CA2419416C - Tetrazolyl-phenyl acetamide glucokinase activators - Google Patents
Tetrazolyl-phenyl acetamide glucokinase activators Download PDFInfo
- Publication number
- CA2419416C CA2419416C CA002419416A CA2419416A CA2419416C CA 2419416 C CA2419416 C CA 2419416C CA 002419416 A CA002419416 A CA 002419416A CA 2419416 A CA2419416 A CA 2419416A CA 2419416 C CA2419416 C CA 2419416C
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- methyl
- mmol
- tetrazol
- reaction mixture
- 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.)
- Expired - Fee Related
Links
- 102000030595 Glucokinase Human genes 0.000 title abstract description 41
- 108010021582 Glucokinase Proteins 0.000 title abstract description 41
- 239000012190 activator Substances 0.000 title abstract description 13
- -1 perfluoro Chemical group 0.000 claims abstract description 46
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 43
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 34
- 150000001721 carbon Chemical group 0.000 claims abstract description 31
- 150000002367 halogens Chemical class 0.000 claims abstract description 28
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 125000003368 amide group Chemical group 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 150000002431 hydrogen Chemical group 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 88
- 150000003536 tetrazoles Chemical class 0.000 claims description 61
- 238000000034 method Methods 0.000 claims description 37
- 230000008569 process Effects 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 229910052757 nitrogen Chemical group 0.000 claims description 14
- 230000008878 coupling Effects 0.000 claims description 12
- 238000010168 coupling process Methods 0.000 claims description 12
- 238000005859 coupling reaction Methods 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- ICORAYQUZBVGMS-SFQUDFHCSA-N (e)-2-[3-chloro-4-(5-methyltetrazol-1-yl)phenyl]-3-cycloheptyl-n-(1,3-thiazol-2-yl)prop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCCCC2)\C(=O)NC=2SC=CN=2)C=C1Cl ICORAYQUZBVGMS-SFQUDFHCSA-N 0.000 claims description 7
- VLMUMBDJCAPBLI-XNTDXEJSSA-N (e)-2-[3-chloro-4-(5-methyltetrazol-1-yl)phenyl]-3-cyclopentyl-n-(1,3-thiazol-2-yl)prop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCC2)\C(=O)NC=2SC=CN=2)C=C1Cl VLMUMBDJCAPBLI-XNTDXEJSSA-N 0.000 claims description 7
- QIMSMHHSGVQCCP-GXDHUFHOSA-N (e)-2-[3-chloro-4-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]-3-cyclohexyl-n-(1,3-thiazol-2-yl)prop-2-enamide Chemical compound FC(F)(F)C1=NN=NN1C1=CC=C(C(=C/C2CCCCC2)\C(=O)NC=2SC=CN=2)C=C1Cl QIMSMHHSGVQCCP-GXDHUFHOSA-N 0.000 claims description 7
- YJDPXMKSUFTHMS-XNTDXEJSSA-N (e)-3-cyclopentyl-2-[3-fluoro-4-(5-methyltetrazol-1-yl)phenyl]-n-(1,3-thiazol-2-yl)prop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCC2)\C(=O)NC=2SC=CN=2)C=C1F YJDPXMKSUFTHMS-XNTDXEJSSA-N 0.000 claims description 7
- HLIOSGRVEWBZSF-MHWRWJLKSA-N (e)-n-(5-bromo-1,3-thiazol-2-yl)-2-[3-chloro-4-(5-methyltetrazol-1-yl)phenyl]-3-cycloheptylprop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCCCC2)\C(=O)NC=2SC(Br)=CN=2)C=C1Cl HLIOSGRVEWBZSF-MHWRWJLKSA-N 0.000 claims description 7
