IL298306A - ampk operators - Google Patents

Info

Publication number

IL298306A

IL298306A IL298306A IL29830622A IL298306A IL 298306 A IL298306 A IL 298306A IL 298306 A IL298306 A IL 298306A IL 29830622 A IL29830622 A IL 29830622A IL 298306 A IL298306 A IL 298306A

Authority

IL

Israel

Prior art keywords

prodrug

stereoisomer

compound

solvate

acceptable salt

Prior art date

2020-05-19

Links

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• Global Dossier
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• 239000012190 activator Substances 0.000 title description 30
• 101100321932 Rattus norvegicus Prkaa2 gene Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 325
• -1 4-morpholinylphenyl Chemical group 0.000 claims description 227
• 229940002612 prodrug Drugs 0.000 claims description 196
• 239000000651 prodrug Substances 0.000 claims description 196
• 150000003839 salts Chemical class 0.000 claims description 149
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 146
• 229910052739 hydrogen Inorganic materials 0.000 claims description 139
• 239000001257 hydrogen Substances 0.000 claims description 139
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 137
• 239000012453 solvate Substances 0.000 claims description 118
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 116
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 108
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 91
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 77
• 229910052736 halogen Inorganic materials 0.000 claims description 68
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 66
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 64
• 208000035475 disorder Diseases 0.000 claims description 63
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 59
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 53
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 50
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 42
• 125000001072 heteroaryl group Chemical group 0.000 claims description 41
• 229910052757 nitrogen Inorganic materials 0.000 claims description 39
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
• 238000000034 method Methods 0.000 claims description 33
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 33
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 33
• 231100000331 toxic Toxicity 0.000 claims description 33
• 230000002588 toxic effect Effects 0.000 claims description 33
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 32
• 239000003814 drug Substances 0.000 claims description 28
• 238000002512 chemotherapy Methods 0.000 claims description 26
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
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• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 22
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• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 19
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• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 16
• 208000008589 Obesity Diseases 0.000 claims description 15
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 15
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 15
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• 125000003386 piperidinyl group Chemical group 0.000 claims description 15
• 238000011282 treatment Methods 0.000 claims description 15
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• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
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• 125000000842 isoxazolyl group Chemical group 0.000 claims description 12
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• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 10
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• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
• 125000004076 pyridyl group Chemical group 0.000 claims description 10
• 238000001959 radiotherapy Methods 0.000 claims description 10
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
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• 206010049416 Short-bowel syndrome Diseases 0.000 claims description 9
• 201000011510 cancer Diseases 0.000 claims description 9
• MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 claims description 9
• 230000007613 environmental effect Effects 0.000 claims description 9
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• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
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• 238000002360 preparation method Methods 0.000 claims description 7
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• 208000024827 Alzheimer disease Diseases 0.000 claims description 6
• UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 claims description 6
• UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 claims description 6
• 229950006790 adenosine phosphate Drugs 0.000 claims description 6
• 208000010706 fatty liver disease Diseases 0.000 claims description 6
• 208000019180 nutritional disease Diseases 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 208000004930 Fatty Liver Diseases 0.000 claims description 5
• 206010019708 Hepatic steatosis Diseases 0.000 claims description 5
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
• 206010051606 Necrotising colitis Diseases 0.000 claims description 5
• 102000001253 Protein Kinase Human genes 0.000 claims description 5
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
• 230000003176 fibrotic effect Effects 0.000 claims description 5
• 208000004995 necrotizing enterocolitis Diseases 0.000 claims description 5
• 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 claims description 5
• 108060006633 protein kinase Proteins 0.000 claims description 5
• 231100000240 steatosis hepatitis Toxicity 0.000 claims description 5
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
• 230000007149 gut brain axis pathway Effects 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 3
• 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 3
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 4
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 4
• 208000007386 hepatic encephalopathy Diseases 0.000 claims 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 100
• 235000002639 sodium chloride Nutrition 0.000 description 99
• 239000000203 mixture Substances 0.000 description 75
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• 125000005843 halogen group Chemical group 0.000 description 60
• 150000002431 hydrogen Chemical group 0.000 description 59
• MPLLLQUZNJSVTK-UHFFFAOYSA-N 5-[3-[4-[2-(4-fluorophenyl)ethoxy]phenyl]propyl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1CCCC(C=C1)=CC=C1OCCC1=CC=C(F)C=C1 MPLLLQUZNJSVTK-UHFFFAOYSA-N 0.000 description 53
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