IL223856A - Heterocyclic compounds activate ampk and their methods - Google Patents
Heterocyclic compounds activate ampk and their methodsInfo
- Publication number
- IL223856A IL223856A IL223856A IL22385612A IL223856A IL 223856 A IL223856 A IL 223856A IL 223856 A IL223856 A IL 223856A IL 22385612 A IL22385612 A IL 22385612A IL 223856 A IL223856 A IL 223856A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- compound
- substituted
- nmr
- compound according
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract description 78
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 516
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 27
- 125000004122 cyclic group Chemical group 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 239000012453 solvate Substances 0.000 claims description 44
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- 125000001188 haloalkyl group Chemical group 0.000 claims description 30
- -1 methoxy, ethoxy Chemical group 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 10
- 125000000732 arylene group Chemical group 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000005549 heteroarylene group Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 8
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims 3
- LEUSDRGCPVXECX-FQLXRVMXSA-N n-[(3r,4r)-1-[(4-cyanophenyl)methyl]-3-fluoropiperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=CC(=CC=3)C#N)CC2)F)CC1 LEUSDRGCPVXECX-FQLXRVMXSA-N 0.000 claims 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
- 150000001204 N-oxides Chemical class 0.000 claims 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 1
- ISSLZKSSYLRMSG-PQHLKRTFSA-N 5-[(3r,4r)-4-(4-cyanophenoxy)-3-fluoropiperidine-1-carbonyl]-n-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]pyridine-2-carboxamide Chemical compound O([C@@H]1CCN(C[C@H]1F)C(=O)C=1C=NC(=CC=1)C(=O)NC1CCN(CC=2C=CC(=CC=2)C#N)CC1)C1=CC=C(C#N)C=C1 ISSLZKSSYLRMSG-PQHLKRTFSA-N 0.000 claims 1
- KMRPXMWIZLSCAG-FTJBHMTQSA-N 5-[4-[(4-fluorophenyl)methyl]piperazine-1-carbonyl]-n-[(3r,4s)-3-fluoro-1-(pyridin-4-ylmethyl)piperidin-4-yl]pyridine-2-carboxamide Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2N=CC(=CC=2)C(=O)N2CCN(CC=3C=CC(F)=CC=3)CC2)F)N1CC1=CC=NC=C1 KMRPXMWIZLSCAG-FTJBHMTQSA-N 0.000 claims 1
- SSXKELDQHCLBAC-UXHICEINSA-N 5-[4-[(4-fluorophenyl)methyl]piperazine-1-carbonyl]-n-[(3r,4s)-3-fluoropiperidin-4-yl]pyridine-2-carboxamide Chemical compound F[C@@H]1CNCC[C@@H]1NC(=O)C1=CC=C(C(=O)N2CCN(CC=3C=CC(F)=CC=3)CC2)C=N1 SSXKELDQHCLBAC-UXHICEINSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- XSTWHJANPVSKRP-FQLXRVMXSA-N n-[(3r,4r)-1-[(4-cyano-3-fluorophenyl)methyl]-3-fluoropiperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=C(F)C(C#N)=CC=3)CC2)F)CC1 XSTWHJANPVSKRP-FQLXRVMXSA-N 0.000 claims 1
- IKZUOIYXCIBCLH-FQLXRVMXSA-N n-[(3r,4r)-1-[(4-cyanophenyl)methyl]-3-fluoropiperidin-4-yl]-5-[4-(4-methylsulfonylbenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(=O)C1CCN(C(=O)C=2C=NC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=CC(=CC=3)C#N)CC2)F)CC1 IKZUOIYXCIBCLH-FQLXRVMXSA-N 0.000 claims 1
- GYXYLTXHDOYGIT-FQLXRVMXSA-N n-[(3r,4r)-1-[(4-cyanophenyl)methyl]-3-fluoropiperidin-4-yl]-5-[4-(4-methylsulfonylphenoxy)piperidine-1-carbonyl]pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1OC1CCN(C(=O)C=2C=NC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=CC(=CC=3)C#N)CC2)F)CC1 GYXYLTXHDOYGIT-FQLXRVMXSA-N 0.000 claims 1
- BFKLKEDGPVUXEU-VSGBNLITSA-N n-[(3r,4r)-1-[(4-cyanophenyl)methyl]-3-fluoropiperidin-4-yl]-6-[4-[4-(trifluoromethylsulfonyl)phenoxy]piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C([C@H]([C@@H](CC1)NC(=O)C=2C=NC(=CC=2)C(=O)N2CCC(CC2)OC=2C=CC(=CC=2)S(=O)(=O)C(F)(F)F)F)N1CC1=CC=C(C#N)C=C1 BFKLKEDGPVUXEU-VSGBNLITSA-N 0.000 claims 1
- MPRAAOIVYGMJKJ-FIRIVFDPSA-N n-[(3r,4r)-3-fluoro-1-[(4-propan-2-yloxyphenyl)methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=CC(OC(C)C)=CC=3)CC2)F)CC1 MPRAAOIVYGMJKJ-FIRIVFDPSA-N 0.000 claims 1
- MWVAIOSVWVODAN-VSGBNLITSA-N n-[(3r,4r)-3-fluoro-1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]-5-[4-(4-methylsulfonylbenzoyl)piperidine-1-carbonyl]pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(=O)C1CCN(C(=O)C=2C=NC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=CC(OC(F)(F)F)=CC=3)CC2)F)CC1 MWVAIOSVWVODAN-VSGBNLITSA-N 0.000 claims 1
- QYKFEEHGZRXLOV-VSGBNLITSA-N n-[(3r,4r)-3-fluoro-1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]-5-[4-(4-methylsulfonylphenoxy)piperidine-1-carbonyl]pyridine-2-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1OC1CCN(C(=O)C=2C=NC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=CC(OC(F)(F)F)=CC=3)CC2)F)CC1 QYKFEEHGZRXLOV-VSGBNLITSA-N 0.000 claims 1
- HWOSDYNCBXZMQP-VSGBNLITSA-N n-[(3r,4r)-3-fluoro-1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@H]2[C@@H](CN(CC=3C=CC(OC(F)(F)F)=CC=3)CC2)F)CC1 HWOSDYNCBXZMQP-VSGBNLITSA-N 0.000 claims 1
- LEUSDRGCPVXECX-WDYNHAJCSA-N n-[(3r,4s)-1-[(4-cyanophenyl)methyl]-3-fluoropiperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@@H]2[C@@H](CN(CC=3C=CC(=CC=3)C#N)CC2)F)CC1 LEUSDRGCPVXECX-WDYNHAJCSA-N 0.000 claims 1
- HWOSDYNCBXZMQP-IZLXSDGUSA-N n-[(3r,4s)-3-fluoro-1-[[4-(trifluoromethoxy)phenyl]methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@@H]2[C@@H](CN(CC=3C=CC(OC(F)(F)F)=CC=3)CC2)F)CC1 HWOSDYNCBXZMQP-IZLXSDGUSA-N 0.000 claims 1
- QECRHJAQOQEILO-IZZNHLLZSA-N n-[(3s,4r)-3-fluoro-1-[(2-methyl-1,3-thiazol-4-yl)methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@H]2[C@H](CN(CC=3N=C(C)SC=3)CC2)F)CC1 QECRHJAQOQEILO-IZZNHLLZSA-N 0.000 claims 1
- HJLLFICFQXAIAT-IZZNHLLZSA-N n-[(3s,4r)-3-fluoro-1-[(5-methyl-1,2-oxazol-3-yl)methyl]piperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@H]2[C@H](CN(CC3=NOC(C)=C3)CC2)F)CC1 HJLLFICFQXAIAT-IZZNHLLZSA-N 0.000 claims 1
- LEUSDRGCPVXECX-VMPREFPWSA-N n-[(3s,4s)-1-[(4-cyanophenyl)methyl]-3-fluoropiperidin-4-yl]-6-[4-(4-methoxybenzoyl)piperidine-1-carbonyl]pyridine-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(C(=O)C=2N=CC(=CC=2)C(=O)N[C@@H]2[C@H](CN(CC=3C=CC(=CC=3)C#N)CC2)F)CC1 LEUSDRGCPVXECX-VMPREFPWSA-N 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 1
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 abstract description 28
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 abstract description 28
- 230000037361 pathway Effects 0.000 abstract description 10
- 150000003222 pyridines Chemical class 0.000 abstract description 3
- 230000004060 metabolic process Effects 0.000 abstract description 2
- 229940125904 compound 1 Drugs 0.000 description 143
- 239000000203 mixture Substances 0.000 description 49
- 210000004027 cell Anatomy 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
- 230000002829 reductive effect Effects 0.000 description 31
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
- 125000000753 cycloalkyl group Chemical group 0.000 description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 19
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 19
- 239000012267 brine Substances 0.000 description 19
- 229940106189 ceramide Drugs 0.000 description 19
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 19
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 208000035475 disorder Diseases 0.000 description 15
- 239000007821 HATU Substances 0.000 description 14
- 125000003725 azepanyl group Chemical group 0.000 description 14
- 235000014113 dietary fatty acids Nutrition 0.000 description 13
- 239000000194 fatty acid Substances 0.000 description 13
- 229930195729 fatty acid Natural products 0.000 description 13
- 150000004665 fatty acids Chemical class 0.000 description 13
- 125000004193 piperazinyl group Chemical group 0.000 description 13
- 150000003254 radicals Chemical class 0.000 description 13
- XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 0.000 description 13
- 230000004913 activation Effects 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 12
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 102000011690 Adiponectin Human genes 0.000 description 11
- 108010076365 Adiponectin Proteins 0.000 description 11
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 11
- 125000005647 linker group Chemical group 0.000 description 11
- 102000004201 Ceramidases Human genes 0.000 description 10
- 108090000751 Ceramidases Proteins 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
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- 238000003786 synthesis reaction Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 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 8
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
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- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
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- 238000001727 in vivo Methods 0.000 description 6
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- 210000004185 liver Anatomy 0.000 description 6
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- 230000001590 oxidative effect Effects 0.000 description 6
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 6
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 6
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
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- 125000006575 electron-withdrawing group Chemical group 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 150000004677 hydrates Chemical class 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
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- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36892810P | 2010-07-29 | 2010-07-29 | |
| PCT/US2011/046019 WO2012016217A1 (en) | 2010-07-29 | 2011-07-29 | Ampk-activating heterocyclic compounds and methods for using the same |
Publications (1)
| Publication Number | Publication Date |
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| IL223856A true IL223856A (en) | 2017-09-28 |
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| IL223856A IL223856A (en) | 2010-07-29 | 2012-12-25 | Heterocyclic compounds activate ampk and their methods |
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