984 hydrogenation reaction Methods 0.000 claims description 5
238000005903 acid hydrolysis reaction Methods 0.000 claims description 4
150000003934 aromatic aldehydes Chemical class 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
150000001261 hydroxy acids Chemical class 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
150000001241 acetals Chemical group 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
150000001735 carboxylic acids Chemical class 0.000 claims description 3
238000011321 prophylaxis Methods 0.000 claims description 3
239000004215 Carbon black (E152) Substances 0.000 claims description 2
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical compound [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 2
125000003302 alkenyloxy group Chemical group 0.000 claims description 2
229930195733 hydrocarbon Natural products 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
HXELGNKCCDGMMN-UHFFFAOYSA-N [F].[Cl] Chemical compound [F].[Cl] HXELGNKCCDGMMN-UHFFFAOYSA-N 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 5
239000003814 drug Substances 0.000 abstract description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 85
239000000203 mixture Substances 0.000 description 53
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 50
239000000047 product Substances 0.000 description 42
239000000243 solution Substances 0.000 description 40
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
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 description 30
238000005160 1H NMR spectroscopy Methods 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
238000004809 thin layer chromatography Methods 0.000 description 20
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
125000001424 substituent group Chemical group 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
238000004587 chromatography analysis Methods 0.000 description 16
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 16
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
238000002844 melting Methods 0.000 description 15
230000008018 melting Effects 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
239000002243 precursor Substances 0.000 description 15
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 14
235000012000 cholesterol Nutrition 0.000 description 14
239000003921 oil Substances 0.000 description 14
235000019198 oils Nutrition 0.000 description 14
210000004940 nucleus Anatomy 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
238000007792 addition Methods 0.000 description 11
239000000460 chlorine Substances 0.000 description 11
229910052801 chlorine Inorganic materials 0.000 description 11
229940060038 chlorine Drugs 0.000 description 11
235000017168 chlorine Nutrition 0.000 description 11
150000002431 hydrogen Chemical class 0.000 description 11
238000012360 testing method Methods 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
239000012230 colorless oil Substances 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
229960001866 silicon dioxide Drugs 0.000 description 10
239000002904 solvent Substances 0.000 description 10
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 9
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 9
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
239000007787 solid Substances 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 8
NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical class F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 7
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 7
239000011737 fluorine Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
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 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
150000001299 aldehydes Chemical class 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
238000001816 cooling Methods 0.000 description 6
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
230000009467 reduction Effects 0.000 description 6
239000011734 sodium Substances 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
239000002585 base Substances 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
229940088598 enzyme Drugs 0.000 description 5
229930182470 glycoside Natural products 0.000 description 5
150000002338 glycosides Chemical class 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
229910052740 iodine Inorganic materials 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
101150041968 CDC13 gene Proteins 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
238000004821 distillation Methods 0.000 description 4
230000007717 exclusion Effects 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
239000001282 iso-butane Substances 0.000 description 4
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000000725 suspension Substances 0.000 description 4
HEVMDQBCAHEHDY-UHFFFAOYSA-N (Dimethoxymethyl)benzene Chemical compound COC(OC)C1=CC=CC=C1 HEVMDQBCAHEHDY-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
150000001336 alkenes Chemical class 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
208000037516 chromosome inversion disease Diseases 0.000 description 3
239000013078 crystal Substances 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000010828 elution Methods 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
230000000055 hyoplipidemic effect Effects 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
239000011630 iodine Substances 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
LSMAIBOZUPTNBR-UHFFFAOYSA-N phosphanium;iodide Chemical compound [PH4+].[I-] LSMAIBOZUPTNBR-UHFFFAOYSA-N 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
150000003254 radicals Chemical class 0.000 description 3
150000003333 secondary alcohols Chemical group 0.000 description 3
235000009518 sodium iodide Nutrition 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000011282 treatment Methods 0.000 description 3
CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 2
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
238000004293 19F NMR spectroscopy Methods 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 2
101150072844 APOM gene Proteins 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 description 2
238000005361 D2 NMR spectroscopy Methods 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
238000005684 Liebig rearrangement reaction Methods 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
102000004316 Oxidoreductases Human genes 0.000 description 2
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229910052744 lithium Inorganic materials 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
210000001853 liver microsome Anatomy 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
LWLPYZUDBNFNAH-UHFFFAOYSA-M magnesium;butane;bromide Chemical compound [Mg+2].[Br-].CCC[CH2-] LWLPYZUDBNFNAH-UHFFFAOYSA-M 0.000 description 1
LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
VKTOBGBZBCELGC-UHFFFAOYSA-M methyl(triphenoxy)phosphanium;iodide Chemical compound [I-].C=1C=CC=CC=1O[P+](OC=1C=CC=CC=1)(C)OC1=CC=CC=C1 VKTOBGBZBCELGC-UHFFFAOYSA-M 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
230000036285 pathological change Effects 0.000 description 1
231100000915 pathological change Toxicity 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
RZGQJANKGMICOP-UHFFFAOYSA-N phenyldiazene Chemical compound N=NC1=CC=CC=C1 RZGQJANKGMICOP-UHFFFAOYSA-N 0.000 description 1
VBQCHPIMZGQLAZ-UHFFFAOYSA-N phosphorane Chemical class [PH5] VBQCHPIMZGQLAZ-UHFFFAOYSA-N 0.000 description 1
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical class OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
230000036515 potency Effects 0.000 description 1
238000000039 preparative column chromatography Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
230000036647 reaction Effects 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001172 regenerating effect Effects 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
230000033764 rhythmic process Effects 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
238000012353 t test Methods 0.000 description 1
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
229930192474 thiophene Natural products 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
229960002622 triacetin Drugs 0.000 description 1
VTDQBKLDBJKTMS-UHFFFAOYSA-N trihydrate;hydrofluoride Chemical compound O.O.O.F VTDQBKLDBJKTMS-UHFFFAOYSA-N 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
239000011701 zinc Substances 0.000 description 1
DJWUNCQRNNEAKC-UHFFFAOYSA-L zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/55—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/72—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages

IL8703788A 1987-07-10 1988-07-08 History of 3-dimethyl-4-fluoromvolonic acid, process for making and using pharmaceutical preparations based on these IL87037A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19873722809 DE3722809A1 (de)	1987-07-10	1987-07-10	3-desmethyl-4-fluor-mevalonsaeurederivate, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen, ihre verwendung und zwischenprodukte

Publications (2)

Publication Number	Publication Date
IL87037A0 IL87037A0 (en)	1988-12-30
IL87037A true IL87037A (en)	1995-03-30

Family

ID=6331294

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL8703788A IL87037A (en)	1987-07-10	1988-07-08	History of 3-dimethyl-4-fluoromvolonic acid, process for making and using pharmaceutical preparations based on these

Country Status (19)

Country	Link
US (1)	US4898868A (fi)
EP (1)	EP0302253B1 (fi)
JP (1)	JPS6438086A (fi)
KR (1)	KR890002084A (fi)
AT (1)	ATE87916T1 (fi)
AU (1)	AU612665B2 (fi)
CA (1)	CA1319363C (fi)
DE (2)	DE3722809A1 (fi)
DK (1)	DK383388A (fi)
ES (1)	ES2054738T3 (fi)
FI (1)	FI883250A (fi)
HU (1)	HU205071B (fi)
IE (1)	IE62528B1 (fi)
IL (1)	IL87037A (fi)
NO (1)	NO172537C (fi)
NZ (1)	NZ225345A (fi)
PH (1)	PH26770A (fi)
PT (1)	PT87930B (fi)
ZA (1)	ZA884922B (fi)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4681893A (en) *	1986-05-30	1987-07-21	Warner-Lambert Company	Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
DE3826814A1 (de) *	1988-08-06	1990-02-08	Hoechst Ag	Neue 6-fluor-3,5-dihydroxycarbonsaeuren und deren derivate, verfahren zu ihrer herstellung, ihre verwendung als arzneimittel, pharmazeutische praeparate und zwischenprodukte
FI94339C (fi) *	1989-07-21	1995-08-25	Warner Lambert Co	Menetelmä farmaseuttisesti käyttökelpoisen /R-(R,R)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
DE3925636A1 (de) *	1989-08-03	1991-02-07	Bayer Ag	Imino-substituierte pyridine
US5093363A (en) *	1989-08-22	1992-03-03	Shionogi & Co., Ltd.	2,4,6-substituted phenol derivatives
DE3929913A1 (de) *	1989-09-08	1991-04-04	Hoechst Ag	4-hydroxytetrahydropyran-2-one sowie die entsprechenden dihydroxycarbonsaeurederivate, salze und ester, verfahren zu ihrer herstellung, ihre verwendung als arzneimittel, pharmazeutische praeparate sowie vorprodukte
IT1237792B (it) *	1989-12-21	1993-06-17	Zambon Spa	Composti attivi come inibitori dell'enzima hmg-coa reduttasi
US5149834A (en) *	1990-03-07	1992-09-22	Fujirebio Inc.	4-hydroxytetrahydropyran-2-one derivatives
GB9013699D0 (en) *	1990-06-20	1990-08-08	Rhone Poulenc Sante	New process
CN102086184A (zh) *	2011-03-03	2011-06-08	上海应用技术学院	5位氟取代的4-羟基-3,4,5,6-四氢-2h-吡喃-2-酮类化合物及其制备方法
CN102153463A (zh) *	2011-03-03	2011-08-17	上海应用技术学院	4位氟取代的3,5-二羟基羧酸化合物及其制备方法
CN104262248A (zh) *	2014-09-03	2015-01-07	上海应用技术学院	5位取代的4,4-二氟-3,5-二羟基羧酸及其金属盐的制备方法
CN104351190A (zh) *	2014-10-23	2015-02-18	上海应用技术学院	4位偕二氟取代的3,5二羟基羧酸化合物在害虫防治中的应用

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS53147073A (en) *	1977-05-24	1978-12-21	Sankyo Co Ltd	Mevalonolactone derivatives
US4562258A (en) *	1982-02-04	1985-12-31	Findlay John W A	6-[3-Amino-1-(4-tolyl)prop-1E-enyl]pyridine-2-carboxylic acid derivatives having antihistaminic activity
US4647576A (en) *	1984-09-24	1987-03-03	Warner-Lambert Company	Trans-6-[2-(substitutedpyrrol-1-yl)alkyl]-pyran-2-one inhibitors of cholesterol synthesis
DE3530797A1 (de) *	1985-08-29	1987-03-05	Hoechst Ag	3-desmethyl-mevalonsaeurederivate, verfahren zu ihrer herstellung pharmazeutische praeparate auf basis dieser verbindungen, ihre verwendung sowie zwischenprodukte
EP0216127B1 (de) *	1985-08-29	1990-09-26	Hoechst Aktiengesellschaft	6-Phenoxymethyl-4-hydroxytetrahydropyran-2-one, Verfahren zu ihrer Herstellung, ihre Verwendung als Arzneimittel, pharmazeutische Präparate und Zwischenprodukte
EP0217092B1 (de) *	1985-08-29	1990-03-28	Hoechst Aktiengesellschaft	3-Desmethyl-mevalonsäurederivate, Verfahren zu ihrer Herstellung, pharmazeutische Präparate auf Basis dieser Verbindungen, ihre Verwendung sowie Zwischenprodukte
DE3530798A1 (de) *	1985-08-29	1987-03-05	Hoechst Ag	6-phenoxymethyl-4-hydroxytetrahydropyran-2-one, verfahren zu ihrer herstellung, ihre verwendung als arzneimittel, pharmazeutische praeparate und zwischenprodukte
US4812460A (en) *	1986-03-25	1989-03-14	Boehringer Ingelheim Pharmaceutical, Inc.	3-[2-(3',5'-di-t-butyl-4'-hydroxyphenyl)ethenyl]pyridine
DE3632893A1 (de) *	1986-09-27	1988-04-07	Hoechst Ag	4-(r)-hydroxy-6(s)-arylthiomethyl-tetrahydropyran-2-one, deren entsprechende sulfoxide und sulfone, verfahren zu ihrer herstellung, ihre verwendung als arzneimittel, pharmazeutische praeparate und zwischenprodukte
PT87929B (pt) *	1987-07-10	1995-03-01	Hoechst Ag	Processo para a preparacao de derivados de acido 3-desmetil-mevalonico e de composicoes farmaceuticas que os contem
DE3826814A1 (de) *	1988-08-06	1990-02-08	Hoechst Ag	Neue 6-fluor-3,5-dihydroxycarbonsaeuren und deren derivate, verfahren zu ihrer herstellung, ihre verwendung als arzneimittel, pharmazeutische praeparate und zwischenprodukte
DE3832570A1 (de) *	1988-09-24	1990-03-29	Hoechst Ag	7-substituierte derivate der 3,5-dihydroxyhept-6-insaeure, verfahren zur ihrer herstellung, ihre verwendung als arzneimittel, sowie zwischenprodukte
US6622253B2 (en) *	2001-08-02	2003-09-16	Scientific-Atlanta, Inc.	Controlling processor clock rate based on thread priority

1987
- 1987-07-10 DE DE19873722809 patent/DE3722809A1/de not_active Withdrawn
1988
- 1988-07-07 ES ES88110834T patent/ES2054738T3/es not_active Expired - Lifetime
- 1988-07-07 EP EP88110834A patent/EP0302253B1/de not_active Expired - Lifetime
- 1988-07-07 PT PT87930A patent/PT87930B/pt not_active IP Right Cessation
- 1988-07-07 FI FI883250A patent/FI883250A/fi not_active Application Discontinuation
- 1988-07-07 DE DE8888110834T patent/DE3880041D1/de not_active Expired - Fee Related
- 1988-07-07 AT AT88110834T patent/ATE87916T1/de not_active IP Right Cessation
- 1988-07-08 PH PH37203A patent/PH26770A/en unknown
- 1988-07-08 DK DK383388A patent/DK383388A/da not_active Application Discontinuation
- 1988-07-08 US US07/216,752 patent/US4898868A/en not_active Expired - Fee Related
- 1988-07-08 NZ NZ225345A patent/NZ225345A/en unknown
- 1988-07-08 IL IL8703788A patent/IL87037A/en not_active IP Right Cessation
- 1988-07-08 CA CA000571559A patent/CA1319363C/en not_active Expired - Fee Related
- 1988-07-08 JP JP63169164A patent/JPS6438086A/ja active Pending
- 1988-07-08 IE IE210088A patent/IE62528B1/en not_active IP Right Cessation
- 1988-07-08 HU HU883595A patent/HU205071B/hu not_active IP Right Cessation
- 1988-07-08 ZA ZA884922A patent/ZA884922B/xx unknown
- 1988-07-08 NO NO883074A patent/NO172537C/no unknown
- 1988-07-08 AU AU18883/88A patent/AU612665B2/en not_active Ceased
- 1988-07-09 KR KR1019880008549A patent/KR890002084A/ko not_active Application Discontinuation

Also Published As

Publication number	Publication date
AU1888388A (en)	1989-01-12
NO883074D0 (no)	1988-07-08
NO172537C (no)	1993-08-04
ES2054738T3 (es)	1994-08-16
NO172537B (no)	1993-04-26
NZ225345A (en)	1991-05-28
EP0302253A1 (de)	1989-02-08
DK383388A (da)	1989-01-11
PH26770A (en)	1992-09-28
HUT51221A (en)	1990-04-28
JPS6438086A (en)	1989-02-08
CA1319363C (en)	1993-06-22
PT87930A (pt)	1989-06-30
FI883250A (fi)	1989-01-11
NO883074L (no)	1989-01-11
AU612665B2 (en)	1991-07-18
ZA884922B (en)	1989-01-17
PT87930B (pt)	1995-03-01
US4898868A (en)	1990-02-06
ATE87916T1 (de)	1993-04-15
EP0302253B1 (de)	1993-04-07
IE62528B1 (en)	1995-02-08
KR890002084A (ko)	1989-04-08
IL87037A0 (en)	1988-12-30
DE3722809A1 (de)	1989-01-19
DE3880041D1 (de)	1993-05-13
DK383388D0 (da)	1988-07-08
IE882100L (en)	1989-01-10
HU205071B (en)	1992-03-30
FI883250A0 (fi)	1988-07-07

Legal Events

Date	Code	Title	Description
1999-07-14	RH	Patent void

Publication	Publication Date	Title
TWI466877B (zh)	2015-01-01	雙環式化合物及其醫藥用途
IL87037A (en)	1995-03-30	History of 3-dimethyl-4-fluoromvolonic acid, process for making and using pharmaceutical preparations based on these
HUT71558A (en)	1995-12-28	Pyran-2-one- and 5,6-dihydro-pyran-2-one derivatives for treating hiv- and other retrovirus infections
JPH01199945A (ja)	1989-08-11	光学活性３‐デメチルメバロン酸誘導体の製法
AU2010211991B2 (en)	2013-09-19	Process for the synthesis of Cleistanthin
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