NL8801330A - Fosfor bevattende remmers van hmg-coa reductase, nieuwe tussenprodukten en werkwijze voor het toepassen daarvan. - Google Patents

Fosfor bevattende remmers van hmg-coa reductase, nieuwe tussenprodukten en werkwijze voor het toepassen daarvan. Download PDF

Info

Publication number: NL8801330A
Authority: NL; Netherlands
Prior art keywords: formula; lower alkyl; phenyl; group; fluoro
Prior art date: 1987-05-22

Application number

NL8801330A

Other languages

English (en)

Dutch (nl)

Original Assignee

Squibb & Sons Inc

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.)

1987-05-22

Filing date

1988-05-24

Publication date

1988-12-16

1988-05-24 Application filed by Squibb & Sons Inc filed Critical Squibb & Sons Inc

1988-12-16 Publication of NL8801330A publication Critical patent/NL8801330A/nl

Links

238000000034 method Methods 0.000 title description 7
239000000543 intermediate Substances 0.000 title description 3
229940121710 HMGCoA reductase inhibitor Drugs 0.000 title description 2
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title description 2
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title description 2
239000000203 mixture Substances 0.000 claims description 75
-1 2,4-dichloro-6- ( 4-fluoro-benzyloxy) phenyl Chemical group 0.000 claims description 64
125000000217 alkyl group Chemical group 0.000 claims description 59
150000001875 compounds Chemical class 0.000 claims description 57
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 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 37
239000001257 hydrogen Substances 0.000 claims description 33
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
150000004702 methyl esters Chemical class 0.000 claims description 27
235000012000 cholesterol Nutrition 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 23
125000003545 alkoxy group Chemical group 0.000 claims description 19
150000002431 hydrogen Chemical class 0.000 claims description 19
230000015572 biosynthetic process Effects 0.000 claims description 17
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 16
102000004190 Enzymes Human genes 0.000 claims description 14
108090000790 Enzymes Proteins 0.000 claims description 14
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical class [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 13
102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
230000002209 hydrophobic effect Effects 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
230000000694 effects Effects 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
230000002401 inhibitory effect Effects 0.000 claims description 8
150000002632 lipids Chemical class 0.000 claims description 7
SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 claims description 6
125000001188 haloalkyl group Chemical group 0.000 claims description 6
239000000758 substrate Substances 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
125000005059 halophenyl group Chemical group 0.000 claims description 4
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 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
125000005002 aryl methyl group Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000004185 ester group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
239000008280 blood Substances 0.000 claims 1
210000004369 blood Anatomy 0.000 claims 1
229940125810 compound 20 Drugs 0.000 claims 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
125000004043 oxo group Chemical group O=* 0.000 claims 1
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 103
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 98
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 81
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 74
239000000243 solution Substances 0.000 description 71
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
229910052786 argon Inorganic materials 0.000 description 49
239000003921 oil Substances 0.000 description 45
235000019198 oils Nutrition 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
235000019439 ethyl acetate Nutrition 0.000 description 35
239000000047 product Substances 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
239000000460 chlorine Substances 0.000 description 26
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
239000012267 brine Substances 0.000 description 23
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
150000002148 esters Chemical class 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000011734 sodium Substances 0.000 description 19
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
239000002253 acid Substances 0.000 description 18
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
239000012074 organic phase Substances 0.000 description 17
239000000725 suspension Substances 0.000 description 17
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
125000003118 aryl group Chemical group 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 16
239000000706 filtrate Substances 0.000 description 16
239000000126 substance Substances 0.000 description 15
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000012043 crude product Substances 0.000 description 12
229940088598 enzyme Drugs 0.000 description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 12
150000001299 aldehydes Chemical class 0.000 description 11
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 11
239000012528 membrane Substances 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
238000012360 testing method Methods 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
238000000921 elemental analysis Methods 0.000 description 10
210000003494 hepatocyte Anatomy 0.000 description 10
239000004417 polycarbonate Substances 0.000 description 10
229920000515 polycarbonate Polymers 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
229910052731 fluorine Inorganic materials 0.000 description 9
125000001153 fluoro group Chemical group F* 0.000 description 9
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 9
238000003756 stirring Methods 0.000 description 9
RZYHXKLKJRGJGP-UHFFFAOYSA-N 2,2,2-trifluoro-n,n-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)N([Si](C)(C)C)C(=O)C(F)(F)F RZYHXKLKJRGJGP-UHFFFAOYSA-N 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
210000004885 white matter Anatomy 0.000 description 8
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 7
239000012298 atmosphere Substances 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
238000001914 filtration Methods 0.000 description 7
239000011737 fluorine Substances 0.000 description 7
239000012362 glacial acetic acid Substances 0.000 description 7
125000005843 halogen group Chemical group 0.000 description 7
210000004185 liver Anatomy 0.000 description 7
239000002609 medium Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 6
235000019502 Orange oil Nutrition 0.000 description 6
241000700159 Rattus Species 0.000 description 6
229910052783 alkali metal Inorganic materials 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
125000003710 aryl alkyl group Chemical group 0.000 description 6
239000010779 crude oil Substances 0.000 description 6
239000013078 crystal Substances 0.000 description 6
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 6
