TWI583683B - 雜芳香環甲基環狀胺衍生物 - Google Patents
雜芳香環甲基環狀胺衍生物 Download PDFInfo
- Publication number
- TWI583683B TWI583683B TW102121127A TW102121127A TWI583683B TW I583683 B TWI583683 B TW I583683B TW 102121127 A TW102121127 A TW 102121127A TW 102121127 A TW102121127 A TW 102121127A TW I583683 B TWI583683 B TW I583683B
- Authority
- TW
- Taiwan
- Prior art keywords
- methyl
- methanone
- phenyl
- pyrazol
- triazol
- Prior art date
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- -1 Heteroaromatic cyclic methyl cyclic amine Chemical class 0.000 title claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 175
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 10
- 125000001425 triazolyl group Chemical group 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 208000019116 sleep disease Diseases 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 206010019233 Headaches Diseases 0.000 claims description 6
- 231100000869 headache Toxicity 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 5
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 208000010643 digestive system disease Diseases 0.000 claims description 5
- 235000014632 disordered eating Nutrition 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 206010013663 drug dependence Diseases 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 150000002576 ketones Chemical class 0.000 claims description 5
- 208000019906 panic disease Diseases 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 208000011117 substance-related disease Diseases 0.000 claims description 5
- RDBXBVVGBXXYNE-UHFFFAOYSA-N 5-methyl-2-(triazol-2-yl)benzaldehyde Chemical compound O=CC1=CC(C)=CC=C1N1N=CC=N1 RDBXBVVGBXXYNE-UHFFFAOYSA-N 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 4
- 230000002124 endocrine Effects 0.000 claims description 4
- 206010027599 migraine Diseases 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- SEQFWYDOYOPPLZ-UHFFFAOYSA-N C1C=COC(N1C(=O)C2=C(C=CC(=C2)F)N3N=CC=N3)CN4C=CC(=N4)C5=NC=C(C=C5)F Chemical compound C1C=COC(N1C(=O)C2=C(C=CC(=C2)F)N3N=CC=N3)CN4C=CC(=N4)C5=NC=C(C=C5)F SEQFWYDOYOPPLZ-UHFFFAOYSA-N 0.000 claims description 2
- PHWGWKLDMNGUQB-UHFFFAOYSA-N CC1=CC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CC4=NOC(=N4)C5=CC=C(C=C5)F Chemical compound CC1=CC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CC4=NOC(=N4)C5=CC=C(C=C5)F PHWGWKLDMNGUQB-UHFFFAOYSA-N 0.000 claims description 2
- JBSPGGUAAKUBMA-UHFFFAOYSA-N CC1=CC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CC4=NOC(=N4)C5=NC=C(C=C5)F Chemical compound CC1=CC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CC4=NOC(=N4)C5=NC=C(C=C5)F JBSPGGUAAKUBMA-UHFFFAOYSA-N 0.000 claims description 2
- ZBRVDOUGQRWQHL-UHFFFAOYSA-N CC1=NC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CN4C=CC(=N4)C5=CC=C(C=C5)F Chemical compound CC1=NC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CN4C=CC(=N4)C5=CC=C(C=C5)F ZBRVDOUGQRWQHL-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- CGEFKPZGJUKITJ-UHFFFAOYSA-N [2-[[3-(5-fluoropyridin-2-yl)pyrazol-1-yl]methyl]-2,4-dihydro-1,3-oxazin-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound FC=1C=CC(=NC=1)C1=NN(C=C1)CC1OC=CCN1C(=O)C1=C(C=CC(=C1)C)N1N=CC=N1 CGEFKPZGJUKITJ-UHFFFAOYSA-N 0.000 claims description 2
- CTNMMUBGLRNOPX-UHFFFAOYSA-N [2-[[4-(4-fluorophenyl)pyrazol-1-yl]methyl]-1,3-oxazolidin-3-yl]-(5-methyl-2-pyrimidin-2-ylphenyl)methanone Chemical compound C=1C(C)=CC=C(C=2N=CC=CN=2)C=1C(=O)N1CCOC1CN(N=C1)C=C1C1=CC=C(F)C=C1 CTNMMUBGLRNOPX-UHFFFAOYSA-N 0.000 claims description 2
- TUYYHZDLQKQJOU-UHFFFAOYSA-N [2-[[4-(4-fluorophenyl)pyrazol-1-yl]methyl]-1,3-oxazolidin-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound C=1C(C)=CC=C(N2N=CC=N2)C=1C(=O)N1CCOC1CN(N=C1)C=C1C1=CC=C(F)C=C1 TUYYHZDLQKQJOU-UHFFFAOYSA-N 0.000 claims description 2
- QUYOMENBDKOHHU-UHFFFAOYSA-N [2-[[4-(5-fluoropyridin-2-yl)pyrazol-1-yl]methyl]-1,3-oxazolidin-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone Chemical compound C=1C(C)=CC=C(N2N=CC=N2)C=1C(=O)N1CCOC1CN(N=C1)C=C1C1=CC=C(F)C=N1 QUYOMENBDKOHHU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims 15
- WKDHORIIWZFUCN-UHFFFAOYSA-N 5-fluoro-2-pyrimidin-2-ylbenzaldehyde Chemical compound O=CC1=CC(F)=CC=C1C1=NC=CC=N1 WKDHORIIWZFUCN-UHFFFAOYSA-N 0.000 claims 1
- BJHOQENIERDSRA-UHFFFAOYSA-N C1=CN=C(N=C1)C2=C(C=C(C=C2)F)C(=O)N3C=COC3CN4C=CC(=N4)C5=NC=C(C=C5)F Chemical compound C1=CN=C(N=C1)C2=C(C=C(C=C2)F)C(=O)N3C=COC3CN4C=CC(=N4)C5=NC=C(C=C5)F BJHOQENIERDSRA-UHFFFAOYSA-N 0.000 claims 1
- OWAGUSDBIIZHGM-UHFFFAOYSA-N CC(N=C1C(C2=NC(C)=CC(N3C(CN(C=C4)N=C4C(C=C4)=CC=C4F)OCC3)=C2N2N=CC=N2)=O)=CC(N2C(CN(C=C3)N=C3C(C=C3)=CC=C3F)OCC2)=C1N1N=CC=N1 Chemical compound CC(N=C1C(C2=NC(C)=CC(N3C(CN(C=C4)N=C4C(C=C4)=CC=C4F)OCC3)=C2N2N=CC=N2)=O)=CC(N2C(CN(C=C3)N=C3C(C=C3)=CC=C3F)OCC2)=C1N1N=CC=N1 OWAGUSDBIIZHGM-UHFFFAOYSA-N 0.000 claims 1
- RHHRQCXJMWJAMM-UHFFFAOYSA-N CC1=CC(=C(C=C1)C2=NC=CC=N2)C(=O)N3C=COC3CN4C=CC(=N4)C5=CC=C(C=C5)F Chemical compound CC1=CC(=C(C=C1)C2=NC=CC=N2)C(=O)N3C=COC3CN4C=CC(=N4)C5=CC=C(C=C5)F RHHRQCXJMWJAMM-UHFFFAOYSA-N 0.000 claims 1
- ZXAYQJCZLZCQTA-UHFFFAOYSA-N CC1=CC(=C(C=C1)C2=NC=CC=N2)C(=O)N3CC=COC3CN4C=CC(=N4)C5=NC=C(C=C5)F Chemical compound CC1=CC(=C(C=C1)C2=NC=CC=N2)C(=O)N3CC=COC3CN4C=CC(=N4)C5=NC=C(C=C5)F ZXAYQJCZLZCQTA-UHFFFAOYSA-N 0.000 claims 1
- LJOOEUAQCLQJOV-UHFFFAOYSA-N CC1=NC(=C(C=C1)C2=NC=CC=N2)C(=O)N3CC=COC3CN4C=C(C=N4)C5=CC=C(C=C5)F Chemical compound CC1=NC(=C(C=C1)C2=NC=CC=N2)C(=O)N3CC=COC3CN4C=C(C=N4)C5=CC=C(C=C5)F LJOOEUAQCLQJOV-UHFFFAOYSA-N 0.000 claims 1
- PLECFYJSGQCBGX-UHFFFAOYSA-N CC1=NC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CN4C=C(C=N4)C5=CC=C(C=C5)F Chemical compound CC1=NC(=C(C=C1)N2N=CC=N2)C(=O)N3CC=COC3CN4C=C(C=N4)C5=CC=C(C=C5)F PLECFYJSGQCBGX-UHFFFAOYSA-N 0.000 claims 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 145
- 238000006243 chemical reaction Methods 0.000 description 103
- 235000019439 ethyl acetate Nutrition 0.000 description 72
- 239000002904 solvent Substances 0.000 description 69
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 61
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 53
- 238000004949 mass spectrometry Methods 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000007864 aqueous solution Substances 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 28
- 229920006395 saturated elastomer Polymers 0.000 description 28
- 239000011780 sodium chloride Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 239000011734 sodium Substances 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- 238000000034 method Methods 0.000 description 23
- 239000012230 colorless oil Substances 0.000 description 21
- 239000007788 liquid Substances 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- 230000014759 maintenance of location Effects 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 17
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- 102000002512 Orexin Human genes 0.000 description 15
- 108060005714 orexin Proteins 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 14
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- 239000011541 reaction mixture Substances 0.000 description 14
- TYEYBOSBBBHJIV-UHFFFAOYSA-M 2-oxobutanoate Chemical compound CCC(=O)C([O-])=O TYEYBOSBBBHJIV-UHFFFAOYSA-M 0.000 description 13
- 239000012046 mixed solvent Substances 0.000 description 13
- 230000003287 optical effect Effects 0.000 description 13
- 239000003643 water by type Substances 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 108050000742 Orexin Receptor Proteins 0.000 description 12
- 102000008834 Orexin receptor Human genes 0.000 description 12
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
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- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 10
- 229910052736 halogen Inorganic materials 0.000 description 10
- 150000002367 halogens Chemical class 0.000 description 10
- 239000002798 polar solvent Substances 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 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 8
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
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- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
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Classifications
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| JP2012135277 | 2012-06-15 |
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Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2585806T3 (es) | 2009-10-23 | 2016-10-10 | Janssen Pharmaceutica N.V. | Octahidropirrolo [3,4-c] pirroles disustituidos como moduladores de receptores de orexina |
| JP2017024990A (ja) * | 2013-12-13 | 2017-02-02 | 大正製薬株式会社 | オキサゾリジン及びオキサジナン誘導体 |
| CN105814042B (zh) * | 2013-12-13 | 2018-09-28 | 大正制药株式会社 | 噁嗪烷化合物的晶形及其制造方法 |
| CN104370755B (zh) * | 2014-08-18 | 2017-04-12 | 江西隆莱生物制药有限公司 | 一种光学活性的3‑氨基丁醇和3‑氨基丁酸的制备方法 |
| JP2018188364A (ja) * | 2015-10-02 | 2018-11-29 | 大正製薬株式会社 | 複素芳香環誘導体 |
| HRP20220642T1 (hr) | 2016-03-10 | 2022-06-24 | Janssen Pharmaceutica Nv | Postupci za liječenje depresije uporabom antagonista receptora oreksina 2 |
| CN108129426B (zh) * | 2016-12-01 | 2021-06-29 | 中国科学院大连化学物理研究所 | 一种2,5-二氰基呋喃催化加氢合成2,5-二甲胺基呋喃的方法 |
| JOP20190156B1 (ar) * | 2016-12-23 | 2023-09-17 | Bayer Pharma AG | أميدات عطرية لحمض الكربوكسيليك بصفتها مضادات لمستقبلة البراديكينين b1 |
| WO2019013244A1 (ja) | 2017-07-13 | 2019-01-17 | 大正製薬株式会社 | （２ｓ）－２－［（１ｈ－ピラゾール－１－イル）メチル］－１，３－オキサジナン誘導体の製造方法 |
| CN110967321A (zh) * | 2018-09-29 | 2020-04-07 | 泰州医药城国科化物生物医药科技有限公司 | 一种用于均一体系细胞荧光检测钙流方法 |
| US20230310652A1 (en) | 2020-05-22 | 2023-10-05 | Neuway Pharma Gmbh | Vlp for the treatment of leukodystrophies |
| CN113336655A (zh) * | 2020-12-30 | 2021-09-03 | 江西迪赛诺制药有限公司 | 一种(r)-3-氨基丁醇的制备方法 |
| CN116925022B (zh) * | 2023-07-06 | 2025-08-01 | 江苏信和生物医药有限公司 | 一种(s)-5-烯丙基-2-氧杂双环[3.3.0]辛-8-烯的制备方法 |
Citations (1)
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| WO2003002559A2 (en) * | 2001-06-28 | 2003-01-09 | Smithkline Beecham P.L.C. | Piperidine compounds for use as orexin receptor antagonist |
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| US7169744B2 (en) * | 2002-06-06 | 2007-01-30 | Procter & Gamble Company | Organic catalyst with enhanced solubility |
| WO2008062878A1 (fr) | 2006-11-22 | 2008-05-29 | Nihon Nohyaku Co., Ltd. | Nouveau dérivé de pyrazole, agent de lutte contre des organismes nuisibles et utilisation de l'agent de lutte contre des organismes nuisibles |
| EP2131654A4 (en) | 2007-03-02 | 2011-02-02 | Merck Sharp & Dohme | Bipyridine-carboxamide-orexin receptor Antagonist |
| WO2008147518A1 (en) * | 2007-05-23 | 2008-12-04 | Merck & Co., Inc. | Pyridyl piperidine orexin receptor antagonists |
| CA2695621A1 (en) * | 2007-08-09 | 2009-02-12 | Merck Sharp & Dohme Corp. | Pyridine carboxamide orexin receptor antagonists |
| WO2010038200A1 (en) * | 2008-10-01 | 2010-04-08 | Actelion Pharmaceuticals Ltd | Oxazolidine compounds as orexin receptor antagonists |
| WO2010044054A1 (en) | 2008-10-14 | 2010-04-22 | Actelion Pharmaceuticals Ltd | Phenethylamide derivatives and their heterocyclic analogues |
| AU2009307916A1 (en) | 2008-10-21 | 2010-04-29 | Merck Sharp & Dohme Corp. | 2,5-disubstituted morpholine orexin receptor antagonists |
| CA2741648A1 (en) * | 2008-10-30 | 2010-05-06 | Merck Sharp & Dohme Corp. | 2,5-disubstituted phenyl carboxamide orexin receptor antagonists |
| EP2350010B1 (en) * | 2008-10-30 | 2014-03-26 | Merck Sharp & Dohme Corp. | Isonicotinamide orexin receptor antagonists |
| US20130281465A1 (en) | 2010-12-17 | 2013-10-24 | Taisho Pharmaceutical Co., Ltd. | Pyrazole derivative |
| EP2708537A4 (en) | 2011-05-10 | 2014-10-01 | Taisho Pharmaceutical Co Ltd | HETEROAROMATIC RING DERIVATIVE |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003002559A2 (en) * | 2001-06-28 | 2003-01-09 | Smithkline Beecham P.L.C. | Piperidine compounds for use as orexin receptor antagonist |
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