KR101456286B1 - Gpr119 효능제로서의 옥심 유도체 - Google Patents
Gpr119 효능제로서의 옥심 유도체 Download PDFInfo
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- KR101456286B1 KR101456286B1 KR20120015736A KR20120015736A KR101456286B1 KR 101456286 B1 KR101456286 B1 KR 101456286B1 KR 20120015736 A KR20120015736 A KR 20120015736A KR 20120015736 A KR20120015736 A KR 20120015736A KR 101456286 B1 KR101456286 B1 KR 101456286B1
- Authority
- KR
- South Korea
- Prior art keywords
- phenyl
- piperidin
- cyclohexyl
- yloxyimino
- urea
- Prior art date
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- 150000002923 oximes Chemical class 0.000 title claims abstract description 19
- 229940100607 GPR119 agonist Drugs 0.000 title abstract description 18
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 11
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 11
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 11
- 208000008589 Obesity Diseases 0.000 claims abstract description 10
- 235000020824 obesity Nutrition 0.000 claims abstract description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 398
- -1 naphthalenylmethyl Chemical group 0.000 claims description 252
- 238000002360 preparation method Methods 0.000 claims description 181
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- SNBYDHCSBZIOQL-UHFFFAOYSA-N 3-hydroxyazetidine-1-carboxylic acid Chemical compound OC1CN(C(O)=O)C1 SNBYDHCSBZIOQL-UHFFFAOYSA-N 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000004202 carbamide Substances 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 22
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 239000011593 sulfur Substances 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- UVBYKOXVPGVXBB-UHFFFAOYSA-N [2,5-difluoro-4-[4-[4-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)cyclohexyl]oxyiminocyclohexyl]phenyl]urea Chemical compound CC(C)C1=NOC(C2CCC(CC2)ON=C2CCC(CC2)C=2C(=CC(NC(N)=O)=C(F)C=2)F)=N1 UVBYKOXVPGVXBB-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- XCZOJQGSKASWBC-UHFFFAOYSA-N propan-2-yl 4-[[4-[2,5-difluoro-4-(hydroxymethyl)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C(=CC(CO)=C(F)C=2)F)CC1 XCZOJQGSKASWBC-UHFFFAOYSA-N 0.000 claims description 4
- VJBHTSHUVPFZSJ-UHFFFAOYSA-N tert-butyl 4-[[4-(2,5-difluoro-4-methoxycarbonylphenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(C(=O)OC)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C(=O)OC(C)(C)C)CC1 VJBHTSHUVPFZSJ-UHFFFAOYSA-N 0.000 claims description 4
- YCWSUIJJEJMNJP-SCSAIBSYSA-N (3r)-3-fluoropyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CC[C@@H](F)C1 YCWSUIJJEJMNJP-SCSAIBSYSA-N 0.000 claims description 3
- JKNNHTDMBYCFRC-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-propylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(3-hydroxypropyl)urea Chemical compound N1=CC(CCC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NCCCO)=C(F)C=2)F)CC1 JKNNHTDMBYCFRC-UHFFFAOYSA-N 0.000 claims description 3
- LVRKSAKIAWFJRL-UHFFFAOYSA-N 3-[2-fluoro-4-[4-[1-(naphthalen-2-ylmethyl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-1,1-dimethylurea Chemical compound C1=C(F)C(NC(=O)N(C)C)=CC=C1C(CC1)CCC1=NOC1CCN(CC=2C=C3C=CC=CC3=CC=2)CC1 LVRKSAKIAWFJRL-UHFFFAOYSA-N 0.000 claims description 3
- TXNYAYJJOPAMFT-UHFFFAOYSA-N 3-[4-[4-(1-benzylpiperidin-4-yl)oxyiminocyclohexyl]-2-fluorophenyl]-1,1-dimethylurea Chemical compound C1=C(F)C(NC(=O)N(C)C)=CC=C1C(CC1)CCC1=NOC1CCN(CC=2C=CC=CC=2)CC1 TXNYAYJJOPAMFT-UHFFFAOYSA-N 0.000 claims description 3
- XDHMORMQXOUOHT-UHFFFAOYSA-N 4-(4-methylphenyl)cyclohexan-1-one Chemical compound C1=CC(C)=CC=C1C1CCC(=O)CC1 XDHMORMQXOUOHT-UHFFFAOYSA-N 0.000 claims description 3
- IWMUXSJDSYQUCF-UHFFFAOYSA-N 4-naphthalen-2-ylcyclohexan-1-one Chemical compound C1CC(=O)CCC1C1=CC=C(C=CC=C2)C2=C1 IWMUXSJDSYQUCF-UHFFFAOYSA-N 0.000 claims description 3
- ZZMSYAWBWSRFQI-UHFFFAOYSA-N FC1=C(C=C(C(=C1)N1N=NN=C1)F)C1C=CC(CC1)=O Chemical compound FC1=C(C=C(C(=C1)N1N=NN=C1)F)C1C=CC(CC1)=O ZZMSYAWBWSRFQI-UHFFFAOYSA-N 0.000 claims description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 3
- ADWAJXSUORNLIR-UHFFFAOYSA-N [2,3-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=C(F)C(NC(N)=O)=CC=2)F)CC1 ADWAJXSUORNLIR-UHFFFAOYSA-N 0.000 claims description 3
- VZTXZGMWCJVHTK-UHFFFAOYSA-N [2,5-difluoro-4-[4-[1-(1,3-thiazol-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound C1=C(F)C(NC(=O)N)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2SC=CN=2)CC1 VZTXZGMWCJVHTK-UHFFFAOYSA-N 0.000 claims description 3
- GAAGASFDWOGPJU-UHFFFAOYSA-N [2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(N)=O)=C(F)C=2)F)CC1 GAAGASFDWOGPJU-UHFFFAOYSA-N 0.000 claims description 3
- AQNRTGKZCYRCEH-UHFFFAOYSA-N [2,5-difluoro-4-[4-[1-(5-propylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound N1=CC(CCC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(N)=O)=C(F)C=2)F)CC1 AQNRTGKZCYRCEH-UHFFFAOYSA-N 0.000 claims description 3
- ROCONRBTJHJWQX-UHFFFAOYSA-N [2,6-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C=C(F)C(NC(N)=O)=C(F)C=2)CC1 ROCONRBTJHJWQX-UHFFFAOYSA-N 0.000 claims description 3
- YYEIODIUKUXVMG-UHFFFAOYSA-N [2-fluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C=C(F)C(NC(N)=O)=CC=2)CC1 YYEIODIUKUXVMG-UHFFFAOYSA-N 0.000 claims description 3
- NIOLYRTYVYIRSX-UHFFFAOYSA-N [3-fluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(N)=O)=CC=2)F)CC1 NIOLYRTYVYIRSX-UHFFFAOYSA-N 0.000 claims description 3
- IMTVDSDSAQYMPW-UHFFFAOYSA-N [4-[4-[1-(1,3-benzothiazol-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2,5-difluorophenyl]urea Chemical compound C1=C(F)C(NC(=O)N)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2SC3=CC=CC=C3N=2)CC1 IMTVDSDSAQYMPW-UHFFFAOYSA-N 0.000 claims description 3
- PVEIGYCGTWBXCY-UHFFFAOYSA-N [4-[4-[1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2,5-difluorophenyl]urea Chemical compound C1=C(F)C(NC(=O)N)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(=CN=2)C2CC2)CC1 PVEIGYCGTWBXCY-UHFFFAOYSA-N 0.000 claims description 3
- ZADFGHUZOQWLJG-UHFFFAOYSA-N [4-[4-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2,3-difluorophenyl]urea Chemical compound N1=CC(CC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=C(F)C(NC(N)=O)=CC=2)F)CC1 ZADFGHUZOQWLJG-UHFFFAOYSA-N 0.000 claims description 3
- LEOJIDLUCHAESD-UHFFFAOYSA-N [4-[4-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2,5-difluorophenyl]urea Chemical compound N1=CC(CC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(N)=O)=C(F)C=2)F)CC1 LEOJIDLUCHAESD-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 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 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- IZWGGTKKRAOYJP-UHFFFAOYSA-N phenyl 3-[[4-[2-fluoro-4-(propylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypyrrolidine-1-carboxylate Chemical compound FC1=CC(NC(=O)NCCC)=CC=C1C(CC1)CCC1=NOC1CN(C(=O)OC=2C=CC=CC=2)CC1 IZWGGTKKRAOYJP-UHFFFAOYSA-N 0.000 claims description 3
- BRSYOOZSDKNZAE-UHFFFAOYSA-N phenyl 3-[[4-[4-(carbamoylamino)-2-fluorophenyl]cyclohexylidene]amino]oxy-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound FC1=CC(NC(=O)N)=CC=C1C(CC1)CCC1=NOC1CC(N2C(=O)OC=3C=CC=CC=3)CCC2C1 BRSYOOZSDKNZAE-UHFFFAOYSA-N 0.000 claims description 3
- QWARLUVNNDCYES-UHFFFAOYSA-N phenyl 4-[[4-[2,5-difluoro-4-(phenoxycarbonylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound FC=1C=C(NC(=O)OC=2C=CC=CC=2)C(F)=CC=1C(CC1)CCC1=NOC(CC1)CCN1C(=O)OC1=CC=CC=C1 QWARLUVNNDCYES-UHFFFAOYSA-N 0.000 claims description 3
- QTWAIPQNGXVJPA-UHFFFAOYSA-N phenyl 4-[[4-[2,5-difluoro-4-(propan-2-ylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NC(C)C)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 QTWAIPQNGXVJPA-UHFFFAOYSA-N 0.000 claims description 3
- OXLBBGIKHYALDC-UHFFFAOYSA-N phenyl 4-[[4-[2,5-difluoro-4-(propylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NCCC)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 OXLBBGIKHYALDC-UHFFFAOYSA-N 0.000 claims description 3
- ZTJSXAHNBZCHDN-UHFFFAOYSA-N phenyl 4-[[4-[2-fluoro-4-(2-hydroxyethylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound FC1=CC(NC(=O)NCCO)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 ZTJSXAHNBZCHDN-UHFFFAOYSA-N 0.000 claims description 3
- QVOPBTYTKWNUGD-UHFFFAOYSA-N phenyl 4-[[4-[2-fluoro-4-(phenoxycarbonylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C=1C=C(C2CCC(CC2)=NOC2CCN(CC2)C(=O)OC=2C=CC=CC=2)C(F)=CC=1NC(=O)OC1=CC=CC=C1 QVOPBTYTKWNUGD-UHFFFAOYSA-N 0.000 claims description 3
- WVMSCPMDRUYNFJ-UHFFFAOYSA-N phenyl 4-[[4-[3-fluoro-4-(2-fluoroethylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NCCF)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 WVMSCPMDRUYNFJ-UHFFFAOYSA-N 0.000 claims description 3
- NQDOVVBHUZFXCA-UHFFFAOYSA-N phenyl 4-[[4-[3-fluoro-4-(2-hydroxyethylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NCCO)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 NQDOVVBHUZFXCA-UHFFFAOYSA-N 0.000 claims description 3
- UBYAQSREUNYPJB-UHFFFAOYSA-N phenyl 4-[[4-[3-fluoro-4-(phenoxycarbonylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound FC1=CC(C2CCC(CC2)=NOC2CCN(CC2)C(=O)OC=2C=CC=CC=2)=CC=C1NC(=O)OC1=CC=CC=C1 UBYAQSREUNYPJB-UHFFFAOYSA-N 0.000 claims description 3
- DFXURHBMOKVCLM-UHFFFAOYSA-N phenyl 4-[[4-[3-fluoro-4-(propylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NCCC)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 DFXURHBMOKVCLM-UHFFFAOYSA-N 0.000 claims description 3
- PMZUEWZXJXKNJM-UHFFFAOYSA-N phenyl 4-[[4-[4-(dimethylcarbamoylamino)-2,5-difluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)N(C)C)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 PMZUEWZXJXKNJM-UHFFFAOYSA-N 0.000 claims description 3
- LVSWESRERZYUFH-UHFFFAOYSA-N phenyl 4-[[4-[4-(dimethylcarbamoylamino)-3-fluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)N(C)C)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 LVSWESRERZYUFH-UHFFFAOYSA-N 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- KSSMEOPKSOQTMR-UHFFFAOYSA-N propan-2-yl 4-[[4-[3-fluoro-4-(methylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NC)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC(C)C)CC1 KSSMEOPKSOQTMR-UHFFFAOYSA-N 0.000 claims description 3
- ZXTPOMWPYNVEFG-UHFFFAOYSA-N propan-2-yl 4-[[4-[3-fluoro-4-(propan-2-ylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NC(C)C)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC(C)C)CC1 ZXTPOMWPYNVEFG-UHFFFAOYSA-N 0.000 claims description 3
- IPFSWHDXTXDEHB-UHFFFAOYSA-N propan-2-yl 4-[[4-[3-fluoro-4-(propylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NCCC)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC(C)C)CC1 IPFSWHDXTXDEHB-UHFFFAOYSA-N 0.000 claims description 3
- SWISQLWEEUTUSZ-UHFFFAOYSA-N propan-2-yl 4-[[4-[4-(carbamoylamino)-2,5-difluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C(=CC(NC(N)=O)=C(F)C=2)F)CC1 SWISQLWEEUTUSZ-UHFFFAOYSA-N 0.000 claims description 3
- VRNXHSIAXPVQGN-UHFFFAOYSA-N propan-2-yl 4-[[4-[4-(carbamoylamino)-2-fluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C(=CC(NC(N)=O)=CC=2)F)CC1 VRNXHSIAXPVQGN-UHFFFAOYSA-N 0.000 claims description 3
- HTCIVBYFVFNUGP-UHFFFAOYSA-N propan-2-yl 4-[[4-[4-(carbamoylamino)-3-fluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C=C(F)C(NC(N)=O)=CC=2)CC1 HTCIVBYFVFNUGP-UHFFFAOYSA-N 0.000 claims description 3
- KMZPHMFDLZUMGP-UHFFFAOYSA-N propan-2-yl 4-[[4-[4-[(3-hydroxyazetidine-1-carbonyl)amino]phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C=CC(NC(=O)N3CC(O)C3)=CC=2)CC1 KMZPHMFDLZUMGP-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- HTEGFWWHJZINMN-UHFFFAOYSA-N tert-butyl 4-[[4-(4-methylsulfonylphenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C=CC(=CC=2)S(C)(=O)=O)CC1 HTEGFWWHJZINMN-UHFFFAOYSA-N 0.000 claims description 3
- DBAPULSKKKVFDY-UHFFFAOYSA-N tert-butyl 4-[[4-[2,5-difluoro-4-(hydroxymethyl)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C(=CC(CO)=C(F)C=2)F)CC1 DBAPULSKKKVFDY-UHFFFAOYSA-N 0.000 claims description 3
- MILWNDGMQOTOGO-UHFFFAOYSA-N tert-butyl 4-[[4-[4-(diaminomethylidenecarbamoyl)-2,5-difluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C(=CC(=C(F)C=2)C(=O)N=C(N)N)F)CC1 MILWNDGMQOTOGO-UHFFFAOYSA-N 0.000 claims description 3
- JTVRGVXSYBMFPS-UHFFFAOYSA-N tert-butyl 4-[[4-[4-[(3-hydroxyazetidine-1-carbonyl)amino]phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C=CC(NC(=O)N3CC(O)C3)=CC=2)CC1 JTVRGVXSYBMFPS-UHFFFAOYSA-N 0.000 claims description 3
- SUDFZIUALLLSFZ-UHFFFAOYSA-N tert-butyl 4-[[[4-[4-(carbamoylamino)-2,5-difluorophenyl]cyclohexylidene]amino]oxymethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CON=C1CCC(C=2C(=CC(NC(N)=O)=C(F)C=2)F)CC1 SUDFZIUALLLSFZ-UHFFFAOYSA-N 0.000 claims description 3
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- XNTGJDWYEXAZFE-UHFFFAOYSA-N phenyl 4-[[4-(4-amino-2-fluorophenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound FC1=CC(N)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 XNTGJDWYEXAZFE-UHFFFAOYSA-N 0.000 description 1
