CA2433183A1 - Composes et utilisations associees - Google Patents
Composes et utilisations associees Download PDFInfo
- Publication number
- CA2433183A1 CA2433183A1 CA002433183A CA2433183A CA2433183A1 CA 2433183 A1 CA2433183 A1 CA 2433183A1 CA 002433183 A CA002433183 A CA 002433183A CA 2433183 A CA2433183 A CA 2433183A CA 2433183 A1 CA2433183 A1 CA 2433183A1
- Authority
- CA
- Canada
- Prior art keywords
- inositol
- deoxy
- amino
- glucopyranosyl
- alpha
- 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
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 235000000346 sugar Nutrition 0.000 claims abstract description 46
- CDAISMWEOUEBRE-UHFFFAOYSA-N inositol Chemical compound OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000005557 antagonist Substances 0.000 claims abstract description 22
- 150000003999 cyclitols Chemical class 0.000 claims abstract description 22
- 230000001668 ameliorated effect Effects 0.000 claims abstract description 7
- 229960000367 inositol Drugs 0.000 claims description 127
- 239000000203 mixture Substances 0.000 claims description 116
- 229910052739 hydrogen Inorganic materials 0.000 claims description 70
- 239000001257 hydrogen Substances 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 229910019142 PO4 Inorganic materials 0.000 claims description 26
- 239000010452 phosphate Substances 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 21
- DSCFFEYYQKSRSV-KLJZZCKASA-N D-pinitol Chemical compound CO[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@H]1O DSCFFEYYQKSRSV-KLJZZCKASA-N 0.000 claims description 19
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- DSCFFEYYQKSRSV-UHFFFAOYSA-N 1L-O1-methyl-muco-inositol Natural products COC1C(O)C(O)C(O)C(O)C1O DSCFFEYYQKSRSV-UHFFFAOYSA-N 0.000 claims description 14
- -1 phosphoryl groups Chemical group 0.000 claims description 14
- VJXUJFAZXQOXMJ-UHFFFAOYSA-N D-1-O-Methyl-muco-inositol Natural products CC12C(OC)(C)OC(C)(C)C2CC(=O)C(C23OC2C(=O)O2)(C)C1CCC3(C)C2C=1C=COC=1 VJXUJFAZXQOXMJ-UHFFFAOYSA-N 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 9
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 8
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 8
- 150000001241 acetals Chemical class 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 6
- 150000008300 phosphoramidites Chemical class 0.000 claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 150000008266 deoxy sugars Chemical class 0.000 claims description 5
- 239000008103 glucose Substances 0.000 claims description 5
- 150000002402 hexoses Chemical class 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 4
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 239000011574 phosphorus Substances 0.000 claims description 4
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004354 sulfur functional group Chemical group 0.000 claims description 4
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 4
- 150000003580 thiophosphoric acid esters Chemical class 0.000 claims description 4
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical group N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 claims description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 3
- 229960002442 glucosamine Drugs 0.000 claims description 3
- 150000002972 pentoses Chemical class 0.000 claims description 3
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 229930182830 galactose Natural products 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 3
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 3
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 3
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 3
- 229910006074 SO2NH2 Inorganic materials 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000003042 antagnostic effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 195
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 190
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 175
- 239000000243 solution Substances 0.000 description 92
- 235000019439 ethyl acetate Nutrition 0.000 description 81
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 71
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 238000003786 synthesis reaction Methods 0.000 description 64
- 230000015572 biosynthetic process Effects 0.000 description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
- 239000011541 reaction mixture Substances 0.000 description 45
- 238000005481 NMR spectroscopy Methods 0.000 description 44
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 39
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 37
- 238000004440 column chromatography Methods 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 33
- 239000012298 atmosphere Substances 0.000 description 33
- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- 238000004809 thin layer chromatography Methods 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 238000004458 analytical method Methods 0.000 description 30
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 29
- 150000002016 disaccharides Chemical class 0.000 description 27
- 230000000694 effects Effects 0.000 description 27
- 238000003818 flash chromatography Methods 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
- 239000012153 distilled water Substances 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 239000012043 crude product Substances 0.000 description 23
- 239000007858 starting material Substances 0.000 description 23
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- 101150041968 CDC13 gene Proteins 0.000 description 21
- 235000021317 phosphate Nutrition 0.000 description 19
- 159000000000 sodium salts Chemical class 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 239000003102 growth factor Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 12
- 102000004877 Insulin Human genes 0.000 description 12
- 108090001061 Insulin Proteins 0.000 description 12
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 12
- 229940125396 insulin Drugs 0.000 description 12
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 12
- ZULNQPCZALKHMF-UHFFFAOYSA-N IPG-A Natural products [NH3+]C1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C2OP([O-])(=O)OC21 ZULNQPCZALKHMF-UHFFFAOYSA-N 0.000 description 11
- 238000006206 glycosylation reaction Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 10
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 10
- 230000009471 action Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- 150000001720 carbohydrates Chemical class 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 230000013595 glycosylation Effects 0.000 description 8
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 7
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 7
- 239000000348 glycosyl donor Substances 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 6
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000004132 lipogenesis Effects 0.000 description 6
- 239000002808 molecular sieve Substances 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 5
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 5
- DSCFFEYYQKSRSV-HMSOCMLXSA-N D-pinitol Natural products CO[C@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](O)[C@H]1O DSCFFEYYQKSRSV-HMSOCMLXSA-N 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 239000007819 coupling partner Substances 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 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 4
- HWPBAVIEENPTJY-MZIUKZFCSA-N (3r,4r,5r,6r)-3-azido-4,5-bis(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-ol Chemical compound C([C@H]1OC([C@@H]([C@@H](OCC=2C=CC=CC=2)[C@H]1OCC=1C=CC=CC=1)N=[N+]=[N-])O)OCC1=CC=CC=C1 HWPBAVIEENPTJY-MZIUKZFCSA-N 0.000 description 4
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000020286 Pyruvate Dehydrogenase (Lipoamide)-Phosphatase Human genes 0.000 description 4
- 108010040259 Pyruvate Dehydrogenase (Lipoamide)-Phosphatase Proteins 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 229940125797 compound 12 Drugs 0.000 description 4
- 229940125898 compound 5 Drugs 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 150000002009 diols Chemical class 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 4
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- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne des composés possédant une propriété antagoniste ou mimétique d'un inositolphosphoglycanne (IPG), ainsi que l'utilisation de ces composés, de même que l'emploi de ceux-ci, par exemple pour traiter un état amélioré par l'administration d'un second messager IPG ou d'un antagoniste IPG de celui-ci. L'invention concerne notamment des composés comportant une liaison 1,6 d'un reste sucre et d'un cyclitol.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20359600P | 2000-05-12 | 2000-05-12 | |
| US60/203,596 | 2000-05-12 | ||
| GB0011594.9 | 2000-05-12 | ||
| GB0011594A GB0011594D0 (en) | 2000-05-12 | 2000-05-12 | Compounds and their uses |
| US09/798,005 | 2001-03-02 | ||
| US09/798,005 US6953781B2 (en) | 2000-05-12 | 2001-03-02 | Compounds and their uses |
| PCT/GB2001/002088 WO2001085740A2 (fr) | 2000-05-12 | 2001-05-11 | Composes et utilisations associees |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2433183A1 true CA2433183A1 (fr) | 2001-11-15 |
Family
ID=27255717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002433183A Abandoned CA2433183A1 (fr) | 2000-05-12 | 2001-05-11 | Composes et utilisations associees |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1406913A2 (fr) |
| AU (1) | AU6042601A (fr) |
| CA (1) | CA2433183A1 (fr) |
| WO (1) | WO2001085740A2 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2878850B1 (fr) | 2004-12-02 | 2008-10-31 | Cis Bio Internat Sa | Derives de l'inositol-1-phosphate |
| WO2008080064A1 (fr) * | 2006-12-21 | 2008-07-03 | Trustees Of Tufts College | Glycanes inositol lipophiles synthétiques pour traiter le cancer et des troubles du métabolisme du glucose |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19649350A1 (de) * | 1996-11-28 | 1998-06-04 | Hoechst Ag | Inositolglykane mit insulinartiger Wirkung |
-
2001
- 2001-05-11 EP EP01934120A patent/EP1406913A2/fr not_active Withdrawn
- 2001-05-11 AU AU60426/01A patent/AU6042601A/en not_active Abandoned
- 2001-05-11 CA CA002433183A patent/CA2433183A1/fr not_active Abandoned
- 2001-05-11 WO PCT/GB2001/002088 patent/WO2001085740A2/fr not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU6042601A (en) | 2001-11-20 |
| EP1406913A2 (fr) | 2004-04-14 |
| WO2001085740A2 (fr) | 2001-11-15 |
| WO2001085740A3 (fr) | 2002-03-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |