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
Links
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 162
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 153
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 148
- 238000003818 flash chromatography Methods 0.000 description 138
- 239000007787 solid Substances 0.000 description 132
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 124
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 122
- 239000000741 silica gel Substances 0.000 description 107
- 229910002027 silica gel Inorganic materials 0.000 description 107
- 229960001866 silicon dioxide Drugs 0.000 description 107
- 229920006395 saturated elastomer Polymers 0.000 description 105
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 92
- 239000012044 organic layer Substances 0.000 description 82
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 74
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 72
- 229910052938 sodium sulfate Inorganic materials 0.000 description 68
- 235000011152 sodium sulphate Nutrition 0.000 description 68
- 239000011780 sodium chloride Substances 0.000 description 62
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 57
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 54
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 50
- 239000003921 oil Substances 0.000 description 50
- 235000019198 oils Nutrition 0.000 description 50
- 239000006260 foam Substances 0.000 description 46
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 46
- 235000019341 magnesium sulphate Nutrition 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 44
- 239000010410 layer Substances 0.000 description 41
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 39
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 38
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 34
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 32
- DUMSKQUKLVSSII-UHFFFAOYSA-N iodomethylcyclopentane Chemical compound ICC1CCCC1 DUMSKQUKLVSSII-UHFFFAOYSA-N 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 32
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 30
- FJSODZKQLZQDHD-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)propanoic acid Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)O)CC1CCCC1 FJSODZKQLZQDHD-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 238000007796 conventional method Methods 0.000 description 25
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 25
- 235000017557 sodium bicarbonate Nutrition 0.000 description 25
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 24
- 229940043279 diisopropylamine Drugs 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 24
- 239000007858 starting material Substances 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 21
- 125000005843 halogen group Chemical group 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 125000003118 aryl group Chemical group 0.000 description 17
- 235000019270 ammonium chloride Nutrition 0.000 description 16
- 239000006071 cream Substances 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 14
- MATVAGMPRLNLPS-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfonyl-3-nitrophenyl)propanoic acid Chemical compound C1=C([N+]([O-])=O)C(S(=O)(=O)C)=CC=C1C(C(O)=O)CC1CCCC1 MATVAGMPRLNLPS-UHFFFAOYSA-N 0.000 description 14
- 229920001429 chelating resin Polymers 0.000 description 14
- 239000000499 gel Substances 0.000 description 14
- 239000003456 ion exchange resin Substances 0.000 description 14
- 229920003303 ion-exchange polymer Polymers 0.000 description 14
- BYUMLEPFXRGCCA-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(trifluoromethylsulfonyl)phenyl]propanoic acid Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=CC=1C(C(=O)O)CC1CCCC1 BYUMLEPFXRGCCA-UHFFFAOYSA-N 0.000 description 13
- LOJNXJAUOTWCJE-UHFFFAOYSA-N methyl 2-(4-chloro-3-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C(Cl)C([N+]([O-])=O)=C1 LOJNXJAUOTWCJE-UHFFFAOYSA-N 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
- ACQAPFAGFLQHOI-UHFFFAOYSA-N methyl 2-(4-chloro-3-nitrophenyl)-3-cyclopentylpropanoate Chemical compound C=1C=C(Cl)C([N+]([O-])=O)=CC=1C(C(=O)OC)CC1CCCC1 ACQAPFAGFLQHOI-UHFFFAOYSA-N 0.000 description 12
- LNEGGTSXXHWEDF-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C(O)=O)CC1CCCC1 LNEGGTSXXHWEDF-UHFFFAOYSA-N 0.000 description 11
- 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 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000008103 glucose Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 10
- XGNSXUCZXQTRAU-UHFFFAOYSA-N methyl 3-cyclopentyl-2-(4-methylsulfonyl-3-nitrophenyl)propanoate Chemical compound C=1C=C(S(C)(=O)=O)C([N+]([O-])=O)=CC=1C(C(=O)OC)CC1CCCC1 XGNSXUCZXQTRAU-UHFFFAOYSA-N 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- CIBJHFJWNXQUGR-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(trifluoromethylsulfanyl)phenyl]propanoic acid Chemical compound C=1C=C(SC(F)(F)F)C=CC=1C(C(=O)O)CC1CCCC1 CIBJHFJWNXQUGR-UHFFFAOYSA-N 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 150000001735 carboxylic acids Chemical class 0.000 description 9
- 230000003197 catalytic effect Effects 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 150000003457 sulfones Chemical class 0.000 description 8
- 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
- FPLQCHARENUDSW-UHFFFAOYSA-N 2-(4-chloro-3-nitrophenyl)acetamide Chemical compound NC(=O)CC1=CC=C(Cl)C([N+]([O-])=O)=C1 FPLQCHARENUDSW-UHFFFAOYSA-N 0.000 description 7
- 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
- GIACSQUDYUHGPP-UHFFFAOYSA-N 3-cyclopentyl-2-(4-nitrophenyl)propanoic acid Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(C(=O)O)CC1CCCC1 GIACSQUDYUHGPP-UHFFFAOYSA-N 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- CCZVEWRRAVASGL-UHFFFAOYSA-N lithium;2-methanidylpropane Chemical compound [Li+].CC(C)[CH2-] CCZVEWRRAVASGL-UHFFFAOYSA-N 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 239000011550 stock solution Substances 0.000 description 7
- BFDKCZMYQOSTJG-UHFFFAOYSA-N 2-[4-(trifluoromethylsulfanyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(SC(F)(F)F)C=C1 BFDKCZMYQOSTJG-UHFFFAOYSA-N 0.000 description 6
- FDZGNIDVCCNKPM-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfanylphenyl)propanoic acid Chemical compound C1=CC(SC)=CC=C1C(C(O)=O)CC1CCCC1 FDZGNIDVCCNKPM-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 125000005907 alkyl ester group Chemical group 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 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
- YOFCVCNRERRIST-UHFFFAOYSA-N methyl 3-cyclopentyl-2-[4-(trifluoromethylsulfanyl)phenyl]propanoate Chemical compound C=1C=C(SC(F)(F)F)C=CC=1C(C(=O)OC)CC1CCCC1 YOFCVCNRERRIST-UHFFFAOYSA-N 0.000 description 6
- JACPDLJUQLKABC-UHFFFAOYSA-N methyl 6-aminopyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(N)N=C1 JACPDLJUQLKABC-UHFFFAOYSA-N 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- LINUHTQTASKYBE-UHFFFAOYSA-N 2-(3-chlorophenyl)-3-cyclopentylpropanoic acid Chemical compound C=1C=CC(Cl)=CC=1C(C(=O)O)CC1CCCC1 LINUHTQTASKYBE-UHFFFAOYSA-N 0.000 description 5
- HZRFNGDBSJETHN-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopentylpropanoic acid Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)O)CC1CCCC1 HZRFNGDBSJETHN-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- SHQNGLYXRFCPGZ-UHFFFAOYSA-N ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound CCOC(=O)CC1=CSC(N)=N1 SHQNGLYXRFCPGZ-UHFFFAOYSA-N 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 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
- 235000019260 propionic acid Nutrition 0.000 description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 5
- 150000003462 sulfoxides Chemical class 0.000 description 5
- VBSHBOKSHWCFCV-UHFFFAOYSA-N 2-(4-chloro-3-nitrophenyl)-3-cyclopentylpropanoic acid Chemical compound C=1C=C(Cl)C([N+]([O-])=O)=CC=1C(C(=O)O)CC1CCCC1 VBSHBOKSHWCFCV-UHFFFAOYSA-N 0.000 description 4
- 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
- HGGWOSYNRVOQJH-UHFFFAOYSA-N 2-(4-methylsulfonylphenyl)acetic acid Chemical compound CS(=O)(=O)C1=CC=C(CC(O)=O)C=C1 HGGWOSYNRVOQJH-UHFFFAOYSA-N 0.000 description 4
- 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
- 229960000583 acetic acid Drugs 0.000 description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- 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
- 239000004744 fabric Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 0.000 description 4
- 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
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001665 trituration Methods 0.000 description 4
- 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
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 3
- HBAZTQMNTUKXSB-UHFFFAOYSA-N 2-[2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 HBAZTQMNTUKXSB-UHFFFAOYSA-N 0.000 description 3
- FDQRYJSBXWMVHG-UHFFFAOYSA-N 2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 FDQRYJSBXWMVHG-UHFFFAOYSA-N 0.000 description 3
- JXHCYNJBUVRFDD-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfonylphenyl)-n-pyridin-2-ylpropanamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 JXHCYNJBUVRFDD-UHFFFAOYSA-N 0.000 description 3
- ZDIMFGCTOCHAMH-UHFFFAOYSA-N 3-cyclopentyl-2-[3-fluoro-4-(trifluoromethyl)phenyl]propanoic acid Chemical compound C=1C=C(C(F)(F)F)C(F)=CC=1C(C(=O)O)CC1CCCC1 ZDIMFGCTOCHAMH-UHFFFAOYSA-N 0.000 description 3
- XQRKLUWRUXNULG-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[4-(trifluoromethylsulfonyl)phenyl]propanamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 XQRKLUWRUXNULG-UHFFFAOYSA-N 0.000 description 3
- OPMYFYZEPWPDGI-UHFFFAOYSA-N 3-cyclopentyl-n-[5-(hydroxymethyl)pyridin-2-yl]-2-(4-methylsulfonylphenyl)propanamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC(CO)=CC=1)CC1CCCC1 OPMYFYZEPWPDGI-UHFFFAOYSA-N 0.000 description 3
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 3
- MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 description 3
- CMBSSVKZOPZBKW-UHFFFAOYSA-N 5-methylpyridin-2-amine Chemical compound CC1=CC=C(N)N=C1 CMBSSVKZOPZBKW-UHFFFAOYSA-N 0.000 description 3
- SOEZTDJGZXJBQP-UHFFFAOYSA-N 6-[[3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoyl]amino]pyridine-3-carboxylic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC(=CC=1)C(O)=O)CC1CCCC1 SOEZTDJGZXJBQP-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000005548 Hexokinase Human genes 0.000 description 3
- 108700040460 Hexokinases Proteins 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 150000001989 diazonium salts Chemical class 0.000 description 3
- 238000006193 diazotization reaction Methods 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- XNVRKLCQBZTGNA-UHFFFAOYSA-N ethyl 2-(2-amino-1,3-thiazol-4-yl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CSC(N)=N1 XNVRKLCQBZTGNA-UHFFFAOYSA-N 0.000 description 3
- WKRQNTYMPQFEDE-UHFFFAOYSA-N ethyl 2-[2-[[2-(4-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(Cl)=CC=2)=N1 WKRQNTYMPQFEDE-UHFFFAOYSA-N 0.000 description 3
- AZDMCWKLNPQMIE-UHFFFAOYSA-N ethyl 2-[[3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)S(C)(=O)=O)=N1 AZDMCWKLNPQMIE-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 230000004153 glucose metabolism Effects 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- SGBUNAYVAMGZPQ-UHFFFAOYSA-N methyl 2-[2-[[2-(3-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C=CC=2)=N1 SGBUNAYVAMGZPQ-UHFFFAOYSA-N 0.000 description 3
- LHFCDJFDFAKZKF-UHFFFAOYSA-N methyl 2-[2-[[2-(4-aminophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(N)=CC=2)=N1 LHFCDJFDFAKZKF-UHFFFAOYSA-N 0.000 description 3
- BAGJSCPJMSMEBH-UHFFFAOYSA-N methyl 2-[3-fluoro-4-(trifluoromethyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(C(F)(F)F)C(F)=C1 BAGJSCPJMSMEBH-UHFFFAOYSA-N 0.000 description 3
- WYVZZWKIKAKUKV-UHFFFAOYSA-N methyl 2-amino-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(N)=N1 WYVZZWKIKAKUKV-UHFFFAOYSA-N 0.000 description 3
- CLBKSATYOZLSTR-UHFFFAOYSA-N methyl 3-cyclopentyl-2-[3-fluoro-4-(trifluoromethyl)phenyl]propanoate Chemical compound C=1C=C(C(F)(F)F)C(F)=CC=1C(C(=O)OC)CC1CCCC1 CLBKSATYOZLSTR-UHFFFAOYSA-N 0.000 description 3
- IWEYOBVWSOOLQG-UHFFFAOYSA-N methyl 6-[[2-(4-chlorophenyl)-3-cyclopentylpropanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)C(C=1C=CC(Cl)=CC=1)CC1CCCC1 IWEYOBVWSOOLQG-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000004149 thio group Chemical group *S* 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- FQQHBEQNAJIPCL-LJQANCHMSA-N (2r)-2,3-dicyclopentyl-2-(3,4-dichlorophenyl)propanoic acid Chemical compound C([C@@](C(=O)O)(C1CCCC1)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 FQQHBEQNAJIPCL-LJQANCHMSA-N 0.000 description 2
- XRIWIBQSPXUIBD-CYBMUJFWSA-N (2r)-2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C([C@@H](C(=O)NC(=O)NC)C=1C=C(Cl)C(=CC=1)S(C)(=O)=O)C1CCCC1 XRIWIBQSPXUIBD-CYBMUJFWSA-N 0.000 description 2
- RYWBGLSCOFFRJE-CYBMUJFWSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1[C@H](C(=O)NC=1SC=CN=1)CC1CCCC1 RYWBGLSCOFFRJE-CYBMUJFWSA-N 0.000 description 2
- VNBJMRAMCGVCPF-CQSZACIVSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-pyrimidin-4-ylpropanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1[C@H](C(=O)NC=1N=CN=CC=1)CC1CCCC1 VNBJMRAMCGVCPF-CQSZACIVSA-N 0.000 description 2
- GBNDXXAFSGHQMN-OAHLLOKOSA-N (2r)-n-(5-chloropyridin-2-yl)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanamide Chemical compound N1=CC(Cl)=CC=C1NC(=O)[C@@H](C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 GBNDXXAFSGHQMN-OAHLLOKOSA-N 0.000 description 2
- RXUBUMUJUSDVOE-SECBINFHSA-N (2r)-n-carbamoyl-2-(3,4-dichlorophenyl)-4-methylpentanamide Chemical compound NC(=O)NC(=O)[C@H](CC(C)C)C1=CC=C(Cl)C(Cl)=C1 RXUBUMUJUSDVOE-SECBINFHSA-N 0.000 description 2
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
- YHALWHDRODYYNZ-UHFFFAOYSA-N 2-(3-amino-4-methylsulfonylphenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(N)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 YHALWHDRODYYNZ-UHFFFAOYSA-N 0.000 description 2
- SSSWIDJKGVZUQR-UHFFFAOYSA-N 2-(3-bromo-4-methylsulfonylphenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C(Br)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 SSSWIDJKGVZUQR-UHFFFAOYSA-N 0.000 description 2
- QQSUNHONYLAAGS-UHFFFAOYSA-N 2-(3-chloro-4-methylsulfanylphenyl)-3-cyclopentylpropanoic acid Chemical compound C1=C(Cl)C(SC)=CC=C1C(C(O)=O)CC1CCCC1 QQSUNHONYLAAGS-UHFFFAOYSA-N 0.000 description 2
- SDIIWCJMPBUTIX-UHFFFAOYSA-N 2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-n-(ethylcarbamoyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C(Cl)=CC=1C(C(=O)NC(=O)NCC)CC1CCCC1 SDIIWCJMPBUTIX-UHFFFAOYSA-N 0.000 description 2
- WFPMUFXQDKMVCO-UHFFFAOYSA-N 2-(3-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Cl)=C1 WFPMUFXQDKMVCO-UHFFFAOYSA-N 0.000 description 2
- AWHQGMJNOZGSDE-UHFFFAOYSA-N 2-(4-aminophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(N)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 AWHQGMJNOZGSDE-UHFFFAOYSA-N 0.000 description 2
- HEPMRJAEEJWANC-UHFFFAOYSA-N 2-(4-bromophenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(Br)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 HEPMRJAEEJWANC-UHFFFAOYSA-N 0.000 description 2
- CUKVIXRFROAXLK-UHFFFAOYSA-N 2-(4-bromophenyl)-3-cyclopentylpropanoic acid Chemical compound C=1C=C(Br)C=CC=1C(C(=O)O)CC1CCCC1 CUKVIXRFROAXLK-UHFFFAOYSA-N 0.000 description 2
- NDKMKDBCWIGFKC-UHFFFAOYSA-N 2-(4-butylsulfonylphenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C1=CC(S(=O)(=O)CCCC)=CC=C1C(C(=O)NC(=O)NC)CC1CCCC1 NDKMKDBCWIGFKC-UHFFFAOYSA-N 0.000 description 2
- GCBARAPAKMYDBN-UHFFFAOYSA-N 2-(4-chloro-3-nitrophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(C(CC2CCCC2)C(=O)NC=2SC=CN=2)=C1 GCBARAPAKMYDBN-UHFFFAOYSA-N 0.000 description 2
- LZPNSCJMZCTWAT-UHFFFAOYSA-N 2-(4-chloro-3-nitrophenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C([N+]([O-])=O)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 LZPNSCJMZCTWAT-UHFFFAOYSA-N 0.000 description 2
- BZEHFFYIAOOMOU-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 BZEHFFYIAOOMOU-UHFFFAOYSA-N 0.000 description 2
- PISHDDFWVOQURY-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopentyl-n-[5-(hydroxymethyl)-1,3-thiazol-2-yl]propanamide Chemical compound S1C(CO)=CN=C1NC(=O)C(C=1C=CC(Cl)=CC=1)CC1CCCC1 PISHDDFWVOQURY-UHFFFAOYSA-N 0.000 description 2
- SAXQLMMJQPHEHD-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopentyl-n-[5-(hydroxymethyl)pyridin-2-yl]propanamide Chemical compound N1=CC(CO)=CC=C1NC(=O)C(C=1C=CC(Cl)=CC=1)CC1CCCC1 SAXQLMMJQPHEHD-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- ZFOWDXKJQNNLMW-UHFFFAOYSA-N 2-[3-fluoro-4-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(C(F)(F)F)C(F)=C1 ZFOWDXKJQNNLMW-UHFFFAOYSA-N 0.000 description 2
- XMMJKZLLOBXNMB-UHFFFAOYSA-N 3-cyclohexyl-2-(3,4-dichlorophenyl)-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NC)CC1CCCCC1 XMMJKZLLOBXNMB-UHFFFAOYSA-N 0.000 description 2
- XTVBTRXYSCHUHU-UHFFFAOYSA-N 3-cyclopentyl-2-(2-nitrophenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound [O-][N+](=O)C1=CC=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 XTVBTRXYSCHUHU-UHFFFAOYSA-N 0.000 description 2
- MUYNGBLZFJKXRQ-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(3-hydroxypropylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCCCO)CC1CCCC1 MUYNGBLZFJKXRQ-UHFFFAOYSA-N 0.000 description 2
- ZYNZNEGACWQDCX-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(5-methyl-1,2-oxazol-3-yl)propanamide Chemical compound O1C(C)=CC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 ZYNZNEGACWQDCX-UHFFFAOYSA-N 0.000 description 2
- IPFOWEUMNGCEDZ-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 IPFOWEUMNGCEDZ-UHFFFAOYSA-N 0.000 description 2
- FNNBZOAAXQXZPB-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(propan-2-ylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NC(C)C)CC1CCCC1 FNNBZOAAXQXZPB-UHFFFAOYSA-N 0.000 description 2
- NBHYTLAIODYUBN-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-[4-(2-hydroxyethyl)-1,3-thiazol-2-yl]propanamide Chemical compound OCCC1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 NBHYTLAIODYUBN-UHFFFAOYSA-N 0.000 description 2
- RYAWRXOEJHSIBV-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-[5-(hydroxymethyl)-1,3-thiazol-2-yl]propanamide Chemical compound S1C(CO)=CN=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 RYAWRXOEJHSIBV-UHFFFAOYSA-N 0.000 description 2
- HBYLPCNILQERJO-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-pyrimidin-2-ylpropanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1N=CC=CN=1)CC1CCCC1 HBYLPCNILQERJO-UHFFFAOYSA-N 0.000 description 2
- MVZIXWFOMRLWSI-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-difluorophenyl)-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(F)C(F)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 MVZIXWFOMRLWSI-UHFFFAOYSA-N 0.000 description 2
- ZIGCXGUYFWUXRX-UHFFFAOYSA-N 3-cyclopentyl-2-(3-nitrophenyl)propanoic acid Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(C(=O)O)CC1CCCC1 ZIGCXGUYFWUXRX-UHFFFAOYSA-N 0.000 description 2
- POXFREUZWCETIK-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfinylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(S(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 POXFREUZWCETIK-UHFFFAOYSA-N 0.000 description 2
- WSKVJPKZDWCVRQ-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methylsulfonyl-3-nitrophenyl)-n-pyridin-2-ylpropanamide Chemical compound C1=C([N+]([O-])=O)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 WSKVJPKZDWCVRQ-UHFFFAOYSA-N 0.000 description 2
- ORQDQRNOLNVQPD-UHFFFAOYSA-N 3-cyclopentyl-2-(4-nitrophenyl)-n-pyridin-2-ylpropanamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 ORQDQRNOLNVQPD-UHFFFAOYSA-N 0.000 description 2
- IAVGBKRTJLZEBF-UHFFFAOYSA-N 3-cyclopentyl-2-[3-(trifluoromethylsulfonyl)phenyl]propanoic acid Chemical compound C=1C=CC(S(=O)(=O)C(F)(F)F)=CC=1C(C(=O)O)CC1CCCC1 IAVGBKRTJLZEBF-UHFFFAOYSA-N 0.000 description 2
- ZZTYQWDLJCNNAU-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(trifluoromethyl)phenyl]propanoic acid Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(C(=O)O)CC1CCCC1 ZZTYQWDLJCNNAU-UHFFFAOYSA-N 0.000 description 2
- DQBDIQOXFMMQTJ-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[3-(trifluoromethylsulfonyl)phenyl]propanamide Chemical compound FC(F)(F)S(=O)(=O)C1=CC=CC(C(CC2CCCC2)C(=O)NC=2SC=CN=2)=C1 DQBDIQOXFMMQTJ-UHFFFAOYSA-N 0.000 description 2
- GRCXQQALVMLQJK-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[4-(trifluoromethyl)phenyl]propanamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 GRCXQQALVMLQJK-UHFFFAOYSA-N 0.000 description 2
- WUQCYCVUVFTLQJ-UHFFFAOYSA-N 3-cyclopentyl-n-(5-methylpyridin-2-yl)-2-(4-methylsulfonylphenyl)propanamide Chemical compound N1=CC(C)=CC=C1NC(=O)C(C=1C=CC(=CC=1)S(C)(=O)=O)CC1CCCC1 WUQCYCVUVFTLQJ-UHFFFAOYSA-N 0.000 description 2
- HEQPQBUWULUJPP-UHFFFAOYSA-N 3-cyclopentyl-n-(5-methylpyridin-2-yl)-2-[4-(trifluoromethylsulfonyl)phenyl]propanamide Chemical compound N1=CC(C)=CC=C1NC(=O)C(C=1C=CC(=CC=1)S(=O)(=O)C(F)(F)F)CC1CCCC1 HEQPQBUWULUJPP-UHFFFAOYSA-N 0.000 description 2
- JALGJZOCFQQQFR-UHFFFAOYSA-N 3-cyclopentyl-n-[4-(2-hydroxyethyl)-1,3-thiazol-2-yl]-2-(4-methylsulfonylphenyl)propanamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=C(CCO)N=1)CC1CCCC1 JALGJZOCFQQQFR-UHFFFAOYSA-N 0.000 description 2
- HOUNRZVIQQUOCW-UHFFFAOYSA-N 3-cyclopentyl-n-[4-(hydroxymethyl)-1,3-thiazol-2-yl]-2-(4-methylsulfonylphenyl)propanamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=C(CO)N=1)CC1CCCC1 HOUNRZVIQQUOCW-UHFFFAOYSA-N 0.000 description 2
- KWZYRUJAPMMFKW-UHFFFAOYSA-N 3-cyclopentyl-n-pyridin-2-yl-2-[4-(trifluoromethylsulfonyl)phenyl]propanamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 KWZYRUJAPMMFKW-UHFFFAOYSA-N 0.000 description 2
- WUXCECMNMNJYSC-UHFFFAOYSA-N 37777-68-7 Chemical compound OC(=O)CC1=CC=C(Cl)C([N+]([O-])=O)=C1 WUXCECMNMNJYSC-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 2
- DWPDIKKXRGBBQI-UHFFFAOYSA-N 6-[[2-(4-chlorophenyl)-3-cyclopentylpropanoyl]amino]pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1NC(=O)C(C=1C=CC(Cl)=CC=1)CC1CCCC1 DWPDIKKXRGBBQI-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- 101150109586 Gk gene Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000035180 MODY Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 150000001356 alkyl thiols Chemical class 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- 159000000032 aromatic acids Chemical class 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N beta-methylpyridine Natural products CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- HUWOBJPVVLCVLG-UHFFFAOYSA-N ethyl 2-(2-amino-1,3-thiazol-5-yl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CN=C(N)S1 HUWOBJPVVLCVLG-UHFFFAOYSA-N 0.000 description 2
- NLMGHLSZGGRFSO-UHFFFAOYSA-N ethyl 2-(3-chloro-4-methylsulfanylphenyl)-2-hydroxyacetate Chemical compound CCOC(=O)C(O)C1=CC=C(SC)C(Cl)=C1 NLMGHLSZGGRFSO-UHFFFAOYSA-N 0.000 description 2
- JYKDSAJCCUTIRL-UHFFFAOYSA-N ethyl 2-(3-chloro-4-methylsulfanylphenyl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CC=C(SC)C(Cl)=C1 JYKDSAJCCUTIRL-UHFFFAOYSA-N 0.000 description 2
- SRHBCKYMYPTZQT-UHFFFAOYSA-N ethyl 2-(3-chloro-4-methylsulfanylphenyl)-3-cyclopentylpropanoate Chemical compound C=1C=C(SC)C(Cl)=CC=1C(C(=O)OCC)CC1CCCC1 SRHBCKYMYPTZQT-UHFFFAOYSA-N 0.000 description 2
- MWVQNJRUTWNGJI-UHFFFAOYSA-N ethyl 2-(3-chloro-4-methylsulfanylphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(SC)C(Cl)=C1 MWVQNJRUTWNGJI-UHFFFAOYSA-N 0.000 description 2
- BIXVINVUKWYSLF-UHFFFAOYSA-N ethyl 2-(3-chlorophenyl)-3-cyclopentylpropanoate Chemical compound C=1C=CC(Cl)=CC=1C(C(=O)OCC)CC1CCCC1 BIXVINVUKWYSLF-UHFFFAOYSA-N 0.000 description 2
- SLNHJHHDMDGTGB-UHFFFAOYSA-N ethyl 2-(3-chlorophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(Cl)=C1 SLNHJHHDMDGTGB-UHFFFAOYSA-N 0.000 description 2
- RLRJCGJYLLUZLG-UHFFFAOYSA-N ethyl 2-(4-chlorophenyl)-3-cyclopentylpropanoate Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)OCC)CC1CCCC1 RLRJCGJYLLUZLG-UHFFFAOYSA-N 0.000 description 2
- UTWBWFXECVFDPZ-UHFFFAOYSA-N ethyl 2-(4-chlorophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(Cl)C=C1 UTWBWFXECVFDPZ-UHFFFAOYSA-N 0.000 description 2
- CIKLMPYJSYDZEK-UHFFFAOYSA-N ethyl 2-[[2-(3-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C=CC=2)=N1 CIKLMPYJSYDZEK-UHFFFAOYSA-N 0.000 description 2
- ZPJDBJMHMCOKKX-UHFFFAOYSA-N ethyl 2-[[2-(4-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(Cl)=CC=2)=N1 ZPJDBJMHMCOKKX-UHFFFAOYSA-N 0.000 description 2
- UJINJBQVRZGYAU-UHFFFAOYSA-N ethyl 2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OCC)=CN=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 UJINJBQVRZGYAU-UHFFFAOYSA-N 0.000 description 2
- IGLOREVOTWYIQQ-UHFFFAOYSA-N ethyl 2-[[3-cyclopentyl-2-(4-nitrophenyl)propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)[N+]([O-])=O)=N1 IGLOREVOTWYIQQ-UHFFFAOYSA-N 0.000 description 2
- PPCNKQIXWDVHHC-UHFFFAOYSA-N ethyl 2-acetyloxy-2-(3-chloro-4-methylsulfanylphenyl)acetate Chemical compound CCOC(=O)C(OC(C)=O)C1=CC=C(SC)C(Cl)=C1 PPCNKQIXWDVHHC-UHFFFAOYSA-N 0.000 description 2
- DBCSSLKEWJGXOG-UHFFFAOYSA-N ethyl 3-cyclopentyl-2-(4-nitrophenyl)propanoate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(C(=O)OCC)CC1CCCC1 DBCSSLKEWJGXOG-UHFFFAOYSA-N 0.000 description 2
- DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical compound CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 229940124828 glucokinase activator Drugs 0.000 description 2
- 230000014101 glucose homeostasis Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 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 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AHCNXVCAVUYIOU-UHFFFAOYSA-M lithium hydroperoxide Chemical compound [Li+].[O-]O AHCNXVCAVUYIOU-UHFFFAOYSA-M 0.000 description 2
- 201000006950 maturity-onset diabetes of the young Diseases 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- XTQKFBGFHDNUFY-UHFFFAOYSA-N methyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound COC(=O)CC1=CSC(N)=N1 XTQKFBGFHDNUFY-UHFFFAOYSA-N 0.000 description 2
- HCMUPMCWKYOOBZ-UHFFFAOYSA-N methyl 2-(4-methylsulfonylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(S(C)(=O)=O)C=C1 HCMUPMCWKYOOBZ-UHFFFAOYSA-N 0.000 description 2
- YJXMHFRYLOMIGS-UHFFFAOYSA-N methyl 2-[2-[[2-(4-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(Cl)=CC=2)=N1 YJXMHFRYLOMIGS-UHFFFAOYSA-N 0.000 description 2
- GNHJXSIKSWYCMU-UHFFFAOYSA-N methyl 2-[2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 GNHJXSIKSWYCMU-UHFFFAOYSA-N 0.000 description 2
- CMCLFWLZQZQTEY-UHFFFAOYSA-N methyl 2-[3-(trifluoromethylsulfanyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(SC(F)(F)F)=C1 CMCLFWLZQZQTEY-UHFFFAOYSA-N 0.000 description 2
- GLJHRZZRWZRDGK-CYBMUJFWSA-N methyl 2-[[(2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)[C@H](CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 GLJHRZZRWZRDGK-CYBMUJFWSA-N 0.000 description 2
- HDKBSJPSLJJDQO-UHFFFAOYSA-N methyl 2-[[2-(3-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C=CC=2)=N1 HDKBSJPSLJJDQO-UHFFFAOYSA-N 0.000 description 2
- FEBTXNSXXXLTFE-UHFFFAOYSA-N methyl 2-[[2-(4-aminophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(N)=CC=2)=N1 FEBTXNSXXXLTFE-UHFFFAOYSA-N 0.000 description 2
- VAWBMWMYWHQDQP-UHFFFAOYSA-N methyl 2-[[2-(4-chlorophenyl)-3-cyclopentylpropanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(Cl)=CC=2)=N1 VAWBMWMYWHQDQP-UHFFFAOYSA-N 0.000 description 2
- FOFAZRPPNQUZIP-UHFFFAOYSA-N methyl 2-[[3-cyclopentyl-2-(4-nitrophenyl)propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)[N+]([O-])=O)=N1 FOFAZRPPNQUZIP-UHFFFAOYSA-N 0.000 description 2
- HWOFZRBQMMLPBZ-UHFFFAOYSA-N methyl 3-cyclopentyl-2-(3-nitrophenyl)propanoate Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(C(=O)OC)CC1CCCC1 HWOFZRBQMMLPBZ-UHFFFAOYSA-N 0.000 description 2
- JZGAQEVYHMXQQF-UHFFFAOYSA-N methyl 3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoate Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C(C(=O)OC)CC1CCCC1 JZGAQEVYHMXQQF-UHFFFAOYSA-N 0.000 description 2
- AAMLYKWPHQQAQE-UHFFFAOYSA-N methyl 3-cyclopentyl-2-[3-(trifluoromethylsulfanyl)phenyl]propanoate Chemical compound C=1C=CC(SC(F)(F)F)=CC=1C(C(=O)OC)CC1CCCC1 AAMLYKWPHQQAQE-UHFFFAOYSA-N 0.000 description 2
- LBZLNDGQKHBEOD-UHFFFAOYSA-N methyl 3-cyclopentyl-2-[3-(trifluoromethylsulfonyl)phenyl]propanoate Chemical compound C=1C=CC(S(=O)(=O)C(F)(F)F)=CC=1C(C(=O)OC)CC1CCCC1 LBZLNDGQKHBEOD-UHFFFAOYSA-N 0.000 description 2
- ZOMRXTAHSVSQEN-UHFFFAOYSA-N methyl 6-[[2-(3-chlorophenyl)-3-cyclopentylpropanoyl]amino]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC(=O)C(C=1C=C(Cl)C=CC=1)CC1CCCC1 ZOMRXTAHSVSQEN-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 2
- 210000004457 myocytus nodalis Anatomy 0.000 description 2
- RWPYDCPJAOZXEH-UHFFFAOYSA-N n-(5-bromopyridin-2-yl)-3-cyclopentyl-2-(4-methylsulfonyl-3-nitrophenyl)propanamide Chemical compound C1=C([N+]([O-])=O)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC(Br)=CC=1)CC1CCCC1 RWPYDCPJAOZXEH-UHFFFAOYSA-N 0.000 description 2
- FQBYIENPHYGTRQ-UHFFFAOYSA-N n-carbamoyl-2-(4-chlorophenyl)-4-methylpentanamide Chemical group NC(=O)NC(=O)C(CC(C)C)C1=CC=C(Cl)C=C1 FQBYIENPHYGTRQ-UHFFFAOYSA-N 0.000 description 2
- NKJGISOTZHOWHH-UHFFFAOYSA-N n-carbamoyl-3-cyclopropyl-2-(3,4-dichlorophenyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)N)CC1CC1 NKJGISOTZHOWHH-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000005809 transesterification reaction Methods 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- SJGXOVGSEZKIHH-SBXXRYSUSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(2-hydroxypropylcarbamoyl)propanamide Chemical compound C([C@@H](C(=O)NC(=O)NCC(O)C)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 SJGXOVGSEZKIHH-SBXXRYSUSA-N 0.000 description 1
- ZMIQNHRRONVEGS-MRXNPFEDSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-[5-(hydroxymethyl)pyridin-2-yl]propanamide Chemical compound N1=CC(CO)=CC=C1NC(=O)[C@@H](C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 ZMIQNHRRONVEGS-MRXNPFEDSA-N 0.000 description 1
- RFZWICAONXFLJJ-OAHLLOKOSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)-n-pyridin-2-ylpropanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1[C@H](C(=O)NC=1N=CC=CC=1)CC1CCCC1 RFZWICAONXFLJJ-OAHLLOKOSA-N 0.000 description 1
- ANFZNKUMVMGLBJ-LLVKDONJSA-N (2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanamide Chemical compound C([C@@H](C(=O)N)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 ANFZNKUMVMGLBJ-LLVKDONJSA-N 0.000 description 1
- OJOFMLDBXPDXLQ-SECBINFHSA-N (4r)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-SECBINFHSA-N 0.000 description 1
- JPDDQTJKMFCJAH-CRAIPNDOSA-N (4s)-3-[(2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)[C@H]1COC(=O)N1C(=O)[C@@H](C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 JPDDQTJKMFCJAH-CRAIPNDOSA-N 0.000 description 1
- JPDDQTJKMFCJAH-MAUKXSAKSA-N (4s)-3-[(2s)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)[C@H]1COC(=O)N1C(=O)[C@H](C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 JPDDQTJKMFCJAH-MAUKXSAKSA-N 0.000 description 1
- YBUPWRYTXGAWJX-RXMQYKEDSA-N (4s)-4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)[C@H]1COC(=O)N1 YBUPWRYTXGAWJX-RXMQYKEDSA-N 0.000 description 1
- DXHCJWMAXVEKGD-UHFFFAOYSA-N 1,2-dinitro-4-(nitromethyl)benzene Chemical compound [O-][N+](=O)CC1=CC=C([N+]([O-])=O)C([N+]([O-])=O)=C1 DXHCJWMAXVEKGD-UHFFFAOYSA-N 0.000 description 1
- IHLDFHCSSCVPQW-UHFFFAOYSA-N 1-chloro-2-methylsulfanylbenzene Chemical compound CSC1=CC=CC=C1Cl IHLDFHCSSCVPQW-UHFFFAOYSA-N 0.000 description 1
- FFJWPGGBISIFHI-UHFFFAOYSA-N 1-methylnaphthalen-2-amine Chemical compound C1=CC=C2C(C)=C(N)C=CC2=C1 FFJWPGGBISIFHI-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
- PTJPIOVAKOVOMS-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-4-methyl-n-(methylcarbamoyl)pentanamide Chemical compound CNC(=O)NC(=O)C(CC(C)C)C1=CC=C(Cl)C(Cl)=C1 PTJPIOVAKOVOMS-UHFFFAOYSA-N 0.000 description 1
- PMLLJKWFFRYTRA-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-(methylcarbamoyl)hexanamide Chemical compound CNC(=O)NC(=O)C(CCCC)C1=CC=C(Cl)C(Cl)=C1 PMLLJKWFFRYTRA-UHFFFAOYSA-N 0.000 description 1
- ZOUPGSMSNQLUNW-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C(Cl)=C1 ZOUPGSMSNQLUNW-UHFFFAOYSA-N 0.000 description 1
- WCXUUMDSWRVBRX-UHFFFAOYSA-N 2-(3,4-dinitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C([N+]([O-])=O)=C1 WCXUUMDSWRVBRX-UHFFFAOYSA-N 0.000 description 1
- QLFPIUAJJXXRRZ-UHFFFAOYSA-N 2-(3-chloro-4-methylsulfanylphenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(Cl)C(SC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 QLFPIUAJJXXRRZ-UHFFFAOYSA-N 0.000 description 1
- CERXYDAYZZMUJI-UHFFFAOYSA-N 2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(Cl)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 CERXYDAYZZMUJI-UHFFFAOYSA-N 0.000 description 1
- XRIWIBQSPXUIBD-UHFFFAOYSA-N 2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C(Cl)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 XRIWIBQSPXUIBD-UHFFFAOYSA-N 0.000 description 1
- KSQUWMUXPVUNQK-UHFFFAOYSA-N 2-(3-chloro-4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C(Cl)=C1 KSQUWMUXPVUNQK-UHFFFAOYSA-N 0.000 description 1
- VFQFGUMXWDQORE-UHFFFAOYSA-N 2-(3-chlorophenyl)-3-cyclopentyl-n-pyridin-2-ylpropanamide Chemical compound ClC1=CC=CC(C(CC2CCCC2)C(=O)NC=2N=CC=CC=2)=C1 VFQFGUMXWDQORE-UHFFFAOYSA-N 0.000 description 1
- KHGOSOVBWBOPNK-UHFFFAOYSA-N 2-(3-cyano-4-methylsulfonylphenyl)-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C(C#N)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 KHGOSOVBWBOPNK-UHFFFAOYSA-N 0.000 description 1
- GIZMCHGSQSJKSH-UHFFFAOYSA-N 2-(3-cyano-4-methylsulfonylphenyl)-3-cyclopentyl-n-pyridin-2-ylpropanamide Chemical compound C1=C(C#N)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 GIZMCHGSQSJKSH-UHFFFAOYSA-N 0.000 description 1
- WUKHOVCMWXMOOA-UHFFFAOYSA-N 2-(3-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC([N+]([O-])=O)=C1 WUKHOVCMWXMOOA-UHFFFAOYSA-N 0.000 description 1
- DFEUXSGSGRXESP-UHFFFAOYSA-N 2-(4-chloro-3-nitrophenyl)-3-cyclopentyl-n-pyridin-2-ylpropanamide Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(C(CC2CCCC2)C(=O)NC=2N=CC=CC=2)=C1 DFEUXSGSGRXESP-UHFFFAOYSA-N 0.000 description 1
- OFCFLKKBUHVJTC-UHFFFAOYSA-N 2-(4-cyanophenyl)-3-cyclopentyl-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1CCCC1CC(C=1C=CC(=CC=1)C#N)C(=O)NC1=NC=CS1 OFCFLKKBUHVJTC-UHFFFAOYSA-N 0.000 description 1
- RADNDPLMPBIZAN-UHFFFAOYSA-N 2-(4-cyanophenyl)-3-cyclopentyl-n-pyridin-2-ylpropanamide Chemical compound C1CCCC1CC(C=1C=CC(=CC=1)C#N)C(=O)NC1=CC=CC=N1 RADNDPLMPBIZAN-UHFFFAOYSA-N 0.000 description 1
- CKUZZJJDLFBRDE-UHFFFAOYSA-N 2-(6-aminopyridin-1-ium-3-yl)acetate Chemical compound NC1=CC=C(CC(O)=O)C=N1 CKUZZJJDLFBRDE-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- MIHADVKEHAFNPG-UHFFFAOYSA-N 2-Amino-5-nitrothiazole Chemical compound NC1=NC=C([N+]([O-])=O)S1 MIHADVKEHAFNPG-UHFFFAOYSA-N 0.000 description 1
- ZLOCOQNMVGDMBT-UHFFFAOYSA-N 2-[(5,6-dihydroxy-4-methoxy-2h-pyran-2-yl)oxy]-4-methoxy-2h-pyran-5,6-diol Chemical class O1C(O)=C(O)C(OC)=CC1OC1C=C(OC)C(O)=C(O)O1 ZLOCOQNMVGDMBT-UHFFFAOYSA-N 0.000 description 1
- NBDVUGUUDMQIJV-UHFFFAOYSA-N 2-[3,4-bis(methylsulfonyl)phenyl]-3-cyclopentyl-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C(S(C)(=O)=O)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 NBDVUGUUDMQIJV-UHFFFAOYSA-N 0.000 description 1
- FSTITWGTGMPLTF-UHFFFAOYSA-N 2-[3-(trifluoromethylsulfanyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(SC(F)(F)F)=C1 FSTITWGTGMPLTF-UHFFFAOYSA-N 0.000 description 1
- HNORVZDAANCHAY-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(C(F)(F)F)C=C1 HNORVZDAANCHAY-UHFFFAOYSA-N 0.000 description 1
- FITMMKNFUXJMAO-UHFFFAOYSA-N 2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazole-4-carboxamide Chemical compound NC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 FITMMKNFUXJMAO-UHFFFAOYSA-N 0.000 description 1
- YSNYFPFEBBRSHS-UHFFFAOYSA-N 2-amino-1,3-thiazole-4-carboxamide Chemical compound NC(=O)C1=CSC(N)=N1 YSNYFPFEBBRSHS-UHFFFAOYSA-N 0.000 description 1
- 229940018167 2-amino-5-nitrothiazole Drugs 0.000 description 1
- MFUIRTDVFGAGCV-UHFFFAOYSA-N 2-methylsulfonyl-2-phenylacetic acid Chemical compound CS(=O)(=O)C(C(O)=O)C1=CC=CC=C1 MFUIRTDVFGAGCV-UHFFFAOYSA-N 0.000 description 1
- GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LDFAKIOLAHFILH-UHFFFAOYSA-N 3-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]carbamoylamino]propanoic acid Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCCC(=O)O)CC1CCCC1 LDFAKIOLAHFILH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NBPYFSIOWHCTAW-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(1h-imidazol-2-yl)propanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1NC=CN=1)CC1CCCC1 NBPYFSIOWHCTAW-UHFFFAOYSA-N 0.000 description 1
- AGVMJUYBMAKEFO-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(2-hydroxyethylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCCO)CC1CCCC1 AGVMJUYBMAKEFO-UHFFFAOYSA-N 0.000 description 1
- SJGXOVGSEZKIHH-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(2-hydroxypropylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCC(O)C)CC1CCCC1 SJGXOVGSEZKIHH-UHFFFAOYSA-N 0.000 description 1
- CHLIYNONVQVQKB-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(4-methyl-1,3-thiazol-2-yl)propanamide Chemical compound CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 CHLIYNONVQVQKB-UHFFFAOYSA-N 0.000 description 1
- CAYWEOIOTIIMOQ-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(5-hydroxypyridin-2-yl)propanamide Chemical compound N1=CC(O)=CC=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 CAYWEOIOTIIMOQ-UHFFFAOYSA-N 0.000 description 1
- OZHXKHHSTCCYRN-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(5-methyl-1,3-thiazol-2-yl)propanamide Chemical compound S1C(C)=CN=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 OZHXKHHSTCCYRN-UHFFFAOYSA-N 0.000 description 1
- UCJASZOKKRTZRQ-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-(ethylcarbamoyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCC)CC1CCCC1 UCJASZOKKRTZRQ-UHFFFAOYSA-N 0.000 description 1
- IGONHSGHMVQSQI-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-[4-(hydroxymethyl)-1,3-thiazol-2-yl]propanamide Chemical compound OCC1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 IGONHSGHMVQSQI-UHFFFAOYSA-N 0.000 description 1
- ZMIQNHRRONVEGS-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-[5-(hydroxymethyl)pyridin-2-yl]propanamide Chemical compound N1=CC(CO)=CC=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 ZMIQNHRRONVEGS-UHFFFAOYSA-N 0.000 description 1
- RFZWICAONXFLJJ-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-pyridin-2-ylpropanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 RFZWICAONXFLJJ-UHFFFAOYSA-N 0.000 description 1
- VNBJMRAMCGVCPF-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dichlorophenyl)-n-pyrimidin-4-ylpropanamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(C(=O)NC=1N=CN=CC=1)CC1CCCC1 VNBJMRAMCGVCPF-UHFFFAOYSA-N 0.000 description 1
- MRNIDJZKMIHWMH-UHFFFAOYSA-N 3-cyclopentyl-2-(3,4-dihydroxyphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(O)C(O)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 MRNIDJZKMIHWMH-UHFFFAOYSA-N 0.000 description 1
- XOYVSZXOXSTTFJ-UHFFFAOYSA-N 3-cyclopentyl-2-(3-fluoro-4-methylsulfonylphenyl)-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(S(C)(=O)=O)C(F)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 XOYVSZXOXSTTFJ-UHFFFAOYSA-N 0.000 description 1
- IHOACTRVJLXSDQ-UHFFFAOYSA-N 3-cyclopentyl-2-(4-ethylsulfonylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 IHOACTRVJLXSDQ-UHFFFAOYSA-N 0.000 description 1
- RRLVPDFQPDSORK-UHFFFAOYSA-N 3-cyclopentyl-2-(4-ethylsulfonylphenyl)-n-(methylcarbamoyl)propanamide Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1C(C(=O)NC(=O)NC)CC1CCCC1 RRLVPDFQPDSORK-UHFFFAOYSA-N 0.000 description 1
- ZJPYTKVODPEAIV-UHFFFAOYSA-N 3-cyclopentyl-2-(4-methoxyphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(OC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 ZJPYTKVODPEAIV-UHFFFAOYSA-N 0.000 description 1
- CDSLDJYPYNYSFN-UHFFFAOYSA-N 3-cyclopentyl-2-(4-propylsulfonylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(S(=O)(=O)CCC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 CDSLDJYPYNYSFN-UHFFFAOYSA-N 0.000 description 1
- DJUSTTDVHNGVCW-UHFFFAOYSA-N 3-cyclopentyl-2-[3-fluoro-4-(trifluoromethyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(C(F)(F)F)C(F)=CC(C(CC2CCCC2)C(=O)NC=2SC=CN=2)=C1 DJUSTTDVHNGVCW-UHFFFAOYSA-N 0.000 description 1
- ZFZFNUMHVJPLPM-UHFFFAOYSA-N 3-cyclopentyl-2-[3-fluoro-4-(trifluoromethyl)phenyl]-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(C(F)(F)F)C(F)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 ZFZFNUMHVJPLPM-UHFFFAOYSA-N 0.000 description 1
- QKJNBEILGRYUIT-UHFFFAOYSA-N 3-cyclopentyl-2-[3-fluoro-4-(trifluoromethyl)phenyl]-n-pyridin-2-ylpropanamide Chemical compound C1=C(C(F)(F)F)C(F)=CC(C(CC2CCCC2)C(=O)NC=2N=CC=CC=2)=C1 QKJNBEILGRYUIT-UHFFFAOYSA-N 0.000 description 1
- YDWMCVKPVADYBU-UHFFFAOYSA-N 3-cyclopentyl-2-[4-fluoro-3-(trifluoromethyl)phenyl]-n-(5-methylpyridin-2-yl)propanamide Chemical compound N1=CC(C)=CC=C1NC(=O)C(C=1C=C(C(F)=CC=1)C(F)(F)F)CC1CCCC1 YDWMCVKPVADYBU-UHFFFAOYSA-N 0.000 description 1
- UONUYXPWUJGXGC-UHFFFAOYSA-N 3-cyclopentyl-2-[4-fluoro-3-(trifluoromethyl)phenyl]-n-(methylcarbamoyl)propanamide Chemical compound C=1C=C(F)C(C(F)(F)F)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 UONUYXPWUJGXGC-UHFFFAOYSA-N 0.000 description 1
- GLIDOAFGXMMAHQ-UHFFFAOYSA-N 3-cyclopentyl-2-[4-methylsulfonyl-3-(trifluoromethyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 GLIDOAFGXMMAHQ-UHFFFAOYSA-N 0.000 description 1
- IPBKPKRBRSQJKK-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[3-(trifluoromethyl)phenyl]propanamide Chemical compound FC(F)(F)C1=CC=CC(C(CC2CCCC2)C(=O)NC=2SC=CN=2)=C1 IPBKPKRBRSQJKK-UHFFFAOYSA-N 0.000 description 1
- PTGLJEXOWPNUTH-UHFFFAOYSA-N 3-cyclopentyl-n-(1,3-thiazol-2-yl)-2-[4-(trifluoromethylsulfanyl)phenyl]propanamide Chemical compound C1=CC(SC(F)(F)F)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 PTGLJEXOWPNUTH-UHFFFAOYSA-N 0.000 description 1
- MMQUFTWSIKXRGI-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-(4-nitrophenyl)propanamide Chemical compound C=1C=C([N+]([O-])=O)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 MMQUFTWSIKXRGI-UHFFFAOYSA-N 0.000 description 1
- HCXMORCBQWQUKM-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-[3-(trifluoromethylsulfonyl)phenyl]propanamide Chemical compound C=1C=CC(S(=O)(=O)C(F)(F)F)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 HCXMORCBQWQUKM-UHFFFAOYSA-N 0.000 description 1
- JXTJEINNTZXCBD-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-[4-(trifluoromethylsulfanyl)phenyl]propanamide Chemical compound C=1C=C(SC(F)(F)F)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 JXTJEINNTZXCBD-UHFFFAOYSA-N 0.000 description 1
- QQGQNUGMCRPNMH-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-[4-(trifluoromethylsulfonyl)phenyl]propanamide Chemical compound C=1C=C(S(=O)(=O)C(F)(F)F)C=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 QQGQNUGMCRPNMH-UHFFFAOYSA-N 0.000 description 1
- QOSOWMGKNQPQDX-UHFFFAOYSA-N 3-cyclopentyl-n-(methylcarbamoyl)-2-[4-methylsulfonyl-3-(trifluoromethyl)phenyl]propanamide Chemical group C=1C=C(S(C)(=O)=O)C(C(F)(F)F)=CC=1C(C(=O)NC(=O)NC)CC1CCCC1 QOSOWMGKNQPQDX-UHFFFAOYSA-N 0.000 description 1
- CYNAXWBMOOCYAY-UHFFFAOYSA-N 3-cyclopentyl-n-pyridin-2-yl-2-[4-(trifluoromethylsulfanyl)phenyl]propanamide Chemical compound C1=CC(SC(F)(F)F)=CC=C1C(C(=O)NC=1N=CC=CC=1)CC1CCCC1 CYNAXWBMOOCYAY-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QOWSWEBLNVACCL-UHFFFAOYSA-N 4-Bromophenyl acetate Chemical compound OC(=O)CC1=CC=C(Br)C=C1 QOWSWEBLNVACCL-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- OUQMXTJYCAJLGO-UHFFFAOYSA-N 4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(N)=N1 OUQMXTJYCAJLGO-UHFFFAOYSA-N 0.000 description 1
- ORLGLBZRQYOWNA-UHFFFAOYSA-N 4-methylpyridin-2-amine Chemical compound CC1=CC=NC(N)=C1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 1
- FKPXGNGUVSHWQQ-UHFFFAOYSA-N 5-methyl-1,2-oxazol-3-amine Chemical compound CC1=CC(N)=NO1 FKPXGNGUVSHWQQ-UHFFFAOYSA-N 0.000 description 1
- GUABFMPMKJGSBQ-UHFFFAOYSA-N 5-methyl-1,3-thiazol-2-amine Chemical compound CC1=CN=C(N)S1 GUABFMPMKJGSBQ-UHFFFAOYSA-N 0.000 description 1
- UGSBCCAHDVCHGI-UHFFFAOYSA-N 5-nitropyridin-2-amine Chemical compound NC1=CC=C([N+]([O-])=O)C=N1 UGSBCCAHDVCHGI-UHFFFAOYSA-N 0.000 description 1
- KMWUTRXLBBOIJE-UHFFFAOYSA-N 5-phenylmethoxypyridin-2-amine Chemical compound C1=NC(N)=CC=C1OCC1=CC=CC=C1 KMWUTRXLBBOIJE-UHFFFAOYSA-N 0.000 description 1
- ZDXZIWYYUYGVRE-UHFFFAOYSA-N 6-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 ZDXZIWYYUYGVRE-UHFFFAOYSA-N 0.000 description 1
- ZCIFWRHIEBXBOY-UHFFFAOYSA-N 6-aminonicotinic acid Chemical compound NC1=CC=C(C(O)=O)C=N1 ZCIFWRHIEBXBOY-UHFFFAOYSA-N 0.000 description 1
- QUXLCYFNVNNRBE-UHFFFAOYSA-N 6-methylpyridin-2-amine Chemical compound CC1=CC=CC(N)=N1 QUXLCYFNVNNRBE-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 238000006418 Brown reaction Methods 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- WTXOVDHQQUMODY-UHFFFAOYSA-N OC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(Cl)=CC=2)=N1 Chemical compound OC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(Cl)=CC=2)=N1 WTXOVDHQQUMODY-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
- HZUHTAWCEXQGSY-UHFFFAOYSA-N [amino(nitro)-lambda3-chloranyl] thiocyanate Chemical group [N+](=O)([O-])Cl(N)SC#N HZUHTAWCEXQGSY-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229950011175 aminopicoline Drugs 0.000 description 1
- 239000000538 analytical sample Substances 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005002 aryl methyl group Chemical group 0.000 description 1
- 125000005164 aryl thioalkyl group Chemical group 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960003887 dichlorophen Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- DWDRNKYLWMKWTH-UHFFFAOYSA-N ethyl 2-(4-nitrophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C([N+]([O-])=O)C=C1 DWDRNKYLWMKWTH-UHFFFAOYSA-N 0.000 description 1
- NJBWORPRIRNTLH-UHFFFAOYSA-N ethyl 2-(benzenesulfonyl)acetate Chemical compound CCOC(=O)CS(=O)(=O)C1=CC=CC=C1 NJBWORPRIRNTLH-UHFFFAOYSA-N 0.000 description 1
- ZNUIDZQGDVWGLU-CQSZACIVSA-N ethyl 2-[2-[[(2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazol-4-yl]-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CSC(NC(=O)[C@H](CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 ZNUIDZQGDVWGLU-CQSZACIVSA-N 0.000 description 1
- ABRUKNWQAFXTLG-CQSZACIVSA-N ethyl 2-[2-[[(2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazol-5-yl]-2-oxoacetate Chemical compound S1C(C(=O)C(=O)OCC)=CN=C1NC(=O)[C@@H](C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 ABRUKNWQAFXTLG-CQSZACIVSA-N 0.000 description 1
- ZNUIDZQGDVWGLU-UHFFFAOYSA-N ethyl 2-[2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazol-4-yl]-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 ZNUIDZQGDVWGLU-UHFFFAOYSA-N 0.000 description 1
- ABRUKNWQAFXTLG-UHFFFAOYSA-N ethyl 2-[2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazol-5-yl]-2-oxoacetate Chemical compound S1C(C(=O)C(=O)OCC)=CN=C1NC(=O)C(C=1C=C(Cl)C(Cl)=CC=1)CC1CCCC1 ABRUKNWQAFXTLG-UHFFFAOYSA-N 0.000 description 1
- QRZDENIGZNOIST-UHFFFAOYSA-N ethyl 2-[2-[[3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)S(C)(=O)=O)=N1 QRZDENIGZNOIST-UHFFFAOYSA-N 0.000 description 1
- VDZCZKADNSVOIG-UHFFFAOYSA-N ethyl 2-[2-[[3-cyclopentyl-2-(4-nitrophenyl)propanoyl]amino]-1,3-thiazol-4-yl]-2-oxoacetate Chemical compound CCOC(=O)C(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)[N+]([O-])=O)=N1 VDZCZKADNSVOIG-UHFFFAOYSA-N 0.000 description 1
- JUXYBFRKUPRJRJ-CQSZACIVSA-N ethyl 2-[[(2r)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]carbamoylamino]acetate Chemical compound C([C@@H](C(=O)NC(=O)NCC(=O)OCC)C=1C=C(Cl)C(Cl)=CC=1)C1CCCC1 JUXYBFRKUPRJRJ-CQSZACIVSA-N 0.000 description 1
- ZFMHSESQCGNGBP-UHFFFAOYSA-N ethyl 2-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=C(Cl)C(Cl)=CC=2)=N1 ZFMHSESQCGNGBP-UHFFFAOYSA-N 0.000 description 1
- JUXYBFRKUPRJRJ-UHFFFAOYSA-N ethyl 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)OCC)CC1CCCC1 JUXYBFRKUPRJRJ-UHFFFAOYSA-N 0.000 description 1
- VNZXERIGKZNEKB-UHFFFAOYSA-N ethyl 2-amino-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)S1 VNZXERIGKZNEKB-UHFFFAOYSA-N 0.000 description 1
- GGBZRGGAZMIDNJ-UHFFFAOYSA-N ethyl 3-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]carbamoylamino]propanoate Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCCC(=O)OCC)CC1CCCC1 GGBZRGGAZMIDNJ-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 238000011905 homologation Methods 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004777 loss-of-function mutation Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- UCMVHBVKHLMIMD-UHFFFAOYSA-N methyl 2-(3-chlorophenyl)-3-cyclopentylpropanoate Chemical compound C=1C=CC(Cl)=CC=1C(C(=O)OC)CC1CCCC1 UCMVHBVKHLMIMD-UHFFFAOYSA-N 0.000 description 1
- BFGYITRIATVARH-UHFFFAOYSA-N methyl 2-(3-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=CC([N+]([O-])=O)=C1 BFGYITRIATVARH-UHFFFAOYSA-N 0.000 description 1
- CXZRBHOGKLZWHY-UHFFFAOYSA-N methyl 2-(4-chlorophenyl)-3-cyclopentylpropanoate Chemical compound C=1C=C(Cl)C=CC=1C(C(=O)OC)CC1CCCC1 CXZRBHOGKLZWHY-UHFFFAOYSA-N 0.000 description 1
- PQRGTRBYCFLHKY-UHFFFAOYSA-N methyl 2-(4-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C([N+]([O-])=O)C=C1 PQRGTRBYCFLHKY-UHFFFAOYSA-N 0.000 description 1
- SGQLOBASWXZYOA-UHFFFAOYSA-N methyl 2-[2-[[3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)S(C)(=O)=O)=N1 SGQLOBASWXZYOA-UHFFFAOYSA-N 0.000 description 1
- BBXFUPOENJACAY-UHFFFAOYSA-N methyl 2-[2-[[3-cyclopentyl-2-[4-(trifluoromethylsulfonyl)phenyl]propanoyl]amino]-1,3-thiazol-4-yl]acetate Chemical compound COC(=O)CC1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)S(=O)(=O)C(F)(F)F)=N1 BBXFUPOENJACAY-UHFFFAOYSA-N 0.000 description 1
- TUFMYICFDXXWFT-UHFFFAOYSA-N methyl 2-[[3-cyclopentyl-2-(4-methylsulfonylphenyl)propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)S(C)(=O)=O)=N1 TUFMYICFDXXWFT-UHFFFAOYSA-N 0.000 description 1
- CMEZFKHHVXCOQI-UHFFFAOYSA-N methyl 2-[[3-cyclopentyl-2-[4-(trifluoromethylsulfonyl)phenyl]propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound COC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)S(=O)(=O)C(F)(F)F)=N1 CMEZFKHHVXCOQI-UHFFFAOYSA-N 0.000 description 1
- CJQUPGBTPTYESJ-UHFFFAOYSA-N methyl 3-[[3-cyclopentyl-2-(3,4-dichlorophenyl)propanoyl]carbamoylamino]propanoate Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCCC(=O)OC)CC1CCCC1 CJQUPGBTPTYESJ-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002763 monocarboxylic acids Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- IBGLUWFAFDZXMC-UHFFFAOYSA-N n-(2-chloroethylcarbamoyl)-3-cyclopentyl-2-(3,4-dichlorophenyl)propanamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C(=O)NC(=O)NCCCl)CC1CCCC1 IBGLUWFAFDZXMC-UHFFFAOYSA-N 0.000 description 1
- HSGZONUFKOTGIR-UHFFFAOYSA-N n-(5-bromopyridin-2-yl)-3-cyclopentyl-2-[4-(trifluoromethylsulfonyl)phenyl]propanamide Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1C(C(=O)NC=1N=CC(Br)=CC=1)CC1CCCC1 HSGZONUFKOTGIR-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000006259 organic additive Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012521 purified sample Substances 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- LETVJWLLIMJADE-UHFFFAOYSA-N pyridazin-3-amine Chemical compound NC1=CC=CN=N1 LETVJWLLIMJADE-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000029964 regulation of glucose metabolic process Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 229940035339 tri-chlor Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
- C07D277/58—Nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- 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)
- 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)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12670799P | 1999-03-29 | 1999-03-29 | |
US16594499P | 1999-11-17 | 1999-11-17 | |
US16594899P | 1999-11-17 | 1999-11-17 | |
PCT/EP2000/002450 WO2000058293A2 (en) | 1999-03-29 | 2000-03-20 | Glucokinase activators |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20014671L NO20014671L (no) | 2001-09-26 |
NO20014671D0 NO20014671D0 (no) | 2001-09-26 |
NO320697B1 true NO320697B1 (no) | 2006-01-16 |
Family
ID=27383463
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
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. |
Country Status (34)
Country | Link |
---|---|
EP (1) | EP1169312B1 (cs) |
JP (1) | JP3884232B2 (cs) |
KR (1) | KR100455635B1 (cs) |
CN (1) | CN1151140C (cs) |
AR (1) | AR031066A1 (cs) |
AT (1) | ATE278680T1 (cs) |
AU (1) | AU767830B2 (cs) |
BR (1) | BR0009486B1 (cs) |
CA (1) | CA2368347C (cs) |
CO (1) | CO5170534A1 (cs) |
CZ (1) | CZ301366B6 (cs) |
DE (1) | DE60014610T2 (cs) |
DK (1) | DK1169312T3 (cs) |
EG (1) | EG23870A (cs) |
ES (1) | ES2226811T3 (cs) |
GC (1) | GC0000333A (cs) |
HK (1) | HK1046139B (cs) |
HR (1) | HRP20010688B1 (cs) |
HU (1) | HUP0200396A3 (cs) |
IL (1) | IL145322A (cs) |
JO (1) | JO2475B1 (cs) |
MA (1) | MA26780A1 (cs) |
MX (1) | MXPA01009814A (cs) |
MY (1) | MY136926A (cs) |
NO (1) | NO320697B1 (cs) |
NZ (1) | NZ514038A (cs) |
PE (1) | PE20001584A1 (cs) |
PL (1) | PL350669A1 (cs) |
PT (1) | PT1169312E (cs) |
RS (1) | RS50045B (cs) |
SI (1) | SI1169312T1 (cs) |
TR (1) | TR200102805T2 (cs) |
TW (1) | TWI229078B (cs) |
WO (1) | WO2000058293A2 (cs) |
Families Citing this family (106)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6353111B1 (en) * | 1999-12-15 | 2002-03-05 | Hoffmann-La Roche Inc. | Trans olefinic glucokinase activators |
JP3839723B2 (ja) * | 2000-05-08 | 2006-11-01 | エフ.ホフマン−ラ ロシュ アーゲー | 置換フェニルアセトアミドおよびグルコキナーゼ活性化剤としてのその使用 |
KR100556323B1 (ko) | 2000-07-20 | 2006-03-03 | 에프. 호프만-라 로슈 아게 | 알파-아실 및 알파-헤테로원자-치환된 벤젠 아세트아미드글루코키나제 활성화제 |
US6369232B1 (en) * | 2000-08-15 | 2002-04-09 | Hoffmann-La Roche Inc. | Tetrazolyl-phenyl acetamide glucokinase activators |
US6433188B1 (en) | 2000-12-06 | 2002-08-13 | Wendy Lea Corbett | Fused heteroaromatic glucokinase activators |
ES2256340T3 (es) | 2000-12-06 | 2006-07-16 | F. Hoffmann-La Roche Ag | Activadores heteroaromaticos fusionados de la glucoquinasa. |
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 |
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 |
EP1336607A1 (en) * | 2002-02-19 | 2003-08-20 | Novo Nordisk A/S | Amide derivatives as glucokinase activators |
US6911545B2 (en) * | 2001-12-19 | 2005-06-28 | Hoffman-La Roche Inc. | Crystals of glucokinase and methods of growing them |
JP2005518391A (ja) | 2001-12-21 | 2005-06-23 | ノボ ノルディスク アクティーゼルスカブ | Gk活性化剤としてのアミド誘導体 |
EP1496052B1 (en) | 2002-03-26 | 2009-08-05 | Banyu Pharmaceutical Co., Ltd. | Novel aminobenzamide derivative |
MXPA04010605A (es) * | 2002-04-26 | 2004-12-13 | Hoffmann La Roche | Fenilacetamidas substituidas y su uso como activadores de flucoquinasa. |
MXPA05000130A (es) | 2002-06-27 | 2005-02-17 | Novo Nordisk As | Derivados de aril-carbonilo como agentes terapeuticos. |
CN1678311A (zh) | 2002-06-27 | 2005-10-05 | 诺沃挪第克公司 | 用作治疗剂的芳基羰基衍生物 |
EP1549626A1 (en) * | 2002-10-03 | 2005-07-06 | Novartis AG | Substituted (thiazol-2-yl) -amide or sulfonamide as glycokinase activators useful in the treatment of type 2 diabetes |
GB0226930D0 (en) * | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
GB0226931D0 (en) | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
US7132425B2 (en) * | 2002-12-12 | 2006-11-07 | Hoffmann-La Roche Inc. | 5-substituted-six-membered heteroaromatic glucokinase activators |
PL378117A1 (pl) * | 2003-02-11 | 2006-03-06 | Prosidion Limited | Tricyklopodstawione związki amidowe |
WO2005066145A1 (en) | 2004-01-06 | 2005-07-21 | Novo Nordisk A/S | Heteroaryl-ureas and their use as glucokinase activators |
EP2048137A1 (en) | 2004-02-18 | 2009-04-15 | AstraZeneca AB | Benzamide derivatives and their use as glucokinase activating agents. |
JP4700684B2 (ja) * | 2004-04-02 | 2011-06-15 | ノバルティス アーゲー | 2型糖尿病の処置に有用なグルコキナーゼアクティベーターとしてのスルホンアミド−チアゾロピリジン誘導体 |
JP2007530631A (ja) | 2004-04-02 | 2007-11-01 | ノバルティス アクチエンゲゼルシャフト | チアゾロピリジン誘導体、それを含む医薬組成物およびグルコキナーゼ介在性状態の処置法 |
US20080242869A1 (en) * | 2004-04-21 | 2008-10-02 | Matthew Fyfe | Tri(Cyclo) Substituted Amide Compounds |
EP1749002B1 (en) | 2004-05-10 | 2009-05-27 | F.Hoffmann-La Roche Ag | Pyrrole or imidazole amides for treating obesity |
TW200600086A (en) | 2004-06-05 | 2006-01-01 | Astrazeneca Ab | Chemical compound |
CN101137631A (zh) * | 2004-12-03 | 2008-03-05 | 转化技术制药公司 | 杂芳族葡糖激酶激活剂 |
RU2404164C2 (ru) | 2005-04-06 | 2010-11-20 | Ф.Хоффманн-Ля Рош Аг | Производные пиридин-3-карбоксамида в качестве обратных агонистов св1 |
MX2008000294A (es) | 2005-07-08 | 2008-04-04 | Novo Nordisk As | Activadores de dicicloalquil urea glucocinasa. |
WO2007006761A1 (en) * | 2005-07-08 | 2007-01-18 | Novo Nordisk A/S | Dicycloalkylcarbamoyl ureas as glucokinase activators |
BRPI0622262A2 (pt) | 2005-07-09 | 2011-08-09 | Astrazeneca Ab | composto, composição farmacêutica, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, processo para a preparação de um composto |
CN101263131B (zh) | 2005-07-14 | 2013-04-24 | 特兰斯特克药品公司 | 脲葡糖激酶活化剂 |
ES2426345T3 (es) | 2005-07-20 | 2013-10-22 | Eli Lilly And Company | Compuesto unidos en posición 1-amino |
EP1945635B1 (en) | 2005-08-18 | 2009-05-06 | F.Hoffmann-La Roche Ag | Thiazolyl piperidine derivatives useful as h3 receptor modulators |
KR20080040046A (ko) | 2005-08-31 | 2008-05-07 | 아스텔라스세이야쿠 가부시키가이샤 | 티아졸 유도체 |
JP2007063225A (ja) | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
WO2007039177A2 (en) | 2005-09-29 | 2007-04-12 | Sanofi-Aventis | Phenyl- and pyridinyl- 1, 2 , 4 - oxadiazolone derivatives, processes for their preparation and their use as pharmaceuticals |
GT200600428A (es) | 2005-09-30 | 2007-05-21 | Compuestos organicos | |
GT200600429A (es) * | 2005-09-30 | 2007-04-30 | Compuestos organicos | |
CA2629223C (en) | 2005-11-17 | 2013-08-06 | Eli Lilly And Company | Glucagon receptor antagonists, preparation and therapeutic uses |
ES2342979T3 (es) | 2005-11-30 | 2010-07-20 | F. Hoffmann-La Roche Ag | Derivados de indol-2-carboxamida sustituidos en 5. |
DE602006020482D1 (de) | 2005-11-30 | 2011-04-14 | Hoffmann La Roche | 1,5-substituierte indol-2-yl amidderivative |
JP4879996B2 (ja) | 2005-11-30 | 2012-02-22 | エフ.ホフマン−ラ ロシュ アーゲー | H3調節剤として使用するための1,1−ジオキソ−チオモルホリニルインドリルメタノン誘導体 |
ATE448230T1 (de) | 2005-12-09 | 2009-11-15 | Hoffmann La Roche | Für die behandlung von obesitas geeignete tricyclische amidderivate |
AU2006326135A1 (en) | 2005-12-15 | 2007-06-21 | F. Hoffmann-La Roche Ag | Pyrrolo[2,3-c]pyridine derivatives |
EP2001875A2 (en) | 2006-03-08 | 2008-12-17 | Takeda San Diego, Inc. | Glucokinase activators |
US8211925B2 (en) | 2006-04-28 | 2012-07-03 | Transtech Pharma, Inc. | Benzamide glucokinase activators |
PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
US7432255B2 (en) | 2006-05-16 | 2008-10-07 | Hoffmann-La Roche Inc. | 1H-indol-5-yl-piperazin-1-yl-methanone derivatives |
EP2032554A1 (en) | 2006-05-30 | 2009-03-11 | F. Hoffmann-Roche AG | Piperidinyl pyrimidine derivatives |
WO2007143434A2 (en) | 2006-05-31 | 2007-12-13 | Takeda San Diego, Inc. | Indazole and isoindole derivatives as glucokinase activating agents |
US7910747B2 (en) | 2006-07-06 | 2011-03-22 | Bristol-Myers Squibb Company | Phosphonate and phosphinate pyrazolylamide glucokinase activators |
US7888504B2 (en) | 2006-07-06 | 2011-02-15 | Bristol-Myers Squibb Company | Glucokinase activators and methods of using same |
KR20090025358A (ko) | 2006-07-24 | 2009-03-10 | 에프. 호프만-라 로슈 아게 | 글루코키나제 활성화제로서의 피라졸 |
ES2581765T3 (es) | 2006-08-24 | 2016-09-07 | University Of Tennessee Research Foundation | Acilanilidas sustituidas y métodos de uso de las mismas |
TW200825060A (en) | 2006-10-26 | 2008-06-16 | Astrazeneca Ab | Chemical compounds |
JP5419706B2 (ja) | 2006-12-20 | 2014-02-19 | タケダ カリフォルニア インコーポレイテッド | グルコキナーゼアクチベーター |
TW200831081A (en) | 2006-12-25 | 2008-08-01 | Kyorin Seiyaku Kk | Glucokinase activator |
JP2010515701A (ja) | 2007-01-09 | 2010-05-13 | ノボ・ノルデイスク・エー/エス | ウレアグルコキナーゼアクチベーター |
WO2008084044A1 (en) | 2007-01-11 | 2008-07-17 | Novo Nordisk A/S | Urea glucokinase activators |
CN101622231B (zh) | 2007-02-28 | 2013-12-04 | 艾德维纳斯医疗私人有限公司 | 作为葡糖激酶激活剂的2,2,2-三取代的乙酰胺衍生物、它们的制造方法和药学应用 |
WO2008116107A2 (en) | 2007-03-21 | 2008-09-25 | Takeda San Diego, Inc. | Piperazine derivatives as glucokinase activators |
WO2008136428A1 (ja) | 2007-04-27 | 2008-11-13 | Takeda Pharmaceutical Company Limited | 含窒素5員複素環化合物 |
EP2183237A1 (en) | 2007-07-25 | 2010-05-12 | F. Hoffmann-Roche AG | Benzofuran- and benzo[b]thiophene-2-carboxylic acid amide derivatives and use thereof as histamine 3 receptor modulators |
US8143280B2 (en) | 2007-09-27 | 2012-03-27 | Hoffmann-La Roche Inc. | Glucocorticoid receptor antagonists |
AU2009205070A1 (en) | 2008-01-18 | 2009-07-23 | Astellas Pharma Inc. | Phenyl acetamide derivative |
PT2239253E (pt) | 2008-02-06 | 2013-09-17 | Daiichi Sankyo Co Ltd | Novo derivado de fenilpirrole |
US8258134B2 (en) | 2008-04-16 | 2012-09-04 | Hoffmann-La Roche Inc. | Pyridazinone glucokinase activators |
US7741327B2 (en) | 2008-04-16 | 2010-06-22 | Hoffmann-La Roche Inc. | Pyrrolidinone glucokinase activators |
EP2266983B1 (en) | 2008-04-16 | 2013-06-05 | Takeda Pharmaceutical Company Limited | Nitrogenated 5-membered heterocyclic compound |
SI2275414T1 (sl) | 2008-04-28 | 2015-10-30 | Kyorin Pharmaceutical Co., Ltd., | Ciklopentilakrilamidni derivat |
BRPI0912802A2 (pt) | 2008-05-16 | 2015-10-13 | Takeda San Diego Inc | ativadores de glicoquinase |
US8268820B2 (en) | 2009-03-26 | 2012-09-18 | Hoffmann-La Roche Inc. | 2,3-diaryl- or heteroaryl-substituted 1,1,1-trifluoro-2-hydroxypropyl compounds |
US8138189B2 (en) | 2009-03-26 | 2012-03-20 | Hoffman-La Roche Inc. | Substituted benzene compounds as modulators of the glucocorticoid receptor |
US20110040091A1 (en) * | 2009-08-13 | 2011-02-17 | Stephan Bachmann | Process for the preparation of (r)-2-phenyl propionic acid derivatives |
WO2011058193A1 (en) | 2009-11-16 | 2011-05-19 | Mellitech | [1,5]-diazocin derivatives |
MY159151A (en) | 2009-12-04 | 2016-12-15 | Nissan Chemical Ind Ltd | 2-pyridone compounds |
US8222416B2 (en) | 2009-12-14 | 2012-07-17 | Hoffmann-La Roche Inc. | Azaindole glucokinase activators |
US8420647B2 (en) | 2010-01-21 | 2013-04-16 | Hoffmann-La Roche Inc. | 4-phenoxy-nicotinamide or 4-phenoxy-pyrimidine-5-carboxamide compounds |
US8252826B2 (en) | 2010-03-24 | 2012-08-28 | Hoffmann-La Roche Inc. | Cyclopentyl- and cycloheptylpyrazoles |
CN102959076B (zh) | 2010-03-31 | 2015-09-16 | 斯克里普斯研究所 | 重编程细胞 |
RU2579114C9 (ru) | 2010-07-12 | 2016-05-27 | Ф. Хоффманн-Ля Рош Аг | 1-гидроксиимино-3-фенил-пропаны |
US8987307B2 (en) | 2011-03-03 | 2015-03-24 | Hoffmann-La Roche Inc. | 3-amino-pyridines as GPBAR1 agonists |
WO2013060653A1 (en) | 2011-10-26 | 2013-05-02 | F. Hoffmann-La Roche Ag | 1-cycloalkyl- or 1-heterocyclyl-hydroxyimino-3-phenyl-propanes |
EP2834226B1 (en) | 2012-04-04 | 2016-05-25 | F.Hoffmann-La Roche Ag | 1,2-pyridazine, 1,6-pyridazine or pyrimidine-benzamide derivatives as gpbar1 modulators |
US10314807B2 (en) | 2012-07-13 | 2019-06-11 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
LT2872482T (lt) | 2012-07-13 | 2020-12-28 | Oncternal Therapeutics, Inc. | Krūties vėžių gydymo būdas selektyviu androgeno receptoriaus moduliatoriumi |
US9744149B2 (en) | 2012-07-13 | 2017-08-29 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
US9969683B2 (en) | 2012-07-13 | 2018-05-15 | Gtx, Inc. | Method of treating estrogen receptor (ER)-positive breast cancers with selective androgen receptor modulator (SARMS) |
US10258596B2 (en) | 2012-07-13 | 2019-04-16 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
US9622992B2 (en) | 2012-07-13 | 2017-04-18 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
US10987334B2 (en) | 2012-07-13 | 2021-04-27 | University Of Tennessee Research Foundation | Method of treating ER mutant expressing breast cancers with selective androgen receptor modulators (SARMs) |
PT2921489T (pt) | 2012-11-13 | 2017-12-01 | Nissan Chemical Ind Ltd | Composto de 2-piridona |
CN104672219A (zh) * | 2015-02-13 | 2015-06-03 | 佛山市赛维斯医药科技有限公司 | 一类含葡萄糖酰胺结构的葡萄糖激酶活化剂及其用途 |
CN104672218A (zh) * | 2015-02-13 | 2015-06-03 | 佛山市赛维斯医药科技有限公司 | 含葡萄糖酰胺结构的葡萄糖激酶活化剂、制备方法及其在治疗2型糖尿病上的用途 |
US10894054B2 (en) | 2015-04-07 | 2021-01-19 | Intercept Pharmaceuticals, Inc. | FXR agonist compositions for combination therapy |
EP3101005A1 (en) * | 2015-06-05 | 2016-12-07 | Lead Pharma Cel Models IP B.V. | Ror gamma (rory) modulators |
GB201714777D0 (en) | 2017-09-14 | 2017-11-01 | Univ London Queen Mary | Agent |
JP2021526130A (ja) | 2018-06-12 | 2021-09-30 | ブイティーブイ・セラピューティクス・エルエルシー | インスリンまたはインスリン類似体と組み合わせたグルコキナーゼ活性化薬の治療的使用 |
TWI845975B (zh) | 2021-07-06 | 2024-06-21 | 中國大陸商甘萊製藥有限公司 | 用於治療肝臟疾病的聯合治療 |
TW202315608A (zh) | 2021-07-06 | 2023-04-16 | 中國大陸商甘萊製藥有限公司 | 用於治療肝臟疾病的聯合治療 |
CN116687850A (zh) | 2022-02-24 | 2023-09-05 | 甘莱制药有限公司 | 包含环状膦酸酯化合物的药物组合物及其制备方法与用途 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE249241C (cs) * | 1910-05-01 | 1912-07-13 | ||
US3776917A (en) * | 1972-06-05 | 1973-12-04 | Schering Corp | 2-amino-6-phenalkyl-aminopyridines and derivatives thereof |
-
2000
- 2000-03-20 PT PT00918816T patent/PT1169312E/pt unknown
- 2000-03-20 HU HU0200396A patent/HUP0200396A3/hu unknown
- 2000-03-20 AT AT00918816T patent/ATE278680T1/de active
- 2000-03-20 JP JP2000607996A patent/JP3884232B2/ja not_active Expired - Fee Related
- 2000-03-20 EP EP00918816A patent/EP1169312B1/en not_active Expired - Lifetime
- 2000-03-20 WO PCT/EP2000/002450 patent/WO2000058293A2/en active IP Right Grant
- 2000-03-20 DK DK00918816T patent/DK1169312T3/da active
- 2000-03-20 KR KR10-2001-7012279A patent/KR100455635B1/ko not_active IP Right Cessation
- 2000-03-20 ES ES00918816T patent/ES2226811T3/es not_active Expired - Lifetime
- 2000-03-20 CA CA002368347A patent/CA2368347C/en not_active Expired - Fee Related
- 2000-03-20 NZ NZ514038A patent/NZ514038A/xx not_active IP Right Cessation
- 2000-03-20 CN CNB00806766XA patent/CN1151140C/zh not_active Expired - Fee Related
- 2000-03-20 DE DE60014610T patent/DE60014610T2/de not_active Expired - Lifetime
- 2000-03-20 RS YUP-695/01A patent/RS50045B/sr unknown
- 2000-03-20 PL PL00350669A patent/PL350669A1/xx not_active Application Discontinuation
- 2000-03-20 MX MXPA01009814A patent/MXPA01009814A/es active IP Right Grant
- 2000-03-20 CZ CZ20013490A patent/CZ301366B6/cs not_active IP Right Cessation
- 2000-03-20 BR BRPI0009486-2A patent/BR0009486B1/pt not_active IP Right Cessation
- 2000-03-20 AU AU39630/00A patent/AU767830B2/en not_active Ceased
- 2000-03-20 TR TR2001/02805T patent/TR200102805T2/xx unknown
- 2000-03-20 SI SI200030538T patent/SI1169312T1/xx unknown
- 2000-03-24 PE PE2000000255A patent/PE20001584A1/es not_active Application Discontinuation
- 2000-03-27 MY MYPI20001212A patent/MY136926A/en unknown
- 2000-03-27 AR ARP000101372A patent/AR031066A1/es active IP Right Grant
- 2000-03-27 JO JO2000301A patent/JO2475B1/en active
- 2000-03-27 EG EG20000365A patent/EG23870A/xx active
- 2000-03-28 CO CO00022164A patent/CO5170534A1/es not_active Application Discontinuation
- 2000-03-28 TW TW089105714A patent/TWI229078B/zh not_active IP Right Cessation
- 2000-03-29 GC GCP2000590 patent/GC0000333A/en active
-
2001
- 2001-09-06 IL IL145322A patent/IL145322A/en not_active IP Right Cessation
- 2001-09-19 HR HR20010688A patent/HRP20010688B1/xx not_active IP Right Cessation
- 2001-09-26 NO NO20014671A patent/NO320697B1/no not_active IP Right Cessation
- 2001-09-28 MA MA26343A patent/MA26780A1/fr unknown
-
2002
- 2002-10-23 HK HK02107692.4A patent/HK1046139B/zh not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1169312B1 (en) | Glucokinase activators | |
RU2242469C2 (ru) | Активаторы глюкокиназы | |
US6320050B1 (en) | Heteroaromatic glucokinase activators | |
US6610846B1 (en) | Heteroaromatic glucokinase activators | |
EP1501815B1 (en) | Substituted phenylacetamides and their use as glucokinase activators | |
AU778036B2 (en) | Substituted phenylacetamides and their use as glucokinase activators | |
AU781029B2 (en) | Trans olefinic glucokinase activators | |
ZA200107833B (en) | Glucokinase activators. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |