JP2004536104A - Mch選択的アンタゴニストとしての置換されたアニリン−ピペリジン誘導体 - Google Patents
Mch選択的アンタゴニストとしての置換されたアニリン−ピペリジン誘導体 Download PDFInfo
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- JP2004536104A JP2004536104A JP2003510038A JP2003510038A JP2004536104A JP 2004536104 A JP2004536104 A JP 2004536104A JP 2003510038 A JP2003510038 A JP 2003510038A JP 2003510038 A JP2003510038 A JP 2003510038A JP 2004536104 A JP2004536104 A JP 2004536104A
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- Prior art keywords
- compound
- phenyl
- branched
- linear
- alkyl
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- 239000005557 antagonist Substances 0.000 title claims abstract description 23
- UKXZWEDNEGGXQX-UHFFFAOYSA-N aniline;piperidine Chemical class C1CCNCC1.NC1=CC=CC=C1 UKXZWEDNEGGXQX-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 334
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 239000003937 drug carrier Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 311
- 230000002829 reductive effect Effects 0.000 claims description 127
- 239000000203 mixture Substances 0.000 claims description 123
- -1 cyclopentanyl Chemical group 0.000 claims description 121
- 125000003118 aryl group Chemical group 0.000 claims description 93
- 125000001072 heteroaryl group Chemical group 0.000 claims description 75
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 75
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 69
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 66
- 208000019901 Anxiety disease Diseases 0.000 claims description 49
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 48
- 230000036506 anxiety Effects 0.000 claims description 42
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 201000010099 disease Diseases 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 31
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 29
- 239000007787 solid Substances 0.000 claims description 29
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 26
- 208000008589 Obesity Diseases 0.000 claims description 25
- 235000020824 obesity Nutrition 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
- 208000000921 Urge Urinary Incontinence Diseases 0.000 claims description 19
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 18
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
- 208000020629 overactive bladder Diseases 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 206010046494 urge incontinence Diseases 0.000 claims description 17
- 230000004580 weight loss Effects 0.000 claims description 17
- 208000024891 symptom Diseases 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 239000000829 suppository Substances 0.000 claims description 4
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 claims description 3
- 101150104680 MCH1 gene Proteins 0.000 claims 4
- 101100382379 Rattus norvegicus Cap1 gene Proteins 0.000 claims 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 331
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 277
- 239000000047 product Substances 0.000 description 188
- 238000005160 1H NMR spectroscopy Methods 0.000 description 178
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 175
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 166
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 143
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 138
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 118
- 239000000243 solution Substances 0.000 description 106
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 101
- 239000011541 reaction mixture Substances 0.000 description 98
- 238000006243 chemical reaction Methods 0.000 description 83
- JETGTGYZDUEQTF-UHFFFAOYSA-N 2-methyl-n-(3-piperidin-4-ylphenyl)propanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCNCC2)=C1 JETGTGYZDUEQTF-UHFFFAOYSA-N 0.000 description 75
- 238000012746 preparative thin layer chromatography Methods 0.000 description 75
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 74
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 68
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 68
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 64
- 101800002739 Melanin-concentrating hormone Proteins 0.000 description 64
- 239000003921 oil Substances 0.000 description 60
- 235000019198 oils Nutrition 0.000 description 60
- 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 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- 239000000377 silicon dioxide Substances 0.000 description 56
- 125000001309 chloro group Chemical group Cl* 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 51
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 47
- 125000001246 bromo group Chemical group Br* 0.000 description 46
- 238000004587 chromatography analysis Methods 0.000 description 46
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 45
- 238000003786 synthesis reaction Methods 0.000 description 42
- 230000015572 biosynthetic process Effects 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- 239000012267 brine Substances 0.000 description 39
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
- 239000010410 layer Substances 0.000 description 38
- 239000000284 extract Substances 0.000 description 37
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 35
- 208000035475 disorder Diseases 0.000 description 35
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 35
- 239000012043 crude product Substances 0.000 description 34
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 34
- 235000019341 magnesium sulphate Nutrition 0.000 description 34
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 31
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 229920005989 resin Polymers 0.000 description 28
- 239000011347 resin Substances 0.000 description 28
- 239000000725 suspension Substances 0.000 description 28
- 101150041968 CDC13 gene Proteins 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 24
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- 108020003175 receptors Proteins 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- LNVITZUWWUEILI-HSZRJFAPSA-N n-[3-[1-[(3r)-3-hydroxy-3-phenylpropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CC[C@@H](O)C=3C=CC=CC=3)CC2)=C1 LNVITZUWWUEILI-HSZRJFAPSA-N 0.000 description 19
- 102000005962 receptors Human genes 0.000 description 19
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 18
- RTJVVRVQRGIVAC-UHFFFAOYSA-N n-[3-[1-[3-(4-fluorophenyl)-3-hydroxypropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CCC(O)C=3C=CC(F)=CC=3)CC2)=C1 RTJVVRVQRGIVAC-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- 125000000304 alkynyl group Chemical group 0.000 description 17
- 208000019906 panic disease Diseases 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 238000004809 thin layer chromatography Methods 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 235000009518 sodium iodide Nutrition 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- PDAZPKYSSKIZGN-UHFFFAOYSA-N n-[3-[1-[3-(4-bromophenyl)-3-hydroxypropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CCC(O)C=3C=CC(Br)=CC=3)CC2)=C1 PDAZPKYSSKIZGN-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 208000016261 weight loss Diseases 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 239000007832 Na2SO4 Substances 0.000 description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- 239000012300 argon atmosphere Substances 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
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- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 235000008504 concentrate Nutrition 0.000 description 12
- 239000012141 concentrate Substances 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 12
- 208000028173 post-traumatic stress disease Diseases 0.000 description 12
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 12
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 11
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 11
- 230000003197 catalytic effect Effects 0.000 description 11
- OQGZJVSTGYMLIO-UHFFFAOYSA-N n-[3-[1-[3-(4-chlorophenyl)-3-hydroxypropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CCC(O)C=3C=CC(Cl)=CC=3)CC2)=C1 OQGZJVSTGYMLIO-UHFFFAOYSA-N 0.000 description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 10
- BLCXBCYVCDPFEU-UHFFFAOYSA-N 4-(4-chlorophenoxy)benzaldehyde Chemical compound C1=CC(Cl)=CC=C1OC1=CC=C(C=O)C=C1 BLCXBCYVCDPFEU-UHFFFAOYSA-N 0.000 description 10
- 206010006550 Bulimia nervosa Diseases 0.000 description 10
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- 125000000392 cycloalkenyl group Chemical group 0.000 description 10
- LNVITZUWWUEILI-QHCPKHFHSA-N n-[3-[1-[(3s)-3-hydroxy-3-phenylpropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CC[C@H](O)C=3C=CC=CC=3)CC2)=C1 LNVITZUWWUEILI-QHCPKHFHSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 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 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
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- 239000007789 gas Substances 0.000 description 9
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- 208000024714 major depressive disease Diseases 0.000 description 9
- AIMHBZDQVCJWPQ-UHFFFAOYSA-N n-[3-[1-[3-(1,2-diphenylindol-3-yl)propyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CCCC=3C4=CC=CC=C4N(C=4C=CC=CC=4)C=3C=3C=CC=CC=3)CC2)=C1 AIMHBZDQVCJWPQ-UHFFFAOYSA-N 0.000 description 9
- IHAYANQJTSFMEJ-UHFFFAOYSA-N n-[3-[1-[3-(2,3-dihydro-1h-inden-5-yl)-3-hydroxypropyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound CC(C)C(=O)NC1=CC=CC(C2CCN(CCC(O)C=3C=C4CCCC4=CC=3)CC2)=C1 IHAYANQJTSFMEJ-UHFFFAOYSA-N 0.000 description 9
- UGCLGCNPIVUWKH-UHFFFAOYSA-N n-[3-[1-[3-hydroxy-3-(4-methoxyphenyl)propyl]piperidin-4-yl]phenyl]-2-methylpropanamide Chemical compound C1=CC(OC)=CC=C1C(O)CCN1CCC(C=2C=C(NC(=O)C(C)C)C=CC=2)CC1 UGCLGCNPIVUWKH-UHFFFAOYSA-N 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 208000014001 urinary system disease Diseases 0.000 description 9
- PGMDHKOCPXCMBL-UHFFFAOYSA-N 2-(3-methylbutoxy)naphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(OCCC(C)C)=CC=C21 PGMDHKOCPXCMBL-UHFFFAOYSA-N 0.000 description 8
- SMFFZOQLHYIRDA-UHFFFAOYSA-N 3,4-dimethoxyphenol Chemical compound COC1=CC=C(O)C=C1OC SMFFZOQLHYIRDA-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 8
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 8
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical compound CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 description 7
- 208000020401 Depressive disease Diseases 0.000 description 7
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 125000004103 aminoalkyl group Chemical group 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 210000003016 hypothalamus Anatomy 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- INZSWUJHGMIAJM-UHFFFAOYSA-N tert-butyl 4-(3-aminophenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=CC(N)=C1 INZSWUJHGMIAJM-UHFFFAOYSA-N 0.000 description 7
- JNIAZBUZSFBRLD-UHFFFAOYSA-N 2-methyl-n-(4-piperidin-4-ylphenyl)propanamide Chemical compound C1=CC(NC(=O)C(C)C)=CC=C1C1CCNCC1 JNIAZBUZSFBRLD-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Applications Claiming Priority (3)
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| US89979401A | 2001-07-05 | 2001-07-05 | |
| US4258202A | 2002-01-09 | 2002-01-09 | |
| PCT/US2002/021063 WO2003004027A1 (en) | 2001-07-05 | 2002-07-03 | Substituted anilinic piperidines as mch selective antagonists |
Publications (2)
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| JP2004536104A true JP2004536104A (ja) | 2004-12-02 |
| JP2004536104A5 JP2004536104A5 (https=) | 2006-01-05 |
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| JP (1) | JP2004536104A (https=) |
| KR (1) | KR20040027870A (https=) |
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| WO2006112549A1 (ja) * | 2005-04-20 | 2006-10-26 | Takeda Pharmaceutical Company Limited | 縮合複素環化合物 |
| WO2009041567A1 (ja) * | 2007-09-27 | 2009-04-02 | Banyu Pharmaceutical Co., Ltd. | メラニン凝集ホルモン受容体拮抗作用を有するジアリールケチミン誘導体 |
| JP2009528362A (ja) * | 2006-02-28 | 2009-08-06 | ヘリコン セラピューティクス,インコーポレイテッド | 治療化合物 |
| JP2011502957A (ja) * | 2007-05-11 | 2011-01-27 | コリア・リサーチ・インスティテュート・オブ・ケミカル・テクノロジー | アリールピペリジン置換基を有するイミダゾール誘導体、その製造方法及びこれを含む医薬組成物 |
| JP2012532172A (ja) * | 2009-07-06 | 2012-12-13 | シンジェンタ パーティシペーションズ アクチェンゲゼルシャフト | 殺虫性化合物 |
| WO2014112646A1 (ja) * | 2013-01-21 | 2014-07-24 | 国立大学法人大阪大学 | フェノキシアルキルアミン化合物 |
| JP2017502010A (ja) * | 2013-12-20 | 2017-01-19 | ラボラトリオス・デル・デエレ・エステベ・エセ・ア | 疼痛に対して多重モードの活性を有するピペリジン誘導体 |
| JP2017522337A (ja) * | 2014-07-29 | 2017-08-10 | ユニヴェルシテ・ドゥ・リール・2・ドロワ・エ・サンテ | 2−オキソ−3,4−ジヒドロピリジン−5−カルボキシラート及びそれらの使用 |
| JP2023512213A (ja) * | 2020-01-29 | 2023-03-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Apol1の阻害剤およびこれを使用する方法 |
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| US6727264B1 (en) | 2001-07-05 | 2004-04-27 | Synaptic Pharmaceutical Corporation | Substituted anilinic piperidines as MCH selective antagonists |
| US7105544B2 (en) * | 2001-07-05 | 2006-09-12 | Synaptic Pharmaceutical Corporation | Substituted alkyl amido piperidines |
| US7199135B2 (en) | 2001-07-05 | 2007-04-03 | H. Lundbeck A/S | Substituted alkyl amido piperidines |
| CA2468015A1 (en) | 2001-11-27 | 2003-06-05 | Merck & Co., Inc. | 2-aminoquinoline compounds |
| EP1465888A2 (en) | 2002-01-10 | 2004-10-13 | Neurogen Corporation | Melanin concentrating hormone receptor ligands: substituted benzoimidazole analogues |
| CA2473236A1 (en) | 2002-01-10 | 2003-07-24 | Neurogen Corporation | Melanin concentrating hormone receptor ligands: substituted 2-(4-benzyl-piperazin-1-ylmethyl)- and 2-(4-benzyl-diazepan-1-ylmethyl)-1h-benzoimidazole analogues |
| US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| UA77536C2 (en) | 2002-07-03 | 2006-12-15 | Lundbeck & Co As H | Secondary aminoaniline piperidines as mch1 antagonists and their use |
| UA77814C2 (en) | 2002-07-03 | 2007-01-15 | Lundbeck & Co As H | Spirocyclic piperidines as antagonists of mch1 and use thereof |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| BRPI0407088A (pt) * | 2003-01-28 | 2006-01-24 | Aventis Pharma Sa | Produtos n-aril-heteroaromáticos, composições contendo os mesmos e seu uso |
| FR2850379B1 (fr) * | 2003-01-28 | 2006-11-17 | Aventis Pharma Sa | Produits n-aryl-heteroaromatiques, compositions les contenant et utilisation |
| US7727998B2 (en) * | 2003-02-10 | 2010-06-01 | Banyu Pharmaceutical Co., Ltd. | Melanin-concentrating hormone receptor antagonists containing piperidine derivatives as the active ingredient |
| CN100448870C (zh) * | 2003-05-21 | 2009-01-07 | 万有制药株式会社 | 2-氨基喹啉衍生物 |
| AU2004274309B2 (en) | 2003-09-22 | 2010-04-08 | Msd K.K. | Novel piperidine derivative |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9810671D0 (en) * | 1998-05-18 | 1998-07-15 | Pfizer Ltd | Anti-pruritic agents |
| GB9912413D0 (en) * | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| JP2004502423A (ja) * | 2000-07-05 | 2004-01-29 | シナプティック・ファーマスーティカル・コーポレーション | ヒトメラニン濃縮ホルモン受容体(mch1)をコードするdna及びその使用 |
-
2002
- 2002-07-03 EP EP02746843A patent/EP1411942A4/en not_active Withdrawn
- 2002-07-03 MX MXPA03011886A patent/MXPA03011886A/es not_active Application Discontinuation
- 2002-07-03 EA EA200400146A patent/EA005934B1/ru not_active IP Right Cessation
- 2002-07-03 JP JP2003510038A patent/JP2004536104A/ja not_active Withdrawn
- 2002-07-03 HU HU0401880A patent/HUP0401880A2/hu unknown
- 2002-07-03 WO PCT/US2002/021063 patent/WO2003004027A1/en not_active Ceased
- 2002-07-03 PL PL02366624A patent/PL366624A1/xx not_active Application Discontinuation
- 2002-07-03 CN CNA028172124A patent/CN1671386A/zh active Pending
- 2002-07-03 NZ NZ530221A patent/NZ530221A/xx unknown
- 2002-07-03 CA CA002454613A patent/CA2454613A1/en not_active Abandoned
- 2002-07-03 KR KR10-2004-7000087A patent/KR20040027870A/ko not_active Ceased
- 2002-07-03 IL IL15969702A patent/IL159697A0/xx unknown
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2003
- 2003-12-18 IS IS7085A patent/IS7085A/is unknown
-
2004
- 2004-01-05 NO NO20040028A patent/NO20040028L/no not_active Application Discontinuation
- 2004-02-02 CO CO04007748A patent/CO5670352A2/es not_active Application Discontinuation
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| WO2006112549A1 (ja) * | 2005-04-20 | 2006-10-26 | Takeda Pharmaceutical Company Limited | 縮合複素環化合物 |
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| JP2012532172A (ja) * | 2009-07-06 | 2012-12-13 | シンジェンタ パーティシペーションズ アクチェンゲゼルシャフト | 殺虫性化合物 |
| WO2014112646A1 (ja) * | 2013-01-21 | 2014-07-24 | 国立大学法人大阪大学 | フェノキシアルキルアミン化合物 |
| JPWO2014112646A1 (ja) * | 2013-01-21 | 2017-01-19 | 国立大学法人大阪大学 | フェノキシアルキルアミン化合物 |
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| JP2017522337A (ja) * | 2014-07-29 | 2017-08-10 | ユニヴェルシテ・ドゥ・リール・2・ドロワ・エ・サンテ | 2−オキソ−3,4−ジヒドロピリジン−5−カルボキシラート及びそれらの使用 |
| JP2023512213A (ja) * | 2020-01-29 | 2023-03-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Apol1の阻害剤およびこれを使用する方法 |
| JP7668804B2 (ja) | 2020-01-29 | 2025-04-25 | バーテックス ファーマシューティカルズ インコーポレイテッド | Apol1の阻害剤およびこれを使用する方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| EA005934B1 (ru) | 2005-08-25 |
| EP1411942A4 (en) | 2005-01-26 |
| EP1411942A1 (en) | 2004-04-28 |
| AU2002316531B2 (en) | 2007-09-13 |
| CN1671386A (zh) | 2005-09-21 |
| CA2454613A1 (en) | 2003-01-16 |
| CO5670352A2 (es) | 2006-08-31 |
| NZ530221A (en) | 2006-03-31 |
| NO20040028L (no) | 2004-03-04 |
| MXPA03011886A (es) | 2005-03-07 |
| HUP0401880A2 (hu) | 2005-01-28 |
| WO2003004027A1 (en) | 2003-01-16 |
| IS7085A (is) | 2003-12-18 |
| EA200400146A1 (ru) | 2004-08-26 |
| PL366624A1 (en) | 2005-02-07 |
| KR20040027870A (ko) | 2004-04-01 |
| IL159697A0 (en) | 2004-06-20 |
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