CA2679185A1 - 2,2,2-tri-substituted acetamide derivatives as glucokinase activators, their process and pharmaceutical application - Google Patents
2,2,2-tri-substituted acetamide derivatives as glucokinase activators, their process and pharmaceutical application Download PDFInfo
- Publication number
- CA2679185A1 CA2679185A1 CA002679185A CA2679185A CA2679185A1 CA 2679185 A1 CA2679185 A1 CA 2679185A1 CA 002679185 A CA002679185 A CA 002679185A CA 2679185 A CA2679185 A CA 2679185A CA 2679185 A1 CA2679185 A1 CA 2679185A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- thiazol
- phenoxy
- propionamide
- difluoro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108010021582 Glucokinase Proteins 0.000 title claims abstract description 140
- 238000000034 method Methods 0.000 title claims abstract description 62
- 239000012190 activator Substances 0.000 title claims abstract description 57
- 230000008569 process Effects 0.000 title claims abstract description 13
- 102000030595 Glucokinase Human genes 0.000 title claims abstract 7
- 150000003869 acetamides Chemical class 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 150000003839 salts Chemical class 0.000 claims abstract description 58
- 239000000651 prodrug Substances 0.000 claims abstract description 54
- 229940002612 prodrug Drugs 0.000 claims abstract description 54
- 239000012453 solvate Substances 0.000 claims abstract description 51
- 230000036961 partial effect Effects 0.000 claims abstract description 46
- 238000002360 preparation method Methods 0.000 claims abstract description 27
- 229940124828 glucokinase activator Drugs 0.000 claims abstract description 17
- -1 arylalyl Chemical group 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 229940080818 propionamide Drugs 0.000 claims description 40
- 206010012601 diabetes mellitus Diseases 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 39
- 239000002904 solvent Substances 0.000 claims description 36
- 125000003342 alkenyl group Chemical group 0.000 claims description 33
- 125000000304 alkynyl group Chemical group 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 230000004913 activation Effects 0.000 claims description 29
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 27
- 125000004043 oxo group Chemical group O=* 0.000 claims description 26
- 208000008589 Obesity Diseases 0.000 claims description 24
- 235000020824 obesity Nutrition 0.000 claims description 24
- 201000001421 hyperglycemia Diseases 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 19
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 16
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 150000001408 amides Chemical class 0.000 claims description 14
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
- 230000001225 therapeutic effect Effects 0.000 claims description 14
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 13
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 231100000673 dose–response relationship Toxicity 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 230000000069 prophylactic effect Effects 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 150000002825 nitriles Chemical class 0.000 claims description 11
- 238000006467 substitution reaction Methods 0.000 claims description 11
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 10
- VSWXAFBANQPLTL-UHFFFAOYSA-N 1-(2,4-difluorophenoxy)cyclopropane-1-carboxylic acid Chemical compound C=1C=C(F)C=C(F)C=1OC1(C(=O)O)CC1 VSWXAFBANQPLTL-UHFFFAOYSA-N 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 230000008878 coupling Effects 0.000 claims description 8
- 238000010168 coupling process Methods 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- 230000001419 dependent effect Effects 0.000 claims description 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 150000003536 tetrazoles Chemical class 0.000 claims description 7
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- WJJRQPAWQBAGJB-UHFFFAOYSA-N 3-[2-methyl-1-oxo-1-(1,3-thiazol-2-ylamino)propan-2-yl]oxybenzoic acid Chemical compound N=1C=CSC=1NC(=O)C(C)(C)OC1=CC=CC(C(O)=O)=C1 WJJRQPAWQBAGJB-UHFFFAOYSA-N 0.000 claims description 5
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 5
- 208000013016 Hypoglycemia Diseases 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 150000007529 inorganic bases Chemical class 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- JTQSGGFCUCPVSY-UHFFFAOYSA-N n-(3-aminopyridin-2-yl)-2-(6-chloropyridin-2-yl)oxy-2-methylpropanamide Chemical compound N=1C=CC=C(N)C=1NC(=O)C(C)(C)OC1=CC=CC(Cl)=N1 JTQSGGFCUCPVSY-UHFFFAOYSA-N 0.000 claims description 5
- RKMATNAAHHJPPQ-UHFFFAOYSA-N 2-[4-(2,5-dimethylpyrrol-1-yl)phenoxy]-2-methyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound CC1=CC=C(C)N1C(C=C1)=CC=C1OC(C)(C)C(=O)NC1=NC=CS1 RKMATNAAHHJPPQ-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- PKCHFLFELCHDFE-UHFFFAOYSA-N ethyl 2-[2-[[2-(2,4-difluorophenoxy)-2-methylbutanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NC(=O)C(C)(CC)OC=2C(=CC(F)=CC=2)F)=N1 PKCHFLFELCHDFE-UHFFFAOYSA-N 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- MPTCPWOTFUIXKN-UHFFFAOYSA-N 1-(4-methylsulfonylphenoxy)cyclohexane-1-carboxylic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1OC1(C(O)=O)CCCCC1 MPTCPWOTFUIXKN-UHFFFAOYSA-N 0.000 claims description 3
- DJQBVNCLTRXLNX-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-2-(4-methylsulfonylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound N=1C=CSC=1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)(C)OC1=CC=C(F)C=C1F DJQBVNCLTRXLNX-UHFFFAOYSA-N 0.000 claims description 3
- UDSUTIZJVOEEKI-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-n-[4-[2-(4-fluoroanilino)-2-oxoethyl]-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound N=1C(CC(=O)NC=2C=CC(F)=CC=2)=CSC=1NC(=O)C(C)(C)OC1=CC=C(F)C=C1F UDSUTIZJVOEEKI-UHFFFAOYSA-N 0.000 claims description 3
- LIYKMEVZIOOVLZ-UHFFFAOYSA-N 2-(4-chlorophenoxy)-2-methyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound N=1C=CSC=1NC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 LIYKMEVZIOOVLZ-UHFFFAOYSA-N 0.000 claims description 3
- HTLWNMBVZSEXFF-UHFFFAOYSA-N 2-(6-chloropyridin-2-yl)oxy-n-[3-(methanesulfonamido)pyridin-2-yl]-2-methylpropanamide Chemical compound N=1C=CC=C(NS(C)(=O)=O)C=1NC(=O)C(C)(C)OC1=CC=CC(Cl)=N1 HTLWNMBVZSEXFF-UHFFFAOYSA-N 0.000 claims description 3
- LILSULIBVAWEMC-UHFFFAOYSA-N 2-[2-[(2-methyl-2-naphthalen-1-yloxypropanoyl)amino]-1,3-thiazol-4-yl]acetic acid Chemical compound C=1C=CC2=CC=CC=C2C=1OC(C)(C)C(=O)NC1=NC(CC(O)=O)=CS1 LILSULIBVAWEMC-UHFFFAOYSA-N 0.000 claims description 3
- WGVGZRMVRUGIDK-UHFFFAOYSA-N 2-[2-[[1-(4-methylsulfonylphenoxy)cyclohexanecarbonyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1OC1(C(=O)NC=2SC=C(CC(O)=O)N=2)CCCCC1 WGVGZRMVRUGIDK-UHFFFAOYSA-N 0.000 claims description 3
- FFNRFQUESGSKHR-UHFFFAOYSA-N 2-[2-[[2-(2,4-difluorophenoxy)-2-methylpropanoyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound N=1C(CC(O)=O)=CSC=1NC(=O)C(C)(C)OC1=CC=C(F)C=C1F FFNRFQUESGSKHR-UHFFFAOYSA-N 0.000 claims description 3
- MQWNQMRVHIXUPE-UHFFFAOYSA-N 2-[5-chloro-2-[[2-(2,4-difluorophenoxy)-2-(4-methylsulfonylphenyl)propanoyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound N=1C(CC(O)=O)=C(Cl)SC=1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)(C)OC1=CC=C(F)C=C1F MQWNQMRVHIXUPE-UHFFFAOYSA-N 0.000 claims description 3
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- DYLZTXAPBLOTQL-UHFFFAOYSA-N n-(3-acetamidopyridin-2-yl)-2-(6-chloropyridin-2-yl)oxy-2-methylpropanamide Chemical compound CC(=O)NC1=CC=CN=C1NC(=O)C(C)(C)OC1=CC=CC(Cl)=N1 DYLZTXAPBLOTQL-UHFFFAOYSA-N 0.000 claims description 3
- WQNMYSJDSJQLER-UHFFFAOYSA-N n-(5-chloro-1,3-thiazol-2-yl)-2-[2-(cyclopentylmethoxy)phenoxy]-2-methylpropanamide Chemical compound N=1C=C(Cl)SC=1NC(=O)C(C)(C)OC1=CC=CC=C1OCC1CCCC1 WQNMYSJDSJQLER-UHFFFAOYSA-N 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- ANEFMHJANNRUNW-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yloxy)-n-[5-chloro-4-[2-(4-fluoroanilino)-2-oxoethyl]-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound C=1C=C2OCOC2=CC=1OC(C)(C)C(=O)NC(SC=1Cl)=NC=1CC(=O)NC1=CC=C(F)C=C1 ANEFMHJANNRUNW-UHFFFAOYSA-N 0.000 claims description 2
- XHCDOPPXRGDOEN-UHFFFAOYSA-N 2-(1-benzothiophen-5-yloxy)-2-methyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C=1C=C2SC=CC2=CC=1OC(C)(C)C(=O)NC1=NC=CS1 XHCDOPPXRGDOEN-UHFFFAOYSA-N 0.000 claims description 2
- XENKQFZHURVGAI-UHFFFAOYSA-N 2-(1h-indol-5-yloxy)-2-methyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C=1C=C2NC=CC2=CC=1OC(C)(C)C(=O)NC1=NC=CS1 XENKQFZHURVGAI-UHFFFAOYSA-N 0.000 claims description 2
- ICABLDLYXDFLQN-UHFFFAOYSA-N 2-(2,3-dihydro-1h-inden-5-yloxy)-2-methyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C=1C=C2CCCC2=CC=1OC(C)(C)C(=O)NC1=NC=CS1 ICABLDLYXDFLQN-UHFFFAOYSA-N 0.000 claims description 2
- LOGGGMXRGAPMSI-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-2-(4-methylsulfonylphenyl)-n-(4-phenyl-1,3-thiazol-2-yl)propanamide Chemical compound N=1C(C=2C=CC=CC=2)=CSC=1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)(C)OC1=CC=C(F)C=C1F LOGGGMXRGAPMSI-UHFFFAOYSA-N 0.000 claims description 2
- LAJALFSCYCUAQD-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-2-(4-methylsulfonylphenyl)-n-(5-phenyl-1,3,4-thiadiazol-2-yl)propanamide Chemical compound N=1N=C(C=2C=CC=CC=2)SC=1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)(C)OC1=CC=C(F)C=C1F LAJALFSCYCUAQD-UHFFFAOYSA-N 0.000 claims description 2
- USWMVAVBTBFYLZ-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-2-(4-methylsulfonylphenyl)-n-pyrazin-2-ylpropanamide Chemical compound C=1N=CC=NC=1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)(C)OC1=CC=C(F)C=C1F USWMVAVBTBFYLZ-UHFFFAOYSA-N 0.000 claims description 2
- YIBXCHVPRCTEKH-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-2-methyl-n-(1,3-thiazol-2-yl)-4-thiophen-3-ylbutanamide Chemical compound C=1C=C(F)C=C(F)C=1OC(C(=O)NC=1SC=CN=1)(C)CCC=1C=CSC=1 YIBXCHVPRCTEKH-UHFFFAOYSA-N 0.000 claims description 2
- PPQCWARFAYXMNP-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-2-methyl-n-(4-methylpyrimidin-2-yl)propanamide Chemical compound CC1=CC=NC(NC(=O)C(C)(C)OC=2C(=CC(F)=CC=2)F)=N1 PPQCWARFAYXMNP-UHFFFAOYSA-N 0.000 claims description 2
- UETWKIDOBQOBFT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-n-(4-methylpyrimidin-2-yl)-2-(4-methylsulfonylphenyl)propanamide Chemical compound CC1=CC=NC(NC(=O)C(C)(OC=2C(=CC(F)=CC=2)F)C=2C=CC(=CC=2)S(C)(=O)=O)=N1 UETWKIDOBQOBFT-UHFFFAOYSA-N 0.000 claims description 2
- NJKUHDQXXQLKSP-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-n-(5-fluoro-1,3-thiazol-2-yl)-2-[4-(oxan-4-ylsulfonyl)phenyl]propanamide Chemical compound N=1C=C(F)SC=1NC(=O)C(C=1C=CC(=CC=1)S(=O)(=O)C1CCOCC1)(C)OC1=CC=C(F)C=C1F NJKUHDQXXQLKSP-UHFFFAOYSA-N 0.000 claims description 2
- KMBYTMNRBFKGCR-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-n-(6-fluoro-1,3-benzothiazol-2-yl)-2-(4-methylsulfonylphenyl)propanamide Chemical compound N=1C2=CC=C(F)C=C2SC=1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)(C)OC1=CC=C(F)C=C1F KMBYTMNRBFKGCR-UHFFFAOYSA-N 0.000 claims description 2
- KCLYZGBBOLIULP-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)-n-[4-[2-(4-fluorophenoxy)ethyl]-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound N=1C(CCOC=2C=CC(F)=CC=2)=CSC=1NC(=O)C(C)(C)OC1=CC=C(F)C=C1F KCLYZGBBOLIULP-UHFFFAOYSA-N 0.000 claims description 2
- YYVVWOUVQVTRKJ-UHFFFAOYSA-N 2-(2h-1,2-benzoxazin-6-yloxy)-2-methyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C=1C=C2ONC=CC2=CC=1OC(C)(C)C(=O)NC1=NC=CS1 YYVVWOUVQVTRKJ-UHFFFAOYSA-N 0.000 claims description 2
- AUSXEHHFTKWTDH-UHFFFAOYSA-N 2-(3,4-difluorophenoxy)-2-methyl-n-(1,2-oxazol-3-yl)propanamide Chemical compound C1=CON=C1NC(=O)C(C)(C)OC1=CC=C(F)C(F)=C1 AUSXEHHFTKWTDH-UHFFFAOYSA-N 0.000 claims description 2
- KRFPMFWAMOLAGQ-UHFFFAOYSA-N 2-(3-acetamidophenoxy)-2-methyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound CC(=O)NC1=CC=CC(OC(C)(C)C(=O)NC=2SC=CN=2)=C1 KRFPMFWAMOLAGQ-UHFFFAOYSA-N 0.000 claims description 2
- GVAOEPKDMFPCOF-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfanyl-2-(4-methylsulfonylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound N=1C=CSC=1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)(C)SC1=CC=C(Cl)C=C1 GVAOEPKDMFPCOF-UHFFFAOYSA-N 0.000 claims description 2
- ICWASQOUUWCANF-UHFFFAOYSA-N 2-[2-[(2-methyl-2-naphthalen-2-yloxypropanoyl)amino]-1,3-thiazol-4-yl]acetic acid Chemical compound C=1C=C2C=CC=CC2=CC=1OC(C)(C)C(=O)NC1=NC(CC(O)=O)=CS1 ICWASQOUUWCANF-UHFFFAOYSA-N 0.000 claims description 2
- BEYLAFMFSJNPAR-UHFFFAOYSA-N 2-[2-[[2-(1,3-benzodioxol-5-yloxy)-2-methylpropanoyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound C=1C=C2OCOC2=CC=1OC(C)(C)C(=O)NC1=NC(CC(O)=O)=CS1 BEYLAFMFSJNPAR-UHFFFAOYSA-N 0.000 claims description 2
- GGOXIYVTDXUCGA-UHFFFAOYSA-N 2-[2-[[2-(1,3-benzodioxol-5-yloxy)-2-methylpropanoyl]amino]-5-chloro-1,3-thiazol-4-yl]acetic acid Chemical compound C=1C=C2OCOC2=CC=1OC(C)(C)C(=O)NC1=NC(CC(O)=O)=C(Cl)S1 GGOXIYVTDXUCGA-UHFFFAOYSA-N 0.000 claims description 2
- DWTJGGRLBLPBEX-UHFFFAOYSA-N 2-[2-[[2-(2,4-difluorophenoxy)-2-methylbutanoyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound N=1C(CC(O)=O)=CSC=1NC(=O)C(C)(CC)OC1=CC=C(F)C=C1F DWTJGGRLBLPBEX-UHFFFAOYSA-N 0.000 claims description 2
- LCSHKPXPZGAWSR-UHFFFAOYSA-N 2-[2-[[2-(4-acetamidophenoxy)-2-methylpropanoyl]amino]-5-chloro-1,3-thiazol-4-yl]acetic acid Chemical compound C1=CC(NC(=O)C)=CC=C1OC(C)(C)C(=O)NC1=NC(CC(O)=O)=C(Cl)S1 LCSHKPXPZGAWSR-UHFFFAOYSA-N 0.000 claims description 2
- CDZRWCKGPBIVPB-UHFFFAOYSA-N 2-[2-[[2-(4-chlorophenoxy)-3-cyclopentyl-2-methylpropanoyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1OC(C(=O)NC=1SC=C(CC(O)=O)N=1)(C)CC1CCCC1 CDZRWCKGPBIVPB-UHFFFAOYSA-N 0.000 claims description 2
- LNUYSEJHQWXCOF-UHFFFAOYSA-N 2-[2-[[2-(4-cyclohexylsulfonylphenyl)-2-(2,4-difluorophenoxy)propanoyl]amino]-5-fluoro-1,3-thiazol-4-yl]acetic acid Chemical compound N=1C(CC(O)=O)=C(F)SC=1NC(=O)C(C=1C=CC(=CC=1)S(=O)(=O)C1CCCCC1)(C)OC1=CC=C(F)C=C1F LNUYSEJHQWXCOF-UHFFFAOYSA-N 0.000 claims description 2
- VGGAQXHFNVASCT-UHFFFAOYSA-N 2-[2-[[2-(4-cyclopentylsulfonylphenyl)-2-(2,4-difluorophenoxy)propanoyl]amino]-5-fluoro-1,3-thiazol-4-yl]acetic acid Chemical compound N=1C(CC(O)=O)=C(F)SC=1NC(=O)C(C=1C=CC(=CC=1)S(=O)(=O)C1CCCC1)(C)OC1=CC=C(F)C=C1F VGGAQXHFNVASCT-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- 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
