AU2014248763B2 - Substituted piperidine compounds and their use as orexin receptor modulators - Google Patents
Substituted piperidine compounds and their use as orexin receptor modulators Download PDFInfo
- Publication number
- AU2014248763B2 AU2014248763B2 AU2014248763A AU2014248763A AU2014248763B2 AU 2014248763 B2 AU2014248763 B2 AU 2014248763B2 AU 2014248763 A AU2014248763 A AU 2014248763A AU 2014248763 A AU2014248763 A AU 2014248763A AU 2014248763 B2 AU2014248763 B2 AU 2014248763B2
- Authority
- AU
- Australia
- Prior art keywords
- methanone
- methyl
- pyridin
- trifluoromethyl
- piperidin
- Prior art date
- 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.)
- Active
Links
- 108050000742 Orexin Receptor Proteins 0.000 title claims description 16
- 102000008834 Orexin receptor Human genes 0.000 title claims description 16
- 150000003053 piperidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 498
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims description 714
- -1 triazol-2-yl Chemical group 0.000 claims description 559
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 250
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 176
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 93
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 62
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 50
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 34
- 208000035475 disorder Diseases 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 16
- 208000012902 Nervous system disease Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 208000019022 Mood disease Diseases 0.000 claims description 13
- 208000019116 sleep disease Diseases 0.000 claims description 13
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 11
- 201000009032 substance abuse Diseases 0.000 claims description 11
- 208000011117 substance-related disease Diseases 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 231100000736 substance abuse Toxicity 0.000 claims description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
- 208000019901 Anxiety disease Diseases 0.000 claims description 9
- 230000036506 anxiety Effects 0.000 claims description 9
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 9
- 208000019906 panic disease Diseases 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 208000020685 sleep-wake disease Diseases 0.000 claims description 9
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 8
- 208000025966 Neurological disease Diseases 0.000 claims description 8
- 208000008589 Obesity Diseases 0.000 claims description 8
- 206010033307 Overweight Diseases 0.000 claims description 8
- 230000001149 cognitive effect Effects 0.000 claims description 8
- 230000007812 deficiency Effects 0.000 claims description 8
- 230000000155 isotopic effect Effects 0.000 claims description 8
- 235000020824 obesity Nutrition 0.000 claims description 8
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 8
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 7
- 206010002383 Angina Pectoris Diseases 0.000 claims description 7
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 208000001871 Tachycardia Diseases 0.000 claims description 7
- 208000030159 metabolic disease Diseases 0.000 claims description 7
- 230000006794 tachycardia Effects 0.000 claims description 7
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 6
- 206010007556 Cardiac failure acute Diseases 0.000 claims description 6
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- 208000025865 Ulcer Diseases 0.000 claims description 6
- 206010003119 arrhythmia Diseases 0.000 claims description 6
- 230000006793 arrhythmia Effects 0.000 claims description 6
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 6
- 230000036512 infertility Effects 0.000 claims description 6
- 231100000535 infertility Toxicity 0.000 claims description 6
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 6
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 230000007958 sleep Effects 0.000 claims description 6
- 231100000397 ulcer Toxicity 0.000 claims description 6
- BGWOURBIBJXZSU-KBXCAEBGSA-N (2-fluoro-6-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 BGWOURBIBJXZSU-KBXCAEBGSA-N 0.000 claims description 5
- GKWZFXJEPUXNKD-IFXJQAMLSA-N (4-fluoro-2-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(F)C=C1C1=NC=CC=N1 GKWZFXJEPUXNKD-IFXJQAMLSA-N 0.000 claims description 5
- 208000006820 Arthralgia Diseases 0.000 claims description 5
- 208000008035 Back Pain Diseases 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 5
- 208000000059 Dyspnea Diseases 0.000 claims description 5
- 206010013975 Dyspnoeas Diseases 0.000 claims description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 5
- 206010022489 Insulin Resistance Diseases 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 5
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 5
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 5
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 5
- 208000016620 Tourette disease Diseases 0.000 claims description 5
- 206010046996 Varicose vein Diseases 0.000 claims description 5
- 206010007776 catatonia Diseases 0.000 claims description 5
- 201000001883 cholelithiasis Diseases 0.000 claims description 5
- 208000001130 gallstones Diseases 0.000 claims description 5
- 208000000509 infertility Diseases 0.000 claims description 5
- 206010022437 insomnia Diseases 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 201000002859 sleep apnea Diseases 0.000 claims description 5
- 208000027185 varicose disease Diseases 0.000 claims description 5
- 206010012218 Delirium Diseases 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- AIUPHYUHIRIDMZ-XJKSGUPXSA-N (3-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-c1ncccn1)Nc1cnc(cn1)C(F)(F)F AIUPHYUHIRIDMZ-XJKSGUPXSA-N 0.000 claims description 3
- LXAUAYZMPQRYNH-KBXCAEBGSA-N (3-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-c1ncccn1)Nc1ccc(cn1)C(F)(F)F LXAUAYZMPQRYNH-KBXCAEBGSA-N 0.000 claims description 3
- OZISHHLQPHTGRU-QFBILLFUSA-N (3-methyl-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(C)c1-c1ncccn1)Oc1ccc(cn1)C(F)(F)F OZISHHLQPHTGRU-QFBILLFUSA-N 0.000 claims description 3
- CWGRWPJFZUVTEE-SUMWQHHRSA-N (4-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncccn1)Nc1cnc(cn1)C(F)(F)F CWGRWPJFZUVTEE-SUMWQHHRSA-N 0.000 claims description 3
- VSTZBRJBYTVKFZ-ORAYPTAESA-N (4-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncccn1)Oc1ncc(cc1F)C(F)(F)F VSTZBRJBYTVKFZ-ORAYPTAESA-N 0.000 claims description 3
- FCEAUETXOHAUPY-IFXJQAMLSA-N (5-fluoro-2-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC(F)=CC=C1C1=NC=CC=N1 FCEAUETXOHAUPY-IFXJQAMLSA-N 0.000 claims description 3
- RXFSUCOETKFBGG-MAUKXSAKSA-N (5-methyl-2-pyrimidin-2-ylpyridin-3-yl)-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(C)cnc1-c1ncccn1)Oc1ccc(cn1)C(F)(F)F RXFSUCOETKFBGG-MAUKXSAKSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000022249 Sleep-Wake Transition disease Diseases 0.000 claims description 3
- HAJHUABFMFMQLD-SCLBCKFNSA-N [2-(5-fluoropyrimidin-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccccc1-c1ncc(F)cn1)Oc1ncc(cn1)C(F)(F)F HAJHUABFMFMQLD-SCLBCKFNSA-N 0.000 claims description 3
- GJNQAHSCYHJSPV-BLLLJJGKSA-N [4-fluoro-2-(1,3-oxazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncco1)Nc1cnc(cn1)C(F)(F)F GJNQAHSCYHJSPV-BLLLJJGKSA-N 0.000 claims description 3
- MLYBOSOAHBELPA-SCLBCKFNSA-N [4-fluoro-2-(1,3-oxazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncco1)Nc1ccc(cn1)C(F)(F)F MLYBOSOAHBELPA-SCLBCKFNSA-N 0.000 claims description 3
- FKULETLRSXORAQ-KPZWWZAWSA-N [4-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(F)C=C1C1=NC(C)=NO1 FKULETLRSXORAQ-KPZWWZAWSA-N 0.000 claims description 3
- HBYGVGPRFRCZDK-SMDDNHRTSA-N (2-chloro-6-methoxypyridin-3-yl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C1(=CC=C(C(=O)N2CCC[C@@H](NC3=NC=C(C=C3)C(F)(F)F)[C@@H]2C)C(Cl)=N1)OC HBYGVGPRFRCZDK-SMDDNHRTSA-N 0.000 claims description 2
- JPLQCTUBLCJAAA-GXFFZTMASA-N (2-chloro-6-methoxypyridin-3-yl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound COc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(cn3)C(F)(F)F)[C@@H]2C)c(Cl)n1 JPLQCTUBLCJAAA-GXFFZTMASA-N 0.000 claims description 2
- BPRKVMQRRVCEFQ-DZGCQCFKSA-N (3-ethoxy-6-methylpyridin-2-yl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound CCOc1ccc(C)nc1C(=O)N1CCC[C@@H](Nc2ncc(cn2)C(F)(F)F)[C@@H]1C BPRKVMQRRVCEFQ-DZGCQCFKSA-N 0.000 claims description 2
- GIXJBYPYHPQASO-SUMWQHHRSA-N (3-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-c1ncccn1)Nc1ncc(cn1)C(F)(F)F GIXJBYPYHPQASO-SUMWQHHRSA-N 0.000 claims description 2
- NBWZSSGPBGGLMV-SCLBCKFNSA-N (3-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-c1ncccn1)Oc1ncc(cc1F)C(F)(F)F NBWZSSGPBGGLMV-SCLBCKFNSA-N 0.000 claims description 2
- LTSCHBJCTYRXGT-IFXJQAMLSA-N (4-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncccn1)Nc1ccc(cn1)C(F)(F)F LTSCHBJCTYRXGT-IFXJQAMLSA-N 0.000 claims description 2
- IJWPNUTUZADCOH-SCLBCKFNSA-N (4-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncccn1)Nc1ncc(cn1)C(F)(F)F IJWPNUTUZADCOH-SCLBCKFNSA-N 0.000 claims description 2
- UHNGBFQNWRGRGJ-ORAYPTAESA-N (5-fluoro-2-pyrimidin-2-ylphenyl)-[(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(F)ccc1-c1ncccn1)Oc1ncc(cc1F)C(F)(F)F UHNGBFQNWRGRGJ-ORAYPTAESA-N 0.000 claims description 2
- SHZWQZQIIDBRSM-MAUKXSAKSA-N (6-methyl-3-pyrimidin-2-ylpyridin-2-yl)-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1nc(C)ccc1-c1ncccn1)Oc1ccc(cn1)C(F)(F)F SHZWQZQIIDBRSM-MAUKXSAKSA-N 0.000 claims description 2
- ZRLSRYKBCNQEGJ-KBXCAEBGSA-N [(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]-(2-pyrimidin-2-ylphenyl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccccc1-c1ncccn1)Oc1ncc(cn1)C(F)(F)F ZRLSRYKBCNQEGJ-KBXCAEBGSA-N 0.000 claims description 2
- NYRCHCPBPDEEDQ-HNAYVOBHSA-N [(2S,3R)-3-(1,3-benzoxazol-2-ylamino)-2-methylpiperidin-1-yl]-(4-fluoro-2-pyrimidin-2-ylphenyl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncccn1)Nc1nc2ccccc2o1 NYRCHCPBPDEEDQ-HNAYVOBHSA-N 0.000 claims description 2
- HEKCICIGPFXLPD-KBXCAEBGSA-N [(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]-(6-methyl-3-pyrimidin-2-ylpyridin-2-yl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)C1=NC(C)=CC=C1C1=NC=CC=N1)OC1=NC=C(C=C1F)C(F)(F)F HEKCICIGPFXLPD-KBXCAEBGSA-N 0.000 claims description 2
- NQJWIGPNIHITHC-KBXCAEBGSA-N [2-(5-fluoropyrimidin-2-yl)-3-methylphenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(C)c1-c1ncc(F)cn1)Oc1ncc(cn1)C(F)(F)F NQJWIGPNIHITHC-KBXCAEBGSA-N 0.000 claims description 2
- RUZMKFKWJMYUGF-SUMWQHHRSA-N [2-(5-fluoropyrimidin-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccccc1-c1ncc(F)cn1)Oc1cnc(cn1)C(F)(F)F RUZMKFKWJMYUGF-SUMWQHHRSA-N 0.000 claims description 2
- CGYASCADFAYDML-KPZWWZAWSA-N [3-fluoro-2-(5-fluoropyrimidin-2-yl)phenyl]-[(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-c1ncc(F)cn1)Oc1ncc(cc1F)C(F)(F)F CGYASCADFAYDML-KPZWWZAWSA-N 0.000 claims description 2
- SNRKZNVVRGYCKT-YVEFUNNKSA-N [4-fluoro-2-(1,3-oxazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1ncco1)Nc1ncc(cn1)C(F)(F)F SNRKZNVVRGYCKT-YVEFUNNKSA-N 0.000 claims description 2
- GWTJUSKJAFQABG-APPDUMDISA-N [4-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-c1nc(C)no1)Nc1ncc(cn1)C(F)(F)F GWTJUSKJAFQABG-APPDUMDISA-N 0.000 claims description 2
- OSSTWTFSVCMTNC-SCLBCKFNSA-N [4-fluoro-2-(triazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound FC1=CC(=C(C=C1)C(=O)N1[C@H]([C@@H](CCC1)OC1=NC=C(C=C1)C(F)(F)F)C)N1N=CC=N1 OSSTWTFSVCMTNC-SCLBCKFNSA-N 0.000 claims description 2
- MCTRLPKOHRESFZ-SUMWQHHRSA-N [4-fluoro-2-(triazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-n1nccn1)Nc1ccc(cn1)C(F)(F)F MCTRLPKOHRESFZ-SUMWQHHRSA-N 0.000 claims description 2
- KCNNJAPULHWXBN-BLLLJJGKSA-N [4-fluoro-2-(triazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(F)cc1-n1nccn1)Nc1ncc(cn1)C(F)(F)F KCNNJAPULHWXBN-BLLLJJGKSA-N 0.000 claims description 2
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 claims 4
- DKVYIRANNWINAT-UHFFFAOYSA-N 5-methyl-3-(1,3-oxazol-2-yl)pyridine-2-carbaldehyde Chemical compound CC=1C=C(C(=NC=1)C=O)C=1OC=CN=1 DKVYIRANNWINAT-UHFFFAOYSA-N 0.000 claims 4
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 claims 3
- UBUCZGCYZIJFBC-WMZOPIPTSA-N (2-ethoxyphenyl)-[(2S,3S)-2-methyl-3-(quinoxalin-2-ylamino)piperidin-1-yl]methanone Chemical compound C(C)OC1=C(C=CC=C1)C(=O)N1[C@H]([C@H](CCC1)NC1=NC2=CC=CC=C2N=C1)C UBUCZGCYZIJFBC-WMZOPIPTSA-N 0.000 claims 1
- GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 claims 1
- DUVJMSPTZMCSTQ-UHFFFAOYSA-N 2-ethoxybenzaldehyde Chemical compound CCOC1=CC=CC=C1C=O DUVJMSPTZMCSTQ-UHFFFAOYSA-N 0.000 claims 1
- VOKLCTVHMXWDKA-UHFFFAOYSA-N 3-pyrimidin-2-ylpyridine-2-carbaldehyde Chemical compound N1=C(N=CC=C1)C=1C(=NC=CC=1)C=O VOKLCTVHMXWDKA-UHFFFAOYSA-N 0.000 claims 1
- VWMQXAYLHOSRKA-UHFFFAOYSA-N 5-chloro-1,3-benzoxazole Chemical compound ClC1=CC=C2OC=NC2=C1 VWMQXAYLHOSRKA-UHFFFAOYSA-N 0.000 claims 1
- BOHVKZOSAMPFQT-UHFFFAOYSA-N 5-methyl-3-pyrimidin-2-ylpyridine-2-carbaldehyde Chemical compound CC=1C=C(C(=NC=1)C=O)C1=NC=CC=N1 BOHVKZOSAMPFQT-UHFFFAOYSA-N 0.000 claims 1
- BYWWIDLMCZNAIS-UHFFFAOYSA-N 6-methyl-3-pyrimidin-2-ylpyridine-2-carbaldehyde Chemical compound O=CC1=NC(C)=CC=C1C1=NC=CC=N1 BYWWIDLMCZNAIS-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 102100030847 Retinal guanylyl cyclase 2 Human genes 0.000 claims 1
- 101710181632 Retinal guanylyl cyclase 2 Proteins 0.000 claims 1
- 208000012981 Traumatic Stress disease Diseases 0.000 claims 1
- OIGTYNDRECFROB-WMLDXEAASA-N [(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]-(2-pyrimidin-2-ylphenyl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccccc1-c1ncccn1)Oc1cnc(cn1)C(F)(F)F OIGTYNDRECFROB-WMLDXEAASA-N 0.000 claims 1
- COIPEATXTCKRLK-GOEBONIOSA-N [(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]-(3-phenylpyrazin-2-yl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1nccnc1-c1ccccc1)Oc1cnc(cn1)C(F)(F)F COIPEATXTCKRLK-GOEBONIOSA-N 0.000 claims 1
- SGIUPRLJWZETCX-WMLDXEAASA-N [(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]-(3-phenylpyrazin-2-yl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)C1=NC=CN=C1C1=CC=CC=C1)OC1=NC=C(C=N1)C(F)(F)F SGIUPRLJWZETCX-WMLDXEAASA-N 0.000 claims 1
- SXTGJLPLQJFADA-WMLDXEAASA-N [(2S,3R)-3-(5-chloropyridin-2-yl)oxy-2-methylpiperidin-1-yl]-(3-pyrimidin-2-ylpyridin-2-yl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)C1=NC=CC=C1C1=NC=CC=N1)OC1=CC=C(Cl)C=N1 SXTGJLPLQJFADA-WMLDXEAASA-N 0.000 claims 1
- OWKKEQNIOAZQBU-BLLLJJGKSA-N [(2S,3R)-3-(5-chloropyrimidin-2-yl)oxy-2-methylpiperidin-1-yl]-[3-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-n1nccn1)Oc1ncc(Cl)cn1 OWKKEQNIOAZQBU-BLLLJJGKSA-N 0.000 claims 1
- FGGZOTNXLWJSCX-IFXJQAMLSA-N [(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]-(2-pyrimidin-2-ylphenyl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccccc1-c1ncccn1)Oc1ncc(cc1F)C(F)(F)F FGGZOTNXLWJSCX-IFXJQAMLSA-N 0.000 claims 1
- FYVJSZXRQQPGQY-HNAYVOBHSA-N [(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]-(3-methyl-2-pyrimidin-2-ylphenyl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(C)c1-c1ncccn1)Oc1ncc(cc1F)C(F)(F)F FYVJSZXRQQPGQY-HNAYVOBHSA-N 0.000 claims 1
- FIOCWYORYODYRN-QFBILLFUSA-N [(2s,3r)-2-methyl-3-(quinazolin-2-ylamino)piperidin-1-yl]-[2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=C3C=CC=CC3=CN=2)CCN1C(=O)C1=CC=CC=C1N1N=CC=N1 FIOCWYORYODYRN-QFBILLFUSA-N 0.000 claims 1
- HPYALEYPTKDHAJ-ORAYPTAESA-N [2-(5-fluoropyrimidin-2-yl)phenyl]-[(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccccc1-c1ncc(F)cn1)Oc1ncc(cc1F)C(F)(F)F HPYALEYPTKDHAJ-ORAYPTAESA-N 0.000 claims 1
- NADZLMLXDCUYLT-XHDPSFHLSA-N [3-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=CC=CC(F)=C1C1=NC(C)=NO1 NADZLMLXDCUYLT-XHDPSFHLSA-N 0.000 claims 1
- 208000026345 acute stress disease Diseases 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 415
- 238000000132 electrospray ionisation Methods 0.000 description 231
- 238000001819 mass spectrum Methods 0.000 description 228
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 182
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 131
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 88
- 239000000203 mixture Substances 0.000 description 87
- 125000000217 alkyl group Chemical group 0.000 description 79
- 238000005160 1H NMR spectroscopy Methods 0.000 description 77
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 74
- 239000000460 chlorine Substances 0.000 description 74
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 56
- 125000005843 halogen group Chemical group 0.000 description 52
- 238000005481 NMR spectroscopy Methods 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 45
- 102000002512 Orexin Human genes 0.000 description 44
- 108060005714 orexin Proteins 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- 239000002904 solvent Substances 0.000 description 40
- 125000000714 pyrimidinyl group Chemical group 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 38
- 102000005962 receptors Human genes 0.000 description 38
- 108020003175 receptors Proteins 0.000 description 38
- 238000000746 purification Methods 0.000 description 37
- 238000011282 treatment Methods 0.000 description 37
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 36
- 238000004128 high performance liquid chromatography Methods 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
- 238000010898 silica gel chromatography Methods 0.000 description 34
- 239000000243 solution Substances 0.000 description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
- 101150041968 CDC13 gene Proteins 0.000 description 30
- 239000012071 phase Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 25
- 125000001425 triazolyl group Chemical group 0.000 description 25
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 125000001424 substituent group Chemical group 0.000 description 23
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 125000002971 oxazolyl group Chemical group 0.000 description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- 125000004076 pyridyl group Chemical group 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 19
- 229910052731 fluorine Inorganic materials 0.000 description 19
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 125000003373 pyrazinyl group Chemical group 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 125000001715 oxadiazolyl group Chemical group 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical group C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 15
- 101000598921 Homo sapiens Orexin Proteins 0.000 description 15
- 125000003545 alkoxy group Chemical group 0.000 description 15
- 125000004429 atom Chemical group 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 229910052794 bromium Inorganic materials 0.000 description 14
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 14
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 229910052801 chlorine Inorganic materials 0.000 description 13
- 125000000842 isoxazolyl group Chemical group 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 125000002098 pyridazinyl group Chemical group 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
- 210000002569 neuron Anatomy 0.000 description 12
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 12
- JFZJMSDDOOAOIV-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(Cl)N=C1 JFZJMSDDOOAOIV-UHFFFAOYSA-N 0.000 description 11
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 11
- 210000004556 brain Anatomy 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 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
- XDZMPRGFOOFSBL-UHFFFAOYSA-N 2-ethoxybenzoic acid Chemical compound CCOC1=CC=CC=C1C(O)=O XDZMPRGFOOFSBL-UHFFFAOYSA-N 0.000 description 10
- MEOOXZGGYVXUSG-UHFFFAOYSA-N 3-fluoro-2-methoxybenzoic acid Chemical compound COC1=C(F)C=CC=C1C(O)=O MEOOXZGGYVXUSG-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 239000000556 agonist Substances 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 description 10
- 239000005711 Benzoic acid Substances 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 235000010233 benzoic acid Nutrition 0.000 description 9
- 229910052740 iodine Chemical group 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 125000000547 substituted alkyl group Chemical group 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- YAMQDSQNPDUGGS-NTSWFWBYSA-N C[C@@H]1NCCC[C@H]1O Chemical compound C[C@@H]1NCCC[C@H]1O YAMQDSQNPDUGGS-NTSWFWBYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 235000015320 potassium carbonate Nutrition 0.000 description 7
- 239000002287 radioligand Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 7
- 125000004385 trihaloalkyl group Chemical group 0.000 description 7
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 6
- CEJAHXLRNZJPQH-UHFFFAOYSA-N 2,5-dichloropyrimidine Chemical compound ClC1=CN=C(Cl)N=C1 CEJAHXLRNZJPQH-UHFFFAOYSA-N 0.000 description 6
- MYUQKYGWKHTRPG-UHFFFAOYSA-N 5-bromo-2-fluoropyridine Chemical compound FC1=CC=C(Br)C=N1 MYUQKYGWKHTRPG-UHFFFAOYSA-N 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 6
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 239000011737 fluorine Chemical group 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 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 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 238000004808 supercritical fluid chromatography Methods 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 5
- PZSVYVZMUOAVFG-UHFFFAOYSA-N 2-[(4,6-dimethylpyrimidin-2-yl)amino]-3-phenyl-1-[3-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]propan-1-one Chemical compound CC1=CC(C)=NC(NC(CC=2C=CC=CC=2)C(=O)N2CC=3N(C(=NN=3)C(F)(F)F)CC2)=N1 PZSVYVZMUOAVFG-UHFFFAOYSA-N 0.000 description 5
- AIEGIFIEQXZBCP-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyrazine Chemical compound FC(F)(F)C1=CN=C(Cl)C=N1 AIEGIFIEQXZBCP-UHFFFAOYSA-N 0.000 description 5
- TYCYTQLXAIDJNF-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CN=C(Cl)N=C1 TYCYTQLXAIDJNF-UHFFFAOYSA-N 0.000 description 5
- CXWLXKZIXLOBCC-UHFFFAOYSA-N 5-chloro-2-iodopyridine Chemical compound ClC1=CC=C(I)N=C1 CXWLXKZIXLOBCC-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 201000000980 schizophrenia Diseases 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 description 5
- 229910052727 yttrium Inorganic materials 0.000 description 5
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- APRMCBSTMFKLEI-UHFFFAOYSA-N 2-chloro-5-methylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1 APRMCBSTMFKLEI-UHFFFAOYSA-N 0.000 description 4
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 4
- JRRZVTVWAISKIX-UHFFFAOYSA-N 7,8-dimethoxy-4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]-5h-pyrimido[5,4-b]indole Chemical compound N1=CN=C2C=3C=C(OC)C(OC)=CC=3NC2=C1N(CC1)CCN1C1=CC=CC(C(F)(F)F)=C1 JRRZVTVWAISKIX-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 101000598922 Rattus norvegicus Orexin Proteins 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical compound Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- OFNHNCAUVYOTPM-IIIOAANCSA-N orexin-a Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@H](C(N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N2)[C@@H](C)O)=O)CSSC1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CNC=N1 OFNHNCAUVYOTPM-IIIOAANCSA-N 0.000 description 4
- OHOWSYIKESXDMN-WMQZXSDYSA-N orexin-b Chemical compound C([C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCSC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(N)=O)C1=CNC=N1 OHOWSYIKESXDMN-WMQZXSDYSA-N 0.000 description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 229940081066 picolinic acid Drugs 0.000 description 4
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 229910052702 rhenium Inorganic materials 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 3
- WZQQLMSKDLDZEL-UHFFFAOYSA-N 2-chloro-3-fluoro-5-(trifluoromethyl)pyridine Chemical compound FC1=CC(C(F)(F)F)=CN=C1Cl WZQQLMSKDLDZEL-UHFFFAOYSA-N 0.000 description 3
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 3
- SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 3
- LSCRTKSNLBBDHM-UHFFFAOYSA-N 6-methyl-3-(1,3-oxazol-2-yl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC(C)=CC=C1C1=NC=CO1 LSCRTKSNLBBDHM-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 206010026749 Mania Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 229910002666 PdCl2 Inorganic materials 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 230000037007 arousal Effects 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000004453 electron probe microanalysis Methods 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000027119 gastric acid secretion Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 210000003016 hypothalamus Anatomy 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 201000003631 narcolepsy Diseases 0.000 description 3
- 235000001968 nicotinic acid Nutrition 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 150000003852 triazoles Chemical class 0.000 description 3
- PPLSIVNRHUSMMC-UHFFFAOYSA-N (2-cyano-6-fluorophenyl)boronic acid Chemical compound OB(O)C1=C(F)C=CC=C1C#N PPLSIVNRHUSMMC-UHFFFAOYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- PHKKOEAUCOEGCR-GOEBONIOSA-N (3-ethoxy-6-methylpyridin-2-yl)-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound CCOc1ccc(C)nc1C(=O)N1CCC[C@@H](Oc2ccc(cn2)C(F)(F)F)[C@@H]1C PHKKOEAUCOEGCR-GOEBONIOSA-N 0.000 description 2
- JPAPUPPGEJYFCC-KBXCAEBGSA-N (3-fluoro-2-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=CC(F)=C1C1=NC=CC=N1 JPAPUPPGEJYFCC-KBXCAEBGSA-N 0.000 description 2
- ULGFPHXZFAAYGH-DOTOQJQBSA-N (3-methyl-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(C)c1-c1ncccn1)Oc1cnc(cn1)C(F)(F)F ULGFPHXZFAAYGH-DOTOQJQBSA-N 0.000 description 2
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- GRDMQGVBKFGUJJ-UHFFFAOYSA-N 2-(5-fluoropyrimidin-2-yl)benzoic acid Chemical compound OC(=O)c1ccccc1-c1ncc(F)cn1 GRDMQGVBKFGUJJ-UHFFFAOYSA-N 0.000 description 2
- FFHZTHYTLGADNT-UHFFFAOYSA-N 2-(triazol-2-yl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1N1N=CC=N1 FFHZTHYTLGADNT-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- BZUUVQCSPHPUQA-UHFFFAOYSA-N 2-bromo-5-chloropyridine Chemical compound ClC1=CC=C(Br)N=C1 BZUUVQCSPHPUQA-UHFFFAOYSA-N 0.000 description 2
- AGYUQBNABXVWMS-UHFFFAOYSA-N 2-chloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1 AGYUQBNABXVWMS-UHFFFAOYSA-N 0.000 description 2
- NEWFEFODKLAVHC-UHFFFAOYSA-N 2-fluoro-6-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 NEWFEFODKLAVHC-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- BCLGTIBYZQQFJW-UHFFFAOYSA-N 2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=NC=CC=N1 BCLGTIBYZQQFJW-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- ARSYSTQQVJUEBW-UHFFFAOYSA-N 3-bromo-6-methylpyridine-2-carbonitrile Chemical compound CC1=CC=C(Br)C(C#N)=N1 ARSYSTQQVJUEBW-UHFFFAOYSA-N 0.000 description 2
- FUDKQJGPXMZYCN-UHFFFAOYSA-N 3-methyl-2-pyrimidin-2-ylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C1=NC=CC=N1 FUDKQJGPXMZYCN-UHFFFAOYSA-N 0.000 description 2
- PHKJXGMOIKCOPR-UHFFFAOYSA-N 4-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid Chemical compound Cc1noc(n1)-c1cc(F)ccc1C(O)=O PHKJXGMOIKCOPR-UHFFFAOYSA-N 0.000 description 2
- RMHYWFYANVLDGS-UHFFFAOYSA-N 5-fluoro-2-(1,3-oxazol-2-yl)benzoic acid Chemical compound OC(=O)c1cc(F)ccc1-c1ncco1 RMHYWFYANVLDGS-UHFFFAOYSA-N 0.000 description 2
- OFJSWBKBSSNTBG-UHFFFAOYSA-N 5-methyl-2-pyrimidin-2-ylpyridine-3-carboxylic acid Chemical compound Cc1cnc(c(c1)C(O)=O)-c1ncccn1 OFJSWBKBSSNTBG-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- DKMACHNQISHMDN-RPLLCQBOSA-N Almorexant Chemical compound C([C@H]1C2=CC(OC)=C(OC)C=C2CCN1[C@@H](C(=O)NC)C=1C=CC=CC=1)CC1=CC=C(C(F)(F)F)C=C1 DKMACHNQISHMDN-RPLLCQBOSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 238000003650 Calcium Assay Kit Methods 0.000 description 2
- XVQGFGKAPKEUFT-UHFFFAOYSA-N Cc1nc(cc(C)cc2)c2[o]1 Chemical compound Cc1nc(cc(C)cc2)c2[o]1 XVQGFGKAPKEUFT-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102100037757 Orexin Human genes 0.000 description 2
- 229940123730 Orexin receptor antagonist Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 206010062519 Poor quality sleep Diseases 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- PGWAAWMSURLNEZ-QFBILLFUSA-N [(2s,3r)-3-[(4,6-dimethylpyrimidin-2-yl)amino]-2-methylpiperidin-1-yl]-(2-fluoro-6-pyrimidin-2-ylphenyl)methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=C(C)C=C(C)N=2)CCN1C(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 PGWAAWMSURLNEZ-QFBILLFUSA-N 0.000 description 2
- QUQAVBRFCYCLKE-GHTZIAJQSA-N [(2s,3r)-3-[(4,6-dimethylpyrimidin-2-yl)amino]-2-methylpiperidin-1-yl]-(5-methyl-2-pyrimidin-2-ylphenyl)methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=C(C)C=C(C)N=2)CCN1C(=O)C1=CC(C)=CC=C1C1=NC=CC=N1 QUQAVBRFCYCLKE-GHTZIAJQSA-N 0.000 description 2
- DCWFMOVQNBGEMC-IFXJQAMLSA-N [2-(5-fluoropyrimidin-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=CC=C1C1=NC=C(F)C=N1 DCWFMOVQNBGEMC-IFXJQAMLSA-N 0.000 description 2
- WYODUPBUNOMCSV-SCLBCKFNSA-N [3-fluoro-2-(5-fluoropyrimidin-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=CC(F)=C1C1=NC=C(F)C=N1 WYODUPBUNOMCSV-SCLBCKFNSA-N 0.000 description 2
- ZRBIBMLFZDCZSU-QAPCUYQASA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2r,3s)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@@H]([C@H]1C)NC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)C=C1N1N=CC=N1 ZRBIBMLFZDCZSU-QAPCUYQASA-N 0.000 description 2
- ICEDUEFIYVQEDT-XJKSGUPXSA-N [6-methyl-2-(triazol-1-yl)pyridin-3-yl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=CN=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)N=C1N1C=CN=N1 ICEDUEFIYVQEDT-XJKSGUPXSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229950003630 almorexant Drugs 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 210000004727 amygdala Anatomy 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 208000028683 bipolar I disease Diseases 0.000 description 2
- 230000036471 bradycardia Effects 0.000 description 2
- 208000006218 bradycardia Diseases 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000007975 buffered saline Substances 0.000 description 2
- 230000001275 ca(2+)-mobilization Effects 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229960003920 cocaine Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- ZXZBMGGWHWRHPS-UHFFFAOYSA-N cyanato(phenyl)borinic acid Chemical compound N#COB(O)C1=CC=CC=C1 ZXZBMGGWHWRHPS-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000003862 health status Effects 0.000 description 2
- 230000000742 histaminergic effect Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 238000000185 intracerebroventricular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- FOKUGIKLNXFRTI-UHFFFAOYSA-N methyl 2-chloro-5-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC(C)=CN=C1Cl FOKUGIKLNXFRTI-UHFFFAOYSA-N 0.000 description 2
- KLHWBYHFWALOIJ-UHFFFAOYSA-N methyl 2-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1C KLHWBYHFWALOIJ-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical group OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 230000001956 orexigenic effect Effects 0.000 description 2
- 229940125636 orexin 1 receptor antagonist Drugs 0.000 description 2
- 230000000446 orexinergic effect Effects 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000012877 positron emission topography Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 2
- 229960003081 probenecid Drugs 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical group OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000008454 sleep-wake cycle Effects 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000008117 stearic acid Chemical group 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ADVNLLSPFSWKPK-DTWKUNHWSA-N tert-butyl (2s,3r)-3-hydroxy-2-methylpiperidine-1-carboxylate Chemical compound C[C@H]1[C@H](O)CCCN1C(=O)OC(C)(C)C ADVNLLSPFSWKPK-DTWKUNHWSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 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 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- YOWGRWHKDCHINP-UHFFFAOYSA-N tributyl(1,3-oxazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CO1 YOWGRWHKDCHINP-UHFFFAOYSA-N 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 210000004515 ventral tegmental area Anatomy 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- XFQNWPYGEGCIMF-HCUGAJCMSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].[Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 XFQNWPYGEGCIMF-HCUGAJCMSA-N 0.000 description 1
- LEUHVAXWCPUPDY-KBXCAEBGSA-N (2-fluoro-6-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1c(F)cccc1-c1ncccn1)Nc1ccc(cn1)C(F)(F)F LEUHVAXWCPUPDY-KBXCAEBGSA-N 0.000 description 1
- BRQJMVDPWOHTPF-XJKSGUPXSA-N (2-fluoro-6-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 BRQJMVDPWOHTPF-XJKSGUPXSA-N 0.000 description 1
- ONHOIWLTBXLKTQ-SUMWQHHRSA-N (2-fluoro-6-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CN=2)C(F)(F)F)CCN1C(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 ONHOIWLTBXLKTQ-SUMWQHHRSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
- TZNCDXAIDIETKV-DTWKUNHWSA-N (2s,3r)-2-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid Chemical compound C[C@H]1[C@H](C(O)=O)CCCN1C(=O)OC(C)(C)C TZNCDXAIDIETKV-DTWKUNHWSA-N 0.000 description 1
- LBLBKHYDUJYKHT-JXFKEZNVSA-N (3-fluoro-2-methoxyphenyl)-[(2S,3S)-2-methyl-3-[(4-phenylpyrimidin-2-yl)amino]piperidin-1-yl]methanone Chemical compound FC=1C(=C(C=CC1)C(=O)N1[C@H]([C@H](CCC1)NC1=NC=CC(=N1)C1=CC=CC=C1)C)OC LBLBKHYDUJYKHT-JXFKEZNVSA-N 0.000 description 1
- RDJTUBZVCVIHQD-XJKSGUPXSA-N (3-fluoro-2-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=CC=CC(F)=C1C1=NC=CC=N1 RDJTUBZVCVIHQD-XJKSGUPXSA-N 0.000 description 1
- STQUTWCJANEVRV-MAUKXSAKSA-N (3-methyl-2-pyrimidin-2-ylphenyl)-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(C)c1-c1ncccn1)Oc1ncc(cn1)C(F)(F)F STQUTWCJANEVRV-MAUKXSAKSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- AFOWXNVTENGQBP-KBXCAEBGSA-N (5-fluoro-2-pyrimidin-2-ylphenyl)-[(2s,3r)-2-methyl-3-[[6-methyl-2-(trifluoromethyl)pyrimidin-4-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=C(N=C(C)C=2)C(F)(F)F)CCN1C(=O)C1=CC(F)=CC=C1C1=NC=CC=N1 AFOWXNVTENGQBP-KBXCAEBGSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 1
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical group C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical group C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 1
- JOXBFDPBVQGJOJ-UHFFFAOYSA-N 2,5-dichloro-1,3-benzoxazole Chemical compound ClC1=CC=C2OC(Cl)=NC2=C1 JOXBFDPBVQGJOJ-UHFFFAOYSA-N 0.000 description 1
- MOPDZJGIHCTDAR-UHFFFAOYSA-N 2-(2-bromo-6-fluorophenyl)-1,3-oxazole Chemical compound Fc1cccc(Br)c1-c1ncco1 MOPDZJGIHCTDAR-UHFFFAOYSA-N 0.000 description 1
- UTENUPFWBIFKPW-UHFFFAOYSA-N 2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1N=CC=N1 UTENUPFWBIFKPW-UHFFFAOYSA-N 0.000 description 1
- CEAMSISEJZMQEP-UHFFFAOYSA-N 2-(trifluoromethyl)pyrazine Chemical compound FC(F)(F)C1=CN=CC=N1 CEAMSISEJZMQEP-UHFFFAOYSA-N 0.000 description 1
- LHVTZXNQBWLUFQ-WCBMZHEXSA-N 2-[(2S,3R)-2-methylpiperidin-3-yl]oxy-5-(trifluoromethyl)pyridine Chemical compound C[C@@H]1NCCC[C@H]1Oc1ccc(cn1)C(F)(F)F LHVTZXNQBWLUFQ-WCBMZHEXSA-N 0.000 description 1
- IRYXZYBYEAEJKX-IONNQARKSA-N 2-[(2s,3r)-2-methylpiperidin-3-yl]oxy-5-(trifluoromethyl)pyrimidine Chemical compound C[C@@H]1NCCC[C@H]1OC1=NC=C(C(F)(F)F)C=N1 IRYXZYBYEAEJKX-IONNQARKSA-N 0.000 description 1
- ZZYYOHPHSYCHQG-UHFFFAOYSA-N 2-bromo-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C(Br)=C1 ZZYYOHPHSYCHQG-UHFFFAOYSA-N 0.000 description 1
- QIFDGTIOMAVGAQ-UHFFFAOYSA-N 2-bromo-5-fluorobenzoyl chloride Chemical compound FC1=CC=C(Br)C(C(Cl)=O)=C1 QIFDGTIOMAVGAQ-UHFFFAOYSA-N 0.000 description 1
- MDAZJVAIZVUWDE-UHFFFAOYSA-N 2-bromo-6-fluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1Br MDAZJVAIZVUWDE-UHFFFAOYSA-N 0.000 description 1
- PGFIHORVILKHIA-UHFFFAOYSA-N 2-bromopyrimidine Chemical compound BrC1=NC=CC=N1 PGFIHORVILKHIA-UHFFFAOYSA-N 0.000 description 1
- RZVPFDOTMFYQHR-UHFFFAOYSA-N 2-chloro-4,6-dimethylpyrimidine Chemical compound CC1=CC(C)=NC(Cl)=N1 RZVPFDOTMFYQHR-UHFFFAOYSA-N 0.000 description 1
- FZRBTBCCMVNZBD-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC=NC(Cl)=N1 FZRBTBCCMVNZBD-UHFFFAOYSA-N 0.000 description 1
- AAZYJKNISGEWEV-UHFFFAOYSA-N 2-chloro-4-phenylpyrimidine Chemical compound ClC1=NC=CC(C=2C=CC=CC=2)=N1 AAZYJKNISGEWEV-UHFFFAOYSA-N 0.000 description 1
- VGYRHYFUTYYEHQ-UHFFFAOYSA-N 2-chloro-5-iodopyrazine Chemical compound ClC1=CN=C(I)C=N1 VGYRHYFUTYYEHQ-UHFFFAOYSA-N 0.000 description 1
- VXLYOURCUVQYLN-UHFFFAOYSA-N 2-chloro-5-methylpyridine Chemical compound CC1=CC=C(Cl)N=C1 VXLYOURCUVQYLN-UHFFFAOYSA-N 0.000 description 1
- JPBUYRWPJMVZKX-UHFFFAOYSA-N 2-chloro-6-methoxypyridine-3-carboxylic acid Chemical compound COC1=CC=C(C(O)=O)C(Cl)=N1 JPBUYRWPJMVZKX-UHFFFAOYSA-N 0.000 description 1
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
- WMPTYRGXBUYONY-UHFFFAOYSA-N 2-chloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC=C21 WMPTYRGXBUYONY-UHFFFAOYSA-N 0.000 description 1
- BYHVGQHIAFURIL-UHFFFAOYSA-N 2-chloroquinoxaline Chemical compound C1=CC=CC2=NC(Cl)=CN=C21 BYHVGQHIAFURIL-UHFFFAOYSA-N 0.000 description 1
- NTPOZDBAGMLNQA-UHFFFAOYSA-N 2-fluoro-6-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1N1N=CC=N1 NTPOZDBAGMLNQA-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical group C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- CCZWSTFVHJPCEM-UHFFFAOYSA-N 2-iodopyridine Chemical compound IC1=CC=CC=N1 CCZWSTFVHJPCEM-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
- YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WGKYSFRFMQHMOF-UHFFFAOYSA-N 3-bromo-5-methylpyridine-2-carbonitrile Chemical compound CC1=CN=C(C#N)C(Br)=C1 WGKYSFRFMQHMOF-UHFFFAOYSA-N 0.000 description 1
- MXOLBWQGTJFFIL-UHFFFAOYSA-N 3-bromo-6-methylpyridine-2-carboxylic acid Chemical compound CC1=CC=C(Br)C(C(O)=O)=N1 MXOLBWQGTJFFIL-UHFFFAOYSA-N 0.000 description 1
- AZNKQIFEMQHORS-UHFFFAOYSA-N 3-chloro-6-(trifluoromethyl)pyridazine Chemical compound FC(F)(F)C1=CC=C(Cl)N=N1 AZNKQIFEMQHORS-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- XUYJQZIULVDUOP-UHFFFAOYSA-N 3-ethoxy-6-methylpyridine-2-carboxylic acid Chemical compound CCOC1=CC=C(C)N=C1C(O)=O XUYJQZIULVDUOP-UHFFFAOYSA-N 0.000 description 1
- DSPARGRXZADGGO-UHFFFAOYSA-N 3-fluoro-2-(1,3-oxazol-2-yl)benzoic acid Chemical compound OC(=O)c1cccc(F)c1-c1ncco1 DSPARGRXZADGGO-UHFFFAOYSA-N 0.000 description 1
- NWDXVJNAXAQTFY-UHFFFAOYSA-N 3-fluoro-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1C1=NC=CC=N1 NWDXVJNAXAQTFY-UHFFFAOYSA-N 0.000 description 1
- JGBSDYQSGSBVTP-UHFFFAOYSA-N 3-fluoro-2-pyrimidin-2-ylbenzonitrile Chemical compound FC1=CC=CC(C#N)=C1C1=NC=CC=N1 JGBSDYQSGSBVTP-UHFFFAOYSA-N 0.000 description 1
- SXPDVQWFDCTUEC-UHFFFAOYSA-N 3-methyl-2-(triazol-2-yl)benzaldehyde Chemical compound CC1=CC=CC(C=O)=C1N1N=CC=N1 SXPDVQWFDCTUEC-UHFFFAOYSA-N 0.000 description 1
- DQLZTJMUULVRNZ-UHFFFAOYSA-N 3-phenylpyrazine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN=C1C1=CC=CC=C1 DQLZTJMUULVRNZ-UHFFFAOYSA-N 0.000 description 1
- RDOFZTRTPMRTIP-UHFFFAOYSA-N 3-pyrimidin-2-ylpyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=C1C1=NC=CC=N1 RDOFZTRTPMRTIP-UHFFFAOYSA-N 0.000 description 1
- KRVXQNFBPMYAEN-UHFFFAOYSA-N 4,6-dimethyl-n-(2-methylpiperidin-3-yl)pyrimidin-2-amine Chemical compound CC1NCCCC1NC1=NC(C)=CC(C)=N1 KRVXQNFBPMYAEN-UHFFFAOYSA-N 0.000 description 1
- VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- UZGKRWRIUHIHDE-UHFFFAOYSA-N 4-chloro-6-methyl-2-(trifluoromethyl)pyrimidine Chemical compound CC1=CC(Cl)=NC(C(F)(F)F)=N1 UZGKRWRIUHIHDE-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- OFAXWDKIIVPXNT-UHFFFAOYSA-N 4-fluoro-2-(1,3-oxazol-2-yl)benzoic acid Chemical compound OC(=O)c1ccc(F)cc1-c1ncco1 OFAXWDKIIVPXNT-UHFFFAOYSA-N 0.000 description 1
- MTEVFUQSWSTKTE-UHFFFAOYSA-N 4-fluoro-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1C1=NC=CC=N1 MTEVFUQSWSTKTE-UHFFFAOYSA-N 0.000 description 1
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 1
- JHOQVQSTUMAGNQ-UHFFFAOYSA-N 4-methyl-2-(trifluoromethyl)pyrimidine Chemical compound CC1=CC=NC(C(F)(F)F)=N1 JHOQVQSTUMAGNQ-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- IMIRQOBEXFQQDT-WCBMZHEXSA-N 5-bromo-N-[(2S,3R)-2-methylpiperidin-3-yl]pyridin-2-amine Chemical compound BrC=1C=CC(=NC1)N[C@H]1[C@@H](NCCC1)C IMIRQOBEXFQQDT-WCBMZHEXSA-N 0.000 description 1
- MCHQXMKKLMBYDB-WCBMZHEXSA-N 5-chloro-N-[(2S,3R)-2-methylpiperidin-3-yl]pyridin-2-amine Chemical compound ClC=1C=CC(=NC1)N[C@H]1[C@@H](NCCC1)C MCHQXMKKLMBYDB-WCBMZHEXSA-N 0.000 description 1
- HCYLTPJADJTYPX-UHFFFAOYSA-N 5-fluoro-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1N1N=CC=N1 HCYLTPJADJTYPX-UHFFFAOYSA-N 0.000 description 1
- SKKQNFJMWPLVDB-UHFFFAOYSA-N 5-fluoro-2-iodopyridine Chemical compound FC1=CC=C(I)N=C1 SKKQNFJMWPLVDB-UHFFFAOYSA-N 0.000 description 1
- LPEYDAWIGDXFNJ-UHFFFAOYSA-N 5-fluoro-2-iodopyrimidine Chemical compound FC1=CN=C(I)N=C1 LPEYDAWIGDXFNJ-UHFFFAOYSA-N 0.000 description 1
- GWFSRJKDYXADOG-UHFFFAOYSA-N 5-fluoro-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1C1=NC=CC=N1 GWFSRJKDYXADOG-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- WKBKHXGASBZRMI-UHFFFAOYSA-N 5-methyl-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1C1=NC=CC=N1 WKBKHXGASBZRMI-UHFFFAOYSA-N 0.000 description 1
- YGZWWVFDICUXSH-UHFFFAOYSA-N 5-methyl-3-(1,3-oxazol-2-yl)pyridine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C(C=2OC=CN=2)=C1 YGZWWVFDICUXSH-UHFFFAOYSA-N 0.000 description 1
- BCXCHIBKOBLJAX-UHFFFAOYSA-N 5-methyl-3-pyrimidin-2-ylpyridine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C(C=2N=CC=CN=2)=C1 BCXCHIBKOBLJAX-UHFFFAOYSA-N 0.000 description 1
- QCOCOZHFOVXTJL-UHFFFAOYSA-N 6-methyl-2-(triazol-1-yl)pyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C(N2N=NC=C2)=N1 QCOCOZHFOVXTJL-UHFFFAOYSA-N 0.000 description 1
- YDJKIHIETNFDIH-UHFFFAOYSA-N 6-methyl-3-pyrimidin-2-ylpyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC(C)=CC=C1C1=NC=CC=N1 YDJKIHIETNFDIH-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- ZPSDIWUHUPZIJW-SNAWJCMRSA-N C/C=C(/C(F)(F)F)\C=C Chemical compound C/C=C(/C(F)(F)F)\C=C ZPSDIWUHUPZIJW-SNAWJCMRSA-N 0.000 description 1
- LIMGNLRTKGGPQM-YZSQISJMSA-N C=C(/C(/CCC1)=N/c2nc(cc(cc3)Cl)c3[o]2)N1C(c(cccc1)c1-[n]1nccn1)=O Chemical compound C=C(/C(/CCC1)=N/c2nc(cc(cc3)Cl)c3[o]2)N1C(c(cccc1)c1-[n]1nccn1)=O LIMGNLRTKGGPQM-YZSQISJMSA-N 0.000 description 1
- FJZJNAKNWDXGEF-UHFFFAOYSA-N CC(c1c(-[n]2nccn2)nc(C)cc1)=O Chemical compound CC(c1c(-[n]2nccn2)nc(C)cc1)=O FJZJNAKNWDXGEF-UHFFFAOYSA-N 0.000 description 1
- SKOQZEUBOZCWAB-UHFFFAOYSA-N CC(c1cccc(F)c1-c1ncc[o]1)=O Chemical compound CC(c1cccc(F)c1-c1ncc[o]1)=O SKOQZEUBOZCWAB-UHFFFAOYSA-N 0.000 description 1
- JYZSZQDDJIAJRE-UHFFFAOYSA-N CC1(C)OB(c2ccccc2C(OC)=C)OC1(C)C Chemical compound CC1(C)OB(c2ccccc2C(OC)=C)OC1(C)C JYZSZQDDJIAJRE-UHFFFAOYSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- HCGXAWRKDSMRAE-UHFFFAOYSA-N COC(CNC(=O)c1c(F)cccc1Br)OC Chemical compound COC(CNC(=O)c1c(F)cccc1Br)OC HCGXAWRKDSMRAE-UHFFFAOYSA-N 0.000 description 1
- ZBUTYPYFXZASFK-SUMWQHHRSA-N COC1=CC(=C(C=C1)C(=O)N1[C@H]([C@@H](CCC1)OC1=NC=C(N=C1)C(F)(F)F)C)C=1OC=CN=1 Chemical compound COC1=CC(=C(C=C1)C(=O)N1[C@H]([C@@H](CCC1)OC1=NC=C(N=C1)C(F)(F)F)C)C=1OC=CN=1 ZBUTYPYFXZASFK-SUMWQHHRSA-N 0.000 description 1
- QCZJMBCRMLNRCE-AWEZNQCLSA-N C[C@@H](/C(/CCC1)=[O]/c(cc2)ncc2F)N1C(c(c(-c1ncccn1)c1)ccc1F)=O Chemical compound C[C@@H](/C(/CCC1)=[O]/c(cc2)ncc2F)N1C(c(c(-c1ncccn1)c1)ccc1F)=O QCZJMBCRMLNRCE-AWEZNQCLSA-N 0.000 description 1
- XPHVDEXAYKBDEU-VIFPVBQESA-N C[C@@H](C(CCC1)=N)N1C(c(c(-c1nc(C)n[o]1)c1)ccc1F)=O Chemical compound C[C@@H](C(CCC1)=N)N1C(c(c(-c1nc(C)n[o]1)c1)ccc1F)=O XPHVDEXAYKBDEU-VIFPVBQESA-N 0.000 description 1
- VFLUSJVJWQZBLK-MAUKXSAKSA-N C[C@@H]([C@@H](CCC1)Nc2ccc(C(F)(F)F)cn2)N1C(c1ncc(C)cc1-c1ncccn1)=O Chemical compound C[C@@H]([C@@H](CCC1)Nc2ccc(C(F)(F)F)cn2)N1C(c1ncc(C)cc1-c1ncccn1)=O VFLUSJVJWQZBLK-MAUKXSAKSA-N 0.000 description 1
- VRSIHZAGCZQYOU-NTSWFWBYSA-N C[C@@H]1NCCC[C@H]1N Chemical compound C[C@@H]1NCCC[C@H]1N VRSIHZAGCZQYOU-NTSWFWBYSA-N 0.000 description 1
- HUSYBQVRQNVSAC-NTSWFWBYSA-N C[C@@H]1NCCC[C@H]1OC(O)=N Chemical compound C[C@@H]1NCCC[C@H]1OC(O)=N HUSYBQVRQNVSAC-NTSWFWBYSA-N 0.000 description 1
- VMIHTVAQWFTSLP-BUSXIPJBSA-N C[C@H]1C(CCCN1C(=O)C1=CC=C(C)N=C1N1N=CC=N1)N(C)C1=CC=C(C=N1)C(F)(F)F Chemical compound C[C@H]1C(CCCN1C(=O)C1=CC=C(C)N=C1N1N=CC=N1)N(C)C1=CC=C(C=N1)C(F)(F)F VMIHTVAQWFTSLP-BUSXIPJBSA-N 0.000 description 1
- WAVFTCZXODJVLZ-ATNAJCNCSA-N C[C@H]1C(CCCN1C(=O)C1=NC=C(C)C=C1N1N=CC=N1)N(C)C1=NC2=C(O1)C=CC=C2 Chemical compound C[C@H]1C(CCCN1C(=O)C1=NC=C(C)C=C1N1N=CC=N1)N(C)C1=NC2=C(O1)C=CC=C2 WAVFTCZXODJVLZ-ATNAJCNCSA-N 0.000 description 1
- VRSIHZAGCZQYOU-PHDIDXHHSA-N C[C@H]1NCCC[C@H]1N Chemical compound C[C@H]1NCCC[C@H]1N VRSIHZAGCZQYOU-PHDIDXHHSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 208000022497 Cocaine-Related disease Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Chemical group OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical group OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 206010020591 Hypercapnia Diseases 0.000 description 1
- 240000007049 Juglans regia Species 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Chemical group OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
- 101100002888 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) asa-1 gene Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 229940127340 Orexin Receptor Agonists Drugs 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910019020 PtO2 Inorganic materials 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 206010042008 Stereotypy Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 101000870046 Sus scrofa Glutamate dehydrogenase 1, mitochondrial Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000037063 Thinness Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- OLWLWNLEWJGDOQ-GXTWGEPZSA-N [(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]-[2-(triazol-2-yl)pyridin-3-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccnc1-n1nccn1)Oc1cnc(cn1)C(F)(F)F OLWLWNLEWJGDOQ-GXTWGEPZSA-N 0.000 description 1
- ISQLCABBZVALSX-XJKSGUPXSA-N [(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-[2-(triazol-2-yl)pyridin-3-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccnc1-n1nccn1)Oc1ccc(cn1)C(F)(F)F ISQLCABBZVALSX-XJKSGUPXSA-N 0.000 description 1
- NFZVAMUIGNMOQC-MAUKXSAKSA-N [(2S,3R)-3-(1,3-benzoxazol-2-ylamino)-2-methylpiperidin-1-yl]-(3-fluoro-2-pyrimidin-2-ylphenyl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-c1ncccn1)Nc1nc2ccccc2o1 NFZVAMUIGNMOQC-MAUKXSAKSA-N 0.000 description 1
- DDSAXTXKKUISNY-MAUKXSAKSA-N [(2S,3R)-3-(5-chloropyridin-2-yl)oxy-2-methylpiperidin-1-yl]-(5-methyl-3-pyrimidin-2-ylpyridin-2-yl)methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ncc(C)cc1-c1ncccn1)Oc1ccc(Cl)cn1 DDSAXTXKKUISNY-MAUKXSAKSA-N 0.000 description 1
- ICXLAGMSOVDTOC-WMLDXEAASA-N [(2S,3R)-3-(5-chloropyridin-2-yl)oxy-2-methylpiperidin-1-yl]-[5-methyl-2-(triazol-2-yl)pyridin-3-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)C1=CC(C)=CN=C1N1N=CC=N1)OC1=CC=C(Cl)C=N1 ICXLAGMSOVDTOC-WMLDXEAASA-N 0.000 description 1
- HRVLQBWKSUMVJP-WMLDXEAASA-N [(2S,3R)-3-(5-chloropyridin-2-yl)oxy-2-methylpiperidin-1-yl]-[6-methyl-3-(triazol-2-yl)pyridin-2-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1nc(C)ccc1-n1nccn1)Oc1ccc(Cl)cn1 HRVLQBWKSUMVJP-WMLDXEAASA-N 0.000 description 1
- KEHNRTZXDJCYLK-XJKSGUPXSA-N [(2S,3R)-3-(5-chloropyrimidin-2-yl)oxy-2-methylpiperidin-1-yl]-[5-methyl-2-(triazol-2-yl)pyridin-3-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(C)cnc1-n1nccn1)Oc1ncc(Cl)cn1 KEHNRTZXDJCYLK-XJKSGUPXSA-N 0.000 description 1
- WZYUHXZJMVLLLY-XJKSGUPXSA-N [(2S,3R)-3-(5-chloropyrimidin-2-yl)oxy-2-methylpiperidin-1-yl]-[6-methyl-3-(triazol-2-yl)pyridin-2-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1nc(C)ccc1-n1nccn1)Oc1ncc(Cl)cn1 WZYUHXZJMVLLLY-XJKSGUPXSA-N 0.000 description 1
- KQKGJZDANPAUKS-SUMWQHHRSA-N [(2S,3R)-3-[(5-chloropyridin-2-yl)amino]-2-methylpiperidin-1-yl]-[4-hydroxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(O)cc1-n1nccn1)Nc1ccc(Cl)cn1 KQKGJZDANPAUKS-SUMWQHHRSA-N 0.000 description 1
- OAUWCQCEUJZMLE-SUMWQHHRSA-N [(2S,3R)-3-[(5-chloropyrimidin-2-yl)amino]-2-methylpiperidin-1-yl]-[4-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound COc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(Cl)cn3)[C@@H]2C)c(c1)-n1nccn1 OAUWCQCEUJZMLE-SUMWQHHRSA-N 0.000 description 1
- KRXWZPSYRRHZES-SUMWQHHRSA-N [(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]-[6-methyl-3-(triazol-2-yl)pyridin-2-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1nc(C)ccc1-n1nccn1)Oc1ncc(cc1F)C(F)(F)F KRXWZPSYRRHZES-SUMWQHHRSA-N 0.000 description 1
- QXXMPXNHRJWCKM-HNAYVOBHSA-N [(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]-(2-pyrimidin-2-ylphenyl)methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=CC=C1C1=NC=CC=N1 QXXMPXNHRJWCKM-HNAYVOBHSA-N 0.000 description 1
- ZOMRKOVTLMRMIZ-SUMWQHHRSA-N [(2s,3r)-3-(5-fluoropyridin-2-yl)oxy-2-methylpiperidin-1-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(F)=CC=2)CCN1C(=O)C1=C(F)C=CC=C1N1N=CC=N1 ZOMRKOVTLMRMIZ-SUMWQHHRSA-N 0.000 description 1
- CSIBWPBLNQANHN-SUMWQHHRSA-N [(2s,3r)-3-(5-fluoropyrimidin-2-yl)oxy-2-methylpiperidin-1-yl]-(2-fluoro-6-pyrimidin-2-ylphenyl)methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(F)=CN=2)CCN1C(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 CSIBWPBLNQANHN-SUMWQHHRSA-N 0.000 description 1
- GWKDUSDVRZEFJY-MAUKXSAKSA-N [(2s,3r)-3-[(4,6-dimethylpyrimidin-2-yl)amino]-2-methylpiperidin-1-yl]-[4-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical group C([C@H]([C@@H]1C)NC=2N=C(C)C=C(C)N=2)CCN1C(=O)C1=CC=C(F)C=C1N1N=CC=N1 GWKDUSDVRZEFJY-MAUKXSAKSA-N 0.000 description 1
- UJACRBAZNUEFHY-WMLDXEAASA-N [(2s,3r)-3-[(5-chloro-1,3-benzoxazol-2-yl)amino]-2-methylpiperidin-1-yl]-(2-ethoxyphenyl)methanone Chemical compound CCOC1=CC=CC=C1C(=O)N1[C@@H](C)[C@H](NC=2OC3=CC=C(Cl)C=C3N=2)CCC1 UJACRBAZNUEFHY-WMLDXEAASA-N 0.000 description 1
- WAZMVFLROLELSK-BLLLJJGKSA-N [(2s,3r)-3-[(5-chloro-1,3-benzoxazol-2-yl)amino]-2-methylpiperidin-1-yl]-(3-fluoro-2-methoxyphenyl)methanone Chemical compound COC1=C(F)C=CC=C1C(=O)N1[C@@H](C)[C@H](NC=2OC3=CC=C(Cl)C=C3N=2)CCC1 WAZMVFLROLELSK-BLLLJJGKSA-N 0.000 description 1
- PUBIAPWPALTDAT-SUMWQHHRSA-N [3-fluoro-2-(1,3-oxazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(F)c1-c1ncco1)Oc1ccc(cn1)C(F)(F)F PUBIAPWPALTDAT-SUMWQHHRSA-N 0.000 description 1
- QTSWRUVIRWJXGX-YVEFUNNKSA-N [3-fluoro-2-(triazol-2-yl)phenyl]-[(2S,3R)-3-[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]oxy-2-methylpiperidin-1-yl]methanone Chemical compound FC=1C(=C(C=CC1)C(=O)N1[C@H]([C@@H](CCC1)OC1=NC=C(C=C1F)C(F)(F)F)C)N1N=CC=N1 QTSWRUVIRWJXGX-YVEFUNNKSA-N 0.000 description 1
- XIYPJKVOOSGFDY-MAUKXSAKSA-N [3-methyl-2-(triazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cccc(C)c1-n1nccn1)Oc1ccc(cn1)C(F)(F)F XIYPJKVOOSGFDY-MAUKXSAKSA-N 0.000 description 1
- UDVCQFHKJXMPAW-WMLDXEAASA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)C=C1N1N=CC=N1 UDVCQFHKJXMPAW-WMLDXEAASA-N 0.000 description 1
- XGEFTTBCWFRPGV-HNAYVOBHSA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)C=C1N1N=CC=N1 XGEFTTBCWFRPGV-HNAYVOBHSA-N 0.000 description 1
- JFXDJLHQJPZLSN-KBXCAEBGSA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CN=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)C=C1N1N=CC=N1 JFXDJLHQJPZLSN-KBXCAEBGSA-N 0.000 description 1
- XVFCQHCDKUDNGJ-GOEBONIOSA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)C=C1N1N=CC=N1 XVFCQHCDKUDNGJ-GOEBONIOSA-N 0.000 description 1
- ZRBIBMLFZDCZSU-MAUKXSAKSA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)C=C1N1N=CC=N1 ZRBIBMLFZDCZSU-MAUKXSAKSA-N 0.000 description 1
- JXGLIITZXXQPKS-WMLDXEAASA-N [4-methyl-2-(triazol-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=CN=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)C=C1N1N=CC=N1 JXGLIITZXXQPKS-WMLDXEAASA-N 0.000 description 1
- HYBZWVLPALMACV-KRWDZBQOSA-N [5-(2-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]-[(2s)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]pyrrolidin-1-yl]methanone Chemical compound C([C@@H]1CCCN1C(=O)C=1N=C(SC=1C=1C(=CC=CC=1)F)C)C(O1)=NN=C1C1=CC=CC=C1 HYBZWVLPALMACV-KRWDZBQOSA-N 0.000 description 1
- VVJYGZWFWUWUJO-BLLLJJGKSA-N [5-fluoro-2-(1,3-oxazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(F)ccc1-c1ncco1)Oc1cnc(cn1)C(F)(F)F VVJYGZWFWUWUJO-BLLLJJGKSA-N 0.000 description 1
- YVEMFGSZPCVSEI-YVEFUNNKSA-N [5-fluoro-2-(1,3-oxazol-2-yl)phenyl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(F)ccc1-c1ncco1)Oc1ncc(cn1)C(F)(F)F YVEMFGSZPCVSEI-YVEFUNNKSA-N 0.000 description 1
- FSJKTNCHWPGSBK-SWLSCSKDSA-N [5-fluoro-2-(triazol-2-yl)phenyl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=CC(F)=CC=C1N1N=CC=N1 FSJKTNCHWPGSBK-SWLSCSKDSA-N 0.000 description 1
- DHWGXSUIOZDQEI-DZGCQCFKSA-N [5-methyl-2-(triazol-2-yl)pyridin-3-yl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(C)cnc1-n1nccn1)Oc1cnc(cn1)C(F)(F)F DHWGXSUIOZDQEI-DZGCQCFKSA-N 0.000 description 1
- RYMAUCKHOKOPRZ-WMLDXEAASA-N [5-methyl-2-(triazol-2-yl)pyridin-3-yl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(C)cnc1-n1nccn1)Oc1ccc(cn1)C(F)(F)F RYMAUCKHOKOPRZ-WMLDXEAASA-N 0.000 description 1
- ORTWHLUQDWPKRE-XJKSGUPXSA-N [5-methyl-2-(triazol-2-yl)pyridin-3-yl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1cc(C)cnc1-n1nccn1)Oc1ncc(cn1)C(F)(F)F ORTWHLUQDWPKRE-XJKSGUPXSA-N 0.000 description 1
- HQKWCPSSDIUZRS-NWDGAFQWSA-N [5-methyl-3-(triazol-2-yl)pyridin-2-yl]-[(2S,3R)-2-methyl-3-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]amino]piperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ncc(C)cc1-n1nccn1)Nc1nnc(s1)C(F)(F)F HQKWCPSSDIUZRS-NWDGAFQWSA-N 0.000 description 1
- YMMFIXZKKPCYLT-WMLDXEAASA-N [5-methyl-3-(triazol-2-yl)pyridin-2-yl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=NC=C(C)C=C1N1N=CC=N1 YMMFIXZKKPCYLT-WMLDXEAASA-N 0.000 description 1
- WTIKCHCKZINZAY-DZGCQCFKSA-N [6-methyl-2-(triazol-1-yl)pyridin-3-yl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)N=C1N1C=CN=N1 WTIKCHCKZINZAY-DZGCQCFKSA-N 0.000 description 1
- YRMUFQJLGZCJOK-WMLDXEAASA-N [6-methyl-2-(triazol-1-yl)pyridin-3-yl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)N=C1N1C=CN=N1 YRMUFQJLGZCJOK-WMLDXEAASA-N 0.000 description 1
- QQXKYUMNBGVDRN-WMLDXEAASA-N [6-methyl-2-(triazol-2-yl)pyridin-3-yl]-[(2S,3R)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C[C@H]1[C@@H](CCCN1C(=O)c1ccc(C)nc1-n1nccn1)Oc1ccc(cn1)C(F)(F)F QQXKYUMNBGVDRN-WMLDXEAASA-N 0.000 description 1
- MJLJSCSONZTZQZ-DZGCQCFKSA-N [6-methyl-2-(triazol-2-yl)pyridin-3-yl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)N=C1N1N=CC=N1 MJLJSCSONZTZQZ-DZGCQCFKSA-N 0.000 description 1
- VNVKHTSBNSOHFL-WMLDXEAASA-N [6-methyl-2-(triazol-2-yl)pyridin-3-yl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyridin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)N=C1N1N=CC=N1 VNVKHTSBNSOHFL-WMLDXEAASA-N 0.000 description 1
- JTVBTTLMGGYEPR-XJKSGUPXSA-N [6-methyl-2-(triazol-2-yl)pyridin-3-yl]-[(2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)NC=2N=CC(=CN=2)C(F)(F)F)CCN1C(=O)C1=CC=C(C)N=C1N1N=CC=N1 JTVBTTLMGGYEPR-XJKSGUPXSA-N 0.000 description 1
- KLTUCVRMBXYZLV-DZGCQCFKSA-N [6-methyl-3-(triazol-2-yl)pyridin-2-yl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyrazin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=NC=2)C(F)(F)F)CCN1C(=O)C1=NC(C)=CC=C1N1N=CC=N1 KLTUCVRMBXYZLV-DZGCQCFKSA-N 0.000 description 1
- DRWCBUCUCHOVIY-WMLDXEAASA-N [6-methyl-3-(triazol-2-yl)pyridin-2-yl]-[(2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyridin-2-yl]oxypiperidin-1-yl]methanone Chemical compound C([C@H]([C@@H]1C)OC=2N=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=NC(C)=CC=C1N1N=CC=N1 DRWCBUCUCHOVIY-WMLDXEAASA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000010210 aluminium Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000012435 analytical chromatography Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- TYZYCTFRZMCXTC-UHFFFAOYSA-N c1cnc(N2[IH]#C2)nc1 Chemical compound c1cnc(N2[IH]#C2)nc1 TYZYCTFRZMCXTC-UHFFFAOYSA-N 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 201000001272 cocaine abuse Diseases 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007357 depressive behavior Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- LZWLLMFYVGUUAL-UHFFFAOYSA-L ditert-butyl(cyclopenta-1,3-dien-1-yl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1 LZWLLMFYVGUUAL-UHFFFAOYSA-L 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical group CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 238000011833 dog model Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000000517 effect on sleep Effects 0.000 description 1
- 230000008918 emotional behaviour Effects 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 210000000105 enteric nervous system Anatomy 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000035611 feeding Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000012048 forced swim test Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
- 230000030135 gastric motility Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000000174 gluconic acid Chemical group 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000004220 glutamic acid Chemical group 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 210000004326 gyrus cinguli Anatomy 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000003796 lateral hypothalamic area Anatomy 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- FCMQMRAFVRTHCR-UHFFFAOYSA-N methyl 2-bromo-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1Br FCMQMRAFVRTHCR-UHFFFAOYSA-N 0.000 description 1
- IUQMIDJSHQTFJN-UHFFFAOYSA-N methyl 3-bromo-6-methylpyridine-2-carboxylate Chemical compound COC(=O)C1=NC(C)=CC=C1Br IUQMIDJSHQTFJN-UHFFFAOYSA-N 0.000 description 1
- NBJLFEJRZGCGJH-UHFFFAOYSA-N methyl 3-fluoro-2-(1,3-oxazol-2-yl)benzoate Chemical compound COC(=O)c1cccc(F)c1-c1ncco1 NBJLFEJRZGCGJH-UHFFFAOYSA-N 0.000 description 1
- MPFSXRMZJIYCGW-UHFFFAOYSA-N methyl 3-methyl-2-pyrimidin-2-ylbenzoate Chemical compound COC(=O)C1=CC=CC(C)=C1C1=NC=CC=N1 MPFSXRMZJIYCGW-UHFFFAOYSA-N 0.000 description 1
- SNQAQKDWFFYFRE-UHFFFAOYSA-N methyl 5-fluoro-2-(1,3-oxazol-2-yl)benzoate Chemical compound COC(=O)c1cc(F)ccc1-c1ncco1 SNQAQKDWFFYFRE-UHFFFAOYSA-N 0.000 description 1
- HWWONBVBEFIPIV-UHFFFAOYSA-N methyl 5-methyl-2-pyrimidin-2-ylpyridine-3-carboxylate Chemical compound COC(=O)c1cc(C)cnc1-c1ncccn1 HWWONBVBEFIPIV-UHFFFAOYSA-N 0.000 description 1
- MGETVQYSFJDWEG-UHFFFAOYSA-N methyl 6-methyl-3-(1,3-oxazol-2-yl)pyridine-2-carboxylate Chemical compound COC(=O)C1=NC(C)=CC=C1C1=NC=CO1 MGETVQYSFJDWEG-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 208000008013 morphine dependence Diseases 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 210000003249 myenteric plexus Anatomy 0.000 description 1
- AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
- RHLNWGPHBXSJBR-UHFFFAOYSA-N n-(2-methylpiperidin-3-yl)-1,3-benzoxazol-2-amine Chemical compound CC1NCCCC1NC1=NC2=CC=CC=C2O1 RHLNWGPHBXSJBR-UHFFFAOYSA-N 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- OMBZCXNZKFAHPP-JGVFFNPUSA-N n-[(2s,3r)-2-methylpiperidin-3-yl]-5-(trifluoromethyl)pyrazin-2-amine Chemical compound C[C@@H]1NCCC[C@H]1NC1=CN=C(C(F)(F)F)C=N1 OMBZCXNZKFAHPP-JGVFFNPUSA-N 0.000 description 1
- RQIMXAAJGXVBHJ-IONNQARKSA-N n-[(2s,3r)-2-methylpiperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine Chemical compound C[C@@H]1NCCC[C@H]1NC1=NC=C(C(F)(F)F)C=N1 RQIMXAAJGXVBHJ-IONNQARKSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- KJPHTXTWFHVJIG-MJVMYBOOSA-N n-ethyl-2-[(2-methylphenyl)sulfonyl-[6-(tritritiomethoxy)pyridin-3-yl]amino]-n-[(6-tritiopyridin-3-yl)methyl]acetamide Chemical compound C1=NC([3H])=CC=C1CN(CC)C(=O)CN(S(=O)(=O)C=1C(=CC=CC=1)C)C1=CC=C(OC([3H])([3H])[3H])N=C1 KJPHTXTWFHVJIG-MJVMYBOOSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- VLZLOWPYUQHHCG-UHFFFAOYSA-N nitromethylbenzene Chemical compound [O-][N+](=O)CC1=CC=CC=C1 VLZLOWPYUQHHCG-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000012346 open field test Methods 0.000 description 1
- 239000008008 oral excipient Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical group OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000012026 peptide coupling reagents Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001144 powder X-ray diffraction data Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940075993 receptor modulator Drugs 0.000 description 1
- 230000003893 regulation of appetite Effects 0.000 description 1
- 230000018406 regulation of metabolic process Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000000470 submucous plexus Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008700 sympathetic activation Effects 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- CZQDFIFYARZSAX-GOEBONIOSA-N tert-butyl (2s,3r)-2-methyl-3-(phenylmethoxycarbonylamino)piperidine-1-carboxylate Chemical compound C1CCN(C(=O)OC(C)(C)C)[C@@H](C)[C@@H]1NC(=O)OCC1=CC=CC=C1 CZQDFIFYARZSAX-GOEBONIOSA-N 0.000 description 1
- ZFVCUWYENNXYNE-CMPLNLGQSA-N tert-butyl (2s,3r)-2-methyl-3-[5-(trifluoromethyl)pyrimidin-2-yl]oxypiperidine-1-carboxylate Chemical compound C1CCN(C(=O)OC(C)(C)C)[C@@H](C)[C@@H]1OC1=NC=C(C(F)(F)F)C=N1 ZFVCUWYENNXYNE-CMPLNLGQSA-N 0.000 description 1
- KTUKFTSZXMAYKP-WDEREUQCSA-N tert-butyl (2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrazin-2-yl]amino]piperidine-1-carboxylate Chemical compound C1CCN(C(=O)OC(C)(C)C)[C@@H](C)[C@@H]1NC1=CN=C(C(F)(F)F)C=N1 KTUKFTSZXMAYKP-WDEREUQCSA-N 0.000 description 1
- QETQHHWBGWEYFV-CMPLNLGQSA-N tert-butyl (2s,3r)-2-methyl-3-[[5-(trifluoromethyl)pyrimidin-2-yl]amino]piperidine-1-carboxylate Chemical compound C1CCN(C(=O)OC(C)(C)C)[C@@H](C)[C@@H]1NC1=NC=C(C(F)(F)F)C=N1 QETQHHWBGWEYFV-CMPLNLGQSA-N 0.000 description 1
- JVTLZONQJOYLBI-UHFFFAOYSA-N tert-butyl 3-(1,3-benzoxazol-2-ylamino)-2-methylpiperidine-1-carboxylate Chemical compound C1CCN(C(=O)OC(C)(C)C)C(C)C1NC1=NC2=CC=CC=C2O1 JVTLZONQJOYLBI-UHFFFAOYSA-N 0.000 description 1
- CKBVIOURJWOFSM-UHFFFAOYSA-N tert-butyl 3-[(4,6-dimethylpyrimidin-2-yl)amino]-2-methylpiperidine-1-carboxylate Chemical group C1CCN(C(=O)OC(C)(C)C)C(C)C1NC1=NC(C)=CC(C)=N1 CKBVIOURJWOFSM-UHFFFAOYSA-N 0.000 description 1
- MEQMNSLPRLOIMT-UHFFFAOYSA-N tert-butyl tert-butylcarbamoyl carbonate tert-butyl (2-methylpropan-2-yl)oxycarbonyl carbonate Chemical compound C(OC(NC(C)(C)C)=O)(OC(C)(C)C)=O.C(OC(=O)OC(C)(C)C)(OC(C)(C)C)=O MEQMNSLPRLOIMT-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- WTFFOOAJSDVASL-UHFFFAOYSA-N tributyl(pyrimidin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CC=N1 WTFFOOAJSDVASL-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 206010048828 underweight Diseases 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- 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
- C07D413/12—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 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
- C07D413/14—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
- C07D417/14—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
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Anesthesiology (AREA)
- Psychology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Reproductive Health (AREA)
- Otolaryngology (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2018229449A AU2018229449A1 (en) | 2013-03-13 | 2018-09-12 | Substituted piperidine compounds and their use as orexin receptor modulators |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361780302P | 2013-03-13 | 2013-03-13 | |
| US61/780,302 | 2013-03-13 | ||
| PCT/US2014/024284 WO2014165065A1 (en) | 2013-03-13 | 2014-03-12 | Substituted piperidine compounds and their use as orexin receptor modulators |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018229449A Division AU2018229449A1 (en) | 2013-03-13 | 2018-09-12 | Substituted piperidine compounds and their use as orexin receptor modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2014248763A1 AU2014248763A1 (en) | 2015-08-27 |
| AU2014248763B2 true AU2014248763B2 (en) | 2018-08-30 |
Family
ID=50842314
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2014248763A Active AU2014248763B2 (en) | 2013-03-13 | 2014-03-12 | Substituted piperidine compounds and their use as orexin receptor modulators |
| AU2018229449A Abandoned AU2018229449A1 (en) | 2013-03-13 | 2018-09-12 | Substituted piperidine compounds and their use as orexin receptor modulators |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018229449A Abandoned AU2018229449A1 (en) | 2013-03-13 | 2018-09-12 | Substituted piperidine compounds and their use as orexin receptor modulators |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US9611251B2 (enExample) |
| EP (1) | EP2970207B1 (enExample) |
| JP (1) | JP6275814B2 (enExample) |
| CN (1) | CN105228995B (enExample) |
| AR (1) | AR095422A1 (enExample) |
| AU (2) | AU2014248763B2 (enExample) |
| TW (1) | TW201444821A (enExample) |
| UY (1) | UY35410A (enExample) |
| WO (1) | WO2014165065A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9180127B2 (en) | 2009-12-29 | 2015-11-10 | Dana-Farber Cancer Institute, Inc. | Type II Raf kinase inhibitors |
| WO2016095204A1 (en) * | 2014-12-19 | 2016-06-23 | Merck Sharp & Dohme Corp. | Pyrrolidine orexin receptor antagonists |
| HK1245260A1 (zh) | 2014-12-23 | 2018-08-24 | Dana-Farber Cancer Institute, Inc. | 细胞周期蛋白依赖性激酶7(cdk7)的抑制剂 |
| JP6861166B2 (ja) | 2015-03-27 | 2021-04-21 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
| AU2016295693B2 (en) | 2015-07-17 | 2020-05-21 | Sunshine Lake Pharma Co., Ltd. | Substituted quinazoline compounds and preparation and uses thereof |
| CN106749269B (zh) | 2015-11-23 | 2019-01-04 | 广东东阳光药业有限公司 | 八氢吡咯并[3,4-c]吡咯衍生物及其用途 |
| GB201601703D0 (en) * | 2016-01-29 | 2016-03-16 | C4X Discovery Ltd | Therapeutic compounds |
| KR102459256B1 (ko) | 2016-06-23 | 2022-10-25 | 세인트 쥬드 칠드런즈 리써치 호스피탈, 인코포레이티드 | 판토테네이트 키나제의 소분자 조절제 |
| CN106045902A (zh) * | 2016-06-30 | 2016-10-26 | 苏州健雄职业技术学院 | 一种3‑溴‑6‑甲基‑2‑吡啶甲醛的制备方法 |
| AU2017363307B2 (en) | 2016-11-22 | 2021-07-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 12 (CDK12) and uses thereof |
| PT3619199T (pt) | 2017-05-03 | 2021-10-01 | Idorsia Pharmaceuticals Ltd | Preparação de derivados de ácido 2-([1,2,3]triazol-2-il)- benzoico |
| JP7352565B2 (ja) | 2017-12-27 | 2023-09-28 | セント ジュード チルドレンズ リサーチ ホスピタル,インコーポレイティド | パントテン酸キナーゼの小分子モジュレーター |
| WO2019133632A1 (en) | 2017-12-27 | 2019-07-04 | St. Jude Children's Research Hospital | Methods of treating disorders associated with castor |
| EP3810132A4 (en) | 2018-06-25 | 2022-06-22 | Dana-Farber Cancer Institute, Inc. | TAIRE FAMILY KINASE INHIBITORS AND RELATED USES |
| CA3124422A1 (en) | 2018-12-28 | 2020-07-02 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 and uses thereof |
| WO2024148210A1 (en) * | 2023-01-05 | 2024-07-11 | Allianthera (Suzhou) Biopharmaceutical Co., Ltd. | Cyclin-dependent kinase 12 modulators and therapeutic uses thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008065626A2 (en) * | 2006-12-01 | 2008-06-05 | Actelion Pharmaceuticals Ltd | 3-heteroaryl (amino or amido)-1- (biphenyl or phenylthiazolyl) carbonylpiperidine derivativesas orexin receptor inhibitors |
| US20090163485A1 (en) * | 2007-12-21 | 2009-06-25 | Henner Knust | Heteroaryl derivatives as orexin receptor antagonists |
| WO2009133522A1 (en) * | 2008-04-30 | 2009-11-05 | Actelion Pharmaceuticals Ltd | Piperidine and pyrrolidine compounds |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3674793A (en) | 1967-03-29 | 1972-07-04 | Sterling Drug Inc | 6-hydroxy-2-azabicyclo(2.2.2)octan-3-ones and 2-azabicyclo(2.2.2.)octane-3,6-diones |
| US6505492B2 (en) | 2001-04-11 | 2003-01-14 | Bethlehem Steel Corporation | Method and apparatus for forming deep-drawn articles |
| JPWO2002094790A1 (ja) | 2001-05-23 | 2004-09-09 | 三菱ウェルファーマ株式会社 | 縮合ヘテロ環化合物およびその医薬用途 |
| AU2003202753A1 (en) | 2003-02-07 | 2004-08-30 | Ranbaxy Laboratories Limited | Oxazolidinone derivatives as antimicrobials |
| WO2004074292A1 (en) | 2003-02-21 | 2004-09-02 | Pharmacia & Upjohn Company Llc | Exo-(t-butyl 2r(+))-2-amino-7-azabicyclo[2.2.1]heptane-7-carboxylate, intermediates, and process to prepare and isolate them |
| WO2007071358A1 (en) | 2005-12-20 | 2007-06-28 | Novartis Ag | Nicotinic acid derivatives as modulators of metabotropic glutamate receptors |
| JP2010502664A (ja) | 2006-09-11 | 2010-01-28 | ノバルティス アクチエンゲゼルシャフト | 代謝型グルタミン酸受容体の調節剤としてのニコチン酸誘導体 |
| CL2007003827A1 (es) | 2006-12-28 | 2008-09-26 | Actelion Pharmaceuticals Ltd | Compuestos derivados de n-(2-aza-biciclo(3.1.0)hex-3-ilmetil)amida; y su uso para prevenir o tratar la depresion, neurosis, esquizofrenia, ansiedad, adicciones, epilepsia, dolor, enfermedades cardiacas, entre otras. |
| JP2010528007A (ja) | 2007-05-23 | 2010-08-19 | メルク・シャープ・エンド・ドーム・コーポレイション | シクロプロピルピロリジンオレキシン受容体アンタゴニスト |
| PT2173737E (pt) | 2007-07-17 | 2012-03-19 | Bristol Myers Squibb Co | Método para modular receptor gpr119 acoplado a proteína g e compostos seleccionados |
| WO2009104155A1 (en) | 2008-02-21 | 2009-08-27 | Actelion Pharmaceuticals Ltd | 2-aza-bicyclo[2.2.1]heptane derivatives |
| AU2009270971A1 (en) | 2008-07-16 | 2010-01-21 | Schering Corporation | Bicyclic Heterocycle Derivatives and use thereof as GPR119 modulators |
| EP2350061B1 (en) | 2008-10-21 | 2013-08-14 | Merck Sharp & Dohme Corp. | 2,3-disubstituted piperidine orexin receptor antagonists |
| EP2349269A4 (en) * | 2008-10-21 | 2012-04-25 | Merck Sharp & Dohme | 2,5-DISUBSTITUTED PIPERIDINOREXINE RECEPTOR ANTAGONISTS |
| UY32277A (es) | 2008-12-02 | 2010-05-31 | Glaxo Group Ltd | Derivados de n-{[1r,4s,6r)-3-(2-piridinilcarbonil)-3-azabiciclo[4.1.0-il}metil}-2heteroarilamina y uso de los mismos |
| AR076024A1 (es) | 2009-04-03 | 2011-05-11 | Schering Corp | Derivados de heterociclos biciclicos puenteados y metodos de uso de los mismos |
| MX2011011127A (es) | 2009-04-24 | 2011-11-18 | Glaxo Group Ltd | 3-azabiciclo[4.1.0] heptanos usados como antagonistas de orexina. |
| US8653263B2 (en) | 2009-10-23 | 2014-02-18 | Janssen Pharmaceutica | Disubstituted octahydropyrrolo[3,4-c]pyrroles as orexin receptor modulators |
| US9062044B2 (en) | 2009-10-23 | 2015-06-23 | Janssen Pharmaceutica Nv | Disubstituted octahydropyrrolo[3,4-c]pyrroles as orexin receptor modulators |
| US8680275B2 (en) | 2009-10-23 | 2014-03-25 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as orexin receptor modulators |
| US9409918B2 (en) | 2009-10-29 | 2016-08-09 | Merck Sharp & Dohme Corp. | Bridged bicyclic piperidine derivatives and methods of use thereof |
| WO2011066137A1 (en) | 2009-11-24 | 2011-06-03 | Schering Corporation | Substituted biaryl derivatives and methods of use thereof |
| EP2512239A4 (en) | 2009-12-14 | 2014-11-26 | Inspire Pharmaceuticals Inc | BROKEN BICYCLIC RHO-KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE |
| US8697691B2 (en) | 2009-12-21 | 2014-04-15 | Vanderbilt University | Alkyl 3-((2-amidoethyl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate analogs as selective M1 agonists and methods of making and using same |
| UY33227A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
| WO2011159657A1 (en) | 2010-06-18 | 2011-12-22 | Merck Sharp & Dohme Corp. | Bicyclic heterocycle derivatives and methods of use thereof |
| WO2012089606A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Azabicyclo [4.1.0] hept - 4 - yl derivatives as human orexin receptor antagonists |
| WO2012145581A1 (en) | 2011-04-20 | 2012-10-26 | Janssen Pharmaceutica Nv | Disubstituted octahy-dropyrrolo [3,4-c] pyrroles as orexin receptor modulators |
| AR088352A1 (es) * | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| US9546152B2 (en) * | 2012-10-23 | 2017-01-17 | Merck Sharp & Dohme Corp. | 2-pyridyloxy-3-substituted-4-nitrile orexin receptor antagonists |
| JP6297582B2 (ja) | 2012-11-16 | 2018-03-20 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | ヒトホスファチジルイノシトール3−キナーゼデルタのプリン阻害剤 |
| TW201444849A (zh) | 2013-03-13 | 2014-12-01 | Janssen Pharmaceutica Nv | 經取代的7-氮雜雙環類及其作為食慾激素受體調節劑之用途 |
| TWI621618B (zh) | 2013-03-13 | 2018-04-21 | 比利時商健生藥品公司 | 經取代2-氮雜雙環類及其作為食慾素受體調控劑之用途 |
| BR112016017996A2 (pt) | 2014-02-06 | 2017-08-08 | Abbvie Inc | 6-heteroariloxi- or 6-ariloxi-quinolina-2-carboxamidas e método de uso |
-
2014
- 2014-03-11 TW TW103108298A patent/TW201444821A/zh unknown
- 2014-03-12 US US14/774,529 patent/US9611251B2/en active Active
- 2014-03-12 US US14/206,662 patent/US9115117B2/en active Active
- 2014-03-12 CN CN201480027361.3A patent/CN105228995B/zh active Active
- 2014-03-12 EP EP14727268.6A patent/EP2970207B1/en active Active
- 2014-03-12 JP JP2016501463A patent/JP6275814B2/ja active Active
- 2014-03-12 AU AU2014248763A patent/AU2014248763B2/en active Active
- 2014-03-12 WO PCT/US2014/024284 patent/WO2014165065A1/en not_active Ceased
- 2014-03-13 UY UY0001035410A patent/UY35410A/es unknown
- 2014-03-13 AR ARP140100966A patent/AR095422A1/es unknown
-
2018
- 2018-09-12 AU AU2018229449A patent/AU2018229449A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008065626A2 (en) * | 2006-12-01 | 2008-06-05 | Actelion Pharmaceuticals Ltd | 3-heteroaryl (amino or amido)-1- (biphenyl or phenylthiazolyl) carbonylpiperidine derivativesas orexin receptor inhibitors |
| US20090163485A1 (en) * | 2007-12-21 | 2009-06-25 | Henner Knust | Heteroaryl derivatives as orexin receptor antagonists |
| WO2009133522A1 (en) * | 2008-04-30 | 2009-11-05 | Actelion Pharmaceuticals Ltd | Piperidine and pyrrolidine compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2018229449A1 (en) | 2018-10-04 |
| JP6275814B2 (ja) | 2018-02-07 |
| EP2970207A1 (en) | 2016-01-20 |
| EP2970207B1 (en) | 2018-05-16 |
| UY35410A (es) | 2014-09-30 |
| AU2014248763A1 (en) | 2015-08-27 |
| CN105228995B (zh) | 2018-12-25 |
| US20140275095A1 (en) | 2014-09-18 |
| US9115117B2 (en) | 2015-08-25 |
| JP2016512534A (ja) | 2016-04-28 |
| CN105228995A (zh) | 2016-01-06 |
| US20160046599A1 (en) | 2016-02-18 |
| TW201444821A (zh) | 2014-12-01 |
| AR095422A1 (es) | 2015-10-14 |
| US9611251B2 (en) | 2017-04-04 |
| WO2014165065A1 (en) | 2014-10-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2014248763B2 (en) | Substituted piperidine compounds and their use as orexin receptor modulators | |
| US9695183B2 (en) | Substituted 7-azabicycles and their use as orexin receptor modulators | |
| US8969352B2 (en) | Substituted 2-azabicycles and their use as orexin receptor modulators | |
| EP3743430B1 (en) | Aminopyrrolotriazines as kinase inhibitors | |
| AU2015314851B2 (en) | Substituted 2-azabicycles and their use as orexin receptor modulators | |
| IL261472A (en) | Inhibitors of linking the wdr5 protein with other proteins | |
| WO2024028169A1 (en) | Novel specifically substituted thiophenolic compounds | |
| NZ793902A (en) | Substituted 2-azabicycles and their use as orexin receptor modulators | |
| HK1219726B (en) | Substituted 7-azabicycles and their use as orexin receptor modulators | |
| HK1240934B (en) | Substituted 2-azabicycles and their use as orexin receptor modulators | |
| HK1240934A1 (en) | Substituted 2-azabicycles and their use as orexin receptor modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |