MXPA05000130A - Derivados de aril-carbonilo como agentes terapeuticos. - Google Patents
Derivados de aril-carbonilo como agentes terapeuticos.Info
- Publication number
- MXPA05000130A MXPA05000130A MXPA05000130A MXPA05000130A MXPA05000130A MX PA05000130 A MXPA05000130 A MX PA05000130A MX PA05000130 A MXPA05000130 A MX PA05000130A MX PA05000130 A MXPA05000130 A MX PA05000130A MX PA05000130 A MXPA05000130 A MX PA05000130A
- Authority
- MX
- Mexico
- Prior art keywords
- compound according
- alkyl
- alkylene
- modality
- hydrogen
- Prior art date
Links
- 125000005129 aryl carbonyl group Chemical group 0.000 title abstract 2
- 239000003814 drug Substances 0.000 title description 54
- 229940124597 therapeutic agent Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 884
- 229910052739 hydrogen Inorganic materials 0.000 claims description 355
- 239000001257 hydrogen Substances 0.000 claims description 355
- -1 C2-s-s.lkenyl Chemical group 0.000 claims description 317
- 125000003118 aryl group Chemical group 0.000 claims description 179
- 125000001424 substituent group Chemical group 0.000 claims description 175
- 150000002431 hydrogen Chemical class 0.000 claims description 159
- 229910052757 nitrogen Inorganic materials 0.000 claims description 158
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 150
- 125000001072 heteroaryl group Chemical group 0.000 claims description 137
- 229910052736 halogen Inorganic materials 0.000 claims description 89
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 89
- 150000002367 halogens Chemical class 0.000 claims description 88
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 79
- 125000000623 heterocyclic group Chemical group 0.000 claims description 78
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 57
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 55
- 229910052760 oxygen Inorganic materials 0.000 claims description 54
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 53
- 239000001301 oxygen Substances 0.000 claims description 53
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 47
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 43
- 229910052717 sulfur Chemical group 0.000 claims description 43
- 125000005842 heteroatom Chemical group 0.000 claims description 42
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 41
- 239000011593 sulfur Chemical group 0.000 claims description 41
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 35
- 125000006413 ring segment Chemical group 0.000 claims description 35
- 125000005936 piperidyl group Chemical group 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000002757 morpholinyl group Chemical group 0.000 claims description 24
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 22
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 21
- 125000000335 thiazolyl group Chemical group 0.000 claims description 21
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 20
- 150000002829 nitrogen Chemical class 0.000 claims description 20
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 20
- 125000001425 triazolyl group Chemical group 0.000 claims description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims description 17
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 17
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 125000001041 indolyl group Chemical group 0.000 claims description 11
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 11
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 10
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 10
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 claims description 8
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 claims description 8
- FLOJNXXFMHCMMR-UHFFFAOYSA-N 1,3-dithiolanyl Chemical group [CH]1SCCS1 FLOJNXXFMHCMMR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 8
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 8
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 125000003551 oxepanyl group Chemical group 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000001166 thiolanyl group Chemical group 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000003566 oxetanyl group Chemical group 0.000 claims description 6
- 239000000651 prodrug Substances 0.000 claims description 6
- 229940002612 prodrug Drugs 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000002053 thietanyl group Chemical group 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 102000030595 Glucokinase Human genes 0.000 abstract description 173
- 108010021582 Glucokinase Proteins 0.000 abstract description 173
- 238000011282 treatment Methods 0.000 abstract description 135
- 230000000694 effects Effects 0.000 abstract description 101
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 39
- 239000012190 activator Substances 0.000 abstract description 30
- 201000010099 disease Diseases 0.000 abstract description 28
- 230000001965 increasing effect Effects 0.000 abstract description 17
- 230000009286 beneficial effect Effects 0.000 abstract description 6
- NCTHHJRIJGFPTG-UHFFFAOYSA-N 6,7-bis(aziridin-1-yl)-4-[7-[[6,7-bis(aziridin-1-yl)-5,8-dioxoquinazolin-4-yl]amino]heptylamino]quinazoline-5,8-dione Chemical compound C1CN1C=1C(=O)C2=C(NCCCCCCCNC=3C=4C(=O)C(N5CC5)=C(N5CC5)C(=O)C=4N=CN=3)N=CN=C2C(=O)C=1N1CC1 NCTHHJRIJGFPTG-UHFFFAOYSA-N 0.000 description 169
- 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 132
- 239000008103 glucose Substances 0.000 description 132
- DSODRWWHAUGSGD-UHFFFAOYSA-N [5-(carbamimidoylsulfanylmethyl)thiophen-2-yl]methyl carbamimidothioate;dihydrochloride Chemical compound Cl.Cl.NC(=N)SCC1=CC=C(CSC(N)=N)S1 DSODRWWHAUGSGD-UHFFFAOYSA-N 0.000 description 112
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 105
- 125000004093 cyano group Chemical group *C#N 0.000 description 90
- 125000000217 alkyl group Chemical group 0.000 description 65
- 238000003556 assay Methods 0.000 description 51
- 108090001061 Insulin Proteins 0.000 description 49
- 102000004877 Insulin Human genes 0.000 description 49
- 230000004913 activation Effects 0.000 description 49
- 229940125396 insulin Drugs 0.000 description 49
- 238000000034 method Methods 0.000 description 40
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 40
- JYNZIOFUHBJABQ-UHFFFAOYSA-N allyl-{6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl-}-methyl-amin Chemical compound C=1OC2=CC(OCCCCCCN(C)CC=C)=CC=C2C=1C1=CC=C(Br)C=C1 JYNZIOFUHBJABQ-UHFFFAOYSA-N 0.000 description 37
- 238000002360 preparation method Methods 0.000 description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- NFGODEMQGQNUKK-UHFFFAOYSA-M [6-(diethylamino)-9-(2-octadecoxycarbonylphenyl)xanthen-3-ylidene]-diethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCCOC(=O)C1=CC=CC=C1C1=C2C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C21 NFGODEMQGQNUKK-UHFFFAOYSA-M 0.000 description 35
- 239000008194 pharmaceutical composition Substances 0.000 description 34
- 208000008589 Obesity Diseases 0.000 description 28
- 125000004429 atom Chemical group 0.000 description 28
- 235000020824 obesity Nutrition 0.000 description 28
- 210000004185 liver Anatomy 0.000 description 27
- 206010020772 Hypertension Diseases 0.000 description 26
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 25
- 239000000825 pharmaceutical preparation Substances 0.000 description 23
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 22
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 22
- 206010012601 diabetes mellitus Diseases 0.000 description 22
- 229940124828 glucokinase activator Drugs 0.000 description 22
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 21
- 208000002705 Glucose Intolerance Diseases 0.000 description 20
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 19
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 19
- 201000009104 prediabetes syndrome Diseases 0.000 description 19
- 210000004369 blood Anatomy 0.000 description 18
- 239000008280 blood Substances 0.000 description 18
- 229940100389 Sulfonylurea Drugs 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- CXBAABOAUNPLDL-UHFFFAOYSA-N 3-(4-benzoylanilino)-4-(2-methoxyphenyl)pyrrole-2,5-dione Chemical compound COc1ccccc1C1=C(Nc2ccc(cc2)C(=O)c2ccccc2)C(=O)NC1=O CXBAABOAUNPLDL-UHFFFAOYSA-N 0.000 description 15
- 125000002947 alkylene group Chemical group 0.000 description 15
- 201000001421 hyperglycemia Diseases 0.000 description 15
- 239000000556 agonist Substances 0.000 description 14
- 239000004202 carbamide Substances 0.000 description 14
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 14
- 229960003105 metformin Drugs 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- 208000011580 syndromic disease Diseases 0.000 description 14
- 208000032928 Dyslipidaemia Diseases 0.000 description 13
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- 230000003213 activating effect Effects 0.000 description 13
- 125000003342 alkenyl group Chemical group 0.000 description 13
- 239000011575 calcium Substances 0.000 description 13
- 210000003494 hepatocyte Anatomy 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 13
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 12
- 208000017170 Lipid metabolism disease Diseases 0.000 description 12
- 125000000304 alkynyl group Chemical group 0.000 description 12
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- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 12
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- ZEMLYWMOSZRCQL-UWSZBUKDSA-N 2-[(3r,5r,6s)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2s)-1-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]-2-oxopiperidin-3-yl]acetic acid Chemical compound C1([C@@H]2[C@H](N(C([C@@H](CC(O)=O)C2)=O)[C@@H](CC)C(=O)OC(C)(C)C)C=2C=CC(Cl)=CC=2)=CC=CC(Cl)=C1 ZEMLYWMOSZRCQL-UWSZBUKDSA-N 0.000 description 9
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- 230000007423 decrease Effects 0.000 description 9
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- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 9
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- 239000002220 antihypertensive agent Substances 0.000 description 8
- 125000005215 cycloalkylheteroaryl group Chemical group 0.000 description 8
- 230000034994 death Effects 0.000 description 8
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- 230000037406 food intake Effects 0.000 description 8
- 125000005549 heteroarylene group Chemical group 0.000 description 8
- 239000004026 insulin derivative Substances 0.000 description 8
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- 230000001105 regulatory effect Effects 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 7
- 239000004215 Carbon black (E152) Substances 0.000 description 7
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- 125000003435 aroyl group Chemical group 0.000 description 7
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 7
- 125000000732 arylene group Chemical group 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
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- 229940122355 Insulin sensitizer Drugs 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 235000019789 appetite Nutrition 0.000 description 6
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- 230000037396 body weight Effects 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
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Classifications
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- 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
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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| US45222803P | 2003-03-05 | 2003-03-05 | |
| PCT/DK2003/000449 WO2004002481A1 (en) | 2002-06-27 | 2003-06-27 | Aryl carbonyl derivatives as therapeutic agents |
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| EP1458382A1 (en) * | 2001-12-21 | 2004-09-22 | Novo Nordisk A/S | Amide derivatives as gk activators |
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| CA2488642C (en) * | 2002-06-27 | 2011-09-06 | Dharma Rao Polisetti | Aryl carbonyl derivatives as glucokinase activators |
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| US8460243B2 (en) | 2003-06-10 | 2013-06-11 | Abbott Diabetes Care Inc. | Glucose measuring module and insulin pump combination |
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| PL1700856T3 (pl) | 2003-12-26 | 2016-05-31 | Kyowa Hakko Kirin Co Ltd | Pochodna tiazolu |
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| WO2005095417A1 (en) | 2004-04-02 | 2005-10-13 | Novartis Ag | Thiazolopyridine derivates, pharmaceutical conditions containing them and methods of treating glucokinase mediated conditions |
| EP1735322B1 (en) | 2004-04-02 | 2011-09-14 | Novartis AG | Sulfonamide-thiazolpyridine derivatives as glucokinase activators useful for the treatment of type 2 diabetes |
| US7550499B2 (en) * | 2004-05-12 | 2009-06-23 | Bristol-Myers Squibb Company | Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
| JP2008500284A (ja) * | 2004-05-12 | 2008-01-10 | ブリストル−マイヤーズ スクイブ カンパニー | 血栓症の治療に有用なp2y1レセプターのウレアアンタゴニスト |
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| TW200600086A (en) | 2004-06-05 | 2006-01-01 | Astrazeneca Ab | Chemical compound |
| JP2008502658A (ja) * | 2004-06-17 | 2008-01-31 | ノボ ノルディスク アクティーゼルスカブ | 肝臓選択的グルコキナーゼ活性化因子の使用 |
| WO2006009726A2 (en) | 2004-06-17 | 2006-01-26 | Cytokinetics, Inc. | Substituted urea derivatives for treating cardiac diseases |
| ATE485300T1 (de) | 2004-07-16 | 2010-11-15 | Sunesis Pharmaceuticals Inc | Als aurora-kinase-inhibitoren nutzbare thienopyrimidine |
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| US7332529B2 (en) * | 2004-10-26 | 2008-02-19 | Carr Andrew J | Thermoreversible organogelators, compositions and methods of making thereof |
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| JP2008521864A (ja) | 2004-12-03 | 2008-06-26 | トランステック・ファーマ、インコーポレイテッド | ヘテロ芳香族グルコキナーゼ活性化剤 |
| JP2008523071A (ja) * | 2004-12-07 | 2008-07-03 | ルーカス ファーマシューティカルズ, インコーポレイテッド | Mapキナーゼの尿素インヒビター |
| JP2008523072A (ja) * | 2004-12-07 | 2008-07-03 | ルーカス ファーマシューティカルズ, インコーポレイテッド | タンパク質キナーゼの阻害剤 |
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| KR101346902B1 (ko) | 2005-07-09 | 2014-01-02 | 아스트라제네카 아베 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체 |
| MX2008000255A (es) | 2005-07-14 | 2008-04-02 | Novo Nordisk As | Activadores de urea glucocinasa. |
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- 2003-06-27 AU AU2003243921A patent/AU2003243921B2/en not_active Ceased
- 2003-06-27 CA CA2744893A patent/CA2744893A1/en not_active Abandoned
- 2003-06-27 EP EP11189145A patent/EP2471533A1/en not_active Withdrawn
- 2003-06-27 WO PCT/DK2003/000449 patent/WO2004002481A1/en not_active Ceased
- 2003-06-27 BR BR0312023-6A patent/BR0312023A/pt not_active Application Discontinuation
- 2003-06-27 MX MXPA05000130A patent/MXPA05000130A/es active IP Right Grant
- 2003-06-27 PL PL374920A patent/PL215132B1/pl unknown
- 2003-06-27 EP EP03761446.8A patent/EP1531815B1/en not_active Expired - Lifetime
- 2003-06-27 JP JP2004548878A patent/JP4881559B2/ja not_active Expired - Fee Related
- 2003-06-27 KR KR1020047021359A patent/KR101116627B1/ko not_active Expired - Fee Related
- 2003-10-06 US US10/679,887 patent/US7384967B2/en not_active Expired - Fee Related
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- 2004-12-02 IL IL165532A patent/IL165532A/en active IP Right Grant
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2007
- 2007-10-31 US US11/981,997 patent/US8063081B2/en not_active Expired - Lifetime
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2010
- 2010-07-16 JP JP2010162302A patent/JP2010265306A/ja active Pending
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2011
- 2011-04-18 JP JP2011092035A patent/JP2011168609A/ja not_active Withdrawn
- 2011-07-15 NO NO20111028A patent/NO20111028L/no not_active Application Discontinuation
- 2011-08-15 US US13/209,565 patent/US20110301158A1/en not_active Abandoned
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Also Published As
| Publication number | Publication date |
|---|---|
| JP4881559B2 (ja) | 2012-02-22 |
| JP2010265306A (ja) | 2010-11-25 |
| AU2003243921B2 (en) | 2009-05-07 |
| WO2004002481A1 (en) | 2004-01-08 |
| NO20111028L (no) | 2005-03-29 |
| US8063081B2 (en) | 2011-11-22 |
| USRE45670E1 (en) | 2015-09-15 |
| KR101116627B1 (ko) | 2012-10-09 |
| CA2488642C (en) | 2011-09-06 |
| EP2471533A1 (en) | 2012-07-04 |
| CA2488642A1 (en) | 2004-01-08 |
| CA2744893A1 (en) | 2004-01-08 |
| BR0312023A (pt) | 2005-03-22 |
| IL165532A0 (en) | 2006-01-15 |
| PL374920A1 (en) | 2005-11-14 |
| JP2005537333A (ja) | 2005-12-08 |
| AU2003243921A1 (en) | 2004-01-19 |
| PL215132B1 (pl) | 2013-10-31 |
| EP1531815A1 (en) | 2005-05-25 |
| EP1531815B1 (en) | 2014-09-24 |
| US7384967B2 (en) | 2008-06-10 |
| US20040122235A1 (en) | 2004-06-24 |
| IL165532A (en) | 2013-06-27 |
| KR20050019801A (ko) | 2005-03-03 |
| US20080119454A1 (en) | 2008-05-22 |
| JP2011168609A (ja) | 2011-09-01 |
| US20110301158A1 (en) | 2011-12-08 |
| US20080119455A1 (en) | 2008-05-22 |
| US7897628B2 (en) | 2011-03-01 |
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