FI87927C - Foerfarande foer framstaellining av nya fosforhaltiga hmg-coa-reduktasinhibitorer och nya mellanprodukter - Google Patents
Foerfarande foer framstaellining av nya fosforhaltiga hmg-coa-reduktasinhibitorer och nya mellanprodukter Download PDFInfo
- Publication number
- FI87927C FI87927C FI882385A FI882385A FI87927C FI 87927 C FI87927 C FI 87927C FI 882385 A FI882385 A FI 882385A FI 882385 A FI882385 A FI 882385A FI 87927 C FI87927 C FI 87927C
- Authority
- FI
- Finland
- Prior art keywords
- alkyl
- formula
- hydroxybutanoic acid
- hydroxyphosphinyl
- methyl ester
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 22
- 238000002360 preparation method Methods 0.000 title claims description 16
- 230000008569 process Effects 0.000 title claims description 9
- 239000000543 intermediate Substances 0.000 title description 15
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title description 3
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title description 3
- 239000000460 chlorine Substances 0.000 claims description 197
- 125000000217 alkyl group Chemical group 0.000 claims description 164
- 229910052739 hydrogen Inorganic materials 0.000 claims description 137
- 150000001875 compounds Chemical class 0.000 claims description 134
- -1 diester phosphinate Chemical class 0.000 claims description 110
- 239000001257 hydrogen Substances 0.000 claims description 106
- SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 claims description 78
- 150000002431 hydrogen Chemical class 0.000 claims description 69
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 51
- 125000003545 alkoxy group Chemical group 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 44
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 43
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 40
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 38
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 37
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 229910052801 chlorine Inorganic materials 0.000 claims description 35
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 150000004702 methyl esters Chemical class 0.000 claims description 28
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims description 27
- OSUKSSHOHKZSJC-UHFFFAOYSA-N 12591-02-5 Chemical compound ClP(=O)=O OSUKSSHOHKZSJC-UHFFFAOYSA-N 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 239000003960 organic solvent Substances 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
- 150000005690 diesters Chemical class 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 230000002209 hydrophobic effect Effects 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
- 150000001450 anions Chemical class 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 229910010271 silicon carbide Inorganic materials 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical compound IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 4
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 claims description 3
- 229910018540 Si C Inorganic materials 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
- 125000005059 halophenyl group Chemical group 0.000 claims description 3
- DLNAOSNXEVENKA-LFUZPPSTSA-N (3s)-3-hydroxy-4-[methoxy-[2-(2-phenylphenyl)ethyl]phosphoryl]butanoic acid Chemical compound OC(=O)C[C@H](O)CP(=O)(OC)CCC1=CC=CC=C1C1=CC=CC=C1 DLNAOSNXEVENKA-LFUZPPSTSA-N 0.000 claims description 2
- QJKCWZDFMJKJPG-KRWDZBQOSA-N (3s)-4-[2-(2,4-dimethyl-6-phenylphenyl)ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=CC=CC=2)=C1 QJKCWZDFMJKJPG-KRWDZBQOSA-N 0.000 claims description 2
- BFNYLDNOIRYKGM-KRWDZBQOSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(C#CP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 BFNYLDNOIRYKGM-KRWDZBQOSA-N 0.000 claims description 2
