CA2567149A1 - Method for producing 1,4-diphenyl azetidinone derivatives - Google Patents
Method for producing 1,4-diphenyl azetidinone derivatives Download PDFInfo
- Publication number
- CA2567149A1 CA2567149A1 CA002567149A CA2567149A CA2567149A1 CA 2567149 A1 CA2567149 A1 CA 2567149A1 CA 002567149 A CA002567149 A CA 002567149A CA 2567149 A CA2567149 A CA 2567149A CA 2567149 A1 CA2567149 A1 CA 2567149A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- general formula
- benzyl
- anion
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 12
- HZVHFGGPXITZGN-UHFFFAOYSA-N 1,4-diphenylazetidin-2-one Chemical class O=C1CC(C=2C=CC=CC=2)N1C1=CC=CC=C1 HZVHFGGPXITZGN-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 78
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 66
- 239000003054 catalyst Substances 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 41
- -1 phosphonium ions Chemical class 0.000 claims abstract description 37
- 150000001450 anions Chemical class 0.000 claims abstract description 31
- 150000001768 cations Chemical class 0.000 claims abstract description 28
- 125000001424 substituent group Chemical group 0.000 claims abstract description 18
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 125000006732 (C1-C15) alkyl group Chemical group 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910000108 silver(I,III) oxide Inorganic materials 0.000 claims abstract description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 38
- 125000000217 alkyl group Chemical group 0.000 claims description 128
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 62
- 150000001875 compounds Chemical class 0.000 claims description 52
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000004122 cyclic group Chemical group 0.000 claims description 11
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
- 239000002243 precursor Substances 0.000 claims description 8
- 150000002466 imines Chemical class 0.000 claims description 7
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 6
- 101150020251 NR13 gene Proteins 0.000 claims description 6
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 6
- 150000005840 aryl radicals Chemical class 0.000 claims description 6
- 239000000543 intermediate Substances 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- SJSSFUMSAFMFNM-NSHDSACASA-N (2s)-5-(diaminomethylideneamino)-2-(phenylmethoxycarbonylamino)pentanoic acid Chemical group NC(N)=NCCC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 SJSSFUMSAFMFNM-NSHDSACASA-N 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 125000005275 alkylenearyl group Chemical group 0.000 claims description 3
- FRZNJFWQVYAVCE-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)phenyl]urea Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C=CC(OCCN3CCOCC3)=CC=2)=CC(C(C)(C)C)=N1 FRZNJFWQVYAVCE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 7
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
- 125000006663 (C1-C6) perfluoroalkyl group Chemical group 0.000 claims 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical group [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 abstract 1
- 150000002500 ions Chemical class 0.000 abstract 1
- 238000006884 silylation reaction Methods 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000000047 product Substances 0.000 description 17
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 15