239000011521 glass Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000010502 orange oil Substances 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
239000007787 solid Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical class OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
125000003282 alkyl amino group Chemical group 0.000 description 5
238000012937 correction Methods 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000007789 gas Substances 0.000 description 5
238000011534 incubation Methods 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 5
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 5
229910000343 potassium bisulfate Inorganic materials 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
108090000623 proteins and genes Proteins 0.000 description 5
239000011347 resin Substances 0.000 description 5
229920005989 resin Polymers 0.000 description 5
239000007858 starting material Substances 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
JOOMLFKONHCLCJ-UHFFFAOYSA-N N-(trimethylsilyl)diethylamine Chemical compound CCN(CC)[Si](C)(C)C JOOMLFKONHCLCJ-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
125000004414 alkyl thio group Chemical group 0.000 description 4
239000002585 base Substances 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000006285 cell suspension Substances 0.000 description 4
125000000753 cycloalkyl group Chemical group 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
150000002596 lactones Chemical group 0.000 description 4
239000007788 liquid Substances 0.000 description 4
210000001589 microsome Anatomy 0.000 description 4
125000001624 naphthyl group Chemical group 0.000 description 4
229910052698 phosphorus Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
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
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
NJLHHACGWKAWKL-UHFFFAOYSA-N ClP(Cl)=O Chemical compound ClP(Cl)=O NJLHHACGWKAWKL-UHFFFAOYSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
229910004373 HOAc Inorganic materials 0.000 description 3
229910010082 LiAlH Inorganic materials 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
125000005236 alkanoylamino group Chemical group 0.000 description 3
125000004658 aryl carbonyl amino group Chemical group 0.000 description 3
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 3
159000000007 calcium salts Chemical class 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
125000004093 cyano group Chemical group *C#N 0.000 description 3
238000010348 incorporation Methods 0.000 description 3
229910003002 lithium salt Inorganic materials 0.000 description 3
159000000002 lithium salts Chemical class 0.000 description 3
239000002808 molecular sieve Substances 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
239000011574 phosphorus Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
210000001626 skin fibroblast Anatomy 0.000 description 3
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
210000003462 vein Anatomy 0.000 description 3
WGNSGQNASYNCBU-VKHMYHEASA-N (3s)-4-bromo-3-hydroxybutanoic acid Chemical compound BrC[C@@H](O)CC(O)=O WGNSGQNASYNCBU-VKHMYHEASA-N 0.000 description 2
OSUKSSHOHKZSJC-UHFFFAOYSA-N 12591-02-5 Chemical compound ClP(=O)=O OSUKSSHOHKZSJC-UHFFFAOYSA-N 0.000 description 2
WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Substances 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
JHVMCOQCMNVEHK-UHFFFAOYSA-N CP(=O)C(C(=O)O)C(C)O Chemical compound CP(=O)C(C(=O)O)C(C)O JHVMCOQCMNVEHK-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
239000007818 Grignard reagent Substances 0.000 description 2
239000012981 Hank's balanced salt solution Substances 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
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239000012894 fetal calf serum Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000011491 glass wool Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
230000000055 hyoplipidemic effect Effects 0.000 description 1
230000000260 hypercholesteremic effect Effects 0.000 description 1
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239000005457 ice water Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000007273 lactonization reaction Methods 0.000 description 1
210000001853 liver microsome Anatomy 0.000 description 1
210000005228 liver tissue Anatomy 0.000 description 1
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
229960004844 lovastatin Drugs 0.000 description 1
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
RDVDTHIVHSZVCT-UHFFFAOYSA-M magnesium;1-fluoro-2-methylbenzene-4-ide;bromide Chemical compound [Mg+2].[Br-].CC1=C[C-]=CC=C1F RDVDTHIVHSZVCT-UHFFFAOYSA-M 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
229960001961 meglutol Drugs 0.000 description 1
JYVXNLLUYHCIIH-LURJTMIESA-N mevalonolactone Chemical class C[C@]1(O)CCOC(=O)C1 JYVXNLLUYHCIIH-LURJTMIESA-N 0.000 description 1
229940057061 mevalonolactone Drugs 0.000 description 1
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 1
BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
238000012986 modification Methods 0.000 description 1
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229940105631 nembutal Drugs 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 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
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000007793 ph indicator Substances 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
239000012071 phase Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
125000005541 phosphonamide group Chemical group 0.000 description 1
XRBCRPZXSCBRTK-UHFFFAOYSA-N phosphonous acid Chemical compound OPO XRBCRPZXSCBRTK-UHFFFAOYSA-N 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
229920000573 polyethylene Chemical group 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000007789 sealing Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000000526 short-path distillation Methods 0.000 description 1
239000004460 silage Substances 0.000 description 1
238000005584 silyl ether cleavage reaction Methods 0.000 description 1
239000002356 single layer Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000035899 viability Effects 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing 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
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (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
- C07F9/28—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
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- 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
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
- 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
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3211—Esters of acyclic saturated acids which can have further substituents on alkyl
- 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
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/36—Amides thereof
- 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
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- 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)]
- C07F9/44—Amides thereof
- C07F9/4403—Amides thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4407—Amides of acyclic saturated acids which can have further substituents on alkyl

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)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Urology & Nephrology (AREA)
Obesity (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Diabetes (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrane Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Steroid Compounds (AREA)

NL8801330A 1987-05-22 1988-05-24 Fosfor bevattende remmers van hmg-coa reductase, nieuwe tussenprodukten en werkwijze voor het toepassen daarvan. NL8801330A (nl)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US5328187A	1987-05-22	1987-05-22
US5328187		1987-05-22
US10968087A	1987-10-19	1987-10-19
US10968087		1987-10-19

Publications (1)

Publication Number	Publication Date
NL8801330A true NL8801330A (nl)	1988-12-16

Family

ID=26731667

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL8801330A NL8801330A (nl)	1987-05-22	1988-05-24	Fosfor bevattende remmers van hmg-coa reductase, nieuwe tussenprodukten en werkwijze voor het toepassen daarvan.

Country Status (24)

Country	Link
JP (1)	JP2680347B2 (fr)
KR (1)	KR880013958A (fr)
CN (1)	CN88103091A (fr)
AU (1)	AU610591B2 (fr)
BE (1)	BE1004193A3 (fr)
CH (1)	CH676984A5 (fr)
DE (1)	DE3817375C2 (fr)
DK (1)	DK277488A (fr)
ES (1)	ES2009918A6 (fr)
FI (1)	FI89493C (fr)
FR (1)	FR2615508B1 (fr)
GB (1)	GB2205837B (fr)
GR (1)	GR1000959B (fr)
HU (1)	HU205125B (fr)
IE (2)	IE63760B1 (fr)
IL (1)	IL86464A (fr)
IT (1)	IT1217685B (fr)
NL (1)	NL8801330A (fr)
NO (1)	NO882218L (fr)
NZ (1)	NZ224733A (fr)
PH (1)	PH25350A (fr)
PL (1)	PL154877B1 (fr)
PT (1)	PT87539B (fr)
SE (1)	SE503210C2 (fr)

Families Citing this family (71)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2009919A6 (es) *	1987-05-22	1989-10-16	Squibb & Sons Inc	Procedimiento para preparar inhibidores de hmg-coa-reductasa que contienen fosforo y nuevos compuestos intermedios.
CA2007643A1 (fr) *	1989-02-01	1990-08-01	Donald S. Karanewsky	Combinaison d'un inhibiteur de hmg coa et d'un inhibiteur de squalene synthetase et methode pour abaisser le taux de cholesterol sanguin par l'utilisation de cette combinaison
CA2042526A1 (fr) *	1990-06-11	1991-12-12	Adeoye Y. Olukotun	Methode permettant de prevenir une deuxieme crise cardiaque a l'aide d'un inhibiteur de la hmg coa-reductase
US5202327A (en) *	1991-07-10	1993-04-13	E. R. Squibb & Sons, Inc.	Phosphorus-containing hmg-coa reductase inhibitors
GB9126144D0 (en) *	1991-12-10	1992-02-12	British Bio Technology	Compounds
US20010006644A1 (en)	1997-07-31	2001-07-05	David J. Bova	Combinations of hmg-coa reductase inhibitors and nicotinic acid and methods for treating hyperlipidemia once a day at night
EE200100155A (et)	1998-09-17	2002-08-15	Bristol-Myers Squibb Company	Ateroskleroosi ravimeetod, kasutades aP2 inhibiitorit ja selle kombinatsiooni
DK1385856T3 (da)	2001-04-11	2006-05-15	Bristol Myers Squibb Co	Aminosyrekomplekser af C-aryl-glucosider til behandling af diabetes og fremgangsmåder
GEP20063908B (en)	2001-10-18	2006-08-25	Bristol Myers Squibb Co	Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions
US7238671B2 (en)	2001-10-18	2007-07-03	Bristol-Myers Squibb Company	Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions
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1988
- 1988-05-20 DK DK277488A patent/DK277488A/da not_active Application Discontinuation
- 1988-05-20 AU AU16508/88A patent/AU610591B2/en not_active Ceased
- 1988-05-20 GR GR880100331A patent/GR1000959B/el unknown
- 1988-05-20 IL IL86464A patent/IL86464A/xx not_active IP Right Cessation
- 1988-05-20 NO NO882218A patent/NO882218L/no unknown
- 1988-05-20 ES ES8801610A patent/ES2009918A6/es not_active Expired
- 1988-05-20 IE IE154388A patent/IE63760B1/en not_active IP Right Cessation
- 1988-05-20 FI FI882384A patent/FI89493C/fi not_active IP Right Cessation
- 1988-05-20 HU HU882614A patent/HU205125B/hu not_active IP Right Cessation
- 1988-05-20 IT IT20682/88A patent/IT1217685B/it active
- 1988-05-20 PT PT87539A patent/PT87539B/pt not_active IP Right Cessation
- 1988-05-20 IE IE930324A patent/IE930324L/xx unknown
- 1988-05-20 GB GB8811929A patent/GB2205837B/en not_active Expired - Fee Related
- 1988-05-20 NZ NZ224733A patent/NZ224733A/en unknown
- 1988-05-20 DE DE3817375A patent/DE3817375C2/de not_active Expired - Fee Related
- 1988-05-20 SE SE8801903A patent/SE503210C2/sv not_active IP Right Cessation
- 1988-05-20 PH PH36956A patent/PH25350A/en unknown
- 1988-05-21 JP JP63124809A patent/JP2680347B2/ja not_active Expired - Lifetime
- 1988-05-21 PL PL1988272597A patent/PL154877B1/pl unknown
- 1988-05-21 CN CN198888103091A patent/CN88103091A/zh active Pending
- 1988-05-21 KR KR1019880006020A patent/KR880013958A/ko not_active Ceased
- 1988-05-24 BE BE8800566A patent/BE1004193A3/fr not_active IP Right Cessation
- 1988-05-24 CH CH1967/88A patent/CH676984A5/fr not_active IP Right Cessation
- 1988-05-24 NL NL8801330A patent/NL8801330A/nl not_active Application Discontinuation
- 1988-05-24 FR FR8806885A patent/FR2615508B1/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
IT8820682A0 (it)	1988-05-20
FI882384A7 (fi)	1988-11-23
NO882218D0 (no)	1988-05-20
IE930324L (en)	1988-11-22
HU205125B (en)	1992-03-30
JP2680347B2 (ja)	1997-11-19
SE8801903L (sv)	1988-11-23
CN88103091A (zh)	1988-12-21
DK277488A (da)	1988-11-23
DE3817375C2 (de)	1997-04-30
GB2205837A (en)	1988-12-21
PH25350A (en)	1991-05-13
PL154877B1 (en)	1991-09-30
IL86464A (en)	1993-06-10
CH676984A5 (fr)	1991-03-28
IE881543L (en)	1988-11-22
AU1650888A (en)	1988-11-24
GB8811929D0 (en)	1988-06-22
ES2009918A6 (es)	1989-10-16
FI882384A0 (fi)	1988-05-20
PT87539A (pt)	1989-05-31
JPS6456689A (en)	1989-03-03
IE63760B1 (en)	1995-06-14
HUT49358A (en)	1989-09-28
GB2205837B (en)	1991-11-20
GR880100331A (en)	1989-02-23
PL272597A1 (en)	1989-03-06
NZ224733A (en)	1990-12-21
AU610591B2 (en)	1991-05-23
BE1004193A3 (fr)	1992-10-13
FI89493C (fi)	1993-10-11
DE3817375A1 (de)	1988-12-08
KR880013958A (ko)	1988-12-22
DK277488D0 (da)	1988-05-20
SE503210C2 (sv)	1996-04-22
IT1217685B (it)	1990-03-30
FR2615508A1 (fr)	1988-11-25
FI89493B (fi)	1993-06-30
SE8801903D0 (sv)	1988-05-20
NO882218L (no)	1988-11-23
GR1000959B (el)	1993-03-16
FR2615508B1 (fr)	1994-11-25
IL86464A0 (en)	1988-11-15
PT87539B (pt)	1992-09-30

Legal Events

Date	Code	Title
1996-05-01	BA	A request for search or an international-type search has been filed
1996-07-01	BB	A search report has been drawn up
1996-11-01	BC	A request for examination has been filed
1999-02-01	BV	The patent application has lapsed

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NZ224733A (en)	1990-12-21	Organophosphorus hmg-coa reductase inhibitors; intermediates and compositions thereof
US5017716A (en)	1991-05-21	Phosphorous-containing HMG-CoA reductase inhibitors, new intermediates and method
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AU612475B2 (en)	1991-07-11	Phenol substituted gem-diphosphonate derivatives, process for their preparation and pharmaceutical compositions containing them
EP0444532A1 (fr)	1991-09-04	Inhibiteurs de réductase HMG-CpA contenant du phosphore, nouveaux intermédiaires et méthode
AU705206B2 (en)	1999-05-20	Compounds and pharmaceutical compositions containing them
DE3805801C2 (de)	2001-03-01	Antihypercholesterinämisch wirkende Tetrazol-Verbindungen, Verfahren zu ihrer Herstellung und pharmazeutische Mittel
HU201085B (en)	1990-09-28	Process for producing phosphor-containing compounds and pharmaceutical compositions containing them as active components
US5374628A (en)	1994-12-20	Aryl and heteroaryl(phosphinylmethyl)phosphonate squalene synthetase inhibitors and method
EP0409181A2 (fr)	1991-01-23	Inhibiteurs de squalène synthétase contenant du phosphore et procédé de leur préparation
AU708266B2 (en)	1999-07-29	1,2 chemiluminescent dioxetanes of improved performance
US5212164A (en)	1993-05-18	Phosphorus-containing squalene synthetase inhibitors
US4702864A (en)	1987-10-27	Analogs of platelet activating factor
CA2043525A1 (fr)	1991-12-25	Inhibiteurs de reductase hmg-coa renfermant du phosphore; nouveaux produits intermediaires et methode d'utilisation
GB2235924A (en)	1991-03-20	Phosphorus-containing 3-hydroxy-butanoic acid intermediates
CA1108176A (fr)	1981-09-01	Obtention d'arylalkyl et d'aryloxyalkylphosphonates
Macomber et al.	1983	Reactions of oxaphospholenes. 2. Hydrolysis of neopentyl esters, phenyl esters, and amides
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US5068346A (en)	1991-11-26	Tetrazole compounds
Shukla et al.	1981	Synthesis of O, O-dialkyl-S-[benzoyl-(benzylidene amino)] dithiophosphorates and their inhibitory effect on acetyl-cholinesterase activity