- SEFTYYXPKYYLBS-KRWDZBQOSA-N (3s)-4-[2-[2-(4-fluorophenyl)-4,6-dimethylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=C1 SEFTYYXPKYYLBS-KRWDZBQOSA-N 0.000 claims description 2
- JAFCYEUATIWTEN-FQEVSTJZSA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-phenyl-5-propan-2-ylpyrazol-4-yl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=C(C#CP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=NN1C1=CC=CC=C1 JAFCYEUATIWTEN-FQEVSTJZSA-N 0.000 claims description 2
- NNVVBSBUDFBEND-WABSOPGISA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-phenyl-5-propan-2-ylpyrazol-4-yl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=C(C#CP(=O)(C[C@@H](O)CC(O)=O)OC)C(C=2C=CC(F)=CC=2)=NN1C1=CC=CC=C1 NNVVBSBUDFBEND-WABSOPGISA-N 0.000 claims description 2
- IIMSXNXPALOVBL-SFHVURJKSA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2N(C(C)C)C(CCP(O)(=O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 IIMSXNXPALOVBL-SFHVURJKSA-N 0.000 claims description 2
- MCBCOKMPOZNAOX-LSJBEEMESA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]ethyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2N(C(C)C)C(CCP(=O)(OC)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 MCBCOKMPOZNAOX-LSJBEEMESA-N 0.000 claims description 2
- NXLGKVBKTRBMTB-WABSOPGISA-N (3s)-4-[2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(=O)(OC)C#CC=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 NXLGKVBKTRBMTB-WABSOPGISA-N 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- PZRJNNIVYSSRMG-VOTSOKGWSA-N 4-[[(e)-2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(\C=C\P(O)(=O)CC(O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 PZRJNNIVYSSRMG-VOTSOKGWSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 150000001447 alkali salts Chemical class 0.000 claims 3
- AAQMQVNMIKIIFW-KRWDZBQOSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 AAQMQVNMIKIIFW-KRWDZBQOSA-N 0.000 claims 2
- 125000003003 spiro group Chemical group 0.000 claims 2
- FJWRNCMFQRIGIW-INIZCTEOSA-N (3s)-3-hydroxy-4-[hydroxy-[2-(2-phenylphenyl)ethynyl]phosphoryl]butanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)C#CC1=CC=CC=C1C1=CC=CC=C1 FJWRNCMFQRIGIW-INIZCTEOSA-N 0.000 claims 1
- IFXNYSIUJLZFNH-IBGZPJMESA-N (3s)-4-[2-[1-(4-fluorophenyl)-3-methylnaphthalen-2-yl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)C#CC=1C(C)=CC2=CC=CC=C2C=1C1=CC=C(F)C=C1 IFXNYSIUJLZFNH-IBGZPJMESA-N 0.000 claims 1
- ZDXISXLUXINJAK-SFHVURJKSA-N (3s)-4-[2-[1-(4-fluorophenyl)-3-propan-2-ylindol-2-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2C(C(C)C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)N1C1=CC=C(F)C=C1 ZDXISXLUXINJAK-SFHVURJKSA-N 0.000 claims 1
- ADKZUWSCAPWKIF-STFFIMJZSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(=O)(OC)C#CC1=C(C)C=C(C)C=C1C1=CC=C(F)C(C)=C1 ADKZUWSCAPWKIF-STFFIMJZSA-N 0.000 claims 1
- RTZIMZYBUXPXPU-IBGZPJMESA-N (3s)-4-[2-[2-(cyclohexylmethyl)-4,6-dimethylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(CC2CCCCC2)=C1 RTZIMZYBUXPXPU-IBGZPJMESA-N 0.000 claims 1
- VSYPBWUUYVLTPL-IBGZPJMESA-N (3s)-4-[2-[2-(cyclohexylmethyl)-4,6-dimethylphenyl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(C#CP(O)(=O)C[C@@H](O)CC(O)=O)C(CC2CCCCC2)=C1 VSYPBWUUYVLTPL-IBGZPJMESA-N 0.000 claims 1
- RXCROTMPEYLNLM-SFHVURJKSA-N (3s)-4-[2-[2-[(4-fluorophenyl)methoxy]-4,6-dimethylphenyl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(C#CP(O)(=O)C[C@@H](O)CC(O)=O)C(OCC=2C=CC(F)=CC=2)=C1 RXCROTMPEYLNLM-SFHVURJKSA-N 0.000 claims 1
- IGODFPWSBOIKCY-FQEVSTJZSA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-phenyl-5-propan-2-ylpyrazol-4-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=NN1C1=CC=CC=C1 IGODFPWSBOIKCY-FQEVSTJZSA-N 0.000 claims 1
- VMEXKHVMPUFJJI-FQEVSTJZSA-N (3s)-4-[2-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C=1C=C(F)C=CC=1N1C(CCP(O)(=O)C[C@@H](O)CC(O)=O)=C(C(C)C)N=C1C1=CC=CC=C1 VMEXKHVMPUFJJI-FQEVSTJZSA-N 0.000 claims 1
- IJVGUKDIBVACFH-WABSOPGISA-N (3s)-4-[2-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]ethyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C=1C=C(F)C=CC=1N1C(CCP(=O)(OC)C[C@@H](O)CC(O)=O)=C(C(C)C)N=C1C1=CC=CC=C1 IJVGUKDIBVACFH-WABSOPGISA-N 0.000 claims 1
- ZKDMUYYXZBOQTI-WABSOPGISA-N (3s)-4-[2-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C=1C=C(F)C=CC=1N1C(C#CP(=O)(C[C@@H](O)CC(O)=O)OC)=C(C(C)C)N=C1C1=CC=CC=C1 ZKDMUYYXZBOQTI-WABSOPGISA-N 0.000 claims 1
- WPEHAQBDTZBUTB-WABSOPGISA-N (3s)-4-[2-[4-(4-fluorophenyl)-5-phenyl-2-propan-2-ylpyrazol-3-yl]ethyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound N=1N(C(C)C)C(CCP(=O)(OC)C[C@@H](O)CC(O)=O)=C(C=2C=CC(F)=CC=2)C=1C1=CC=CC=C1 WPEHAQBDTZBUTB-WABSOPGISA-N 0.000 claims 1
- KFMWRSMTOMOJGE-WABSOPGISA-N (3s)-4-[2-[4-(4-fluorophenyl)-5-phenyl-2-propan-2-ylpyrazol-3-yl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound N=1N(C(C)C)C(C#CP(=O)(C[C@@H](O)CC(O)=O)OC)=C(C=2C=CC(F)=CC=2)C=1C1=CC=CC=C1 KFMWRSMTOMOJGE-WABSOPGISA-N 0.000 claims 1
- IJJBMJBRFVKIFA-FQEVSTJZSA-N (3s)-4-[2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)CCC=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 IJJBMJBRFVKIFA-FQEVSTJZSA-N 0.000 claims 1
- AAQMQVNMIKIIFW-UHFFFAOYSA-N 4-[2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)CC(O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 AAQMQVNMIKIIFW-UHFFFAOYSA-N 0.000 claims 1
- QFVOVARNXVZLKL-UHFFFAOYSA-N 4-[2-[2-(cyclohexylmethyl)-4,6-dimethylphenyl]ethenyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(C=CP(O)(=O)CC(O)CC(O)=O)C(CC2CCCCC2)=C1 QFVOVARNXVZLKL-UHFFFAOYSA-N 0.000 claims 1
- IAPAGYSRQCTBSI-UHFFFAOYSA-N 4-[3-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]propyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)CC(O)CP(=O)(OC)CCCC1=C(C)C=C(C)C=C1C1=CC=C(F)C(C)=C1 IAPAGYSRQCTBSI-UHFFFAOYSA-N 0.000 claims 1
- RSCLNVKWGOFXDY-ZHACJKMWSA-N 4-[[(e)-2-[1-(4-fluorophenyl)-3-methylnaphthalen-2-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)CC(O)CP(O)(=O)/C=C/C=1C(C)=CC2=CC=CC=C2C=1C1=CC=C(F)C=C1 RSCLNVKWGOFXDY-ZHACJKMWSA-N 0.000 claims 1
- PZUMNTHIHVFVEB-OUKQBFOZSA-N 4-[[(e)-2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)CC(O)CP(O)(=O)/C=C/C=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 PZUMNTHIHVFVEB-OUKQBFOZSA-N 0.000 claims 1
- XUWHWHKLDSCKDJ-UHFFFAOYSA-N 4-[[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]methyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CP(O)(=O)CC(O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 XUWHWHKLDSCKDJ-UHFFFAOYSA-N 0.000 claims 1
- KLIAJVJCJXRUFP-KRWDZBQOSA-N C=1C=CC=CC=1[Si](O[C@@H](CC(O)=O)CP(=O)OCO)(C(C)(C)C)C1=CC=CC=C1 Chemical compound C=1C=CC=CC=1[Si](O[C@@H](CC(O)=O)CP(=O)OCO)(C(C)(C)C)C1=CC=CC=C1 KLIAJVJCJXRUFP-KRWDZBQOSA-N 0.000 claims 1
- ALVRLMOJROXISK-MXVAIDLSSA-N CC(C)C1=NCN(C1(C#CP(=O)(C[C@H](CC(=O)O)O)OC)C2=CC=CC=C2)C3=CC=C(C=C3)F Chemical compound CC(C)C1=NCN(C1(C#CP(=O)(C[C@H](CC(=O)O)O)OC)C2=CC=CC=C2)C3=CC=C(C=C3)F ALVRLMOJROXISK-MXVAIDLSSA-N 0.000 claims 1
- AXWHOFSHSPLPLL-UHFFFAOYSA-N CC1=CC(=CC(C1)(C)CCCP(=O)(CC(CC(=O)O)O)O)C2=CC(=C(C=C2)F)C Chemical compound CC1=CC(=CC(C1)(C)CCCP(=O)(CC(CC(=O)O)O)O)C2=CC(=C(C=C2)F)C AXWHOFSHSPLPLL-UHFFFAOYSA-N 0.000 claims 1
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- 239000000571 coke Substances 0.000 claims 1
- 239000013067 intermediate product Substances 0.000 claims 1
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- JVRGLGIDPIOAFN-UHFFFAOYSA-N methoxyphosphane Chemical compound COP JVRGLGIDPIOAFN-UHFFFAOYSA-N 0.000 claims 1
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 297
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 276
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 165
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- 229910002027 silica gel Inorganic materials 0.000 description 140
- 229910052786 argon Inorganic materials 0.000 description 138
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 131
- 229910001868 water Inorganic materials 0.000 description 110
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 104
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- 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
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- ARNWQMJQALNBBV-UHFFFAOYSA-N lithium carbide Chemical compound [Li+].[Li+].[C-]#[C-] ARNWQMJQALNBBV-UHFFFAOYSA-N 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
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- 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
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- 159000000003 magnesium salts Chemical class 0.000 description 1
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
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- 239000000155 melt Substances 0.000 description 1
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- 229940060942 methylin Drugs 0.000 description 1
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- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
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- 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
- 125000002347 octyl 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])[H] 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 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
- WYMSBXTXOHUIGT-UHFFFAOYSA-N paraoxon Chemical compound CCOP(=O)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 WYMSBXTXOHUIGT-UHFFFAOYSA-N 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
- 239000007793 ph indicator Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000011045 prefiltration Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000000526 short-path distillation Methods 0.000 description 1
- 201000010153 skin papilloma Diseases 0.000 description 1
- 238000002791 soaking Methods 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical compound [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 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
- 238000011287 therapeutic dose Methods 0.000 description 1
- 150000003573 thiols Chemical class 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
- SJHCUXCOGGKFAI-UHFFFAOYSA-N tripropan-2-yl phosphite Chemical compound CC(C)OP(OC(C)C)OC(C)C SJHCUXCOGGKFAI-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000012588 trypsin Substances 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
- 238000005292 vacuum distillation 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
-
- 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
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- C—CHEMISTRY; METALLURGY
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- 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
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
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- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/302—Acyclic unsaturated acids
-
- 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)]
- C07F9/303—Cycloaliphatic acids
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- C—CHEMISTRY; METALLURGY
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- 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)]
- C07F9/306—Arylalkanephosphinic acids, e.g. Ar-(CH2)n-P(=X)(R)(XH), (X = O,S, Se; n>=1)
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- C—CHEMISTRY; METALLURGY
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- 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
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- 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
- C07F9/3217—Esters of acyclic unsaturated acids
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- 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
- C07F9/3241—Esters of arylalkanephosphinic acids
-
- C—CHEMISTRY; METALLURGY
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5323887A | 1987-05-22 | 1987-05-22 | |
US5323887 | 1987-05-22 | ||
US10968187A | 1987-10-19 | 1987-10-19 | |
US10968187 | 1987-10-19 |
Publications (4)
Publication Number | Publication Date |
---|---|
FI882385A0 FI882385A0 (fi) | 1988-05-20 |
FI882385A FI882385A (fi) | 1988-11-23 |
FI87927B FI87927B (fi) | 1992-11-30 |
FI87927C true FI87927C (fi) | 1993-03-10 |
Family
ID=26731613
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI882385A FI87927C (fi) | 1987-05-22 | 1988-05-20 | Foerfarande foer framstaellining av nya fosforhaltiga hmg-coa-reduktasinhibitorer och nya mellanprodukter |
Country Status (24)
Country | Link |
---|---|
JP (1) | JPH01139589A (pt) |
KR (1) | KR880013959A (pt) |
CN (1) | CN1030761A (pt) |
AU (2) | AU610174B2 (pt) |
BE (1) | BE1002251A3 (pt) |
CH (3) | CH675582A5 (pt) |
DE (1) | DE3817298C2 (pt) |
DK (1) | DK277388A (pt) |
ES (1) | ES2009919A6 (pt) |
FI (1) | FI87927C (pt) |
FR (1) | FR2615516B1 (pt) |
GB (1) | GB2205838B (pt) |
GR (1) | GR880100332A (pt) |
HU (1) | HU201085B (pt) |
IE (1) | IE63715B1 (pt) |
IL (1) | IL86463A (pt) |
IT (1) | IT1217684B (pt) |
NL (1) | NL8801331A (pt) |
NO (1) | NO882219L (pt) |
NZ (1) | NZ224734A (pt) |
PH (2) | PH25581A (pt) |
PL (1) | PL157761B1 (pt) |
PT (1) | PT87540B (pt) |
SE (3) | SE501541C2 (pt) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2009918A6 (es) * | 1987-05-22 | 1989-10-16 | Squibb & Sons Inc | Procedimiento para preparar inhibidores de hmg-coa-reductasa que contienen fosforo. |
JPH03184961A (ja) * | 1989-10-10 | 1991-08-12 | Glaxo Group Ltd | 化合物 |
US5025000A (en) * | 1990-03-02 | 1991-06-18 | E. R. Squibb & Sons, Inc. | Phosphorus-containing HMG-CoA reductase inhibitor compounds |
US5124453A (en) * | 1990-03-02 | 1992-06-23 | E. R. Squibb & Sons, Inc. | Process for preparing certain 5,6,7,8-tetrahydroindolizinyl (ethyl or ethynyl)-hydroxy or methoxy-phosphinyl-3-hydroxy-butanoates and derivatives thereof |
CA2042526A1 (en) * | 1990-06-11 | 1991-12-12 | Adeoye Y. Olukotun | Method for preventing a second heart attack employing an hmg coa reductase inhibitor |
CA2043525A1 (en) * | 1990-06-24 | 1991-12-25 | Donald S. Karanewsky | Phosphorus-containing hmg-coa reductase inhibitors, new intermediates and method |
DE4023308A1 (de) * | 1990-07-21 | 1992-01-23 | Bayer Ag | Substituierte pyrido-oxazine |
DE4025818A1 (de) * | 1990-08-16 | 1992-02-20 | Bayer Ag | Phenylsulfonamid substituierte pyridinalken- und -aminooxyalkancarbonsaeure-derivate |
NZ241574A (en) * | 1991-02-22 | 1993-08-26 | Ishihara Sangyo Kaisha | Substituted phenyl derivatives of hydrazone and pesticidal compositions |
US5202327A (en) * | 1991-07-10 | 1993-04-13 | E. R. Squibb & Sons, Inc. | Phosphorus-containing hmg-coa reductase inhibitors |
US5256692A (en) * | 1992-01-07 | 1993-10-26 | E. R. Squibb & Sons, Inc. | Sulfur-containing HMG-COA reductase inhibitors |
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 |
AU2003218758A1 (en) * | 2002-03-14 | 2003-09-22 | Syngenta Participations Ag | Derivatives of 1-phenyl-3-phenylpyrazole as herbicides |
JP4407237B2 (ja) * | 2002-12-24 | 2010-02-03 | 三菱化学株式会社 | 非水系電解液及びそれを用いる非水系電解液二次電池 |
JP4485169B2 (ja) | 2003-05-16 | 2010-06-16 | 花王株式会社 | 腸管ミネラル吸収能改善剤 |
CN1760363B (zh) * | 2004-10-14 | 2010-04-28 | 蒋继宏 | 杜仲3-羟基-3-甲基戊二酰辅酶a还原酶蛋白编码序列 |
WO2007081019A1 (ja) * | 2006-01-16 | 2007-07-19 | Sankyo Agro Company, Limited | (3-硫黄原子置換フェニル)ピラゾール誘導体 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR339233A (fr) * | 1903-12-23 | 1905-01-26 | Cyanidgesellschaft Mit Beschra | Nouveau procédé pour l'obtention d'explosifs |
DE803645C (de) * | 1949-10-11 | 1951-04-05 | Dynamit Act Ges Vormals Alfred | Schagwettersichere Sprengkapsel in Verbindung mit elektrischen Zuendern |
DE918196C (de) * | 1952-12-23 | 1954-09-20 | J G W Berckholtz Fa | Masse zur Erzeugung von farbigem Rauch |
US3274035A (en) * | 1964-06-15 | 1966-09-20 | Lohr A Burkardt | Metallic composition for production of hygroscopic smoke |
US3862866A (en) * | 1971-08-02 | 1975-01-28 | Specialty Products Dev Corp | Gas generator composition and method |
DE2841815C2 (de) * | 1978-09-26 | 1985-02-21 | Buck Chemisch-Technische Werke GmbH & Co, 7347 Bad Überkingen | Verfahren zur Herstellung einer Geschoßfüllung |
US4438700A (en) * | 1982-07-19 | 1984-03-27 | The United States Of America As Represented By The Secretary Of The Army | White smoke spotting composition for training ammunition |
FR2596393B1 (fr) * | 1986-04-01 | 1988-06-03 | Sanofi Sa | Derives de l'acide hydroxy-3 dihydroxyoxophosphorio-4 butanoique, leur procede de preparation, leur application comme medicament et les compositions les renfermant |
ES2009918A6 (es) * | 1987-05-22 | 1989-10-16 | Squibb & Sons Inc | Procedimiento para preparar inhibidores de hmg-coa-reductasa que contienen fosforo. |
-
1988
- 1988-05-20 FI FI882385A patent/FI87927C/fi not_active IP Right Cessation
- 1988-05-20 IT IT20681/88A patent/IT1217684B/it active
- 1988-05-20 PT PT87540A patent/PT87540B/pt not_active IP Right Cessation
- 1988-05-20 GB GB8811931A patent/GB2205838B/en not_active Expired - Fee Related
- 1988-05-20 DK DK277388A patent/DK277388A/da not_active Application Discontinuation
- 1988-05-20 SE SE8801904A patent/SE501541C2/sv not_active IP Right Cessation
- 1988-05-20 ES ES8801611A patent/ES2009919A6/es not_active Expired
- 1988-05-20 GR GR880100332A patent/GR880100332A/el unknown
- 1988-05-20 DE DE3817298A patent/DE3817298C2/de not_active Expired - Fee Related
- 1988-05-20 AU AU16502/88A patent/AU610174B2/en not_active Ceased
- 1988-05-20 IL IL8646388A patent/IL86463A/en not_active IP Right Cessation
- 1988-05-20 HU HU882613A patent/HU201085B/hu not_active IP Right Cessation
- 1988-05-20 NZ NZ224734A patent/NZ224734A/en unknown
- 1988-05-20 NO NO882219A patent/NO882219L/no unknown
- 1988-05-20 PH PH36953A patent/PH25581A/en unknown
- 1988-05-20 IE IE154488A patent/IE63715B1/en not_active IP Right Cessation
- 1988-05-21 PL PL1988286491A patent/PL157761B1/pl unknown
- 1988-05-21 KR KR1019880006019A patent/KR880013959A/ko not_active Application Discontinuation
- 1988-05-21 CN CN88103699A patent/CN1030761A/zh active Pending
- 1988-05-23 JP JP63125630A patent/JPH01139589A/ja active Pending
- 1988-05-24 CH CH1966/88A patent/CH675582A5/fr not_active IP Right Cessation
- 1988-05-24 BE BE8800565A patent/BE1002251A3/fr not_active IP Right Cessation
- 1988-05-24 NL NL8801331A patent/NL8801331A/nl not_active Application Discontinuation
- 1988-05-24 CH CH1463/90A patent/CH678626A5/fr not_active IP Right Cessation
- 1988-05-24 CH CH1462/90A patent/CH678625A5/fr not_active IP Right Cessation
- 1988-05-24 FR FR888806884A patent/FR2615516B1/fr not_active Expired - Fee Related
-
1989
- 1989-05-19 PH PH38673A patent/PH26578A/en unknown
-
1991
- 1991-02-21 AU AU71266/91A patent/AU643501B2/en not_active Ceased
-
1992
- 1992-05-14 SE SE9201587A patent/SE9201587D0/xx not_active Application Discontinuation
- 1992-05-20 SE SE9201588A patent/SE9201588D0/xx not_active Application Discontinuation
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Legal Events
Date | Code | Title | Description |
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FG | Patent granted |
Owner name: E.R. SQUIBB & SONS, INC. |
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MA | Patent expired |