ZA200208503B - Para-amine substituted pheylamide glocokinase activators. - Google Patents
Para-amine substituted pheylamide glocokinase activators. Download PDFInfo
- Publication number
- ZA200208503B ZA200208503B ZA200208503A ZA200208503A ZA200208503B ZA 200208503 B ZA200208503 B ZA 200208503B ZA 200208503 A ZA200208503 A ZA 200208503A ZA 200208503 A ZA200208503 A ZA 200208503A ZA 200208503 B ZA200208503 B ZA 200208503B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- cyclopentyl
- carbon atom
- compound
- amide
- Prior art date
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- 239000012190 activator Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 121
- 229910052799 carbon Inorganic materials 0.000 claims description 58
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- 238000006243 chemical reaction Methods 0.000 claims description 52
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- 150000001408 amides Chemical class 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 239000011593 sulfur Substances 0.000 claims description 19
- 229920006395 saturated elastomer Polymers 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
- 125000003368 amide group Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- -1 perfluoro Chemical group 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- XAESKCXILHIZHM-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(methanesulfonamido)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 XAESKCXILHIZHM-UHFFFAOYSA-N 0.000 claims description 4
- WUDPJTQWLKCINY-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[4-(trifluoromethylsulfonylamino)phenyl]propanamide Chemical compound C1=CC(NS(=O)(=O)C(F)(F)F)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 WUDPJTQWLKCINY-UHFFFAOYSA-N 0.000 claims description 4
- RXDFOJRCFVFDGU-UHFFFAOYSA-N [2-[4-[3-cyclopentyl-1-oxo-1-(1,3-thiazol-2-ylamino)propan-2-yl]anilino]-2-oxoethyl] acetate Chemical compound C1=CC(NC(=O)COC(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 RXDFOJRCFVFDGU-UHFFFAOYSA-N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- DOLJSIBUKBKKJF-UHFFFAOYSA-N ethyl 2-[[3-cyclopentyl-2-[4-(pyridine-3-carbonylamino)phenyl]propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(NC(=O)C=3C=NC=CC=3)=CC=2)=N1 DOLJSIBUKBKKJF-UHFFFAOYSA-N 0.000 claims description 4
- IIMARVHELKQFHG-UHFFFAOYSA-N n-[4-[3-cyclopentyl-1-oxo-1-(pyridin-2-ylamino)propan-2-yl]phenyl]pyridine-3-carboxamide Chemical compound C1CCCC1CC(C=1C=CC(NC(=O)C=2C=NC=CC=2)=CC=1)C(=O)NC1=CC=CC=N1 IIMARVHELKQFHG-UHFFFAOYSA-N 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- ISSYRSCWEYOQOP-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(dimethylsulfamoylamino)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(NS(=O)(=O)N(C)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 ISSYRSCWEYOQOP-UHFFFAOYSA-N 0.000 claims description 3
- QGIUKOWSRBTHND-UHFFFAOYSA-N 3-cyclopentyl-2-[4-[(4-nitrophenyl)sulfonylamino]phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C(CC2CCCC2)C(=O)NC=2SC=CN=2)C=C1 QGIUKOWSRBTHND-UHFFFAOYSA-N 0.000 claims description 3
- IIJTVGNSHAIJED-UHFFFAOYSA-N n-[4-[3-cyclopentyl-1-oxo-1-(1,3-thiazol-2-ylamino)propan-2-yl]phenyl]benzamide Chemical compound C1CCCC1CC(C=1C=CC(NC(=O)C=2C=CC=CC=2)=CC=1)C(=O)NC1=NC=CS1 IIJTVGNSHAIJED-UHFFFAOYSA-N 0.000 claims description 3
- BJMGTVDVCHGRJB-UHFFFAOYSA-N n-[4-[3-cyclopentyl-1-oxo-1-(1,3-thiazol-2-ylamino)propan-2-yl]phenyl]pyridine-4-carboxamide Chemical compound C1CCCC1CC(C=1C=CC(NC(=O)C=2C=CN=CC=2)=CC=1)C(=O)NC1=NC=CS1 BJMGTVDVCHGRJB-UHFFFAOYSA-N 0.000 claims description 3
- KECVGJNBHGYTSE-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[4-[(2-thiophen-2-ylacetyl)amino]phenyl]propanamide Chemical compound C=1C=C(C(CC2CCCC2)C(=O)NC=2SC=CN=2)C=CC=1NC(=O)CC1=CC=CS1 KECVGJNBHGYTSE-UHFFFAOYSA-N 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- OXHCWRKIOCKZLO-UHFFFAOYSA-N ethyl 2-[2-[[3-cyclopentyl-2-[4-(pyridine-3-carbonylamino)phenyl]propanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(NC(=O)C=3C=NC=CC=3)=CC=2)=N1 OXHCWRKIOCKZLO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- FYORGSRGJHRFHO-UHFFFAOYSA-N n-[4-[3-cyclopentyl-1-oxo-1-(1,3-thiazol-2-ylamino)propan-2-yl]phenyl]-4-nitrobenzamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)NC1=CC=C(C(CC2CCCC2)C(=O)NC=2SC=CN=2)C=C1 FYORGSRGJHRFHO-UHFFFAOYSA-N 0.000 claims description 2
- LYMBKXFULJQPLT-UHFFFAOYSA-N n-[4-[3-cyclopentyl-1-oxo-1-(1,3-thiazol-2-ylamino)propan-2-yl]phenyl]pyridine-3-carboxamide Chemical compound C1CCCC1CC(C=1C=CC(NC(=O)C=2C=NC=CC=2)=CC=1)C(=O)NC1=NC=CS1 LYMBKXFULJQPLT-UHFFFAOYSA-N 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 2
- 239000011664 nicotinic acid Substances 0.000 claims 1
- 229960003512 nicotinic acid Drugs 0.000 claims 1
- 235000001968 nicotinic acid Nutrition 0.000 claims 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
- 239000000243 solution Substances 0.000 description 83
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- 102000030595 Glucokinase Human genes 0.000 description 34
- 108010021582 Glucokinase Proteins 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 33
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- 239000007787 solid Substances 0.000 description 27
- 150000001721 carbon Chemical group 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 15
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 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 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 150000002148 esters Chemical group 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000007796 conventional method Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000008103 glucose Substances 0.000 description 11
- AWHQGMJNOZGSDE-UHFFFAOYSA-N 2-(4-aminophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(N)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 AWHQGMJNOZGSDE-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- GIACSQUDYUHGPP-UHFFFAOYSA-N 3-cyclopentyl-2-(4-nitrophenyl)propanoic acid Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(C(=O)O)CC1CCCC1 GIACSQUDYUHGPP-UHFFFAOYSA-N 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
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- 239000011780 sodium chloride Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
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- 229910052763 palladium Inorganic materials 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- BJNUVSBAOBTREE-UHFFFAOYSA-N 2-(4-aminophenyl)-3-cyclopentylpropanoic acid Chemical compound C1=CC(N)=CC=C1C(C(O)=O)CC1CCCC1 BJNUVSBAOBTREE-UHFFFAOYSA-N 0.000 description 5
- 239000001828 Gelatine Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- DBCSSLKEWJGXOG-UHFFFAOYSA-N ethyl 3-cyclopentyl-2-(4-nitrophenyl)propanoate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(C(=O)OCC)CC1CCCC1 DBCSSLKEWJGXOG-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
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- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
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- 150000003077 polyols Chemical class 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 3
- PTWXOVIJTRGJJJ-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(pyridine-3-carbonylamino)phenyl]propanoic acid Chemical compound C=1C=C(NC(=O)C=2C=NC=CC=2)C=CC=1C(C(=O)O)CC1CCCC1 PTWXOVIJTRGJJJ-UHFFFAOYSA-N 0.000 description 3
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
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- 238000003556 assay Methods 0.000 description 3
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 3
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- YLPIXGLFJNZLNK-UHFFFAOYSA-N 2-(4-aminophenyl)-3-cyclopentyl-n-pyridin-2-ylpropanamide Chemical compound C1=CC(N)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 YLPIXGLFJNZLNK-UHFFFAOYSA-N 0.000 description 2
- CDGVZAAKEREJLY-UHFFFAOYSA-N 2-(4-benzamidophenyl)-3-cyclopentylpropanoic acid Chemical compound C=1C=C(NC(=O)C=2C=CC=CC=2)C=CC=1C(C(=O)O)CC1CCCC1 CDGVZAAKEREJLY-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
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- WTYBLBICEQHSSK-UHFFFAOYSA-N methyl 6-[[2-(4-aminophenyl)-3-cyclopentylpropanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)C(C=1C=CC(N)=CC=1)CC1CCCC1 WTYBLBICEQHSSK-UHFFFAOYSA-N 0.000 description 1
- JACPDLJUQLKABC-UHFFFAOYSA-N methyl 6-aminopyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(N)N=C1 JACPDLJUQLKABC-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000029964 regulation of glucose metabolic process Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- GACTWZZMVMUKNG-ZXXMMSQZSA-N sorbitol 6-phosphate Chemical compound OC[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)COP(O)(O)=O GACTWZZMVMUKNG-ZXXMMSQZSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20238900P | 2000-05-08 | 2000-05-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200208503B true ZA200208503B (en) | 2004-01-22 |
Family
ID=22749673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200208503A ZA200208503B (en) | 2000-05-08 | 2002-10-21 | Para-amine substituted pheylamide glocokinase activators. |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1283830B1 (fr) |
| JP (1) | JP3971189B2 (fr) |
| KR (1) | KR100519826B1 (fr) |
| CN (1) | CN1185220C (fr) |
| AR (1) | AR030279A1 (fr) |
| AT (1) | ATE398611T1 (fr) |
| AU (2) | AU2001265914B2 (fr) |
| BR (1) | BR0110703A (fr) |
| CA (1) | CA2407763C (fr) |
| DE (1) | DE60134470D1 (fr) |
| DK (1) | DK1283830T3 (fr) |
| EC (1) | ECSP014062A (fr) |
| ES (1) | ES2307623T3 (fr) |
| MX (1) | MXPA02010795A (fr) |
| PE (1) | PE20020049A1 (fr) |
| PT (1) | PT1283830E (fr) |
| UY (1) | UY26695A1 (fr) |
| WO (1) | WO2001085707A1 (fr) |
| ZA (1) | ZA200208503B (fr) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6610846B1 (en) | 1999-03-29 | 2003-08-26 | Hoffman-La Roche Inc. | Heteroaromatic glucokinase activators |
| SE0102299D0 (sv) | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
| EP1724270A3 (fr) | 2001-07-19 | 2007-01-03 | Pfizer Italia S.r.l. | Dérivés de phenylacetamido-thiazole, leur procédé de préparation et leur utilisation en tant qu'agents antitumoraux |
| SE0102764D0 (sv) | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
| EP1336607A1 (fr) * | 2002-02-19 | 2003-08-20 | Novo Nordisk A/S | Dérivés d'amides comme activateus de la glucokinase |
| US6911545B2 (en) | 2001-12-19 | 2005-06-28 | Hoffman-La Roche Inc. | Crystals of glucokinase and methods of growing them |
| JP2005518391A (ja) | 2001-12-21 | 2005-06-23 | ノボ ノルディスク アクティーゼルスカブ | Ｇｋ活性化剤としてのアミド誘導体 |
| CA2744893A1 (fr) | 2002-06-27 | 2004-01-08 | Novo Nordisk A/S | Derives d'arylcarbonyle servant d'activateurs de glucokinase |
| KR101124245B1 (ko) | 2002-06-27 | 2012-07-02 | 노보 노르디스크 에이/에스 | 치료제로서 아릴 카르보닐 유도체 |
| PL375021A1 (en) * | 2002-10-03 | 2005-11-14 | Novartis Ag | Substituted (thiazol-2-yl) -amide or sulfonamide as glycokinase activators useful in the treatment of type 2 diabetes |
| GB0226931D0 (en) | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
| JP4716734B2 (ja) | 2003-01-06 | 2011-07-06 | イーライ リリー アンド カンパニー | グルコキナーゼ活性化物質としての置換されたアリールシクロプロピルアセトアミド |
| AU2003294376A1 (en) * | 2003-01-06 | 2004-08-10 | Eli Lilly And Company | Heteroaryl compounds |
| PL378117A1 (pl) | 2003-02-11 | 2006-03-06 | Prosidion Limited | Tricyklopodstawione związki amidowe |
| BRPI0506662B8 (pt) | 2004-01-06 | 2021-05-25 | Novo Nordisk As | compostos ativadores de glucoquinase |
| BRPI0509573A (pt) * | 2004-04-02 | 2007-09-25 | Novartis Ag | derivados de sulfonamida-tiazolpiridina como ativadores de glicocinase úteis para o tratamento de diabetes do tipo 2 |
| JP2007530631A (ja) | 2004-04-02 | 2007-11-01 | ノバルティス アクチエンゲゼルシャフト | チアゾロピリジン誘導体、それを含む医薬組成物およびグルコキナーゼ介在性状態の処置法 |
| BRPI0518798A2 (pt) * | 2004-12-03 | 2008-12-09 | Transtech Pharma Inc | composto, composiÇço farmacÊutica, e, mÉtodos para tratar diabete tipo ii e para tratar uma condiÇço ou distérbio |
| KR20080024211A (ko) | 2005-07-08 | 2008-03-17 | 노보 노르디스크 에이/에스 | 디시클로알킬 우레아 글루코키나제 활성제 |
| US8106090B2 (en) | 2005-07-20 | 2012-01-31 | Eli Lilly And Company | 1-amino linked compounds |
| KR20080040046A (ko) | 2005-08-31 | 2008-05-07 | 아스텔라스세이야쿠 가부시키가이샤 | 티아졸 유도체 |
| JP2007063225A (ja) | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
| AU2006299091A1 (en) | 2005-09-29 | 2007-04-12 | Sanofi-Aventis | Phenyl- and pyridinyl- 1, 2 , 4 - oxadiazolone derivatives, processes for their preparation and their use as pharmaceuticals |
| GT200600428A (es) | 2005-09-30 | 2007-05-21 | Compuestos organicos | |
| GT200600429A (es) | 2005-09-30 | 2007-04-30 | Compuestos organicos | |
| WO2007123581A1 (fr) | 2005-11-17 | 2007-11-01 | Eli Lilly And Company | Antagonistes des récepteurs du glucagon, leur préparation et leurs utilisations thérapeutiques |
| EP2001875A2 (fr) | 2006-03-08 | 2008-12-17 | Takeda San Diego, Inc. | Activateurs de la glucokinase |
| US8211925B2 (en) | 2006-04-28 | 2012-07-03 | Transtech Pharma, Inc. | Benzamide glucokinase activators |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| ATE522518T1 (de) * | 2006-05-31 | 2011-09-15 | Takeda San Diego Inc | Indazol- und isoindolderivate als glucokinaseaktivierende stoffe |
| AU2007278261A1 (en) | 2006-07-24 | 2008-01-31 | F. Hoffmann-La Roche Ag | Pyrazoles as glucokinase activators |
| WO2008079787A2 (fr) | 2006-12-20 | 2008-07-03 | Takeda San Diego, Inc. | Activateurs de glucokinase |
| TW200831081A (en) | 2006-12-25 | 2008-08-01 | Kyorin Seiyaku Kk | Glucokinase activator |
| JP5491871B2 (ja) | 2007-02-28 | 2014-05-14 | アドビナス セラピュティックス プライベート リミテッド | グルコキナーゼ活性化因子としての２，２，２−三置換アセトアミド誘導体、その方法及び薬学的応用 |
| US8173645B2 (en) | 2007-03-21 | 2012-05-08 | Takeda San Diego, Inc. | Glucokinase activators |
| US20100190980A1 (en) | 2007-06-21 | 2010-07-29 | Taisho Pharmaceutical Co., Ltd | Pyrazinamide compound |
| BRPI0906888A2 (pt) | 2008-01-18 | 2015-11-03 | Astellas Pharma Inc | derivado de fenilacetamida |
| US8258134B2 (en) | 2008-04-16 | 2012-09-04 | Hoffmann-La Roche Inc. | Pyridazinone glucokinase activators |
| US7741327B2 (en) | 2008-04-16 | 2010-06-22 | Hoffmann-La Roche Inc. | Pyrrolidinone glucokinase activators |
| ME02198B (me) | 2008-04-28 | 2016-02-20 | Kyorin Seiyaku Kk | Derivati ciklopentilakrilamida |
| AU2009246167B2 (en) | 2008-05-16 | 2013-08-22 | Takeda California, Inc. | Glucokinase activators |
| UA104742C2 (uk) | 2008-12-19 | 2014-03-11 | Эли Лилли Энд Компани | Похідні арилциклопропілацетаміду, застосовні як активатори глюкокінази |
| JP5750050B2 (ja) | 2009-12-04 | 2015-07-15 | 大正製薬株式会社 | ２−ピリドン化合物 |
| US8222416B2 (en) | 2009-12-14 | 2012-07-17 | Hoffmann-La Roche Inc. | Azaindole glucokinase activators |
| JP5909482B2 (ja) | 2010-03-31 | 2016-04-26 | ザ スクリプス リサーチ インスティテュート | 細胞の再プログラム |
| US8877794B2 (en) * | 2010-08-13 | 2014-11-04 | Abbott Laboratories | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| KR20210020866A (ko) | 2018-06-12 | 2021-02-24 | 브이티브이 테라퓨틱스 엘엘씨 | 인슐린 또는 인슐린 유사체와 조합된 글루코키나제 활성제의 치료적 용도 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4317320A1 (de) * | 1993-05-25 | 1994-12-01 | Boehringer Mannheim Gmbh | Neue Thiazolidindione und diese enthaltende Arzneimittel |
| US6011048A (en) * | 1997-01-28 | 2000-01-04 | Merck & Co., Inc. | Thiazole benzenesulfonamides as β3 agonists for treatment of diabetes and obesity |
-
2001
- 2001-04-30 DK DK01943302T patent/DK1283830T3/da active
- 2001-04-30 PT PT01943302T patent/PT1283830E/pt unknown
- 2001-04-30 ES ES01943302T patent/ES2307623T3/es not_active Expired - Lifetime
- 2001-04-30 EP EP01943302A patent/EP1283830B1/fr not_active Expired - Lifetime
- 2001-04-30 KR KR10-2002-7014921A patent/KR100519826B1/ko not_active IP Right Cessation
- 2001-04-30 BR BR0110703-8A patent/BR0110703A/pt not_active IP Right Cessation
- 2001-04-30 WO PCT/EP2001/004859 patent/WO2001085707A1/fr active IP Right Grant
- 2001-04-30 AU AU2001265914A patent/AU2001265914B2/en not_active Ceased
- 2001-04-30 AT AT01943302T patent/ATE398611T1/de not_active IP Right Cessation
- 2001-04-30 DE DE60134470T patent/DE60134470D1/de not_active Expired - Lifetime
- 2001-04-30 CN CNB018092233A patent/CN1185220C/zh not_active Expired - Fee Related
- 2001-04-30 AU AU6591401A patent/AU6591401A/xx active Pending
- 2001-04-30 JP JP2001582308A patent/JP3971189B2/ja not_active Expired - Fee Related
- 2001-04-30 CA CA002407763A patent/CA2407763C/fr not_active Expired - Fee Related
- 2001-04-30 MX MXPA02010795A patent/MXPA02010795A/es active IP Right Grant
- 2001-05-02 PE PE2001000395A patent/PE20020049A1/es not_active Application Discontinuation
- 2001-05-04 AR ARP010102124A patent/AR030279A1/es unknown
- 2001-05-07 UY UY26695A patent/UY26695A1/es not_active Application Discontinuation
- 2001-05-08 EC EC2001004062A patent/ECSP014062A/es unknown
-
2002
- 2002-10-21 ZA ZA200208503A patent/ZA200208503B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR0110703A (pt) | 2003-01-28 |
| DK1283830T3 (da) | 2008-08-25 |
| EP1283830A1 (fr) | 2003-02-19 |
| JP2003532719A (ja) | 2003-11-05 |
| ATE398611T1 (de) | 2008-07-15 |
| PE20020049A1 (es) | 2002-02-01 |
| ECSP014062A (es) | 2002-02-25 |
| PT1283830E (pt) | 2008-08-18 |
| AU2001265914B2 (en) | 2005-11-03 |
| EP1283830B1 (fr) | 2008-06-18 |
| KR20020094019A (ko) | 2002-12-16 |
| AR030279A1 (es) | 2003-08-20 |
| ES2307623T3 (es) | 2008-12-01 |
| CN1427830A (zh) | 2003-07-02 |
| AU6591401A (en) | 2001-11-20 |
| KR100519826B1 (ko) | 2005-10-06 |
| CN1185220C (zh) | 2005-01-19 |
| UY26695A1 (es) | 2001-11-30 |
| MXPA02010795A (es) | 2003-03-27 |
| DE60134470D1 (de) | 2008-07-31 |
| CA2407763C (fr) | 2007-04-24 |
| WO2001085707A1 (fr) | 2001-11-15 |
| JP3971189B2 (ja) | 2007-09-05 |
| CA2407763A1 (fr) | 2001-11-15 |
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