IL124109A - Pharmaceutical composition of 2-alkylpyrrolidines for use in the manufacture of medicaments for the treatment of diabetes - Google Patents
Pharmaceutical composition of 2-alkylpyrrolidines for use in the manufacture of medicaments for the treatment of diabetesInfo
- Publication number
- IL124109A IL124109A IL12410996A IL12410996A IL124109A IL 124109 A IL124109 A IL 124109A IL 12410996 A IL12410996 A IL 12410996A IL 12410996 A IL12410996 A IL 12410996A IL 124109 A IL124109 A IL 124109A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- substituted
- optionally substituted
- alkyl
- pharmaceutically acceptable
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 206010012601 diabetes mellitus Diseases 0.000 title claims description 19
- 239000003814 drug Substances 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 87
- 239000000203 mixture Substances 0.000 claims abstract description 27
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 230000009229 glucose formation Effects 0.000 claims abstract description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 14
- 210000004185 liver Anatomy 0.000 claims abstract description 13
- 150000004677 hydrates Chemical class 0.000 claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
- 230000003287 optical effect Effects 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 14
- 229920002527 Glycogen Polymers 0.000 claims description 6
- 229940096919 glycogen Drugs 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 12
- 150000002367 halogens Chemical class 0.000 abstract description 12
- -1 hydroxy, mercapto Chemical class 0.000 abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 8
- 239000001257 hydrogen Substances 0.000 abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 abstract description 5
- 150000002431 hydrogen Chemical group 0.000 abstract description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract description 4
- 125000002252 acyl group Chemical group 0.000 abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 3
- 125000003342 alkenyl group Chemical group 0.000 abstract description 2
- 239000003937 drug carrier Substances 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- 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 description 22
- 239000008103 glucose Substances 0.000 description 22
- 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 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 102000004877 Insulin Human genes 0.000 description 11
- 108090001061 Insulin Proteins 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 229940125396 insulin Drugs 0.000 description 11
- GNMPTPJZKQHGBR-TWJOJJKGSA-N (2r,3r,4r)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidine Chemical compound C([C@@H]1[C@H]([C@H](OCC=2C=CC=CC=2)CN1)OCC=1C=CC=CC=1)OCC1=CC=CC=C1 GNMPTPJZKQHGBR-TWJOJJKGSA-N 0.000 description 10
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 101150041968 CDC13 gene Proteins 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- 210000005229 liver cell Anatomy 0.000 description 8
- 229940125904 compound 1 Drugs 0.000 description 7
- 229960004132 diethyl ether Drugs 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 102000051325 Glucagon Human genes 0.000 description 6
- 108060003199 Glucagon Proteins 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 6
- 229960004666 glucagon Drugs 0.000 description 6
- 230000002440 hepatic effect Effects 0.000 description 6
- 235000011167 hydrochloric acid Nutrition 0.000 description 6
- 229960000443 hydrochloric acid Drugs 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- OQEBIHBLFRADNM-UOWFLXDJSA-N (2r,3r,4r)-2-(hydroxymethyl)pyrrolidine-3,4-diol Chemical compound OC[C@H]1NC[C@@H](O)[C@@H]1O OQEBIHBLFRADNM-UOWFLXDJSA-N 0.000 description 5
- OQEBIHBLFRADNM-UHFFFAOYSA-N D-iminoxylitol Natural products OCC1NCC(O)C1O OQEBIHBLFRADNM-UHFFFAOYSA-N 0.000 description 5
- 102000009097 Phosphorylases Human genes 0.000 description 5
- 108010073135 Phosphorylases Proteins 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 150000003235 pyrrolidines Chemical class 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229940100389 Sulfonylurea Drugs 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000001424 substituent group Chemical group 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
- 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 2
- UHFWEDDFLFAJHG-FSDSQADBSA-N (2r,3r,4r)-1-(2-aminoethyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol Chemical compound NCCN1C[C@@H](O)[C@H](O)[C@H]1CO UHFWEDDFLFAJHG-FSDSQADBSA-N 0.000 description 2
- SPYQWYTVWZBEHS-FSDSQADBSA-N (2r,3r,4r)-1-(2-hydroxyethyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol Chemical compound OCCN1C[C@@H](O)[C@H](O)[C@H]1CO SPYQWYTVWZBEHS-FSDSQADBSA-N 0.000 description 2
- SFDXFWDKUXSSNN-IDZRBWSNSA-N (2r,3r,4r)-1-(cyclopropylmethyl)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidine Chemical compound C([C@H]1N(C[C@H]([C@@H]1OCC=1C=CC=CC=1)OCC=1C=CC=CC=1)CC1CC1)OCC1=CC=CC=C1 SFDXFWDKUXSSNN-IDZRBWSNSA-N 0.000 description 2
- VIJATBGUXVYNNB-ZONZVBGPSA-N (2r,3r,4r)-1-methyl-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidine Chemical compound O([C@@H]1CN([C@@H]([C@H]1OCC=1C=CC=CC=1)COCC=1C=CC=CC=1)C)CC1=CC=CC=C1 VIJATBGUXVYNNB-ZONZVBGPSA-N 0.000 description 2
- UBVOJPDDTVFNFJ-HSUXUTPPSA-N (2r,3r,4r)-2-(hydroxymethyl)-1-methylpyrrolidine-3,4-diol Chemical compound CN1C[C@@H](O)[C@H](O)[C@H]1CO UBVOJPDDTVFNFJ-HSUXUTPPSA-N 0.000 description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 2
- 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 2
- SPPKZKQXTFBLLK-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol Chemical compound OCC1C(O)C(O)CN1CC1CC1 SPPKZKQXTFBLLK-UHFFFAOYSA-N 0.000 description 2
- CUBCENUYRSMMCE-TWJOJJKGSA-N 1-[(2r,3r,4r)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidin-1-yl]-2,2,2-trifluoroethanone Chemical compound O([C@@H]1CN([C@@H]([C@H]1OCC=1C=CC=CC=1)COCC=1C=CC=CC=1)C(=O)C(F)(F)F)CC1=CC=CC=C1 CUBCENUYRSMMCE-TWJOJJKGSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- OTFWVJHPTXLHFX-JCYYIGJDSA-N 2-[(2r,3r,4r)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidin-1-yl]ethanamine Chemical compound O([C@@H]1CN([C@@H]([C@H]1OCC=1C=CC=CC=1)COCC=1C=CC=CC=1)CCN)CC1=CC=CC=C1 OTFWVJHPTXLHFX-JCYYIGJDSA-N 0.000 description 2
- OPDLDNVTAURDGW-JCYYIGJDSA-N 2-[(2r,3r,4r)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidin-1-yl]ethanol Chemical compound O([C@@H]1CN([C@@H]([C@H]1OCC=1C=CC=CC=1)COCC=1C=CC=CC=1)CCO)CC1=CC=CC=C1 OPDLDNVTAURDGW-JCYYIGJDSA-N 0.000 description 2
- RGHPCLZJAFCTIK-UHFFFAOYSA-N 2-methylpyrrolidine Chemical class CC1CCCN1 RGHPCLZJAFCTIK-UHFFFAOYSA-N 0.000 description 2
- VIJYZXOMZYNRON-STXVGSIRSA-N 3-[(2r,3r,4r)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidin-1-yl]propane-1,2-diol Chemical compound O([C@@H]1CN([C@@H]([C@H]1OCC=1C=CC=CC=1)COCC=1C=CC=CC=1)CC(O)CO)CC1=CC=CC=C1 VIJYZXOMZYNRON-STXVGSIRSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- WPRCMXASRHJGNG-UHFFFAOYSA-N 5-methylpiperidine-3,4-diol Chemical compound CC1CNCC(O)C1O WPRCMXASRHJGNG-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
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- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
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- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
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- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 230000004116 glycogenolysis Effects 0.000 description 1
- 239000003316 glycosidase inhibitor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
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- 239000007924 injection Substances 0.000 description 1
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- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
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- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
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- 229920001277 pectin Polymers 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- ZLCITKRJBDSPOZ-UHFFFAOYSA-N piperidine-2,3,4,5-tetrol Chemical compound OC1CNC(O)C(O)C1O ZLCITKRJBDSPOZ-UHFFFAOYSA-N 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- GUFUWKKDHIABBW-UHFFFAOYSA-N pyrrolidin-1-ylmethanol Chemical compound OCN1CCCC1 GUFUWKKDHIABBW-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL13733400A IL137334A0 (en) | 1995-09-08 | 2000-07-17 | 2-alkylpyrrolidines |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK99295 | 1995-09-08 | ||
PCT/DK1996/000373 WO1997009040A1 (fr) | 1995-09-08 | 1996-09-06 | 2-alkylpyrrolidines |
Publications (2)
Publication Number | Publication Date |
---|---|
IL124109A0 IL124109A0 (en) | 1998-12-06 |
IL124109A true IL124109A (en) | 2001-10-31 |
Family
ID=8099807
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL12410996A IL124109A (en) | 1995-09-08 | 1996-09-06 | Pharmaceutical composition of 2-alkylpyrrolidines for use in the manufacture of medicaments for the treatment of diabetes |
Country Status (12)
Country | Link |
---|---|
US (2) | US5854272A (fr) |
EP (3) | EP0858335B1 (fr) |
JP (2) | JP3043430B2 (fr) |
CN (1) | CN1202105A (fr) |
AT (1) | ATE234092T1 (fr) |
AU (1) | AU724003B2 (fr) |
CZ (1) | CZ120398A3 (fr) |
DE (1) | DE69626660T2 (fr) |
HU (1) | HUP9901132A2 (fr) |
IL (1) | IL124109A (fr) |
NO (1) | NO982055L (fr) |
WO (1) | WO1997009040A1 (fr) |
Families Citing this family (56)
Publication number | Priority date | Publication date | Assignee | Title |
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CZ120398A3 (cs) * | 1995-09-08 | 1998-12-16 | Novo Nordisk A/S | Použití 2-alkylpyrrolidinových derivátů pro přípravu léčiva pro léčbu diabetu, 2-alkylpyrrolidiné deriváty |
US5952363A (en) * | 1997-03-04 | 1999-09-14 | Novo Nordisk A/S | Pyrrolidine compounds useful in the treatment of diabetes |
AU6291098A (en) * | 1997-03-07 | 1998-09-29 | Novo Nordisk A/S | Novel heterocyclic compounds |
AU2535700A (en) * | 1999-02-12 | 2000-08-29 | Novo Nordisk A/S | Use of pyrrolidine derivatives for the manufacture of a pharmaceutical composition for the treatment or prophylaxis of obesity or appetite regulation |
US6239163B1 (en) | 1999-03-15 | 2001-05-29 | Novo Nordisk A/S | Salt of (2R,3R,4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine |
DE60022172D1 (de) * | 1999-03-15 | 2005-09-29 | Novo Nordisk As | Salz des (2r,3r,4r)3,4-dihydroxy-2-hydroxymethylpyrrolidins |
US6316489B1 (en) * | 1999-03-15 | 2001-11-13 | Novo Nordisk A/S | Salt of (2R,3R,4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine |
DE60022742D1 (de) * | 1999-03-15 | 2006-02-02 | Novo Nordisk As | Salz des (2r,3r,4r)-3,4-dihydroxy-2-hydroxmethylpyrrolidins |
EP1185269B1 (fr) * | 1999-05-24 | 2007-11-14 | Abaron Biosciences, Inc. | Inhibiteurs de glycosyltransferase |
US6043091A (en) * | 1999-07-19 | 2000-03-28 | Isis Pharmaceuticals Inc. | Antisense modulation of liver glycogen phosphorylase expression |
CO5271699A1 (es) | 2000-01-24 | 2003-04-30 | Pfizer Prod Inc | Procedimiento para el tratamiento de cardiomiopatia utilizando inhibidores de la glucogeno fosforilasa |
US6414163B1 (en) * | 2000-08-02 | 2002-07-02 | Board Of Trustees Of Michigan State University | Process and intermediate compounds for the preparation of pyrrolidines |
US20030171411A1 (en) | 2001-12-21 | 2003-09-11 | Kodra Janos Tibor | Amide derivatives as therapeutic agents |
GB0205176D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205166D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205170D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205165D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205175D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205162D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
KR101116627B1 (ko) | 2002-06-27 | 2012-10-09 | 노보 노르디스크 에이/에스 | 치료제로서 아릴 카르보닐 유도체 |
US6960610B2 (en) | 2002-10-28 | 2005-11-01 | Novo Nordick, A/S | Use of glycogen phosphorylase inhibitors for treatment of cardiovascular diseases |
JP2006507359A (ja) * | 2002-10-28 | 2006-03-02 | ノボ・ノルデイスク・エー/エス | 心循環器疾患の治療のためのグリコーゲンホスホリラーゼ阻害剤の使用 |
WO2004101505A1 (fr) | 2003-05-14 | 2004-11-25 | Novo Nordisk A/S | Nouveaux composes pour le traitement de l'obesite |
JP4486792B2 (ja) * | 2003-06-12 | 2010-06-23 | 学校法人近畿大学 | 環状オニウム化合物およびグルコシダーゼ阻害剤 |
WO2005030797A2 (fr) | 2003-09-30 | 2005-04-07 | Novo Nordisk A/S | Nouveaux agonistes du recepteur de la melanocortine |
JP4865565B2 (ja) | 2003-12-09 | 2012-02-01 | ノヴォ ノルディスク アー/エス | Glp−1アゴニストを用いた食物選択の制御 |
SI1723128T1 (sl) | 2004-01-06 | 2013-04-30 | Transtech Pharma, Inc. | Heteroaril uree in njihova uporaba kot aktivatorji glukokinaze |
WO2005105785A2 (fr) | 2004-05-04 | 2005-11-10 | Novo Nordisk A/S | Nouveaux derives d'indole |
EP2316446A1 (fr) | 2004-06-11 | 2011-05-04 | Novo Nordisk A/S | Remède contre l'obésité induite par les médicaments au moyen d'agonistes GLP-1 |
WO2006059163A1 (fr) * | 2004-12-02 | 2006-06-08 | Prosidion Limited | Traitement du diabete par des inhibiteurs de la glycogene phosphorylase |
CA2590720A1 (fr) | 2004-12-03 | 2006-06-08 | Lone Jeppesen | Composes heteroaromatiques activants de glucokinase |
KR100696187B1 (ko) | 2005-05-03 | 2007-03-20 | (주)리드젠 | 2-(2-아미노에틸)-1-메틸피롤리딘의 제조방법 |
ES2422383T3 (es) | 2005-07-14 | 2013-09-11 | Novo Nordisk As | Activadores de urea glucoquinasa |
ATE523497T1 (de) | 2006-11-15 | 2011-09-15 | High Point Pharmaceuticals Llc | Neue 2-(2-hydroxyphenyl)benzimidazole, die sich für die behandlung von obesitas und diabetes eignen |
AU2008204530B2 (en) | 2007-01-11 | 2013-08-01 | Vtv Therapeutics Llc | Urea glucokinase activators |
WO2010049678A2 (fr) * | 2008-10-31 | 2010-05-06 | Summit Corporation Plc | Traitement de maladies utilisant de l’énergie |
JP5645137B2 (ja) * | 2009-11-11 | 2014-12-24 | 国立大学法人富山大学 | 食後過血糖改善剤、およびピロリジン型イミノ糖またはその塩 |
BR112012021231A2 (pt) | 2010-02-26 | 2015-09-08 | Basf Plant Science Co Gmbh | método para acentuar o rendimento em plantas, planta, construto, uso de um construto, método para a produção de uma planta transgênica, partes coletáveis de uma planta, produtos derivados de uma planta, uso de um ácido nucleíco e método para a produção de um produto |
WO2011104378A1 (fr) | 2010-02-26 | 2011-09-01 | Novo Nordisk A/S | Peptides de traitement de l'obésité |
BR112012024379A2 (pt) | 2010-03-26 | 2017-01-10 | Novo Nordisk As | "peptídeos glucagon, seu uso, bem como composição farmacêutica" |
DK2655388T3 (en) | 2010-12-23 | 2016-09-19 | Alectos Therapeutics Inc | Selective glykosidaseinhibitorer and uses thereof |
AU2012234276A1 (en) | 2011-03-28 | 2013-08-29 | Novo Nordisk A/S | Novel glucagon analogues |
WO2012129651A1 (fr) | 2011-03-31 | 2012-10-04 | Alectos Therapeutics Inc. | Inhibiteurs sélectifs de glycosidases et leurs utilisations |
WO2013000086A1 (fr) | 2011-06-27 | 2013-01-03 | Alectos Therapeutics Inc. | Inhibiteurs de glycosidases sélectifs et leurs utilisations |
MX354705B (es) | 2011-09-23 | 2018-03-16 | Novo Nordisk As | Analogos de glucagon novedosos. |
US20150050371A1 (en) | 2012-03-09 | 2015-02-19 | Biotropics Malaysia Berhad | Extract Formulations of Rhodamnia Cinerea And Uses Thereof |
EP2890676B1 (fr) | 2012-08-31 | 2018-12-05 | Alectos Therapeutics Inc. | Inhibiteurs de glycosidases et leurs utilisations |
EP2890675A4 (fr) | 2012-08-31 | 2016-01-13 | Alectos Therapeutics Inc | Inhibiteurs des glycosidases et leurs utilisations |
CN104837845B (zh) | 2012-10-31 | 2018-08-28 | 阿勒克图治疗公司 | 糖苷酶抑制剂及其用途 |
MY174727A (en) | 2013-04-18 | 2020-05-11 | Novo Nordisk As | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
US10570184B2 (en) | 2014-06-04 | 2020-02-25 | Novo Nordisk A/S | GLP-1/glucagon receptor co-agonists for medical use |
CN106349141B (zh) * | 2016-08-30 | 2020-10-27 | 中国科学院化学研究所 | 多羟基吡咯烷类化合物及其制备方法和应用 |
JP2020514365A (ja) | 2017-03-15 | 2020-05-21 | ノヴォ ノルディスク アー/エス | メラノコルチン4受容体に結合可能な二環式化合物 |
WO2019219714A1 (fr) | 2018-05-15 | 2019-11-21 | Novo Nordisk A/S | Composés capables de se lier au récepteur de la mélanocortine 4 |
WO2020023390A1 (fr) | 2018-07-25 | 2020-01-30 | Modernatx, Inc. | Traitement enzymatique substitutif basé sur l'arnm combiné à un chaperon pharmacologique pour le traitement de troubles du stockage lysosomal |
WO2020053414A1 (fr) | 2018-09-14 | 2020-03-19 | Novo Nordisk A/S | Composés bicycliques aptes à se lier aux agonistes du récepteur de la mélanocortine 4 |
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FR1602744A (fr) | 1968-02-16 | 1971-01-18 | ||
JPS5346967A (en) | 1976-10-08 | 1978-04-27 | Kyowa Hakko Kogyo Co Ltd | R-2-(beta-halogenoethyl)-1-methyl-pyrrolidine |
JPS6058749B2 (ja) | 1978-02-09 | 1985-12-21 | 日清製粉株式会社 | 光学活性n‐メチル‐2‐ピロリジンエタノ−ルの製造法 |
JPS61118360A (ja) | 1984-11-13 | 1986-06-05 | Mitsubishi Chem Ind Ltd | ピロリジン誘導体またはその塩 |
US4999360A (en) * | 1987-12-21 | 1991-03-12 | Monsanto Company | Method of inhibiting virus |
US4876268A (en) * | 1988-11-03 | 1989-10-24 | G. D. Searle & Co. | Antiviral compounds and use thereof |
US4973602A (en) * | 1988-11-03 | 1990-11-27 | G. D. Searle & Co. | Antiviral compounds and a method of use thereas |
DE68925940T2 (de) * | 1988-11-03 | 1996-10-24 | Searle & Co | Dideoxy-L-arabinitol Derivate als Antivirus-Verbindungen |
US4894388A (en) | 1988-12-22 | 1990-01-16 | Monsanto Company | Glycosidase inhibitors and use thereof |
EP0389723A1 (fr) * | 1989-03-29 | 1990-10-03 | Merrell Dow Pharmaceuticals Inc. | Inhibiteurs d'alpha-glucosidases |
FR2648486B1 (fr) * | 1989-06-16 | 1991-08-30 | Gerland Sa | Composition pour le traitement antifeutrant de la laine |
EP0422307A1 (fr) * | 1989-10-10 | 1991-04-17 | Merrell Dow Pharmaceuticals Inc. | Inhibiteurs de alpha-glucosidase |
US5013842A (en) * | 1990-01-22 | 1991-05-07 | Monsanto Company | Synthesis of chiral pyrrolidine and piperidine glycosidase inhibitors |
US5290948A (en) * | 1990-09-17 | 1994-03-01 | Mcneilab, Inc. | Process for producing polyhydroxylated piperidines and pyrrolidines and compounds thereof |
US5401645A (en) | 1992-03-16 | 1995-03-28 | Monsanto Company | Process for producing n-substituted polyhydroxy nitrogen-containing heterocycles utilizing acetobacteraceae and corynebacterium |
JPH0625157A (ja) | 1992-07-13 | 1994-02-01 | Taisho Pharmaceut Co Ltd | ポリヒドロキシピロリジン誘導体類およびその製造方法 |
CZ120398A3 (cs) * | 1995-09-08 | 1998-12-16 | Novo Nordisk A/S | Použití 2-alkylpyrrolidinových derivátů pro přípravu léčiva pro léčbu diabetu, 2-alkylpyrrolidiné deriváty |
-
1996
- 1996-09-06 CZ CZ981203A patent/CZ120398A3/cs unknown
- 1996-09-06 AT AT96928360T patent/ATE234092T1/de not_active IP Right Cessation
- 1996-09-06 JP JP9510787A patent/JP3043430B2/ja not_active Expired - Fee Related
- 1996-09-06 AU AU67859/96A patent/AU724003B2/en not_active Ceased
- 1996-09-06 CN CN96198204A patent/CN1202105A/zh active Pending
- 1996-09-06 EP EP96928360A patent/EP0858335B1/fr not_active Expired - Lifetime
- 1996-09-06 DE DE69626660T patent/DE69626660T2/de not_active Expired - Fee Related
- 1996-09-06 EP EP00113261A patent/EP1040827A3/fr not_active Withdrawn
- 1996-09-06 EP EP97120546A patent/EP0884050A1/fr not_active Withdrawn
- 1996-09-06 WO PCT/DK1996/000373 patent/WO1997009040A1/fr not_active Application Discontinuation
- 1996-09-06 HU HU9901132A patent/HUP9901132A2/hu unknown
- 1996-09-06 IL IL12410996A patent/IL124109A/en not_active IP Right Cessation
-
1997
- 1997-07-14 US US08/892,660 patent/US5854272A/en not_active Expired - Fee Related
-
1998
- 1998-05-06 NO NO982055A patent/NO982055L/no not_active Application Discontinuation
- 1998-08-24 US US09/138,712 patent/US6451836B1/en not_active Expired - Fee Related
-
1999
- 1999-09-29 JP JP11276958A patent/JP2000095686A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
ATE234092T1 (de) | 2003-03-15 |
US6451836B1 (en) | 2002-09-17 |
CN1202105A (zh) | 1998-12-16 |
EP0858335B1 (fr) | 2003-03-12 |
EP1040827A2 (fr) | 2000-10-04 |
JPH11503762A (ja) | 1999-03-30 |
EP1040827A3 (fr) | 2000-10-11 |
JP2000095686A (ja) | 2000-04-04 |
EP0858335A1 (fr) | 1998-08-19 |
NO982055D0 (no) | 1998-05-06 |
HUP9901132A2 (hu) | 1999-07-28 |
EP0884050A1 (fr) | 1998-12-16 |
IL124109A0 (en) | 1998-12-06 |
NO982055L (no) | 1998-05-06 |
DE69626660T2 (de) | 2003-08-21 |
AU6785996A (en) | 1997-03-27 |
WO1997009040A1 (fr) | 1997-03-13 |
JP3043430B2 (ja) | 2000-05-22 |
CZ120398A3 (cs) | 1998-12-16 |
DE69626660D1 (en) | 2003-04-17 |
AU724003B2 (en) | 2000-09-07 |
US5854272A (en) | 1998-12-29 |
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