JP5198439B2 - 新規なｍｃｈ受容体アンタゴニスト - Google Patents

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Publication number

JP5198439B2

JP5198439B2 JP2009514544A JP2009514544A JP5198439B2 JP 5198439 B2 JP5198439 B2 JP 5198439B2 JP 2009514544 A JP2009514544 A JP 2009514544A JP 2009514544 A JP2009514544 A JP 2009514544A JP 5198439 B2 JP5198439 B2 JP 5198439B2

Authority

JP

Japan

Prior art keywords

phenyl

methoxy

chloro

thieno

mmol

Prior art date

2006-06-08

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

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• 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 title 1
• 102000006953 melanin-concentrating hormone receptor activity proteins Human genes 0.000 title 1
• 239000002464 receptor antagonist Substances 0.000 title 1
• 229940044551 receptor antagonist Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 237
• 239000000203 mixture Substances 0.000 claims description 149
• -1 C 1 -C 4 alkoxy Chemical group 0.000 claims description 136
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 82
• 229910052739 hydrogen Inorganic materials 0.000 claims description 72
• 239000001257 hydrogen Substances 0.000 claims description 71
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
• 229910052757 nitrogen Inorganic materials 0.000 claims description 44
• 125000001153 fluoro group Chemical group F* 0.000 claims description 40
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
• 150000002431 hydrogen Chemical class 0.000 claims description 34
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 29
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 26
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 18
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 16
• 208000008589 Obesity Diseases 0.000 claims description 15
• 125000005843 halogen group Chemical group 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
• 235000020824 obesity Nutrition 0.000 claims description 15
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
• 125000004043 oxo group Chemical group O=* 0.000 claims description 13
• 125000000217 alkyl group Chemical group 0.000 claims description 12
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000000623 heterocyclic group Chemical group 0.000 claims description 11
• 125000004193 piperazinyl group Chemical group 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 10
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
• 125000002393 azetidinyl group Chemical group 0.000 claims description 9
• 125000002883 imidazolyl group Chemical group 0.000 claims description 9
• 125000003386 piperidinyl group Chemical group 0.000 claims description 9
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
• CZRGFNLUHBYQMI-DENIHFKCSA-N 2-(4-chlorophenyl)-6-[4-[(3r,4r)-4-hydroxy-1-methylpyrrolidin-3-yl]oxy-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CN(C)C[C@H]1O CZRGFNLUHBYQMI-DENIHFKCSA-N 0.000 claims description 5
• 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
• DANNXIYTSPUKNZ-HXUWFJFHSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-piperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCCNC1 DANNXIYTSPUKNZ-HXUWFJFHSA-N 0.000 claims description 3
• NRPHIGGEADJUSS-LJQANCHMSA-N 2-(4-chlorophenyl)-6-[4-[(3r)-3-hydroxypyrrolidin-1-yl]-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CC[C@@H](O)C1 NRPHIGGEADJUSS-LJQANCHMSA-N 0.000 claims description 3
• LCIHRXSOFXUFGE-UHFFFAOYSA-N n-[4-[2-(4-chlorophenyl)-7-oxo-4,5-dihydrothieno[2,3-c]pyridin-6-yl]-2-methoxyphenyl]-2-pyrrolidin-1-ylacetamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=CC=C1NC(=O)CN1CCCC1 LCIHRXSOFXUFGE-UHFFFAOYSA-N 0.000 claims description 3
• GVZOAZDOGPCEIG-UHFFFAOYSA-N n-[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]-2-methoxyphenyl]-2-pyrrolidin-1-ylacetamide Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1NC(=O)CN1CCCC1 GVZOAZDOGPCEIG-UHFFFAOYSA-N 0.000 claims description 3
• MRPMZDZHOMJYJI-FQEVSTJZSA-N (5s)-5-[[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]-2-methoxyphenoxy]methyl]-4-methylmorpholin-3-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC[C@@H]1COCC(=O)N1C MRPMZDZHOMJYJI-FQEVSTJZSA-N 0.000 claims description 2
• RDXDDIURVFTSGG-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-fluoro-4-(1-methylazetidin-3-yl)oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CC1OC1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1F RDXDDIURVFTSGG-UHFFFAOYSA-N 0.000 claims description 2
• PSULEVZMDDCOLR-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(1-methylazetidin-3-yl)oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC1CN(C)C1 PSULEVZMDDCOLR-UHFFFAOYSA-N 0.000 claims description 2
• RFSADOOPEMNMGH-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCCN1CCCC1 RFSADOOPEMNMGH-UHFFFAOYSA-N 0.000 claims description 2
• BYWIKAYNGOZCQR-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3-methylimidazol-4-yl)methoxy]phenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OCC1=CN=CN1C BYWIKAYNGOZCQR-UHFFFAOYSA-N 0.000 claims description 2
• AGDPDWYQZACUSZ-OAQYLSRUSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-1-methylpiperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCCN(C)C1 AGDPDWYQZACUSZ-OAQYLSRUSA-N 0.000 claims description 2
• NEQYTWHZDNXZAF-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[4-(1-methylpyrrolidine-3-carbonyl)phenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CCC1C(=O)C1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 NEQYTWHZDNXZAF-UHFFFAOYSA-N 0.000 claims description 2
• LLCLILFROPNCQU-WIYYLYMNSA-N 2-(4-chlorophenyl)-6-[4-[(3R,4R)-4-hydroxypyrrolidin-3-yl]oxy-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound ClC1=CC=C(C=C1)C1=CC2=C(C(N(C=C2)C2=CC(=C(C=C2)O[C@@H]2CNC[C@H]2O)OC)=O)S1 LLCLILFROPNCQU-WIYYLYMNSA-N 0.000 claims description 2
• NGSRPWCECXHPGY-NRFANRHFSA-N 2-(4-chlorophenyl)-6-[4-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CC[C@H](N(C)C)C1 NGSRPWCECXHPGY-NRFANRHFSA-N 0.000 claims description 2
• DYHPKCICOMNEHT-UHFFFAOYSA-N 2-(4-methoxyphenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(OC)C(OCCN3CCCC3)=CC=1)CC2 DYHPKCICOMNEHT-UHFFFAOYSA-N 0.000 claims description 2
• NAWFRFAJOADEHA-UHFFFAOYSA-N 6-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]-2-(4-methoxyphenyl)-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound C1=CC(OC)=CC=C1C(S1)=CC2=C1C(=O)N(C=1C=C(OC)C(OCCN3CCOCC3)=CC=1)CC2 NAWFRFAJOADEHA-UHFFFAOYSA-N 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
• SKTCYPNSGXYYLI-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C(=CC(Cl)=CC=2)Cl)=O)=CC=C1OCCN1CCCC1 SKTCYPNSGXYYLI-UHFFFAOYSA-N 0.000 claims 1
• ACVJLNZNERVECQ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(3-fluoro-4-piperazin-1-ylphenyl)thieno[2,3-c]pyridin-7-one Chemical compound FC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CCNCC1 ACVJLNZNERVECQ-UHFFFAOYSA-N 0.000 claims 1
• ZMAHJOALZXKRCN-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-(3-methoxy-4-piperidin-4-yloxyphenyl)thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC1CCNCC1 ZMAHJOALZXKRCN-UHFFFAOYSA-N 0.000 claims 1
• LIUNOICECXIDLZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-(1-methylazetidin-3-yl)oxyphenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(Cl)=CC=2)=O)=CC=C1OC1CN(C)C1 LIUNOICECXIDLZ-UHFFFAOYSA-N 0.000 claims 1
• KUZMWADQWJCNMH-LJQANCHMSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3r)-pyrrolidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@@H]1CCNC1 KUZMWADQWJCNMH-LJQANCHMSA-N 0.000 claims 1
• AGDPDWYQZACUSZ-NRFANRHFSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3s)-1-methylpiperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@H]1CCCN(C)C1 AGDPDWYQZACUSZ-NRFANRHFSA-N 0.000 claims 1
• QXSOSEXLDZKZSG-IBGZPJMESA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3s)-3-(methylamino)pyrrolidin-1-yl]phenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1[C@@H](NC)CCN1C1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1OC QXSOSEXLDZKZSG-IBGZPJMESA-N 0.000 claims 1
• DANNXIYTSPUKNZ-FQEVSTJZSA-N 2-(4-chlorophenyl)-6-[3-methoxy-4-[(3s)-piperidin-3-yl]oxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1O[C@H]1CCCNC1 DANNXIYTSPUKNZ-FQEVSTJZSA-N 0.000 claims 1
• ARTILZSBVXIGSZ-UHFFFAOYSA-N 2-(4-chlorophenyl)-6-[4-(1-methylazetidine-3-carbonyl)phenyl]thieno[2,3-c]pyridin-7-one Chemical compound C1N(C)CC1C(=O)C1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 ARTILZSBVXIGSZ-UHFFFAOYSA-N 0.000 claims 1
• NGSRPWCECXHPGY-OAQYLSRUSA-N 2-(4-chlorophenyl)-6-[4-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-3-methoxyphenyl]thieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)=CC=C1N1CC[C@@H](N(C)C)C1 NGSRPWCECXHPGY-OAQYLSRUSA-N 0.000 claims 1
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
• XAAKSDZMQPTDBS-UHFFFAOYSA-N 6-[3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenyl]-2-[4-(trifluoromethyl)phenyl]-4,5-dihydrothieno[2,3-c]pyridin-7-one Chemical compound COC1=CC(N2C(C=3SC(=CC=3CC2)C=2C=CC(=CC=2)C(F)(F)F)=O)=CC=C1OCCN1CCCC1 XAAKSDZMQPTDBS-UHFFFAOYSA-N 0.000 claims 1
• YMWUTSHORUIBBG-UHFFFAOYSA-N n-[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]phenyl]-1-methylpyrrolidine-3-carboxamide Chemical compound C1N(C)CCC1C(=O)NC1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1 YMWUTSHORUIBBG-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 229
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
• 238000002360 preparation method Methods 0.000 description 130
• 239000000243 solution Substances 0.000 description 125
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 120
• 235000019439 ethyl acetate Nutrition 0.000 description 103
• 238000006243 chemical reaction Methods 0.000 description 83
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 78
• 239000011734 sodium Substances 0.000 description 77
• 238000000034 method Methods 0.000 description 67
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 57
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• 239000007787 solid Substances 0.000 description 50
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
• 239000012043 crude product Substances 0.000 description 48
• 239000012044 organic layer Substances 0.000 description 47
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 45
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 45
• 239000000047 product Substances 0.000 description 40
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
• 239000012267 brine Substances 0.000 description 29
• 238000004587 chromatography analysis Methods 0.000 description 29
• 239000002904 solvent Substances 0.000 description 29
• 238000003756 stirring Methods 0.000 description 26
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 24
• 238000010898 silica gel chromatography Methods 0.000 description 24
• 229920006395 saturated elastomer Polymers 0.000 description 22
• 239000002002 slurry Substances 0.000 description 22
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
• 101800002739 Melanin-concentrating hormone Proteins 0.000 description 19
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
• ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 19
• 102000047659 melanin-concentrating hormone Human genes 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 19
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 18
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
• 238000003818 flash chromatography Methods 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 16
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• 150000001412 amines Chemical class 0.000 description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
• 239000000284 extract Substances 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 15
• 201000010099 disease Diseases 0.000 description 15
• 239000012458 free base Substances 0.000 description 15
• 239000000543 intermediate Substances 0.000 description 15
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• FUVDTGRXBMKYIC-UHFFFAOYSA-N tert-butyl 3-[4-[2-(4-chlorophenyl)-7-oxothieno[2,3-c]pyridin-6-yl]-2-fluorophenoxy]azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1OC1=CC=C(N2C(C=3SC(=CC=3C=C2)C=2C=CC(Cl)=CC=2)=O)C=C1F FUVDTGRXBMKYIC-UHFFFAOYSA-N 0.000 description 1
• OXFWAVQYUXISNK-UHFFFAOYSA-N tert-butyl 3-[4-[[5-(4-chlorophenyl)-3-(2-trimethylsilylethynyl)thiophene-2-carbonyl]amino]-2-methoxyphenoxy]azetidine-1-carboxylate Chemical compound C=1C=C(OC2CN(C2)C(=O)OC(C)(C)C)C(OC)=CC=1NC(=O)C(=C(C=1)C#C[Si](C)(C)C)SC=1C1=CC=C(Cl)C=C1 OXFWAVQYUXISNK-UHFFFAOYSA-N 0.000 description 1
• NHDGOVOBEZPXMY-UHFFFAOYSA-N tert-butyl 3-carbamoylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(N)=O)C1 NHDGOVOBEZPXMY-UHFFFAOYSA-N 0.000 description 1
• XRRXRQJQQKMFBC-UHFFFAOYSA-N tert-butyl 3-hydroxyazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(O)C1 XRRXRQJQQKMFBC-UHFFFAOYSA-N 0.000 description 1
• NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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• QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 238000012795 verification Methods 0.000 description 1
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