TW201309639A - 作為gpr119促效劑之肟衍生物 - Google Patents
作為gpr119促效劑之肟衍生物 Download PDFInfo
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- TW201309639A TW201309639A TW101104637A TW101104637A TW201309639A TW 201309639 A TW201309639 A TW 201309639A TW 101104637 A TW101104637 A TW 101104637A TW 101104637 A TW101104637 A TW 101104637A TW 201309639 A TW201309639 A TW 201309639A
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- Taiwan
- Prior art keywords
- phenyl
- piperidin
- difluoro
- cyclohexyl
- yloxyimino
- Prior art date
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- 229940100607 GPR119 agonist Drugs 0.000 title abstract description 12
- 150000002923 oximes Chemical class 0.000 title abstract 3
- 238000000034 method Methods 0.000 claims abstract description 39
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 11
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 10
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 10
- 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 6
- -1 respectively Chemical group 0.000 claims description 192
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 74
- 239000000203 mixture Substances 0.000 claims description 68
- 239000004202 carbamide Substances 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 45
- 229910052760 oxygen Inorganic materials 0.000 claims description 40
- 229910052717 sulfur Inorganic materials 0.000 claims description 40
- SNBYDHCSBZIOQL-UHFFFAOYSA-N 3-hydroxyazetidine-1-carboxylic acid Chemical compound OC1CN(C(O)=O)C1 SNBYDHCSBZIOQL-UHFFFAOYSA-N 0.000 claims description 39
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 38
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 38
- 239000001301 oxygen Substances 0.000 claims description 38
- 239000011593 sulfur Substances 0.000 claims description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- 150000001412 amines Chemical class 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- 229920006395 saturated elastomer Polymers 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000005842 heteroatom Chemical group 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000006413 ring segment Chemical group 0.000 claims description 19
- 229910052799 carbon Chemical group 0.000 claims description 17
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 150000002148 esters Chemical class 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 10
- RZVHIXYEVGDQDX-UHFFFAOYSA-N 9,10-anthraquinone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C(=O)C2=C1 RZVHIXYEVGDQDX-UHFFFAOYSA-N 0.000 claims description 9
- 208000002249 Diabetes Complications Diseases 0.000 claims description 9
- 206010012655 Diabetic complications Diseases 0.000 claims description 9
- 239000000556 agonist Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 150000001454 anthracenes Chemical class 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 239000011574 phosphorus Substances 0.000 claims description 4
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical group [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 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
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- DXVUSRWZURLXAA-UHFFFAOYSA-N 1-[2,3-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(2-hydroxypropyl)urea Chemical compound FC1=C(F)C(NC(=O)NCC(O)C)=CC=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 DXVUSRWZURLXAA-UHFFFAOYSA-N 0.000 claims description 3
- GJOUKGNFLYTUCO-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(1,3-dihydroxypropan-2-yl)urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NC(CO)CO)=C(F)C=2)F)CC1 GJOUKGNFLYTUCO-UHFFFAOYSA-N 0.000 claims description 3
- IWJYYXHEJCRIOV-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(1-hydroxy-2-methylpropan-2-yl)urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NC(C)(C)CO)=C(F)C=2)F)CC1 IWJYYXHEJCRIOV-UHFFFAOYSA-N 0.000 claims description 3
- ZDSDYIGFHGHITM-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(1-hydroxypropan-2-yl)urea Chemical compound C1=C(F)C(NC(=O)NC(CO)C)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 ZDSDYIGFHGHITM-UHFFFAOYSA-N 0.000 claims description 3
- YZFIXBRRNGZFBT-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(2-ethoxyethyl)urea Chemical compound C1=C(F)C(NC(=O)NCCOCC)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 YZFIXBRRNGZFBT-UHFFFAOYSA-N 0.000 claims description 3
- SGOXCQVYDIOXNU-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NCCO)=C(F)C=2)F)CC1 SGOXCQVYDIOXNU-UHFFFAOYSA-N 0.000 claims description 3
- KMKNNAVZRWBOJO-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(3-hydroxypropyl)urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NCCCO)=C(F)C=2)F)CC1 KMKNNAVZRWBOJO-UHFFFAOYSA-N 0.000 claims description 3
- ZDSDYIGFHGHITM-QNSVNVJESA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-[(2r)-1-hydroxypropan-2-yl]urea Chemical compound C1=C(F)C(NC(=O)N[C@@H](CO)C)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 ZDSDYIGFHGHITM-QNSVNVJESA-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
- RUGLYJSKLDZJRM-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(2-hydroxypropyl)urea Chemical compound C1=C(F)C(NC(=O)NCC(O)C)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=C(C=CN=2)C(F)(F)F)CC1 RUGLYJSKLDZJRM-UHFFFAOYSA-N 0.000 claims description 3
- UCNAFTCEUIMXJT-UHFFFAOYSA-N 1-[2,6-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(3-hydroxypropyl)urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C=C(F)C(NC(=O)NCCCO)=C(F)C=2)CC1 UCNAFTCEUIMXJT-UHFFFAOYSA-N 0.000 claims description 3
- BCHOYJSJEUIUMQ-UHFFFAOYSA-N 1-[2-fluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(3-hydroxypropyl)urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C=C(F)C(NC(=O)NCCCO)=CC=2)CC1 BCHOYJSJEUIUMQ-UHFFFAOYSA-N 0.000 claims description 3
- MNZGAGLESFBEDZ-UHFFFAOYSA-N 1-[4-[4-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2,5-difluorophenyl]-3-(2-hydroxypropyl)urea Chemical compound N1=CC(CC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NCC(C)O)=C(F)C=2)F)CC1 MNZGAGLESFBEDZ-UHFFFAOYSA-N 0.000 claims description 3
- QKQXILUBUMDRBH-UHFFFAOYSA-N 1-[4-[4-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2,5-difluorophenyl]-3-propan-2-ylurea Chemical compound N1=CC(CC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NC(C)C)=C(F)C=2)F)CC1 QKQXILUBUMDRBH-UHFFFAOYSA-N 0.000 claims description 3
- SYGLKYPHLONKIA-UHFFFAOYSA-N 1-[4-[4-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2-fluorophenyl]-3-(2-hydroxypropyl)urea Chemical compound N1=CC(CC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C=C(F)C(NC(=O)NCC(C)O)=CC=2)CC1 SYGLKYPHLONKIA-UHFFFAOYSA-N 0.000 claims description 3
- XSCSBQWSVKSPPZ-UHFFFAOYSA-N 3-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-1,1-dimethylurea Chemical compound C1=C(F)C(NC(=O)N(C)C)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 XSCSBQWSVKSPPZ-UHFFFAOYSA-N 0.000 claims description 3
- UMKKPVAGAASAMR-UHFFFAOYSA-N 3-[2,6-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-1,1-dimethylurea Chemical compound C1=C(F)C(NC(=O)N(C)C)=C(F)C=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 UMKKPVAGAASAMR-UHFFFAOYSA-N 0.000 claims description 3
- OFBBXTGRCVMEFF-UHFFFAOYSA-N 3-[4-[4-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-2,5-difluorophenyl]-1,1-dimethylurea Chemical compound N1=CC(CC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)N(C)C)=C(F)C=2)F)CC1 OFBBXTGRCVMEFF-UHFFFAOYSA-N 0.000 claims description 3
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
- CPZJSABHFFQCIE-UHFFFAOYSA-N [2,5-difluoro-4-[4-[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]urea Chemical compound C1=C(F)C(NC(=O)N)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(F)=CN=2)CC1 CPZJSABHFFQCIE-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
- HVRDGXYTIYLYGI-UHFFFAOYSA-N [4-[4-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-3-fluorophenyl]urea Chemical compound FC1=CC(NC(=O)N)=CC=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(Cl)=CN=2)CC1 HVRDGXYTIYLYGI-UHFFFAOYSA-N 0.000 claims description 3
- UKSHHEYGGHGXRD-UHFFFAOYSA-N [4-[4-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]-3-fluorophenyl]urea Chemical compound N1=CC(CC)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(N)=O)=CC=2)F)CC1 UKSHHEYGGHGXRD-UHFFFAOYSA-N 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- JJYFPENIPGWFMD-UHFFFAOYSA-N n-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]methanesulfonamide Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NS(C)(=O)=O)=C(F)C=2)F)CC1 JJYFPENIPGWFMD-UHFFFAOYSA-N 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
- 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
- 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 3
- 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 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 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 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 2
- JAJOTVNKLRFLNH-UHFFFAOYSA-N 1-[2,3-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(3-hydroxypropyl)urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=C(F)C(NC(=O)NCCCO)=CC=2)F)CC1 JAJOTVNKLRFLNH-UHFFFAOYSA-N 0.000 claims description 2
- YDCUAAPLZMCHQB-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-(2-hydroxypropyl)urea Chemical compound C1=C(F)C(NC(=O)NCC(O)C)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(F)=CN=2)CC1 YDCUAAPLZMCHQB-UHFFFAOYSA-N 0.000 claims description 2
- QRVSSOFVDQJTRU-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-[2-(2-hydroxyethoxy)ethyl]urea Chemical compound N1=CC(C)=CN=C1N1CCC(ON=C2CCC(CC2)C=2C(=CC(NC(=O)NCCOCCO)=C(F)C=2)F)CC1 QRVSSOFVDQJTRU-UHFFFAOYSA-N 0.000 claims description 2
- YULSVKDPRZISPQ-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-methylurea Chemical compound C1=C(F)C(NC(=O)NC)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 YULSVKDPRZISPQ-UHFFFAOYSA-N 0.000 claims description 2
- WKMZAGWWBFHPTG-UHFFFAOYSA-N 1-[2,5-difluoro-4-[4-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]oxyiminocyclohexyl]phenyl]-3-propylurea Chemical compound C1=C(F)C(NC(=O)NCCC)=CC(F)=C1C(CC1)CCC1=NOC1CCN(C=2N=CC(C)=CN=2)CC1 WKMZAGWWBFHPTG-UHFFFAOYSA-N 0.000 claims description 2
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- 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
- 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
- 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 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
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 1
- DBPGMIBBYIGDII-UHFFFAOYSA-N thiophen-2-ylmethylurea Chemical compound NC(=O)NCC1=CC=CS1 DBPGMIBBYIGDII-UHFFFAOYSA-N 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 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
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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KR20110014298 | 2011-02-17 |
Publications (1)
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TW201309639A true TW201309639A (zh) | 2013-03-01 |
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TW101104637A TW201309639A (zh) | 2011-02-17 | 2012-02-14 | 作為gpr119促效劑之肟衍生物 |
Country Status (5)
Country | Link |
---|---|
KR (1) | KR101456286B1 (ko) |
AR (1) | AR085249A1 (ko) |
TW (1) | TW201309639A (ko) |
UY (1) | UY33912A (ko) |
WO (1) | WO2012111995A1 (ko) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
Families Citing this family (2)
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CN104780915A (zh) | 2012-07-11 | 2015-07-15 | 埃尔舍利克斯治疗公司 | 包含他汀、双胍和用于减小心脏代谢风险的其它药剂的组合物 |
MY187540A (en) | 2014-08-01 | 2021-09-28 | Nuevolution As | Compounds active towards bromodomains |
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GB0302548D0 (en) * | 2003-02-04 | 2003-03-12 | Syngenta Participations Ag | Avermectins substituted in the 4"- and 4' -positions having pesticidal properties |
PE20070854A1 (es) | 2006-01-20 | 2007-09-10 | Schering Corp | Compuestos heterociclos como agonistas del receptor de acido nicotinico |
TW201612182A (en) * | 2008-06-10 | 2016-04-01 | Abbvie Inc | Novel tricyclic compounds |
-
2012
- 2012-02-14 TW TW101104637A patent/TW201309639A/zh unknown
- 2012-02-15 UY UY33912A patent/UY33912A/es not_active Application Discontinuation
- 2012-02-16 AR ARP120100513 patent/AR085249A1/es not_active Application Discontinuation
- 2012-02-16 WO PCT/KR2012/001185 patent/WO2012111995A1/en active Application Filing
- 2012-02-16 KR KR20120015736A patent/KR101456286B1/ko active IP Right Grant
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
Also Published As
Publication number | Publication date |
---|---|
KR101456286B1 (ko) | 2014-11-03 |
WO2012111995A1 (en) | 2012-08-23 |
UY33912A (es) | 2012-09-28 |
KR20120094859A (ko) | 2012-08-27 |
AR085249A1 (es) | 2013-09-18 |
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