WO2003076404A1 - Thioester d'acide oligolactique en chaine - Google Patents
Thioester d'acide oligolactique en chaine Download PDFInfo
- Publication number
- WO2003076404A1 WO2003076404A1 PCT/JP2003/001696 JP0301696W WO03076404A1 WO 2003076404 A1 WO2003076404 A1 WO 2003076404A1 JP 0301696 W JP0301696 W JP 0301696W WO 03076404 A1 WO03076404 A1 WO 03076404A1
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- WO
- WIPO (PCT)
- Prior art keywords
- group
- compound
- formula
- compound represented
- lactic acid
- Prior art date
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- 150000007970 thio esters Chemical class 0.000 title abstract description 15
- 239000002253 acid Substances 0.000 title abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 63
- 125000003118 aryl group Chemical group 0.000 claims abstract description 21
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000006618 5- to 10-membered aromatic heterocyclic group Chemical group 0.000 claims description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- -1 disulfide compound Chemical class 0.000 description 37
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 235000014655 lactic acid Nutrition 0.000 description 11
- 239000004310 lactic acid Substances 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000005185 salting out Methods 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- GNWXVOQHLPBSSR-UHFFFAOYSA-N oxolane;toluene Chemical compound C1CCOC1.CC1=CC=CC=C1 GNWXVOQHLPBSSR-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229920000747 poly(lactic acid) Polymers 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000013638 trimer Substances 0.000 description 4
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229940125797 compound 12 Drugs 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000004626 polylactic acid Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 229940125810 compound 20 Drugs 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
- 150000003949 imides Chemical class 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- OZZQHCBFUVFZGT-BKLSDQPFSA-N (2s)-2-(2-hydroxypropanoyloxy)propanoic acid Chemical compound CC(O)C(=O)O[C@@H](C)C(O)=O OZZQHCBFUVFZGT-BKLSDQPFSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical compound SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- FQXRXTUXSODUFZ-UHFFFAOYSA-N 1h-imidazol-2-ylmethanethiol Chemical class SCC1=NC=CN1 FQXRXTUXSODUFZ-UHFFFAOYSA-N 0.000 description 1
- FFFIRKXTFQCCKJ-UHFFFAOYSA-M 2,4,6-trimethylbenzoate Chemical compound CC1=CC(C)=C(C([O-])=O)C(C)=C1 FFFIRKXTFQCCKJ-UHFFFAOYSA-M 0.000 description 1
- UIOKLEZTPFZUMQ-UHFFFAOYSA-N 2-(1h-imidazol-2-yldisulfanyl)-1h-imidazole Chemical compound N=1C=CNC=1SSC1=NC=CN1 UIOKLEZTPFZUMQ-UHFFFAOYSA-N 0.000 description 1
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- LAXBNTIAOJWAOP-UHFFFAOYSA-N 2-chlorobiphenyl Chemical group ClC1=CC=CC=C1C1=CC=CC=C1 LAXBNTIAOJWAOP-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- JOOXCMJARBKPKM-UHFFFAOYSA-M 4-oxopentanoate Chemical compound CC(=O)CCC([O-])=O JOOXCMJARBKPKM-UHFFFAOYSA-M 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 229930182843 D-Lactic acid Natural products 0.000 description 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
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- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- RMIODHQZRUFFFF-UHFFFAOYSA-M methoxyacetate Chemical compound COCC([O-])=O RMIODHQZRUFFFF-UHFFFAOYSA-M 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229920002601 oligoester Polymers 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000005547 pivalate group Chemical group 0.000 description 1
- 229920001432 poly(L-lactide) Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 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
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- 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
- A61K31/695—Silicon 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/22—Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings 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
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the present invention relates to a linear oligolactic acid thioester and a method for producing the same. More specifically, the present invention relates to a chain oligoester thioester having a thioester group at a terminal, and a method for producing the same.
- Cyclic and / or chain poly-L-lactic acid mixtures having a degree of condensation of 3 to 19 can be used as antineoplastic agents (JP-A-9-227388 and JP-A-10-13015). 3) and as a QOL improver for cancer patients (Japanese Patent Application No. 11-39,894; Japanese Journal of Cancer Therapy Vol. 33, No. 3, page 493) Is reported.
- the cyclic and / or chain polylactic acid mixture having a condensation degree of 3 to 19 has a hypoglycemic effect and is useful as a drug for preventing and / or treating diabetes or diabetic complications. (Japanese Patent Application No. 111-224883), which is also useful for suppressing excessive appetite, promoting basal metabolism, improving obesity and preventing or preventing Z or Z. I have.
- cyclic and / or chain oligolactic acid mixtures having a condensation degree of 3 to 19 are being demonstrated to exhibit a wide variety of medicinal effects, and are expected to be developed as pharmaceuticals in the future .
- polylactic acid having a specific chain length as a single compound For the purpose of isolating polylactic acid having a specific chain length as a single compound, attempts have been made to synthesize a chain oligolactic acid ester having a degree of condensation of 3 to 20 by esterifying a terminal carboxyl group.
- the present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, using lactic acid as a starting material and reacting it with a disulfide compound, a linear oligolactic acid thioester having a thioester group at the terminal is obtained.
- a linear oligolactic acid thioester having a thioester group at the terminal is obtained.
- the present invention has been completed based on this finding.
- X represents a hydrogen atom or a hydroxyl-protecting group
- Y represents an aliphatic group, an aryl group, or a heterocyclic group
- n represents an integer of 0 to 19
- n represents an integer of 0 to 5, and particularly preferably, n is 0 or 2.
- Y is a heterocyclic group, more preferably, Y is a 5- to 10-membered aromatic heterocyclic group containing 1 or 2 heteroatoms, particularly preferably, Y is And a pyridyl group or a (4-tributyl-1 ⁇ -isopropyl) imidazolyl group.
- a compound represented by the formula CH 3 CH (OX) COOH (where X represents a hydrogen atom or a protecting group for a hydroxyl group), and a compound represented by the formula Y—S—S—Y ( formula Wherein Y represents an aliphatic group, an aryl group or a heterocyclic group), and producing a compound represented by the formula CH 3 CH (OX) CO—S—Y
- X represents a hydrogen atom or a protecting group for a hydroxyl group
- Y—S—S—Y formula Wherein Y represents an aliphatic group, an aryl group or a heterocyclic group
- X represents a hydrogen atom or a protecting group of hydroxyl group
- CH 3 CH (OX) COOCH (CH 3) COO H with a compound represented by the formula CH 3
- Y represents an aliphatic group, an aryl group or a heterocyclic group
- CH 3 CH (OX) COOCH (CH 3 ) COOCH (CH 3 ) CO—S—Y wherein X represents a hydrogen atom or a hydroxyl-protecting group, and Y represents an aliphatic group, an aryl group or a heterocyclic group
- the present invention relates to a compound represented by the following general formula (1) or a salt thereof.
- X represents a hydrogen atom or a hydroxyl-protecting group
- Y represents an aliphatic group, an aryl group or a heterocyclic group
- n represents 0 or an integer of 19
- the type of the protecting group for the hydroxyl group represented by X is not particularly limited, and can be appropriately selected by those skilled in the art.
- Specific examples of the hydroxyl-protecting group include the following.
- the type of the aliphatic group, aryl group or heterocyclic group represented by Y is not particularly limited.
- aliphatic group in the present invention a lower alkyl group, a lower alkenyl group or And higher alkynyl groups.
- carbon number of the aliphatic group is not particularly limited, it is generally 1 to 10, preferably 1 to 6, and more preferably 1 to 4.
- the chain type of the aliphatic group is not particularly limited, and may be any of a linear chain, a branched chain, a cyclic chain, or a combination thereof.
- a lower alkyl group is particularly preferred.
- Specific examples of lower alkyl groups include methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopropylmethyl, cyclobutyl , A pentyl group and a hexyl group.