- 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- 238000004611 spectroscopical analysis Methods 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical group O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 5
- 238000004811 liquid chromatography Methods 0.000 description 5
- 238000004949 mass spectrometry Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 4
- BJQWBACJIAKDTJ-UHFFFAOYSA-N tetrabutylphosphanium Chemical compound CCCC[P+](CCCC)(CCCC)CCCC BJQWBACJIAKDTJ-UHFFFAOYSA-N 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- JHMCCBLFRSWDAL-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-trimethylsilyloxypropyl]-4-(4-trimethylsilyloxyphenyl)azetidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O[Si](C)(C)C)CCC(C1=O)C(C=2C=CC(O[Si](C)(C)C)=CC=2)N1C1=CC=C(F)C=C1 JHMCCBLFRSWDAL-UHFFFAOYSA-N 0.000 description 3
- XXMINDVVBVJXLN-UHFFFAOYSA-N 3-[2-[(4-fluoroanilino)-(4-trimethylsilyloxyphenyl)methyl]-5-(4-fluorophenyl)-5-trimethylsilyloxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one Chemical compound C=1C=C(F)C=CC=1C(O[Si](C)(C)C)CCC(C(=O)N1C(OCC1C=1C=CC=CC=1)=O)C(C=1C=CC(O[Si](C)(C)C)=CC=1)NC1=CC=C(F)C=C1 XXMINDVVBVJXLN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- LKWREPCOICZYPW-UHFFFAOYSA-N isoindole-1,3-dione;tetrabutylphosphanium Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1.CCCC[P+](CCCC)(CCCC)CCCC LKWREPCOICZYPW-UHFFFAOYSA-N 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- IBWGNZVCJVLSHB-UHFFFAOYSA-M tetrabutylphosphanium;chloride Chemical compound [Cl-].CCCC[P+](CCCC)(CCCC)CCCC IBWGNZVCJVLSHB-UHFFFAOYSA-M 0.000 description 3
- VDOXIAUNJCHYRC-UHFFFAOYSA-N 1,3-diphenylazetidin-2-one Chemical class O=C1C(C=2C=CC=CC=2)CN1C1=CC=CC=C1 VDOXIAUNJCHYRC-UHFFFAOYSA-N 0.000 description 2
- MIDFBQUKDSNNJB-UHFFFAOYSA-N 1-methylimidazolidine-2,4-dione;tetrabutylphosphanium Chemical compound CN1CC(=O)NC1=O.CCCC[P+](CCCC)(CCCC)CCCC MIDFBQUKDSNNJB-UHFFFAOYSA-N 0.000 description 2
- RZORHCYZIPDOEQ-UHFFFAOYSA-N 1-phenylpyrazolidin-3-one;tetrabutylphosphanium Chemical compound N1C(=O)CCN1C1=CC=CC=C1.CCCC[P+](CCCC)(CCCC)CCCC RZORHCYZIPDOEQ-UHFFFAOYSA-N 0.000 description 2
- TVZDIFXOIOIPJG-UHFFFAOYSA-N 2,3,4-trichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C(Cl)=C1Cl TVZDIFXOIOIPJG-UHFFFAOYSA-N 0.000 description 2
- CJHVARBIOIEEDV-UHFFFAOYSA-M 2-carbamoylbenzoate;tetrabutylphosphanium Chemical compound NC(=O)C1=CC=CC=C1C([O-])=O.CCCC[P+](CCCC)(CCCC)CCCC CJHVARBIOIEEDV-UHFFFAOYSA-M 0.000 description 2
- BPPWPENTHHVITF-UHFFFAOYSA-N 3-(4-chlorophenyl)-2h-1,2-oxazol-5-one;tetrabutylphosphanium Chemical compound C1=CC(Cl)=CC=C1C1=CC(=O)ON1.CCCC[P+](CCCC)(CCCC)CCCC BPPWPENTHHVITF-UHFFFAOYSA-N 0.000 description 2
- SMAIVJWFFJTXMR-UHFFFAOYSA-N 4-phenyl-1,3-oxazolidin-2-one;tetrabutylphosphanium Chemical compound C1OC(=O)NC1C1=CC=CC=C1.CCCC[P+](CCCC)(CCCC)CCCC SMAIVJWFFJTXMR-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- RHYBFKMFHLPQPH-UHFFFAOYSA-N N-methylhydantoin Chemical compound CN1CC(=O)NC1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000005604 azodicarboxylate group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- ITVPBBDAZKBMRP-UHFFFAOYSA-N chloro-dioxido-oxo-$l^{5}-phosphane;hydron Chemical compound OP(O)(Cl)=O ITVPBBDAZKBMRP-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 229960000815 ezetimibe Drugs 0.000 description 2
- 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 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- SZKMOHANKVSMDV-UHFFFAOYSA-N methanolate;tetrabutylphosphanium Chemical compound [O-]C.CCCC[P+](CCCC)(CCCC)CCCC SZKMOHANKVSMDV-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CMCWWLVWPDLCRM-UHFFFAOYSA-N phenidone Chemical compound N1C(=O)CCN1C1=CC=CC=C1 CMCWWLVWPDLCRM-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- KUWWEBCTNVMTHS-UHFFFAOYSA-N pyrrolidine-2,5-dione;tetrabutylphosphanium Chemical compound O=C1CCC(=O)N1.CCCC[P+](CCCC)(CCCC)CCCC KUWWEBCTNVMTHS-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- DFQPZDGUFQJANM-UHFFFAOYSA-M tetrabutylphosphanium;hydroxide Chemical compound [OH-].CCCC[P+](CCCC)(CCCC)CCCC DFQPZDGUFQJANM-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- DPJYJNYYDJOJNO-UHFFFAOYSA-N (2s)-bornane-10,2-sultam Chemical compound C1S(=O)(=O)NC2CC3C(C)(C)C12CC3 DPJYJNYYDJOJNO-UHFFFAOYSA-N 0.000 description 1
- UEFCKYIRXORTFI-UHFFFAOYSA-N 1,2-thiazolidin-3-one Chemical compound O=C1CCSN1 UEFCKYIRXORTFI-UHFFFAOYSA-N 0.000 description 1
- MQTYLLBYHMUFRG-UHFFFAOYSA-N 1,3-dihydro-2,1,3-benzothiadiazole Chemical class C1=CC=C2NSNC2=C1 MQTYLLBYHMUFRG-UHFFFAOYSA-N 0.000 description 1
- HOBYPSNNFBRLIX-UHFFFAOYSA-N 1,8-naphthosultam Chemical compound C1=CC(S(=O)(=O)N2)=C3C2=CC=CC3=C1 HOBYPSNNFBRLIX-UHFFFAOYSA-N 0.000 description 1
- KEAYDQMHQHNAIG-UHFFFAOYSA-N 1-sulfanylpyrazolidine Chemical compound SN1CCCN1 KEAYDQMHQHNAIG-UHFFFAOYSA-N 0.000 description 1
- NMGAIVHDKODUHC-UHFFFAOYSA-N 10,10-dimethyl-3lambda6-thia-4-azatricyclo[5.2.1.01,5]decane 3,3-dioxide tetrabutylphosphanium Chemical compound C1S(=O)(=O)NC2CC3C(C)(C)C12CC3.CCCC[P+](CCCC)(CCCC)CCCC NMGAIVHDKODUHC-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- YBONBWJSFMTXLE-UHFFFAOYSA-N 2,3-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1Cl YBONBWJSFMTXLE-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- 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 1
- SUCDHPJUXCCMDN-UHFFFAOYSA-N 2-ethyl-1,3-oxazole Chemical compound CCC1=NC=CO1 SUCDHPJUXCCMDN-UHFFFAOYSA-N 0.000 description 1
- QRKDOAWSBBGNLE-UHFFFAOYSA-N 2h-1,2,4-benzothiadiazine Chemical compound C1=CC=C2N=CNSC2=C1 QRKDOAWSBBGNLE-UHFFFAOYSA-N 0.000 description 1
- ITVJGZHBGBXTFV-UHFFFAOYSA-N 3-(4-chlorophenyl)-2h-1,2-oxazol-5-one Chemical compound C1=CC(Cl)=CC=C1C1=CC(=O)ON1 ITVJGZHBGBXTFV-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QDMNNMIOWVJVLY-UHFFFAOYSA-N 4-phenyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)NC1C1=CC=CC=C1 QDMNNMIOWVJVLY-UHFFFAOYSA-N 0.000 description 1
- QICFUFOXXNIZFF-UHFFFAOYSA-N 5,5-dimethyl-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)C1NC(=O)OC1(C)C QICFUFOXXNIZFF-UHFFFAOYSA-N 0.000 description 1
- LODBQQPVSRUAKI-UHFFFAOYSA-N 5-methyl-2,2-dioxooxathiazin-4-one Chemical class CC1=COS(=O)(=O)NC1=O LODBQQPVSRUAKI-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- NAARKURBWFMSLI-UHFFFAOYSA-L C(C=1C(C(=O)N)=CC=CC1)(=O)[O-].C(CCC)[P+](CCCC)(CCCC)CCCC.C(C=1C(C(=O)N)=CC=CC1)(=O)[O-].C(CCC)[P+](CCCC)(CCCC)CCCC Chemical compound C(C=1C(C(=O)N)=CC=CC1)(=O)[O-].C(CCC)[P+](CCCC)(CCCC)CCCC.C(C=1C(C(=O)N)=CC=CC1)(=O)[O-].C(CCC)[P+](CCCC)(CCCC)CCCC NAARKURBWFMSLI-UHFFFAOYSA-L 0.000 description 1
- MXKOACVKWBZESK-UHFFFAOYSA-N C1(C=2C(C(N1)=O)=CC=CC2)=O.N2C=NC=C2.CN2C(NC(C2)=C)=O.C(C)(C)C2NC(OC2(C2=CC=CC=C2)C2=CC=CC=C2)=O Chemical compound C1(C=2C(C(N1)=O)=CC=CC2)=O.N2C=NC=C2.CN2C(NC(C2)=C)=O.C(C)(C)C2NC(OC2(C2=CC=CC=C2)C2=CC=CC=C2)=O MXKOACVKWBZESK-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108010038807 Oligopeptides Chemical group 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 229910010066 TiC14 Inorganic materials 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- DNPYPKCWCLZLPN-UHFFFAOYSA-L [Cl-].C(CCC)[P+](CCCC)(CCCC)CCCC.O1C(NCC1)=O.C(CCC)[P+](CCCC)(CCCC)CCCC.[Cl-] Chemical compound [Cl-].C(CCC)[P+](CCCC)(CCCC)CCCC.O1C(NCC1)=O.C(CCC)[P+](CCCC)(CCCC)CCCC.[Cl-] DNPYPKCWCLZLPN-UHFFFAOYSA-L 0.000 description 1
- YGPWEUCPSFPTJY-UHFFFAOYSA-N [K].C[O-].C(CCC)[P+](CCCC)(CCCC)CCCC Chemical compound [K].C[O-].C(CCC)[P+](CCCC)(CCCC)CCCC YGPWEUCPSFPTJY-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- SIOVKLKJSOKLIF-UHFFFAOYSA-N bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)OC(C)=N[Si](C)(C)C SIOVKLKJSOKLIF-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000001309 chloro group Chemical class Cl* 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- WYURNTSHIVDZCO-SVYQBANQSA-N deuterated tetrahydrofuran Substances [2H]C1([2H])OC([2H])([2H])C([2H])([2H])C1([2H])[2H] WYURNTSHIVDZCO-SVYQBANQSA-N 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 150000002016 disaccharides Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 210000000936 intestine Anatomy 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- LULXBAGMGMJJRW-UHFFFAOYSA-N n,2-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)CC(=O)N[Si](C)(C)C LULXBAGMGMJJRW-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- FJPVQQBRWYYCNK-UHFFFAOYSA-N oxathiazinane-4,5-dione Chemical class O=C1C(NSOC1)=O FJPVQQBRWYYCNK-UHFFFAOYSA-N 0.000 description 1
- MBACRDZWRXWNMY-UHFFFAOYSA-N oxathiazolidine 2,2-dioxide Chemical class O=S1(=O)NCCO1 MBACRDZWRXWNMY-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000011593 sulfur Chemical group 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
- ZANXRXPJKJZFMU-UHFFFAOYSA-L tetrabutylphosphanium dibenzoate Chemical compound [O-]C(=O)c1ccccc1.[O-]C(=O)c1ccccc1.CCCC[P+](CCCC)(CCCC)CCCC.CCCC[P+](CCCC)(CCCC)CCCC ZANXRXPJKJZFMU-UHFFFAOYSA-L 0.000 description 1
- GFZMLBWMGBLIDI-UHFFFAOYSA-M tetrabutylphosphanium;acetate Chemical compound CC([O-])=O.CCCC[P+](CCCC)(CCCC)CCCC GFZMLBWMGBLIDI-UHFFFAOYSA-M 0.000 description 1
- SZWHXXNVLACKBV-UHFFFAOYSA-N tetraethylphosphanium Chemical compound CC[P+](CC)(CC)CC SZWHXXNVLACKBV-UHFFFAOYSA-N 0.000 description 1
- WFIYFFUAOQKJJS-UHFFFAOYSA-N tetraoctylphosphanium Chemical compound CCCCCCCC[P+](CCCCCCCC)(CCCCCCCC)CCCCCCCC WFIYFFUAOQKJJS-UHFFFAOYSA-N 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000004043 trisaccharides Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen 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
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen 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 one oxygen atom directly attached in position 2, e.g. beta-lactams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE200410025071 DE102004025071B4 (de) | 2004-05-21 | 2004-05-21 | Verfahren zur Herstellung von Diphenylazetidinon-Derivaten |
| DE102004025071.5 | 2004-05-21 | ||
| DE102005010770A DE102005010770A1 (de) | 2005-03-09 | 2005-03-09 | Verfahren zur Herstellung von 1,4-Diphenylazetidinon-Derivaten |
| DE102005010770.2 | 2005-03-09 | ||
| PCT/EP2005/005498 WO2005113496A1 (de) | 2004-05-21 | 2005-05-20 | Verfahren zur herstellung von 1,4-diphenylazetidinon-derivaten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2567149A1 true CA2567149A1 (en) | 2005-12-01 |
Family
ID=37561403
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002567149A Abandoned CA2567149A1 (en) | 2004-05-21 | 2005-05-20 | Method for producing 1,4-diphenyl azetidinone derivatives |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US7488818B2 (https=) |
| EP (1) | EP1756049B1 (https=) |
| JP (1) | JP2007538042A (https=) |
| KR (1) | KR20070027554A (https=) |
| AR (1) | AR049184A1 (https=) |
| AT (1) | ATE376997T1 (https=) |
| AU (1) | AU2005245124A1 (https=) |
| BR (1) | BRPI0510150A (https=) |
| CA (1) | CA2567149A1 (https=) |
| CY (1) | CY1107425T1 (https=) |
| DE (1) | DE502005001841D1 (https=) |
| DK (1) | DK1756049T3 (https=) |
| ES (1) | ES2294712T3 (https=) |
| HR (1) | HRP20070570T3 (https=) |
| IL (1) | IL178991A0 (https=) |
| MA (1) | MA28635B1 (https=) |
| MX (1) | MXPA06013456A (https=) |
| NZ (1) | NZ551413A (https=) |
| PL (1) | PL1756049T3 (https=) |
| PT (1) | PT1756049E (https=) |
| RS (1) | RS50539B (https=) |
| RU (1) | RU2380361C2 (https=) |
| TW (1) | TW200611896A (https=) |
| UY (1) | UY28912A1 (https=) |
| WO (1) | WO2005113496A1 (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0215579D0 (en) | 2002-07-05 | 2002-08-14 | Astrazeneca Ab | Chemical compounds |
| CN100471835C (zh) * | 2003-12-23 | 2009-03-25 | 默克公司 | 抗高胆固醇血症化合物 |
| EP1699759B1 (en) | 2003-12-23 | 2010-10-20 | AstraZeneca AB | Diphenylazetidinone derivates possessing cholesterol absorption inhibitory activity |
| UY29607A1 (es) | 2005-06-20 | 2007-01-31 | Astrazeneca Ab | Compuestos quimicos |
| MY148538A (en) | 2005-06-22 | 2013-04-30 | Astrazeneca Ab | Novel 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions |
| SA06270191B1 (ar) | 2005-06-22 | 2010-03-29 | استرازينيكا ايه بي | مشتقات من 2- أزيتيدينون جديدة باعتبارها مثبطات لامتصاص الكوليسترول لعلاج حالات فرط نسبة الدهون في الدم |
| TW200811098A (en) | 2006-04-27 | 2008-03-01 | Astrazeneca Ab | Chemical compounds |
| US20090047716A1 (en) * | 2007-06-07 | 2009-02-19 | Nurit Perlman | Reduction processes for the preparation of ezetimibe |
| EP2414529A2 (en) | 2009-04-01 | 2012-02-08 | Matrix Laboratories Ltd | Enzymatic process for the preparation of (s)-5-(4-fluoro-phenyl)-5-hydroxy- 1morpholin-4-yl-pentan-1-one, an intermediate of ezetimibe and further conversion to ezetimibe |
| WO2011056895A1 (en) * | 2009-11-03 | 2011-05-12 | University Of Notre Dame Du Lac | Ionic liquids comprising heteraromatic anions |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US9670237B2 (en) | 2011-09-22 | 2017-06-06 | Ut-Battelle, Llc | Phosphonium-based ionic liquids and their use in the capture of polluting gases |
| WO2015048765A1 (en) | 2013-09-30 | 2015-04-02 | University Of Notre Dame Du Lac | Compounds, complexes, compositions, methods and systems for heating and cooling |
| US10086331B2 (en) | 2013-11-05 | 2018-10-02 | University Of Notre Dame Du Lac | Carbon dioxide capture using phase change ionic liquids |
| JP6803138B2 (ja) * | 2014-10-22 | 2020-12-23 | 三星エスディアイ株式会社Samsung SDI Co., Ltd. | ホスホニウム系化合物、それを含むエポキシ樹脂組成物、およびそれを用いて製造された半導体装置 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2107548T3 (es) * | 1991-07-23 | 1997-12-01 | Schering Corp | Compuestos de beta-lactama sustituidos utiles como agentes hipocolesterolemicos y procedimientos para su preparacion. |
| FI960095L (fi) * | 1993-07-09 | 1996-01-09 | Schering Corp | Menetelmä atsetidinonien syntetitoimiseksi |
| US5631365A (en) * | 1993-09-21 | 1997-05-20 | Schering Corporation | Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents |
| HRP20030498A2 (en) * | 2000-12-21 | 2005-04-30 | Aventis Pharma Deutschland Gmbh | Novel 1,2-diphenzylazetidinones, method for producing the same, medicaments containing said compounds, and the use thereof for treating disorders of the lipid metabolism |
| TWI291957B (en) * | 2001-02-23 | 2008-01-01 | Kotobuki Pharmaceutical Co Ltd | Beta-lactam compounds, process for repoducing the same and serum cholesterol-lowering agents containing the same |
-
2005
- 2005-05-20 TW TW094116483A patent/TW200611896A/zh unknown
- 2005-05-20 CA CA002567149A patent/CA2567149A1/en not_active Abandoned
- 2005-05-20 DE DE502005001841T patent/DE502005001841D1/de not_active Expired - Lifetime
- 2005-05-20 AT AT05747892T patent/ATE376997T1/de not_active IP Right Cessation
- 2005-05-20 AR ARP050102099A patent/AR049184A1/es not_active Application Discontinuation
- 2005-05-20 PT PT05747892T patent/PT1756049E/pt unknown
- 2005-05-20 RU RU2006145444/04A patent/RU2380361C2/ru not_active IP Right Cessation
- 2005-05-20 JP JP2007517094A patent/JP2007538042A/ja not_active Abandoned
- 2005-05-20 PL PL05747892T patent/PL1756049T3/pl unknown
- 2005-05-20 HR HR20070570T patent/HRP20070570T3/xx unknown
- 2005-05-20 ES ES05747892T patent/ES2294712T3/es not_active Expired - Lifetime
- 2005-05-20 MX MXPA06013456A patent/MXPA06013456A/es active IP Right Grant
- 2005-05-20 EP EP05747892A patent/EP1756049B1/de not_active Expired - Lifetime
- 2005-05-20 AU AU2005245124A patent/AU2005245124A1/en not_active Abandoned
- 2005-05-20 DK DK05747892T patent/DK1756049T3/da active
- 2005-05-20 UY UY28912A patent/UY28912A1/es unknown
- 2005-05-20 RS RSP-2007/0483A patent/RS50539B/sr unknown
- 2005-05-20 NZ NZ551413A patent/NZ551413A/en unknown
- 2005-05-20 KR KR1020067024431A patent/KR20070027554A/ko not_active Withdrawn
- 2005-05-20 BR BRPI0510150-6A patent/BRPI0510150A/pt not_active IP Right Cessation
- 2005-05-20 WO PCT/EP2005/005498 patent/WO2005113496A1/de not_active Ceased
-
2006
- 2006-11-01 IL IL178991A patent/IL178991A0/en unknown
- 2006-11-17 MA MA29462A patent/MA28635B1/fr unknown
- 2006-11-20 US US11/561,626 patent/US7488818B2/en not_active Expired - Fee Related
-
2008
- 2008-01-10 CY CY20081100037T patent/CY1107425T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE502005001841D1 (de) | 2007-12-13 |
| EP1756049A1 (de) | 2007-02-28 |
| KR20070027554A (ko) | 2007-03-09 |
| AR049184A1 (es) | 2006-07-05 |
| BRPI0510150A (pt) | 2007-10-02 |
| US20070149776A1 (en) | 2007-06-28 |
| TW200611896A (en) | 2006-04-16 |
| IL178991A0 (en) | 2007-03-08 |
| NZ551413A (en) | 2009-07-31 |
| MA28635B1 (fr) | 2007-06-01 |
| PT1756049E (pt) | 2007-12-17 |
| MXPA06013456A (es) | 2007-03-01 |
| WO2005113496A1 (de) | 2005-12-01 |
| US7488818B2 (en) | 2009-02-10 |
| JP2007538042A (ja) | 2007-12-27 |
| PL1756049T3 (pl) | 2008-02-29 |
| RU2380361C2 (ru) | 2010-01-27 |
| CY1107425T1 (el) | 2013-03-13 |
| RS50539B (sr) | 2010-05-07 |
| AU2005245124A1 (en) | 2005-12-01 |
| RU2006145444A (ru) | 2008-06-27 |
| ES2294712T3 (es) | 2008-04-01 |
| EP1756049B1 (de) | 2007-10-31 |
| DK1756049T3 (da) | 2008-02-25 |
| HRP20070570T3 (en) | 2008-01-31 |
| ATE376997T1 (de) | 2007-11-15 |
| UY28912A1 (es) | 2005-12-30 |
| HK1103296A1 (zh) | 2007-12-14 |
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