NO320697B1 - Glucokinase-aktivatorer, fremstilling av disse, og anvendelse til fremstilling av medikamenter samt anvendelse av disse til forebygging og behandling av diabetes. - Google Patents
Glucokinase-aktivatorer, fremstilling av disse, og anvendelse til fremstilling av medikamenter samt anvendelse av disse til forebygging og behandling av diabetes. Download PDFInfo
- Publication number
- NO320697B1 NO320697B1 NO20014671A NO20014671A NO320697B1 NO 320697 B1 NO320697 B1 NO 320697B1 NO 20014671 A NO20014671 A NO 20014671A NO 20014671 A NO20014671 A NO 20014671A NO 320697 B1 NO320697 B1 NO 320697B1
- Authority
- NO
- Norway
- Prior art keywords
- cyclopentyl
- phenyl
- propionamide
- thiazol
- methanesulfonyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 7
- 239000003814 drug Substances 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 230000002265 prevention Effects 0.000 title claims 2
- 102000030595 Glucokinase Human genes 0.000 title abstract description 24
- 108010021582 Glucokinase Proteins 0.000 title abstract description 24
- 239000012190 activator Substances 0.000 title abstract description 5
- 206010012601 diabetes mellitus Diseases 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 276
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 95
- 229910052799 carbon Inorganic materials 0.000 claims description 89
- 229940080818 propionamide Drugs 0.000 claims description 87
- 239000001257 hydrogen Substances 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 83
- 150000002367 halogens Chemical class 0.000 claims description 81
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
- -1 amino, hydroxyamino Chemical group 0.000 claims description 71
- 238000006243 chemical reaction Methods 0.000 claims description 70
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 150000001408 amides Chemical class 0.000 claims description 51
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 150000001721 carbon Chemical group 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 229910052757 nitrogen Chemical group 0.000 claims description 37
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 30
- 125000003277 amino group Chemical group 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 150000002148 esters Chemical class 0.000 claims description 15
- 150000004702 methyl esters Chemical class 0.000 claims description 15
- 239000004202 carbamide Substances 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 239000000654 additive Substances 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- NEQSWPCDHDQINX-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfonylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 NEQSWPCDHDQINX-UHFFFAOYSA-N 0.000 claims description 7
- 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 7
- 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
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
- 239000011664 nicotinic acid Substances 0.000 claims description 7
- 229960003512 nicotinic acid Drugs 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- NEQSWPCDHDQINX-MRXNPFEDSA-N (2R)-3-cyclopentyl-2-(4-methylsulfonylphenyl)-N-(2-thiazolyl)propanamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1[C@H](C(=O)NC=1SC=CN=1)CC1CCCC1 NEQSWPCDHDQINX-MRXNPFEDSA-N 0.000 claims description 5
- SPHMVBLDKHUISJ-UHFFFAOYSA-N 3-cyclopentyl-2-(4-nitrophenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 SPHMVBLDKHUISJ-UHFFFAOYSA-N 0.000 claims description 5
- OFKYROVDFKBXPL-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-(4-methylsulfonylphenyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 OFKYROVDFKBXPL-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- ACZNTOJWUHHVOR-UHFFFAOYSA-N 2-(3-aminophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound NC1=CC=CC(C(CC2CCCC2)C(=O)NC=2SC=CN=2)=C1 ACZNTOJWUHHVOR-UHFFFAOYSA-N 0.000 claims description 4
- LTNVPMFMCXWTTF-UHFFFAOYSA-N 2-(3-chlorophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound ClC1=CC=CC(C(CC2CCCC2)C(=O)NC=2SC=CN=2)=C1 LTNVPMFMCXWTTF-UHFFFAOYSA-N 0.000 claims description 4
- RYWBGLSCOFFRJE-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 RYWBGLSCOFFRJE-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 4
- UCJASZOKKRTZRQ-CYBMUJFWSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(ethylcarbamoyl)propanamide Chemical compound C([C@@H](C(=O)NC(=O)NCC)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 UCJASZOKKRTZRQ-CYBMUJFWSA-N 0.000 claims description 3
- DCAJZFIGUVVDIW-CQSZACIVSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(prop-2-enylcarbamoyl)propanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1[C@H](C(=O)NC(=O)NCC=C)CC1CCCC1 DCAJZFIGUVVDIW-CQSZACIVSA-N 0.000 claims description 3
- RVQHSJOQTPWKBX-UHFFFAOYSA-N 2-(3-chlorophenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=CC(Cl)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 RVQHSJOQTPWKBX-UHFFFAOYSA-N 0.000 claims description 3
- CJJJMCHPRVFQJF-UHFFFAOYSA-N 2-(4-cyanophenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(C#N)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 CJJJMCHPRVFQJF-UHFFFAOYSA-N 0.000 claims description 3
- UKPWBJLLDLQOMR-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(propylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCCC)CC1CCCC1 UKPWBJLLDLQOMR-UHFFFAOYSA-N 0.000 claims description 3
- OHDOUZGNTKSPFV-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfanylphenyl)-n-pyridin-2-ylpropanamide Chemical compound C1=CC(SC)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 OHDOUZGNTKSPFV-UHFFFAOYSA-N 0.000 claims description 3
- BSKWDMIUUDRESB-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-phenylpropanamide Chemical compound C=1C=CC=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 BSKWDMIUUDRESB-UHFFFAOYSA-N 0.000 claims description 3
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 150000002500 ions Chemical class 0.000 claims description 3
- XSJRZLZLXXYZDQ-UHFFFAOYSA-N methyl 2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]carbamoylamino]acetate Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCC(=O)OC)CC1CCCC1 XSJRZLZLXXYZDQ-UHFFFAOYSA-N 0.000 claims description 3
- WEJXSOOSQGAQRE-UHFFFAOYSA-N methyl 6-[[3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)CC1CCCC1 WEJXSOOSQGAQRE-UHFFFAOYSA-N 0.000 claims description 3
- QOYXFQDAAFJZAQ-UHFFFAOYSA-N n-carbamoyl-3-cyclobutyl-2-(3,4-dichlorophenyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)N)CC1CCC1 QOYXFQDAAFJZAQ-UHFFFAOYSA-N 0.000 claims description 3
- MQAMSFQGHCGMRE-UHFFFAOYSA-N n-carbamoyl-3-cycloheptyl-2-(3,4-dichlorophenyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)N)CC1CCCCCC1 MQAMSFQGHCGMRE-UHFFFAOYSA-N 0.000 claims description 3
- JMRYUUKIWGVQSW-UHFFFAOYSA-N n-carbamoyl-3-cyclohexyl-2-(3,4-dichlorophenyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)N)CC1CCCCC1 JMRYUUKIWGVQSW-UHFFFAOYSA-N 0.000 claims description 3
- UTSSQUFMGVEPGN-UHFFFAOYSA-N n-carbamoyl-3-cyclopentyl-2-(3,4-dichlorophenyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)N)CC1CCCC1 UTSSQUFMGVEPGN-UHFFFAOYSA-N 0.000 claims description 3
- 101150115538 nero gene Proteins 0.000 claims description 3
- MUYNGBLZFJKXRQ-CQSZACIVSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(3-hydroxypropylcarbamoyl)propanamide Chemical compound C([C@@H](C(=O)NC(=O)NCCCO)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 MUYNGBLZFJKXRQ-CQSZACIVSA-N 0.000 claims description 2
- HDJJNAJYYNXSOO-UHFFFAOYSA-N 2-(3-bromo-4-methylsulfonylphenyl)-n-(5-bromopyridin-2-yl)-3-cyclopentylpropanamide Chemical compound C1=C(Br)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC(Br)=CC=1)CC1CCCC1 HDJJNAJYYNXSOO-UHFFFAOYSA-N 0.000 claims description 2
- LYVQHKLYOQUHDM-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopentyl-n-pyridin-2-ylpropanamide Chemical compound C1=CC(Cl)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 LYVQHKLYOQUHDM-UHFFFAOYSA-N 0.000 claims description 2
- VNNVSTYMOQUULL-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(1,3-oxazol-2-yl)propanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1OC=CN=1)CC1CCCC1 VNNVSTYMOQUULL-UHFFFAOYSA-N 0.000 claims description 2
- DCAJZFIGUVVDIW-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(prop-2-enylcarbamoyl)propanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC(=O)NCC=C)CC1CCCC1 DCAJZFIGUVVDIW-UHFFFAOYSA-N 0.000 claims description 2
- BZOQNRPLKSBAFC-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-pyridazin-3-ylpropanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1N=NC=CC=1)CC1CCCC1 BZOQNRPLKSBAFC-UHFFFAOYSA-N 0.000 claims description 2
- ITDZOKFTXRMCDJ-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dimethoxyphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(OC)C(OC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 ITDZOKFTXRMCDJ-UHFFFAOYSA-N 0.000 claims description 2
- LIZHAGYRYXFRFJ-UHFFFAOYSA-N 3-cyclopentyl-2-[3-(hydroxyamino)-4-methylsulfonylphenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(NO)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 LIZHAGYRYXFRFJ-UHFFFAOYSA-N 0.000 claims description 2
- GFQAFLLNBYKEJX-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-(4-methylsulfanylphenyl)propanamide Chemical compound C=1C=C(SC)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 GFQAFLLNBYKEJX-UHFFFAOYSA-N 0.000 claims description 2
- UWDNNIFVQDNLEM-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-(4-methylsulfonyl-3-nitrophenyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C([N+]([O-])=O)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 UWDNNIFVQDNLEM-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- XYZQDANSANGSJQ-UHFFFAOYSA-N ethyl 3-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]carbamoylamino]-3-oxopropanoate Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NC(=O)CC(=O)OCC)CC1CCCC1 XYZQDANSANGSJQ-UHFFFAOYSA-N 0.000 claims description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N gamma-methylpyridine Natural products CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 claims description 2
- NBKBSEBPJKFBRP-UHFFFAOYSA-N methyl 4-[3-cyclopentyl-1-oxo-1-(1,3-thiazol-2-ylamino)propan-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 NBKBSEBPJKFBRP-UHFFFAOYSA-N 0.000 claims description 2
- PHRGVWXIAKHPMO-MRXNPFEDSA-N methyl 6-[[(2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)[C@@H](C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 PHRGVWXIAKHPMO-MRXNPFEDSA-N 0.000 claims description 2
- DTISLNHPGONUBO-UHFFFAOYSA-N n-(5-bromopyridin-2-yl)-2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentylpropanamide Chemical compound C1=C(Cl)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC(Br)=CC=1)CC1CCCC1 DTISLNHPGONUBO-UHFFFAOYSA-N 0.000 claims description 2
- PALVBJAWECILHO-UHFFFAOYSA-N n-[2-(4-methylsulfonylphenyl)cycloheptyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound N=1C=CSC=1N(C(=O)CC)C1CCCCCC1C1=CC=C(S(C)(=O)=O)C=C1 PALVBJAWECILHO-UHFFFAOYSA-N 0.000 claims description 2
- SDHQKRAPPMMCIT-UHFFFAOYSA-N n-[2-(4-methylsulfonylphenyl)cyclohexyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound N=1C=CSC=1N(C(=O)CC)C1CCCCC1C1=CC=C(S(C)(=O)=O)C=C1 SDHQKRAPPMMCIT-UHFFFAOYSA-N 0.000 claims description 2
- 238000005897 peptide coupling reaction Methods 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 9
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 4
- 125000004494 ethyl ester group Chemical group 0.000 claims 3
- HJRBBNKMQKFENA-UHFFFAOYSA-N 2-cyclopentyl-N-(1,3-thiazol-2-yl)propanamide Chemical compound C1(CCCC1)C(C(=O)NC=1SC=CN=1)C HJRBBNKMQKFENA-UHFFFAOYSA-N 0.000 claims 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 2
- PXCGDHFIGOGNFA-UHFFFAOYSA-N 2-(3-bromo-4-methylsulfonylphenyl)-3-cyclopentyl-n-pyridin-2-ylpropanamide Chemical compound C1=C(Br)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 PXCGDHFIGOGNFA-UHFFFAOYSA-N 0.000 claims 1
- NSKZVLLRTKHYAG-UHFFFAOYSA-N 2-(3-cyano-4-methylsulfonylphenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(C#N)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 NSKZVLLRTKHYAG-UHFFFAOYSA-N 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- XFEJWDFQJFOHGL-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(1,3,4-thiadiazol-2-yl)propanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1SC=NN=1)CC1CCCC1 XFEJWDFQJFOHGL-UHFFFAOYSA-N 0.000 claims 1
- IKXKFQSJRXTADM-UHFFFAOYSA-N 3-cyclopentyl-2-(3-fluoro-4-hydroxyphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(F)C(O)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 IKXKFQSJRXTADM-UHFFFAOYSA-N 0.000 claims 1
- VVOJMUDDFYXFJP-UHFFFAOYSA-N 3-cyclopentyl-2-(3-fluoro-4-methoxyphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(F)C(OC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 VVOJMUDDFYXFJP-UHFFFAOYSA-N 0.000 claims 1
- VMQJOEOBCOZPBP-UHFFFAOYSA-N 3-cyclopentyl-2-(4-ethylsulfonylphenyl)-n-pyridin-2-ylpropanamide Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 VMQJOEOBCOZPBP-UHFFFAOYSA-N 0.000 claims 1
- OTFGUTVJOKCGJA-UHFFFAOYSA-N 3-cyclopentyl-2-[4-methylsulfanyl-3-(trifluoromethyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(C(F)(F)F)C(SC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 OTFGUTVJOKCGJA-UHFFFAOYSA-N 0.000 claims 1
- BDHNKBDGERTMEG-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[4-(trifluoromethoxy)phenyl]propanamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 BDHNKBDGERTMEG-UHFFFAOYSA-N 0.000 claims 1
- KPKVJUGCRPBUSL-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound N=1C=CSC=1NC(=O)CCC1CCCC1 KPKVJUGCRPBUSL-UHFFFAOYSA-N 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- KUWWRNNYEYGSBQ-UHFFFAOYSA-N methyl 1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC=N1 KUWWRNNYEYGSBQ-UHFFFAOYSA-N 0.000 claims 1
- SBDSHCDZEWFJNQ-UHFFFAOYSA-N methyl 6-[[3-cyclopentyl-2-[4-(trifluoromethylsulfonyl)phenyl]propanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)C(C=1C=CC(=CC=1)S(=O)(=O)C(F)(F)F)CC1CCCC1 SBDSHCDZEWFJNQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims 1
- 230000003914 insulin secretion Effects 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 780
- 239000011541 reaction mixture Substances 0.000 description 503
- 239000000243 solution Substances 0.000 description 480
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 340
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 306
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 303
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 153
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- 239000000126 substance Substances 0.000 description 10
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- FJSODZKQLZQDHD-LLVKDONJSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 FJSODZKQLZQDHD-LLVKDONJSA-N 0.000 description 7
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- FFOVIUVZTYPAIB-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfanylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(SC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 FFOVIUVZTYPAIB-UHFFFAOYSA-N 0.000 description 7
- JGIVQCXQTGYATL-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfonyl-3-nitrophenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C([N+]([O-])=O)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 JGIVQCXQTGYATL-UHFFFAOYSA-N 0.000 description 7
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- XHFUVBWCMLLKOZ-UHFFFAOYSA-N ethyl 2-amino-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(N)=N1 XHFUVBWCMLLKOZ-UHFFFAOYSA-N 0.000 description 6
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- 239000012535 impurity Substances 0.000 description 5
- MLUMNBUZYZXADO-UHFFFAOYSA-N methyl 3-cyclopentyl-2-[4-(trifluoromethylsulfonyl)phenyl]propanoate Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=CC=1C(C(=O)OC)CC1CCCC1 MLUMNBUZYZXADO-UHFFFAOYSA-N 0.000 description 5
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- AHMLFHMRRBJCRM-UHFFFAOYSA-N 2-(4-methylsulfanylphenyl)acetic acid Chemical compound CSC1=CC=C(CC(O)=O)C=C1 AHMLFHMRRBJCRM-UHFFFAOYSA-N 0.000 description 4
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- RKKJCQFKGLTEBD-UHFFFAOYSA-N 2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C(=O)O)=CN=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 RKKJCQFKGLTEBD-UHFFFAOYSA-N 0.000 description 4
- JNETYVLEGPSOFY-UHFFFAOYSA-N 3-bromopyrrolidine-2,5-dione Chemical compound BrC1CC(=O)NC1=O JNETYVLEGPSOFY-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
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- LQYMYFLHZNKBIW-UHFFFAOYSA-N ethyl 2-[2-[[2-(3-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C=CC=2)=N1 LQYMYFLHZNKBIW-UHFFFAOYSA-N 0.000 description 4
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- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
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- SXQQYTWMGOXJGZ-UHFFFAOYSA-N methyl 2-[2-[[3-cyclopentyl-2-(4-nitrophenyl)propanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)[N+]([O-])=O)=N1 SXQQYTWMGOXJGZ-UHFFFAOYSA-N 0.000 description 4
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- 229910052720 vanadium Inorganic materials 0.000 description 4
- IPFOWEUMNGCEDZ-GFCCVEGCSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(methylcarbamoyl)propanamide Chemical compound C([C@@H](C(=O)NC(=O)NC)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 IPFOWEUMNGCEDZ-GFCCVEGCSA-N 0.000 description 3
- LNEGGTSXXHWEDF-CQSZACIVSA-N (2r)-3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1[C@H](C(O)=O)CC1CCCC1 LNEGGTSXXHWEDF-CQSZACIVSA-N 0.000 description 3
- VZHKONVMVRJXCH-UHFFFAOYSA-N 2-(3-bromo-4-methylsulfonylphenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(Br)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 VZHKONVMVRJXCH-UHFFFAOYSA-N 0.000 description 3
- FPHKKMNYRHYIQT-UHFFFAOYSA-N 2-(4-bromophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(Br)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 FPHKKMNYRHYIQT-UHFFFAOYSA-N 0.000 description 3
- SGNFVZHFDYJMIW-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(Cl)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 SGNFVZHFDYJMIW-UHFFFAOYSA-N 0.000 description 3
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
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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
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/46—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
- C07C275/48—Y being a hydrogen or a carbon atom
- C07C275/50—Y being a hydrogen or an acyclic carbon atom
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/88—Nitrogen atoms, e.g. allantoin
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
- C07D237/22—Nitrogen and oxygen atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- 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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having 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
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- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/14—Nitrogen atoms
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- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
- C07D263/48—Nitrogen atoms not forming part of a nitro radical
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- 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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- 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- 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
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- C07D277/58—Nitro radicals
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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
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C07C2601/00—Systems containing only non-condensed rings
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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PCT/EP2000/002450 WO2000058293A2 (en) | 1999-03-29 | 2000-03-20 | Glucokinase activators |
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NO20014671D0 NO20014671D0 (no) | 2001-09-26 |
NO20014671L NO20014671L (no) | 2001-09-26 |
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NO20014671A NO320697B1 (no) | 1999-03-29 | 2001-09-26 | Glucokinase-aktivatorer, fremstilling av disse, og anvendelse til fremstilling av medikamenter samt anvendelse av disse til forebygging og behandling av diabetes. |
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Families Citing this family (106)
Publication number | Priority date | Publication date | Assignee | Title |
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US6353111B1 (en) * | 1999-12-15 | 2002-03-05 | Hoffmann-La Roche Inc. | Trans olefinic glucokinase activators |
WO2001085706A1 (en) | 2000-05-08 | 2001-11-15 | F. Hoffmann-La Roche Ag | Substituted phenylacetamides and their use as glucokinase activators |
AU8760001A (en) * | 2000-07-20 | 2002-02-05 | Hoffmann La Roche | Alpha-acyl and alpha-heteroatom-substituted benzene acetamide glucokinase activators |
US6369232B1 (en) * | 2000-08-15 | 2002-04-09 | Hoffmann-La Roche Inc. | Tetrazolyl-phenyl acetamide glucokinase activators |
BR0115999A (pt) | 2000-12-06 | 2003-09-30 | Hoffmann La Roche | Composto, composição farmacêutica que compreende o mesmo, sua utilização, processo para o tratamento profilático ou terapêutico de diabetes do tipo ii e processo para a preparação do composto |
US6433188B1 (en) | 2000-12-06 | 2002-08-13 | Wendy Lea Corbett | Fused heteroaromatic glucokinase activators |
US6482951B2 (en) * | 2000-12-13 | 2002-11-19 | Hoffmann-La Roche Inc. | Isoindolin-1-one glucokinase activators |
SE0102300D0 (sv) * | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
SE0102299D0 (sv) * | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
SE0102764D0 (sv) * | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
EP1336607A1 (en) * | 2002-02-19 | 2003-08-20 | Novo Nordisk A/S | Amide derivatives as glucokinase activators |
JP2005526702A (ja) * | 2001-12-03 | 2005-09-08 | ノボ ノルディスク アクティーゼルスカブ | グルカゴンアンタゴニストとの組み合わせにおける2型糖尿病治療のためのグルコキナーゼ活性化剤の使用 |
US6911545B2 (en) * | 2001-12-19 | 2005-06-28 | Hoffman-La Roche Inc. | Crystals of glucokinase and methods of growing them |
AU2002351748B2 (en) | 2001-12-21 | 2009-07-09 | Novo Nordisk A/S | Amide derivatives as GK activators |
CA2488161A1 (en) | 2002-03-26 | 2003-10-02 | Banyu Pharmaceutical Co., Ltd. | Novel aminobenzamide derivative |
EA011297B1 (ru) | 2002-04-26 | 2009-02-27 | Ф. Хоффманн-Ля Рош Аг | Замещённые фенилацетамиды и их применение в качестве активаторов глюкокиназы |
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