- JGXAEYXCPWTPJH-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(5-methyltetrazol-1-yl)-3-(trifluoromethyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound CC1=NN=NN1C1=CC=C(C(CC2CCCC2)C(=O)NC=2SC=CN=2)C=C1C(F)(F)F JGXAEYXCPWTPJH-UHFFFAOYSA-N 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- SBAGURZBQXASIS-UHFFFAOYSA-N n-(5-bromopyridin-2-yl)-2-[3-chloro-4-(5-methyltetrazol-1-yl)phenyl]-3-cyclopentylpropanamide Chemical compound CC1=NN=NN1C1=CC=C(C(CC2CCCC2)C(=O)NC=2N=CC(Br)=CC=2)C=C1Cl SBAGURZBQXASIS-UHFFFAOYSA-N 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- LKVCBZIKYUSOKK-LFIBNONCSA-N (e)-2-[3-chloro-4-(5-methyltetrazol-1-yl)phenyl]-3-cyclohexyl-n-(1,3-thiazol-2-yl)prop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCCC2)\C(=O)NC=2SC=CN=2)C=C1Cl LKVCBZIKYUSOKK-LFIBNONCSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- RDFQPBCYHXYWEC-UHFFFAOYSA-N n-(5-bromopyridin-2-yl)-3-cyclopentyl-2-[4-(5-methyltetrazol-1-yl)-3-(trifluoromethyl)phenyl]propanamide Chemical compound CC1=NN=NN1C1=CC=C(C(CC2CCCC2)C(=O)NC=2N=CC(Br)=CC=2)C=C1C(F)(F)F RDFQPBCYHXYWEC-UHFFFAOYSA-N 0.000 claims description 6
- LFTGTOLTMYTROZ-LFIBNONCSA-N (e)-3-cyclopentyl-2-[3-methylsulfonyl-4-(5-methyltetrazol-1-yl)phenyl]-n-(1,3-thiazol-2-yl)prop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCC2)\C(=O)NC=2SC=CN=2)C=C1S(C)(=O)=O LFTGTOLTMYTROZ-LFIBNONCSA-N 0.000 claims description 5
- NKHVFFJXXOWCEU-LICLKQGHSA-N (e)-n-(5-bromopyridin-2-yl)-3-cyclopentyl-2-[3-fluoro-4-(5-methyltetrazol-1-yl)phenyl]prop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCC2)\C(=O)NC=2N=CC(Br)=CC=2)C=C1F NKHVFFJXXOWCEU-LICLKQGHSA-N 0.000 claims description 5
- FUDILUPVYTXZOP-UHFFFAOYSA-N 2-[3-chloro-4-(5-methyltetrazol-1-yl)phenyl]-3-cyclohexyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound CC1=NN=NN1C1=CC=C(C(CC2CCCCC2)C(=O)NC=2SC=CN=2)C=C1Cl FUDILUPVYTXZOP-UHFFFAOYSA-N 0.000 claims description 5
- VCAPFFJIUXFVLZ-UHFFFAOYSA-N 2-[3-chloro-4-(5-methyltetrazol-1-yl)phenyl]-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound CC1=NN=NN1C1=CC=C(C(CC2CCCC2)C(=O)NC=2SC=CN=2)C=C1Cl VCAPFFJIUXFVLZ-UHFFFAOYSA-N 0.000 claims description 5
- IFFDTWTYMFUYKO-UHFFFAOYSA-N 2-[3-chloro-4-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]-3-cyclohexyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound FC(F)(F)C1=NN=NN1C1=CC=C(C(CC2CCCCC2)C(=O)NC=2SC=CN=2)C=C1Cl IFFDTWTYMFUYKO-UHFFFAOYSA-N 0.000 claims description 5
- PIGACGIYJAENBN-UHFFFAOYSA-N 3-cyclopentyl-2-[4-methylsulfonyl-3-(5-methyltetrazol-1-yl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound CC1=NN=NN1C1=CC(C(CC2CCCC2)C(=O)NC=2SC=CN=2)=CC=C1S(C)(=O)=O PIGACGIYJAENBN-UHFFFAOYSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- VKWFRNZZSJDCLP-UHFFFAOYSA-N n-(5-bromopyridin-2-yl)-3-cyclopentyl-2-[3-fluoro-4-(5-methyltetrazol-1-yl)phenyl]propanamide Chemical compound CC1=NN=NN1C1=CC=C(C(CC2CCCC2)C(=O)NC=2N=CC(Br)=CC=2)C=C1F VKWFRNZZSJDCLP-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- TVJZYYHQBQGIPR-XNTDXEJSSA-N (e)-3-cyclopentyl-2-[4-(5-methyltetrazol-1-yl)-3-(trifluoromethyl)phenyl]-n-(1,3-thiazol-2-yl)prop-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/C2CCCC2)\C(=O)NC=2SC=CN=2)C=C1C(F)(F)F TVJZYYHQBQGIPR-XNTDXEJSSA-N 0.000 claims description 4
- ADUWEZAFXRWDTE-LZYBPNLTSA-N (e)-4-cyclopentyl-2-[4-(5-methyltetrazol-1-yl)-3-(trifluoromethyl)phenyl]-n-(1,3-thiazol-2-yl)but-2-enamide Chemical compound CC1=NN=NN1C1=CC=C(C(=C/CC2CCCC2)\C(=O)NC=2SC=CN=2)C=C1C(F)(F)F ADUWEZAFXRWDTE-LZYBPNLTSA-N 0.000 claims description 4
- LPAHTBLLEJHMNM-UHFFFAOYSA-N 3-cyclopentyl-2-[3-fluoro-4-(5-methyltetrazol-1-yl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound CC1=NN=NN1C1=CC=C(C(CC2CCCC2)C(=O)NC=2SC=CN=2)C=C1F LPAHTBLLEJHMNM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 3
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 55
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract description 19
- 230000003914 insulin secretion Effects 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 585
- 239000000243 solution Substances 0.000 description 511
- 239000011541 reaction mixture Substances 0.000 description 446
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 322
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 246
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 218
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 215
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 192
- 229920006395 saturated elastomer Polymers 0.000 description 188
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 161
- 239000007787 solid Substances 0.000 description 136
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 134
- 239000000725 suspension Substances 0.000 description 124
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 122
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 121
- 239000011780 sodium chloride Substances 0.000 description 109
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 108
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 106
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 106
- 239000010410 layer Substances 0.000 description 99
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 83
- 239000000284 extract Substances 0.000 description 73
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 70
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- 238000004587 chromatography analysis Methods 0.000 description 56
- 239000000377 silicon dioxide Substances 0.000 description 56
- 229910052786 argon Inorganic materials 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- 238000004458 analytical method Methods 0.000 description 49
- 239000000203 mixture Substances 0.000 description 48
- 238000004809 thin layer chromatography Methods 0.000 description 48
- 239000007858 starting material Substances 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 45
- 239000012044 organic layer Substances 0.000 description 44
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 40
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 39
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 38
- 150000002894 organic compounds Chemical class 0.000 description 36
- 239000002253 acid Substances 0.000 description 35
- 235000019270 ammonium chloride Nutrition 0.000 description 35
- 229910052740 iodine Inorganic materials 0.000 description 33
- 235000017557 sodium bicarbonate Nutrition 0.000 description 31
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 31
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 30
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 29
- 239000011630 iodine Substances 0.000 description 29
- 239000011701 zinc Substances 0.000 description 28
- 229910052725 zinc Inorganic materials 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 26
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 25
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 24
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 24
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 23
- 238000001914 filtration Methods 0.000 description 23
- 238000003818 flash chromatography Methods 0.000 description 23
- 239000003921 oil Substances 0.000 description 23
- 235000019198 oils Nutrition 0.000 description 23
- 239000000543 intermediate Substances 0.000 description 20
- BJVBKJRYBWMNAB-SOFGYWHQSA-N methyl (e)-3-cyclopentyl-2-iodoprop-2-enoate Chemical compound COC(=O)C(\I)=C/C1CCCC1 BJVBKJRYBWMNAB-SOFGYWHQSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 19
- 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 19
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 19
- 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 description 19
- 239000011449 brick Substances 0.000 description 19
- 125000005843 halogen group Chemical group 0.000 description 19
- 239000012535 impurity Substances 0.000 description 19
- 230000007935 neutral effect Effects 0.000 description 19
- 150000003752 zinc compounds Chemical class 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 239000008103 glucose Substances 0.000 description 16
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 15
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 15
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 14
- 239000000908 ammonium hydroxide Substances 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 14
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 14
- 235000019345 sodium thiosulphate Nutrition 0.000 description 14
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 13
- 238000007796 conventional method Methods 0.000 description 13
- KYQDTFZELMTOMH-UHFFFAOYSA-N 1-(2-chloro-4-iodophenyl)-5-methyltetrazole Chemical compound CC1=NN=NN1C1=CC=C(I)C=C1Cl KYQDTFZELMTOMH-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 239000004202 carbamide Substances 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- WUDOURUBZWRKFX-UHFFFAOYSA-N 1-(2-fluoro-4-iodophenyl)-5-methyltetrazole Chemical compound CC1=NN=NN1C1=CC=C(I)C=C1F WUDOURUBZWRKFX-UHFFFAOYSA-N 0.000 description 8
- MLQLDZFAHZJCNG-UHFFFAOYSA-N 1-[4-bromo-2-(trifluoromethyl)phenyl]-5-methyltetrazole Chemical compound CC1=NN=NN1C1=CC=C(Br)C=C1C(F)(F)F MLQLDZFAHZJCNG-UHFFFAOYSA-N 0.000 description 8
- MYDAOWXYGPEPJT-UHFFFAOYSA-N 2-chloro-4-iodoaniline Chemical compound NC1=CC=C(I)C=C1Cl MYDAOWXYGPEPJT-UHFFFAOYSA-N 0.000 description 8
- 125000001246 bromo group Chemical group Br* 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 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
- 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
- 230000009261 transgenic effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22549400P | 2000-08-15 | 2000-08-15 | |
| US60/225,494 | 2000-08-15 | ||
| PCT/EP2001/009207 WO2002014312A1 (en) | 2000-08-15 | 2001-08-09 | Tetrazolyl-phenyl acetamide glucokinase activators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2419416A1 CA2419416A1 (en) | 2002-02-21 |
| CA2419416C true CA2419416C (en) | 2009-10-13 |
Family
ID=22845106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002419416A Expired - Fee Related CA2419416C (en) | 2000-08-15 | 2001-08-09 | Tetrazolyl-phenyl acetamide glucokinase activators |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US6369232B1 (enExample) |
| EP (1) | EP1311504B1 (enExample) |
| JP (1) | JP3961948B2 (enExample) |
| KR (1) | KR100518061B1 (enExample) |
| CN (1) | CN1209362C (enExample) |
| AR (1) | AR031718A1 (enExample) |
| AT (1) | ATE297921T1 (enExample) |
| AU (2) | AU2001283998B2 (enExample) |
| BR (1) | BR0113312A (enExample) |
| CA (1) | CA2419416C (enExample) |
| DE (1) | DE60111540T2 (enExample) |
| DK (1) | DK1311504T3 (enExample) |
| ES (1) | ES2243541T3 (enExample) |
| MX (1) | MXPA03001275A (enExample) |
| PA (1) | PA8525201A1 (enExample) |
| PE (1) | PE20020386A1 (enExample) |
| PT (1) | PT1311504E (enExample) |
| UY (1) | UY26885A1 (enExample) |
| WO (1) | WO2002014312A1 (enExample) |
| ZA (1) | ZA200300904B (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0102299D0 (sv) | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
| SE0102764D0 (sv) | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
| US7078423B2 (en) * | 2002-07-18 | 2006-07-18 | Inotek Pharmaceuticals Corporation | 5-Aryltetrazole compounds, compositions thereof, and uses therefor |
| US7087631B2 (en) * | 2002-07-18 | 2006-08-08 | Inotek Pharmaceuticals Corporation | Aryltetrazole compounds, and compositions thereof |
| 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 |
| MY141521A (en) | 2002-12-12 | 2010-05-14 | Hoffmann La Roche | 5-substituted-six-membered heteroaromatic glucokinase activators |
| 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 |
| US7262196B2 (en) * | 2003-02-11 | 2007-08-28 | Prosidion Limited | Tri(cyclo) substituted amide glucokinase activator compounds |
| BRPI0509543A (pt) * | 2004-04-02 | 2007-09-18 | Novartis Ag | derivados de tiazolopiridina, condições farmacêuticas que contêm os mesmos e métodos para tratar condições mediadas por glucocinase |
| WO2005095418A1 (en) * | 2004-04-02 | 2005-10-13 | Novartis Ag | Sulfonamide-thiazolpyridine derivatives as glucokinase activators useful the treatment of type 2 diabetes |
| EP2305674A1 (en) | 2005-07-09 | 2011-04-06 | AstraZeneca AB | Heteroaryl benzamide derivatives for use as GLK activators in the treatment of diabetes |
| AU2006267387B2 (en) | 2005-07-11 | 2010-11-18 | Mitsubishi Tanabe Pharma Corporation | An oxime derivative and preparations thereof |
| JPWO2007026761A1 (ja) | 2005-08-31 | 2009-03-12 | アステラス製薬株式会社 | チアゾール誘導体 |
| 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 |
| GT200600429A (es) * | 2005-09-30 | 2007-04-30 | Compuestos organicos | |
| GT200600428A (es) * | 2005-09-30 | 2007-05-21 | Compuestos organicos | |
| CA2626475A1 (en) * | 2005-11-03 | 2007-05-10 | Prosidion Limited | Tricyclo substituted amides |
| JP2009515997A (ja) * | 2005-11-18 | 2009-04-16 | タケダ サン ディエゴ インコーポレイテッド | グルコキナーゼ活性剤 |
| BRPI0619980A2 (pt) * | 2005-12-15 | 2014-10-14 | Nihon Nohyaku Co Ltd | Derivados de ftalamida e de anilina, inseticida agrícola ou hortícula, e, método de uso do mesmo |
| EP2001875A2 (en) | 2006-03-08 | 2008-12-17 | Takeda San Diego, Inc. | Glucokinase activators |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| WO2007143434A2 (en) * | 2006-05-31 | 2007-12-13 | Takeda San Diego, Inc. | Indazole and isoindole derivatives as glucokinase activating agents |
| US7910747B2 (en) * | 2006-07-06 | 2011-03-22 | Bristol-Myers Squibb Company | Phosphonate and phosphinate pyrazolylamide glucokinase activators |
| US7902248B2 (en) | 2006-12-14 | 2011-03-08 | Hoffmann-La Roche Inc. | Oxime glucokinase activators |
| JP5419706B2 (ja) | 2006-12-20 | 2014-02-19 | タケダ カリフォルニア インコーポレイテッド | グルコキナーゼアクチベーター |
| TW200831081A (en) * | 2006-12-25 | 2008-08-01 | Kyorin Seiyaku Kk | Glucokinase activator |
| US8314247B2 (en) * | 2007-01-10 | 2012-11-20 | Mitsubishi Tanabe Pharma Corporation | Hydrazone derivative |
| CN101687800B (zh) * | 2007-03-07 | 2012-03-21 | 杏林制药株式会社 | 葡糖激酶活化物质 |
| US8173645B2 (en) * | 2007-03-21 | 2012-05-08 | Takeda San Diego, Inc. | Glucokinase activators |
| AU2008310519B2 (en) * | 2007-10-08 | 2013-05-02 | Advinus Therapeutics Private Limited | Acetamide derivatives as glucokinase activators, their process and medicinal applications |
| AR070107A1 (es) * | 2008-01-15 | 2010-03-17 | Lilly Co Eli | R-2-(4-ciclopropansulfonil-fenil)-n-pirazin-2-il-3-(tetrahidropiran-4-il)-propionamida en forma cristalina, composicion farmaceutica que la comprende y su uso para la manufactura de un medicamento util para la prevencion o tratamiento de hiperglicemia |
| JP5287730B2 (ja) | 2008-01-18 | 2013-09-11 | アステラス製薬株式会社 | フェニルアセトアミド誘導体 |
| AU2009241137B2 (en) * | 2008-04-28 | 2013-10-03 | Kyorin Pharmaceutical Co., Ltd. | Cyclopentylacrylic acid amide derivative |
| CN102959076B (zh) | 2010-03-31 | 2015-09-16 | 斯克里普斯研究所 | 重编程细胞 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3776917A (en) * | 1972-06-05 | 1973-12-04 | Schering Corp | 2-amino-6-phenalkyl-aminopyridines and derivatives thereof |
| GB8909574D0 (en) | 1989-04-26 | 1989-06-14 | Ici Plc | Chemical process |
| US5859052A (en) * | 1993-01-14 | 1999-01-12 | G. D. Searle & Co. | Fatty acid analogs and prodrugs |
| US5461049A (en) * | 1994-05-27 | 1995-10-24 | Warner-Lambert Company | Amide tetrazole ACAT inhibitors |
| US5468867A (en) * | 1994-05-27 | 1995-11-21 | Syntex (U.S.A.) Inc. | Process for preparing1-butyl-2-[2'-(2H-tetrazol-5-yl)biphenyl-4-ylmethyl1-1H-indole-3-carboxylic acid |
| WO1998032753A1 (en) * | 1997-01-28 | 1998-07-30 | Merck & Co., Inc. | THIAZOLE BENZENESULFONAMIDES AS β3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY |
| SI1169312T1 (en) * | 1999-03-29 | 2005-02-28 | F. Hoffmann-La Roche Ag | Glucokinase activators |
-
2001
- 2001-08-08 US US09/924,247 patent/US6369232B1/en not_active Expired - Fee Related
- 2001-08-09 ES ES01962926T patent/ES2243541T3/es not_active Expired - Lifetime
- 2001-08-09 BR BR0113312-8A patent/BR0113312A/pt not_active IP Right Cessation
- 2001-08-09 AU AU2001283998A patent/AU2001283998B2/en not_active Ceased
- 2001-08-09 KR KR10-2003-7002231A patent/KR100518061B1/ko not_active Expired - Fee Related
- 2001-08-09 MX MXPA03001275A patent/MXPA03001275A/es active IP Right Grant
- 2001-08-09 WO PCT/EP2001/009207 patent/WO2002014312A1/en not_active Ceased
- 2001-08-09 CN CNB018163475A patent/CN1209362C/zh not_active Expired - Fee Related
- 2001-08-09 JP JP2002519452A patent/JP3961948B2/ja not_active Expired - Fee Related
- 2001-08-09 DE DE60111540T patent/DE60111540T2/de not_active Expired - Lifetime
- 2001-08-09 CA CA002419416A patent/CA2419416C/en not_active Expired - Fee Related
- 2001-08-09 PT PT01962926T patent/PT1311504E/pt unknown
- 2001-08-09 AT AT01962926T patent/ATE297921T1/de not_active IP Right Cessation
- 2001-08-09 AU AU8399801A patent/AU8399801A/xx active Pending
- 2001-08-09 DK DK01962926T patent/DK1311504T3/da active
- 2001-08-09 EP EP01962926A patent/EP1311504B1/en not_active Expired - Lifetime
- 2001-08-14 UY UY26885A patent/UY26885A1/es not_active Application Discontinuation
- 2001-08-14 PA PA20018525201A patent/PA8525201A1/es unknown
- 2001-08-14 AR ARP010103886A patent/AR031718A1/es active IP Right Grant
- 2001-08-15 PE PE2001000814A patent/PE20020386A1/es not_active Application Discontinuation
- 2001-10-11 US US09/975,713 patent/US6388088B1/en not_active Expired - Fee Related
-
2002
- 2002-01-16 US US10/050,508 patent/US6441180B1/en not_active Expired - Fee Related
-
2003
- 2003-01-31 ZA ZA200300904A patent/ZA200300904B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20020035267A1 (en) | 2002-03-21 |
| AU2001283998B2 (en) | 2005-10-20 |
| JP3961948B2 (ja) | 2007-08-22 |
| AU8399801A (en) | 2002-02-25 |
| BR0113312A (pt) | 2003-07-01 |
| US20020065275A1 (en) | 2002-05-30 |
| JP2004506632A (ja) | 2004-03-04 |
| KR100518061B1 (ko) | 2005-09-28 |
| KR20030022408A (ko) | 2003-03-15 |
| WO2002014312A1 (en) | 2002-02-21 |
| CN1209362C (zh) | 2005-07-06 |
| ES2243541T3 (es) | 2005-12-01 |
| ATE297921T1 (de) | 2005-07-15 |
| MXPA03001275A (es) | 2003-06-30 |
| DK1311504T3 (da) | 2005-10-17 |
| US6369232B1 (en) | 2002-04-09 |
| ZA200300904B (en) | 2004-04-30 |
| DE60111540D1 (de) | 2005-07-21 |
| AR031718A1 (es) | 2003-10-01 |
| PA8525201A1 (es) | 2002-07-30 |
| EP1311504A1 (en) | 2003-05-21 |
| US6388088B1 (en) | 2002-05-14 |
| PE20020386A1 (es) | 2002-05-13 |
| PT1311504E (pt) | 2005-10-31 |
| EP1311504B1 (en) | 2005-06-15 |
| DE60111540T2 (de) | 2006-03-16 |
| US20020035266A1 (en) | 2002-03-21 |
| US6441180B1 (en) | 2002-08-27 |
| CN1466584A (zh) | 2004-01-07 |
| CA2419416A1 (en) | 2002-02-21 |
| UY26885A1 (es) | 2002-02-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130809 |