MX2007002419A - Sintesis alternativa de inhibidores de renina e intermediarios de los mismos. - Google Patents
Sintesis alternativa de inhibidores de renina e intermediarios de los mismos.Info
- Publication number
- MX2007002419A MX2007002419A MX2007002419A MX2007002419A MX2007002419A MX 2007002419 A MX2007002419 A MX 2007002419A MX 2007002419 A MX2007002419 A MX 2007002419A MX 2007002419 A MX2007002419 A MX 2007002419A MX 2007002419 A MX2007002419 A MX 2007002419A
- Authority
- MX
- Mexico
- Prior art keywords
- carbon atoms
- alkyl
- formula
- alkoxy
- aryl
- Prior art date
Links
- 239000000543 intermediate Substances 0.000 title claims abstract description 23
- 230000015572 biosynthetic process Effects 0.000 title claims description 16
- 238000003786 synthesis reaction Methods 0.000 title description 14
- 239000002461 renin inhibitor Substances 0.000 title description 3
- 229940086526 renin-inhibitors Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 230
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 83
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 45
- 238000002360 preparation method Methods 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 638
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 406
- 229910052799 carbon Inorganic materials 0.000 claims description 404
- 125000000217 alkyl group Chemical group 0.000 claims description 266
- 125000003545 alkoxy group Chemical group 0.000 claims description 186
- 125000003118 aryl group Chemical group 0.000 claims description 166
- -1 benzoyl compound Chemical class 0.000 claims description 163
- 238000000034 method Methods 0.000 claims description 91
- 150000002367 halogens Chemical class 0.000 claims description 81
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 59
- 238000006243 chemical reaction Methods 0.000 claims description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 45
- 125000001188 haloalkyl group Chemical group 0.000 claims description 36
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 33
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
- 150000002148 esters Chemical class 0.000 claims description 28
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 24
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 17
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 150000001299 aldehydes Chemical class 0.000 claims description 9
- 150000002596 lactones Chemical class 0.000 claims description 9
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 238000005755 formation reaction Methods 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- 238000006722 reduction reaction Methods 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 230000032050 esterification Effects 0.000 claims description 7
- 238000005886 esterification reaction Methods 0.000 claims description 7
- NGEWQZIDQIYUNV-SCSAIBSYSA-N (R)-2-hydroxy-3-methylbutyric acid Chemical compound CC(C)[C@@H](O)C(O)=O NGEWQZIDQIYUNV-SCSAIBSYSA-N 0.000 claims description 6
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 claims description 6
- 150000001336 alkenes Chemical class 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 238000005984 hydrogenation reaction Methods 0.000 claims description 6
- 150000002690 malonic acid derivatives Chemical class 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 claims description 5
- 229930182831 D-valine Natural products 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 238000006114 decarboxylation reaction Methods 0.000 claims description 5
- 239000012039 electrophile Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 238000007273 lactonization reaction Methods 0.000 claims description 4
- 238000011916 stereoselective reduction Methods 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- HKQZJXVIXAPOPZ-UHFFFAOYSA-N 3-amino-2,2-dimethylpropanamide Chemical compound NCC(C)(C)C(N)=O HKQZJXVIXAPOPZ-UHFFFAOYSA-N 0.000 claims description 3
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- 150000003934 aromatic aldehydes Chemical class 0.000 claims description 3
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 3
- 238000006317 isomerization reaction Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 238000005897 peptide coupling reaction Methods 0.000 claims description 3
- 238000003420 transacetalization reaction Methods 0.000 claims description 3
- 238000006359 acetalization reaction Methods 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 238000006193 diazotization reaction Methods 0.000 claims description 2
- 150000003951 lactams Chemical group 0.000 claims description 2
- 150000002902 organometallic compounds Chemical class 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 238000007142 ring opening reaction Methods 0.000 claims description 2
- 238000007127 saponification reaction Methods 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 5
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 5
- 150000001733 carboxylic acid esters Chemical group 0.000 claims 2
- 230000003647 oxidation Effects 0.000 claims 2
- 238000007254 oxidation reaction Methods 0.000 claims 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
- IDRKJJDZFVGWCW-UHFFFAOYSA-N 5-amino-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-2-propan-2-ylnonanoic acid Chemical compound COCCCOC1=CC(CC(CC(N)C(O)CC(C(C)C)C(O)=O)C(C)C)=CC=C1OC IDRKJJDZFVGWCW-UHFFFAOYSA-N 0.000 claims 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 1
- 238000010640 amide synthesis reaction Methods 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 238000010931 ester hydrolysis Methods 0.000 claims 1
- 235000011090 malic acid Nutrition 0.000 claims 1
- 239000001630 malic acid Substances 0.000 claims 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 1
- 238000005935 nucleophilic addition reaction Methods 0.000 claims 1
- 230000007420 reactivation Effects 0.000 claims 1
- 230000000707 stereoselective effect Effects 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
- 125000005843 halogen group Chemical group 0.000 abstract 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
- 239000000243 solution Substances 0.000 description 74
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
- 239000002904 solvent Substances 0.000 description 59
- 239000000203 mixture Substances 0.000 description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000002253 acid Substances 0.000 description 42
- 239000003921 oil Substances 0.000 description 41
- 235000019198 oils Nutrition 0.000 description 41
- 235000019439 ethyl acetate Nutrition 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 239000012074 organic phase Substances 0.000 description 22
- 239000000725 suspension Substances 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 125000006239 protecting group Chemical group 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 14
- 235000019256 formaldehyde Nutrition 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- 238000007792 addition Methods 0.000 description 9
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000012448 Lithium borohydride Substances 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
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 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 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 150000003509 tertiary alcohols Chemical class 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- OURKKNDNLSPPQY-CMPLNLGQSA-N (3r,7as)-3-phenyl-3,6,7,7a-tetrahydro-1h-pyrrolo[1,2-c][1,3]oxazol-5-one Chemical compound C1([C@H]2OC[C@@H]3CCC(N23)=O)=CC=CC=C1 OURKKNDNLSPPQY-CMPLNLGQSA-N 0.000 description 2
- MZARDIUTIFMTSJ-BQBZGAKWSA-N (3s,5s)-5-(hydroxymethyl)-3-propan-2-ylpyrrolidin-2-one Chemical compound CC(C)[C@@H]1C[C@@H](CO)NC1=O MZARDIUTIFMTSJ-BQBZGAKWSA-N 0.000 description 2
- HOBJEFOCIRXQKH-BYPYZUCNSA-N (5s)-5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OC[C@@H]1CCC(=O)N1 HOBJEFOCIRXQKH-BYPYZUCNSA-N 0.000 description 2
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 2
- GHELJWBGTIKZQW-UHFFFAOYSA-N 1-propan-2-ylpyrrolidin-2-one Chemical compound CC(C)N1CCCC1=O GHELJWBGTIKZQW-UHFFFAOYSA-N 0.000 description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 2
- OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 description 2
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 125000004001 thioalkyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
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- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- CEXKZNVRJUEZEG-SSDOTTSWSA-N trimethyl (2r)-3-methylbutane-1,1,2-tricarboxylate Chemical compound COC(=O)[C@H](C(C)C)C(C(=O)OC)C(=O)OC CEXKZNVRJUEZEG-SSDOTTSWSA-N 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/126—Acids containing more than four carbon atoms
- C07C53/128—Acids containing more than four carbon atoms the carboxylic group being bound to a carbon atom bound to at least two other carbon atoms, e.g. neo-acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- 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
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- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-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
- C07D307/30—Heterocyclic compounds containing five-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
- C07D307/32—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-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
- C07D307/30—Heterocyclic compounds containing five-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
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0419361.1A GB0419361D0 (en) | 2004-08-31 | 2004-08-31 | Organic compounds |
| PCT/EP2005/009347 WO2006024501A1 (en) | 2004-08-31 | 2005-08-30 | Alternative synthesis of renin inhibitors and intermediates thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007002419A true MX2007002419A (es) | 2007-04-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007002419A MX2007002419A (es) | 2004-08-31 | 2005-08-30 | Sintesis alternativa de inhibidores de renina e intermediarios de los mismos. |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US7910774B2 (enExample) |
| EP (2) | EP1789377B1 (enExample) |
| JP (1) | JP2008511573A (enExample) |
| KR (1) | KR20070045300A (enExample) |
| CN (2) | CN102417464A (enExample) |
| AT (1) | ATE485257T1 (enExample) |
| AU (1) | AU2005279351B2 (enExample) |
| BR (1) | BRPI0514742A (enExample) |
| CA (1) | CA2576749C (enExample) |
| DE (1) | DE602005024282D1 (enExample) |
| ES (1) | ES2354986T3 (enExample) |
| GB (1) | GB0419361D0 (enExample) |
| MX (1) | MX2007002419A (enExample) |
| PL (1) | PL1789377T3 (enExample) |
| PT (1) | PT1789377E (enExample) |
| RU (1) | RU2411230C2 (enExample) |
| WO (1) | WO2006024501A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB0511686D0 (en) * | 2005-06-08 | 2005-07-13 | Novartis Ag | Organic compounds |
| GB0519764D0 (en) | 2005-09-28 | 2005-11-09 | Novartis Ag | Organic compounds |
| GB0521083D0 (en) * | 2005-10-17 | 2005-11-23 | Novartis Ag | Organic compounds |
| GB2431653A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
| GB2431651A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Synthesis of aryl-octanoyl amide compounds |
| GB2431642A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
| GB2431648A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
| GB2431649A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
| GB2431646A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
| GB0522789D0 (en) | 2005-11-08 | 2005-12-14 | Novartis Ag | Organic compounds |
| PE20081157A1 (es) * | 2006-11-07 | 2008-09-26 | Novartis Ag | Forma cristalina de hemifumarato de alisquireno |
| DE102007049039A1 (de) | 2007-10-11 | 2009-04-16 | Reuter Chemischer Apparatebau Kg | Verfahren zur Herstellung von 8-Hydrazino-8-Aryl-Octanoylderivaten und deren Verwendung |
| EP2062874B1 (en) | 2007-11-20 | 2014-12-17 | KRKA, tovarna zdravil, d.d., Novo mesto | Process and intermediates for the preparation of aliskiren |
| SI2189442T1 (sl) | 2008-11-20 | 2015-03-31 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Postopek in intermediati za pripravo aliskirena |
| JP5746696B2 (ja) * | 2009-08-11 | 2015-07-08 | ノバルティス アーゲー | ラクトンおよびラクタムの開環 |
| WO2011051853A1 (en) | 2009-10-29 | 2011-05-05 | CarboDesign LLC | Manufacturing process for preparing enaniomerically pure 8- aryloctanoic acid derivatives such as aliskiren |
| CN101774986B (zh) | 2010-01-06 | 2012-03-28 | 浙江天宇药业股份有限公司 | 一种制备阿利克伦及其中间体的方法 |
| CN102329244A (zh) * | 2010-07-13 | 2012-01-25 | 凯瑞斯德生化(苏州)有限公司 | 一种rs-托特罗定的制备方法及中间体化合物 |
| CN102372653A (zh) * | 2010-08-10 | 2012-03-14 | 江苏恒瑞医药股份有限公司 | 二苯甲醇类衍生物、其制备方法及其在医药上的应用 |
| EP2551260A1 (en) | 2011-07-28 | 2013-01-30 | Chemo Ibérica, S.A. | Chemical process for opening ring compounds |
| US8703976B2 (en) | 2011-10-02 | 2014-04-22 | Milan Soukup | Manufacturing process for 8-aryloctanoic acids such as Aliskiren |
| ITMI20120354A1 (it) * | 2012-03-07 | 2013-09-08 | Friulchem Spa | Processo per la produzione di aliskirene |
| CN103044273B (zh) * | 2012-11-29 | 2014-12-24 | 珠海保税区丽珠合成制药有限公司 | 一种酒石酸托特罗定的合成方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL88619A0 (en) * | 1987-12-15 | 1989-07-31 | Pfizer | Non-peptidic renin inhibitors |
| DE3837197A1 (de) | 1988-11-02 | 1990-05-03 | Continental Ag | Vorrichtung zum aufbereiten von unvulkanisiertem kautschuk |
| MY119161A (en) | 1994-04-18 | 2005-04-30 | Novartis Ag | Delta-amino-gamma-hydroxy-omega-aryl-alkanoic acid amides with enzyme especially renin inhibiting activities |
| GB9523493D0 (en) * | 1995-11-16 | 1996-01-17 | British Biotech Pharm | Preparation of allyl succinate derivatives and starting materials therefore |
| PT1296935E (pt) | 2000-07-05 | 2009-05-15 | Novartis Ag | Processo para a preparação de octanoil amidas substituídas |
| EP1303478B1 (en) * | 2000-07-25 | 2004-05-26 | Speedel Pharma AG | Process for the preparation of substituted octanoyl amides |
| PT1215201E (pt) * | 2000-12-14 | 2007-02-28 | Speedel Pharma Ag | Processo para a preparação de ariloctanoil amidas |
| US20060154926A1 (en) * | 2002-06-11 | 2006-07-13 | Elan Pharmaceuticals, Inc. | Methods of treating alzheimer's disease using aryl alkanoic acid amides |
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2004
- 2004-08-31 GB GBGB0419361.1A patent/GB0419361D0/en not_active Ceased
-
2005
- 2005-08-30 WO PCT/EP2005/009347 patent/WO2006024501A1/en not_active Ceased
- 2005-08-30 CN CN2011103045513A patent/CN102417464A/zh active Pending
- 2005-08-30 EP EP05775930A patent/EP1789377B1/en not_active Expired - Lifetime
- 2005-08-30 DE DE602005024282T patent/DE602005024282D1/de not_active Expired - Lifetime
- 2005-08-30 CA CA2576749A patent/CA2576749C/en not_active Expired - Fee Related
- 2005-08-30 AT AT05775930T patent/ATE485257T1/de active
- 2005-08-30 KR KR1020077004734A patent/KR20070045300A/ko not_active Abandoned
- 2005-08-30 ES ES05775930T patent/ES2354986T3/es not_active Expired - Lifetime
- 2005-08-30 PL PL05775930T patent/PL1789377T3/pl unknown
- 2005-08-30 MX MX2007002419A patent/MX2007002419A/es active IP Right Grant
- 2005-08-30 CN CN2005800292634A patent/CN101010281B/zh not_active Expired - Fee Related
- 2005-08-30 JP JP2007528770A patent/JP2008511573A/ja active Pending
- 2005-08-30 AU AU2005279351A patent/AU2005279351B2/en not_active Ceased
- 2005-08-30 US US11/573,790 patent/US7910774B2/en not_active Expired - Fee Related
- 2005-08-30 EP EP08158568A patent/EP1978012A1/en not_active Withdrawn
- 2005-08-30 PT PT05775930T patent/PT1789377E/pt unknown
- 2005-08-30 RU RU2007111752/04A patent/RU2411230C2/ru not_active IP Right Cessation
- 2005-08-30 BR BRPI0514742-5A patent/BRPI0514742A/pt not_active IP Right Cessation
-
2011
- 2011-02-07 US US13/022,243 patent/US8143416B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20070208055A1 (en) | 2007-09-06 |
| KR20070045300A (ko) | 2007-05-02 |
| CN101010281A (zh) | 2007-08-01 |
| DE602005024282D1 (de) | 2010-12-02 |
| CN101010281B (zh) | 2011-12-21 |
| CA2576749A1 (en) | 2006-03-09 |
| EP1978012A1 (en) | 2008-10-08 |
| JP2008511573A (ja) | 2008-04-17 |
| RU2411230C2 (ru) | 2011-02-10 |
| EP1789377B1 (en) | 2010-10-20 |
| CN102417464A (zh) | 2012-04-18 |
| US8143416B2 (en) | 2012-03-27 |
| RU2007111752A (ru) | 2008-10-10 |
| AU2005279351A1 (en) | 2006-03-09 |
| US7910774B2 (en) | 2011-03-22 |
| BRPI0514742A (pt) | 2008-06-24 |
| AU2005279351B2 (en) | 2009-04-23 |
| PT1789377E (pt) | 2011-01-25 |
| ES2354986T3 (es) | 2011-03-21 |
| PL1789377T3 (pl) | 2011-04-29 |
| WO2006024501A1 (en) | 2006-03-09 |
| EP1789377A1 (en) | 2007-05-30 |
| US20110137044A1 (en) | 2011-06-09 |
| CA2576749C (en) | 2012-10-16 |
| ATE485257T1 (de) | 2010-11-15 |
| GB0419361D0 (en) | 2004-10-06 |
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