- the aryl group in the present invention is an aryl group having 6 to 24 carbon atoms, preferably 6 to 12 carbon atoms, and the aryl group may have one or more substituents.
- Specific examples of aryl groups include, for example, phenyl, naphthyl, p-methoxyphenyl and the like.
- the heterocyclic group in the present invention is a 5- to 10-membered saturated or unsaturated monocyclic or condensed ring containing at least one oxygen atom, nitrogen atom or sulfur atom.
- Specific examples of the heterocyclic group include, for example, pyridyl, imidazolyl, quinolyl, isoquinolyl, pyrimidinyl, pyrazul, pyridazinyl, phthalazinyl, triazinyl, furyl, chenyl, pyrrolyl, thixazolyl, thiazolyl, thiadiazolyl, triazolyl, triazolyl Imidazolinole, pyrrolidino, morpholino and the like.
- these hetero rings may have one or more substituents.
- Examples of the substituent which the aryl group or heterocyclic group may have include a halogen atom (fluorine, chlorine, bromine, or iodine), an alkyl group, an aryl group, a carboxamide group, an alkylsulfonamide group, Arylsulfonamide, alkoxy, aryloxy, alkylthio, arylthio, carpamoyl, sulfamoyl, cyano, alkylsulfonyl, arylsulfonyl, alkoxycarbonyl, aryloxycarbo- And a hydroxyl group.
- a halogen atom fluorine, chlorine, bromine, or iodine
- Y is preferably an aromatic group, and particularly preferably, Y is a 5- to 10-membered aromatic heterocyclic group containing one or two hetero atoms. Most preferably, Y is a pyridyl group or a (4-4--butyl-N-isopropyl) imidazolyl group.
- ⁇ represents an integer of 0 to 19. When ⁇ is 0, it becomes a monomer of lactic acid, when ⁇ is 1, it becomes a dimer of lactic acid, when ⁇ is 2, it becomes a trimer of lactic acid, and when ⁇ is 3, it becomes a trimer of lactic acid. When ⁇ is 19 in the same manner, it becomes a 20-mer of lactic acid.
- ⁇ preferably represents an integer of 0 to 5, and in a particularly preferred embodiment, ⁇ is 0 or 2.
- the compound of the present invention can also exist as a metal salt.
- a metal salt include an alkali metal salt such as a sodium salt and a potassium salt, and magnesium. Salts, alkaline earth metal salts such as calcium salts, aluminum salts, zinc salts and the like.
- the compounds of the present invention contain asymmetric carbon atoms, stereoisomers exist, and all possible isomers and mixtures containing two or more of these isomers in any ratio are within the scope of the present invention. Things. That is, the compound of the present invention includes a mixture of various optical isomers such as an optically active substance, a racemate and a diastereomer, and an isolated form thereof.
- the configuration of the compound of the present invention depends on the configuration of a lactic acid unit in the compound used as a raw material. That is, the configuration of the compound of the present invention varies depending on whether the L-form, the D-form or a mixture thereof is used as the lactic acid unit in the compound used as a raw material. In the present invention, it is preferable to use the L-form as the configuration of the lactic acid unit.
- the compound represented by CH 3 CH (OX) CO-S—Y corresponding to the compound in which ⁇ is 0 is CH.
- CH (OX) COOH where X is a hydrogen source Reacting with a compound represented by the general formula Y—S—S—Y (wherein Y represents an aliphatic group, an aryl group or a heterocyclic group) Can be manufactured.
- L-lactic acid As CH 3 CH (OX) COOH used as a starting material, L-lactic acid, D-lactic acid, or a mixture thereof can be used. The hydroxyl group in lactic acid may be protected.
- the reaction temperature is not particularly limited as long as the reaction proceeds, but is preferably from 1100 ° C to room temperature.
- the reaction is preferably performed in the presence of a reaction solvent.
- the reaction solvent is not particularly limited as long as it is an inert solvent for the reaction, but is preferably an aromatic hydrocarbon solvent such as benzene, toluene, xylene, and ethylbenzene, tetrahydrofuran (THF), getyl ether, and dimethoxetane. Can be used.
- reaction atmosphere an inert gas atmosphere such as nitrogen gas or argon gas can be used.
- a toluene solution of triphenylphosphine is added to a toluene solution of L-lactic acid, and a compound represented by the formula Y—S—S—Y (for example, pyridyl disulfide or 2,2-bis- (4- --butyl-N-isopropyl) imidazo Toluene solution) and stirred for 15 hours. After concentration under reduced pressure, add water and extract several times with black-mouthed form.
- Y—S—S—Y for example, pyridyl disulfide or 2,2-bis- (4- --butyl-N-isopropyl) imidazo Toluene solution
- CH 3 CH (OX) CO OCH (CH 3 ) CO—S—Y which corresponds to the compound in which n is 1 in the general formula (1), is used as a starting material for CH 3 CH (OX) COOH
- CH 3 CH (OX) COOCH (CH 3 ) CO OH By using CH 3 CH (OX) COOCH (CH 3 ) CO OH instead of using, as described above, by reacting with the compound represented by the formula Y—S—S—Y be able to.
- the compound represented by the formula CH 3 CH (OX) COOCH (CH 3 ) COOH (wherein X represents a hydrogen atom or a hydroxyl-protecting group) is lactoyl lactic acid optionally protected with a hydroxyl group.
- X represents a hydrogen atom or a hydroxyl-protecting group
- the esterification reaction may be, for example, a solution containing the formula CH 3 CH (OX) COOCH ( CH 3) a compound represented by C OOH, after stirring added cyclohexyl Cal positive imide solution dicyclohexyl formula CH 3 CH ( OH) CO—S—Y can be carried out by adding a solution of the compound represented by S—Y and a dimethylaminopyridine solution and stirring for a certain period of time.
- the reaction temperature is not particularly limited as long as the reaction proceeds, but is preferably from 1100 ° C to room temperature.
- the reaction is preferably carried out in the presence of a reaction solvent.
- the reaction solvent is not particularly limited as long as it is a solvent inert to the reaction, and preferably, toluene, benzene, xylene, alkylbenzene, tetrahydrofuran (THF), ethynoleatel, dimethoxetane, or the like can be used.
- an inert gas atmosphere such as a nitrogen gas or an argon gas can be used.
- a compound in which n is 0, 1 or 2 in the general formula (1) can be produced.
- a thioester compound containing a desired number of lactic acid units is used as a starting material for the compound in which n is 3, and this is represented by the formula CH 3 CH (OX) COOCH (CH 3 ) COOH (wherein X represents a protecting group for a hydroxyl group).
- Example Example 1 Synthesis of L-lactic acid pyridyl thiol ester
- the obtained product was directly used for the next reaction.
- the present invention it has become possible to provide a linear oligolactic acid thioester having a thioester group at a terminal as a single compound.
- the oligolactic acid thioester It will be possible to develop Teru as pharmaceuticals, pharmaceutical ingredients, food additives, cosmetic ingredients, pharmaceutical ingredients, and pharmaceutical additives.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2004-7012861A KR20040085202A (ko) | 2002-02-19 | 2003-02-18 | 쇄상 올리고유산 티오에스테르 |
AU2003211386A AU2003211386A1 (en) | 2002-02-19 | 2003-02-18 | Chain oligolactic acid thioester |
JP2003574625A JPWO2003076404A1 (ja) | 2002-02-19 | 2003-02-18 | 鎖状オリゴ乳酸チオエステル |
CA002480001A CA2480001A1 (en) | 2002-02-19 | 2003-02-18 | Chain oligolactic acid thioester |
US10/503,582 US20050222420A1 (en) | 2002-02-19 | 2003-02-18 | Chain oligolactic acid thioester |
EP03705267A EP1484319A4 (en) | 2002-02-19 | 2003-02-18 | CHAIN OLIGOMIC ACID ETHANOL |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002042008 | 2002-02-19 | ||
JP2002-42008 | 2002-02-19 |
Publications (1)
Publication Number | Publication Date |
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WO2003076404A1 true WO2003076404A1 (fr) | 2003-09-18 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2003/001696 WO2003076404A1 (fr) | 2002-02-19 | 2003-02-18 | Thioester d'acide oligolactique en chaine |
Country Status (10)
Country | Link |
---|---|
US (1) | US20050222420A1 (ja) |
EP (1) | EP1484319A4 (ja) |
JP (1) | JPWO2003076404A1 (ja) |
KR (1) | KR20040085202A (ja) |
CN (1) | CN1646492A (ja) |
AU (1) | AU2003211386A1 (ja) |
CA (1) | CA2480001A1 (ja) |
RU (1) | RU2004127918A (ja) |
TW (1) | TW200303299A (ja) |
WO (1) | WO2003076404A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2005290255A (ja) * | 2004-04-01 | 2005-10-20 | Sanyo Chem Ind Ltd | ポリエステル樹脂配合用エステル化合物 |
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RU2527471C1 (ru) * | 2013-04-19 | 2014-08-27 | Федеральное государственное унитарное предприятие "Научно-исследовательский институт химии и технологии полимеров имени академика В.А. Каргина с опытным заводом" (ФГУП "НИИ полимеров") | Полиэфирполикарбонаты олигомолочной кислоты |
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AU779592B2 (en) * | 1999-08-09 | 2005-02-03 | Amato Pharmaceutical Products, Ltd. | Therapeutic agent for diabetes |
WO2001021612A1 (fr) * | 1999-09-20 | 2001-03-29 | Amato Pharmaceutical Products, Ltd. | Procede de preparation d'oligomeres cycliques d'acide lactique |
EP1219617A4 (en) * | 1999-09-20 | 2002-11-06 | Amato Pharm Prod Ltd | PROCESS FOR THE PREPARATION OF CYCLIC LACTIC ACID OLIGOMERS |
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- 2003-02-18 KR KR10-2004-7012861A patent/KR20040085202A/ko not_active Application Discontinuation
- 2003-02-18 WO PCT/JP2003/001696 patent/WO2003076404A1/ja not_active Application Discontinuation
- 2003-02-18 AU AU2003211386A patent/AU2003211386A1/en not_active Abandoned
- 2003-02-18 CN CNA038087715A patent/CN1646492A/zh active Pending
- 2003-02-18 RU RU2004127918/04A patent/RU2004127918A/ru not_active Application Discontinuation
- 2003-02-18 CA CA002480001A patent/CA2480001A1/en not_active Abandoned
- 2003-02-18 JP JP2003574625A patent/JPWO2003076404A1/ja active Pending
- 2003-02-18 TW TW092103323A patent/TW200303299A/zh unknown
- 2003-02-18 US US10/503,582 patent/US20050222420A1/en not_active Abandoned
- 2003-02-18 EP EP03705267A patent/EP1484319A4/en not_active Withdrawn
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JP2005290255A (ja) * | 2004-04-01 | 2005-10-20 | Sanyo Chem Ind Ltd | ポリエステル樹脂配合用エステル化合物 |
JP4655496B2 (ja) * | 2004-04-01 | 2011-03-23 | 東レ株式会社 | ポリエステル樹脂配合用エステル化合物 |
Also Published As
Publication number | Publication date |
---|---|
CN1646492A (zh) | 2005-07-27 |
EP1484319A1 (en) | 2004-12-08 |
RU2004127918A (ru) | 2005-04-10 |
CA2480001A1 (en) | 2003-09-18 |
KR20040085202A (ko) | 2004-10-07 |
AU2003211386A1 (en) | 2003-09-22 |
JPWO2003076404A1 (ja) | 2005-07-07 |
TW200303299A (en) | 2003-09-01 |
EP1484319A4 (en) | 2007-01-24 |
US20050222420A1 (en) | 2005-10-06 |
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