- NEVISFIBMWBYFX-UHFFFAOYSA-N phenyl 4-[[4-(4-amino-3-fluorophenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(N)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC=2C=CC=CC=2)CC1 NEVISFIBMWBYFX-UHFFFAOYSA-N 0.000 description 1
- NGCXCJCBQDTSGJ-UHFFFAOYSA-N phenyl 4-[[4-[2,5-difluoro-4-[(3-hydroxyazetidine-1-carbonyl)amino]phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1C(O)CN1C(=O)NC1=CC(F)=C(C2CCC(CC2)=NOC2CCN(CC2)C(=O)OC=2C=CC=CC=2)C=C1F NGCXCJCBQDTSGJ-UHFFFAOYSA-N 0.000 description 1
- ZEXQENDQGFGCIX-UHFFFAOYSA-N phenyl 4-[[4-[3-fluoro-4-[(3-hydroxyazetidine-1-carbonyl)amino]phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1C(O)CN1C(=O)NC1=CC=C(C2CCC(CC2)=NOC2CCN(CC2)C(=O)OC=2C=CC=CC=2)C=C1F ZEXQENDQGFGCIX-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000010077 post-prandial secretion Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- UMFIHLUEKWHKDK-UHFFFAOYSA-N propan-2-yl 4-[[4-(4-aminophenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C=CC(N)=CC=2)CC1 UMFIHLUEKWHKDK-UHFFFAOYSA-N 0.000 description 1
- DZMDVPWJDFZMTJ-UHFFFAOYSA-N propan-2-yl 4-[[4-[2,5-difluoro-4-[(3-hydroxyazetidine-1-carbonyl)amino]phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C(=CC(NC(=O)N3CC(O)C3)=C(F)C=2)F)CC1 DZMDVPWJDFZMTJ-UHFFFAOYSA-N 0.000 description 1
- RMQWRZSCWWBAGU-UHFFFAOYSA-N propan-2-yl 4-[[4-[2-fluoro-4-(3-hydroxypropylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C(=CC(NC(=O)NCCCO)=CC=2)F)CC1 RMQWRZSCWWBAGU-UHFFFAOYSA-N 0.000 description 1
- PJSJHPUNBKYFEO-UHFFFAOYSA-N propan-2-yl 4-[[4-[3-fluoro-4-(2-fluoroethylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C=C(F)C(NC(=O)NCCF)=CC=2)CC1 PJSJHPUNBKYFEO-UHFFFAOYSA-N 0.000 description 1
- GVMUIRVWTOSQTB-UHFFFAOYSA-N propan-2-yl 4-[[4-[3-fluoro-4-(2-hydroxyethylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C=C(F)C(NC(=O)NCCO)=CC=2)CC1 GVMUIRVWTOSQTB-UHFFFAOYSA-N 0.000 description 1
- GWIJJQYUVJUBFQ-UHFFFAOYSA-N propan-2-yl 4-[[4-[3-fluoro-4-(2-hydroxypropylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)NCC(O)C)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC(C)C)CC1 GWIJJQYUVJUBFQ-UHFFFAOYSA-N 0.000 description 1
- ZBDIPDZSTWYZFC-UHFFFAOYSA-N propan-2-yl 4-[[4-[3-fluoro-4-(3-hydroxypropylcarbamoylamino)phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C=C(F)C(NC(=O)NCCCO)=CC=2)CC1 ZBDIPDZSTWYZFC-UHFFFAOYSA-N 0.000 description 1
- MKLYYJDFRSBEFG-UHFFFAOYSA-N propan-2-yl 4-[[4-[4-(2,3-dihydroxypropylcarbamoylamino)-2,5-difluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1ON=C1CCC(C=2C(=CC(NC(=O)NCC(O)CO)=C(F)C=2)F)CC1 MKLYYJDFRSBEFG-UHFFFAOYSA-N 0.000 description 1
- LAYRIBVBAXQMCT-UHFFFAOYSA-N propan-2-yl 4-[[4-[4-(2-ethoxyethylcarbamoylamino)-2-fluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound FC1=CC(NC(=O)NCCOCC)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC(C)C)CC1 LAYRIBVBAXQMCT-UHFFFAOYSA-N 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- PYNUOAIJIQGACY-UHFFFAOYSA-N propylazanium;chloride Chemical compound Cl.CCCN PYNUOAIJIQGACY-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 231100000438 skin toxicity Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- SEGZJJSZYOEABC-UHFFFAOYSA-N tert-butyl 3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(O)CC2CCC1N2C(=O)OC(C)(C)C SEGZJJSZYOEABC-UHFFFAOYSA-N 0.000 description 1
- APCBTRDHCDOPNY-UHFFFAOYSA-N tert-butyl 3-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)C1 APCBTRDHCDOPNY-UHFFFAOYSA-N 0.000 description 1
- WZWFTKHPPATADI-UHFFFAOYSA-N tert-butyl 4-(aminooxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CON)CC1 WZWFTKHPPATADI-UHFFFAOYSA-N 0.000 description 1
- RTCCYWMZJJIGNU-UHFFFAOYSA-N tert-butyl 4-[[4-(4-amino-2,5-difluorophenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C(=CC(N)=C(F)C=2)F)CC1 RTCCYWMZJJIGNU-UHFFFAOYSA-N 0.000 description 1
- HTTICXYLLZXHMB-UHFFFAOYSA-N tert-butyl 4-[[4-(4-amino-2-fluorophenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C(=CC(N)=CC=2)F)CC1 HTTICXYLLZXHMB-UHFFFAOYSA-N 0.000 description 1
- YELKJWPZXWASSN-UHFFFAOYSA-N tert-butyl 4-[[4-(4-aminophenyl)cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C=CC(N)=CC=2)CC1 YELKJWPZXWASSN-UHFFFAOYSA-N 0.000 description 1
- OSCJFGAAHXZOIT-UHFFFAOYSA-N tert-butyl 4-[[4-[2,5-difluoro-4-[(3-hydroxyazetidine-1-carbonyl)amino]phenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1ON=C1CCC(C=2C(=CC(NC(=O)N3CC(O)C3)=C(F)C=2)F)CC1 OSCJFGAAHXZOIT-UHFFFAOYSA-N 0.000 description 1
- RTANEBJDMRMBCC-UHFFFAOYSA-N tert-butyl 4-[[4-[4-(dimethylcarbamoylamino)-3-fluorophenyl]cyclohexylidene]amino]oxypiperidine-1-carboxylate Chemical compound C1=C(F)C(NC(=O)N(C)C)=CC=C1C(CC1)CCC1=NOC1CCN(C(=O)OC(C)(C)C)CC1 RTANEBJDMRMBCC-UHFFFAOYSA-N 0.000 description 1
- FARKJZOWANIQNP-UHFFFAOYSA-N tert-butyl 4-[[[4-(4-amino-2,5-difluorophenyl)cyclohexylidene]amino]oxymethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CON=C1CCC(C=2C(=CC(N)=C(F)C=2)F)CC1 FARKJZOWANIQNP-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- General Health & Medical Sciences (AREA)
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KR101456286B1 true KR101456286B1 (ko) | 2014-11-03 |
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KR (1) | KR101456286B1 (es) |
AR (1) | AR085249A1 (es) |
TW (1) | TW201309639A (es) |
UY (1) | UY33912A (es) |
WO (1) | WO2012111995A1 (es) |
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AU2013290100A1 (en) | 2012-07-11 | 2015-01-29 | Elcelyx Therapeutics, Inc. | Compositions comprising statins, biguanides and further agents for reducing cardiometabolic risk |
BR112017002053A2 (pt) | 2014-08-01 | 2018-01-30 | Nuevolution A/S | composto de acordo com a fórmula (i), composição farmacêutica, e usos de um composto |
CN106632302A (zh) * | 2016-12-15 | 2017-05-10 | 苏州汉德创宏生化科技有限公司 | 1‑(噻唑‑2‑基)哌啶‑4‑醇的合成方法 |
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US20070173495A1 (en) | 2006-01-20 | 2007-07-26 | Anandan Palani | Heterocycles as nicotinic acid receptor agonists for the treatment of dyslipidemia |
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CN104592231A (zh) * | 2008-06-10 | 2015-05-06 | Abbvie公司 | 新的三环化合物 |
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US20070173495A1 (en) | 2006-01-20 | 2007-07-26 | Anandan Palani | Heterocycles as nicotinic acid receptor agonists for the treatment of dyslipidemia |
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AR085249A1 (es) | 2013-09-18 |
TW201309639A (zh) | 2013-03-01 |
UY33912A (es) | 2012-09-28 |
KR20120094859A (ko) | 2012-08-27 |
WO2012111995A1 (en) | 2012-08-23 |
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