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- 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
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- 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
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- 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
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- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
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- C07D277/82—Nitrogen atoms
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- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
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- 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
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| IN409/CHE/2007 | 2007-02-28 | ||
| IN409CH2007 | 2007-02-28 | ||
| PCT/IN2008/000109 WO2008104994A2 (en) | 2007-02-28 | 2008-02-25 | 2,2,2-tri-substituted acetamide derivatives as glucokinase activators, their process and pharmaceutical application |
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| EP2217565B1 (en) | 2007-11-07 | 2013-05-22 | Boehringer Ingelheim International GmbH | Compounds which modulate the cb2 receptor |
| JP5749162B2 (ja) | 2008-07-10 | 2015-07-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Cb2受容体を調節するスルホン化合物 |
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| WO2005033072A2 (en) | 2003-09-30 | 2005-04-14 | Scios Inc. | Heterocyclic amides and sulfonamides |
| JP2006025403A (ja) * | 2004-06-08 | 2006-01-26 | Ricoh Co Ltd | 画像読取装置及び画像形成装置 |
| RU2006147263A (ru) | 2004-06-08 | 2008-07-20 | ПРАЙМДЖЕН БАЙОТЕК ЭлЭлСи (US) | Терапевтическое перепрограммирование, гибридные стволовые клетки и созревание |
| US20080026987A1 (en) | 2004-06-17 | 2008-01-31 | Novo Nordisk A/S | Use of Liver-Selective Glucokinase Activators |
| SE0401653D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | New compounds |
| GB0423043D0 (en) | 2004-10-16 | 2004-11-17 | Astrazeneca Ab | Compounds |
| EP1972151B1 (en) * | 2006-01-09 | 2017-03-29 | Thomson Licensing | Method and apparatus for providing adaptation of deblocking filtering for multiview video coding |
| TWI385161B (zh) * | 2006-02-02 | 2013-02-11 | Mitsubishi Tanabe Pharma Corp | 含氮雜雙環化合物 |
| JP5099814B2 (ja) | 2006-02-02 | 2012-12-19 | 田辺三菱製薬株式会社 | 含窒素複素二環式化合物 |
| EP1994011B1 (en) | 2006-03-06 | 2010-10-13 | RaQualia Pharma Inc | Sulfonyl benzimidazole derivatives |
| AU2007249891A1 (en) * | 2006-05-12 | 2007-11-22 | Vertex Pharmaceuticals Incorporated | Selective inhibitors of ROCK protein kinase and uses thereof |
| JP5448164B2 (ja) | 2006-07-28 | 2014-03-19 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Cb2受容体を変調する化合物 |
-
2008
- 2008-02-25 CN CN2008800064275A patent/CN101622231B/zh not_active Expired - Fee Related
- 2008-02-25 JP JP2009551312A patent/JP5491871B2/ja not_active Expired - Fee Related
- 2008-02-25 CA CA002679185A patent/CA2679185A1/en not_active Abandoned
- 2008-02-25 EP EP08738368A patent/EP2125735B1/en active Active
- 2008-02-25 US US12/528,770 patent/US8940900B2/en active Active
- 2008-02-25 WO PCT/IN2008/000109 patent/WO2008104994A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US20100144772A1 (en) | 2010-06-10 |
| CN101622231A (zh) | 2010-01-06 |
| WO2008104994A2 (en) | 2008-09-04 |
| WO2008104994A3 (en) | 2009-04-02 |
| EP2125735B1 (en) | 2012-06-27 |
| JP2010520195A (ja) | 2010-06-10 |
| JP5491871B2 (ja) | 2014-05-14 |
| CN101622231B (zh) | 2013-12-04 |
| US8940900B2 (en) | 2015-01-27 |
| EP2125735A2 (en) | 2009-12-02 |
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