JP2013515032A - 二置換ヘテロアリール縮合ピリジン類 - Google Patents
二置換ヘテロアリール縮合ピリジン類 Download PDFInfo
- Publication number
- JP2013515032A JP2013515032A JP2012545276A JP2012545276A JP2013515032A JP 2013515032 A JP2013515032 A JP 2013515032A JP 2012545276 A JP2012545276 A JP 2012545276A JP 2012545276 A JP2012545276 A JP 2012545276A JP 2013515032 A JP2013515032 A JP 2013515032A
- Authority
- JP
- Japan
- Prior art keywords
- pyridin
- pyrazolo
- yloxy
- acetamide
- ring system
- 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.)
- Pending
Links
- 150000003222 pyridines Chemical class 0.000 title description 3
- 125000001072 heteroaryl group Chemical group 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 262
- 239000003814 drug Substances 0.000 claims abstract description 17
- -1 C 2-6 halogenalkynyl Chemical group 0.000 claims description 464
- 125000000217 alkyl group Chemical group 0.000 claims description 384
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 359
- 125000004122 cyclic group Chemical group 0.000 claims description 310
- 229910052736 halogen Inorganic materials 0.000 claims description 304
- 150000002367 halogens Chemical class 0.000 claims description 270
- 229910052757 nitrogen Inorganic materials 0.000 claims description 248
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 217
- 125000001188 haloalkyl group Chemical group 0.000 claims description 195
- 125000001424 substituent group Chemical group 0.000 claims description 133
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 125
- 229910052717 sulfur Chemical group 0.000 claims description 125
- 239000011593 sulfur Chemical group 0.000 claims description 125
- 229910052760 oxygen Inorganic materials 0.000 claims description 124
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 123
- 125000005842 heteroatom Chemical group 0.000 claims description 123
- 239000001301 oxygen Chemical group 0.000 claims description 123
- 125000004434 sulfur atom Chemical group 0.000 claims description 119
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 118
- 229910052739 hydrogen Inorganic materials 0.000 claims description 114
- 239000001257 hydrogen Substances 0.000 claims description 114
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 114
- 125000006413 ring segment Chemical group 0.000 claims description 114
- 125000003545 alkoxy group Chemical group 0.000 claims description 103
- 125000000623 heterocyclic group Chemical group 0.000 claims description 100
- 125000002950 monocyclic group Chemical group 0.000 claims description 97
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 94
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 80
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 80
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 76
- 125000002947 alkylene group Chemical group 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 69
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 66
- 229910052799 carbon Inorganic materials 0.000 claims description 65
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 59
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 50
- 150000002431 hydrogen Chemical class 0.000 claims description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims description 41
- 150000003839 salts Chemical group 0.000 claims description 39
- 125000002619 bicyclic group Chemical group 0.000 claims description 33
- 229920006395 saturated elastomer Polymers 0.000 claims description 33
- GVLRTOYGRNLSDW-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine Chemical group C1=CC=C2C=NNC2=N1 GVLRTOYGRNLSDW-UHFFFAOYSA-N 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 22
- 208000035475 disorder Diseases 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 108050000742 Orexin Receptor Proteins 0.000 claims description 18
- 102000008834 Orexin receptor Human genes 0.000 claims description 18
- 125000003367 polycyclic group Chemical group 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 208000011117 substance-related disease Diseases 0.000 claims description 13
- 208000019116 sleep disease Diseases 0.000 claims description 12
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 208000030814 Eating disease Diseases 0.000 claims description 9
- 235000014632 disordered eating Nutrition 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- RRXSYZFVDIRTFB-UHFFFAOYSA-N C[CH]C1=CC=C(OC)C=C1 Chemical group C[CH]C1=CC=C(OC)C=C1 RRXSYZFVDIRTFB-UHFFFAOYSA-N 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 4
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- XUYCYHNBDBGUMX-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-(2-methylpropyl)acetamide Chemical compound N=1N(C)C2=NC(OCC(=O)NCC(C)C)=CC(C)=C2C=1C1CC1 XUYCYHNBDBGUMX-UHFFFAOYSA-N 0.000 claims description 2
- NMCMCGLHCMEIBI-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-(2-phenylethyl)acetamide Chemical compound N=1C=2N(C)N=C(C3CC3)C=2C(C)=CC=1OCC(=O)NCCC1=CC=CC=C1 NMCMCGLHCMEIBI-UHFFFAOYSA-N 0.000 claims description 2
- NMMWQPMWGUPQBP-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-[1-(1-methylpyrrolo[2,3-b]pyridin-5-yl)ethyl]acetamide Chemical compound C=1N=C2N(C)C=CC2=CC=1C(C)NC(=O)COC(N=C1N(C)N=2)=CC(C)=C1C=2C1CC1 NMMWQPMWGUPQBP-UHFFFAOYSA-N 0.000 claims description 2
- NGKRQGAFUPJDRL-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-[1-(4-methoxyphenyl)ethyl]-n-methylacetamide Chemical compound C1=CC(OC)=CC=C1C(C)N(C)C(=O)COC1=CC(C)=C(C(=NN2C)C3CC3)C2=N1 NGKRQGAFUPJDRL-UHFFFAOYSA-N 0.000 claims description 2
- PCEVUHYTSUIWRI-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-methylacetamide Chemical compound N=1N(C)C2=NC(OCC(=O)NC)=CC(C)=C2C=1C1CC1 PCEVUHYTSUIWRI-UHFFFAOYSA-N 0.000 claims description 2
- GVYPHKXSRUWKBP-UHFFFAOYSA-N 2-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxy-n-propylacetamide Chemical compound N=1N(C)C2=NC(OCC(=O)NCCC)=CC(C(F)(F)F)=C2C=1C1=CC=CC=C1 GVYPHKXSRUWKBP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
- 241000162682 Heterogen Species 0.000 claims 2
- 238000002360 preparation method Methods 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 61
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 56
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 42
- 239000007787 solid Substances 0.000 description 41
- 239000002904 solvent Substances 0.000 description 37
- 230000002829 reductive effect Effects 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- 150000001721 carbon Chemical group 0.000 description 29
- 238000003756 stirring Methods 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 24
- 208000002193 Pain Diseases 0.000 description 21
- 239000012043 crude product Substances 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000003480 eluent Substances 0.000 description 19
- 239000011734 sodium Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 17
- 239000000651 prodrug Substances 0.000 description 17
- 229940002612 prodrug Drugs 0.000 description 17
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 239000005457 ice water Substances 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 15
- 239000012267 brine Substances 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 102000002512 Orexin Human genes 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 13
- 108060005714 orexin Proteins 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 206010022437 insomnia Diseases 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 239000003643 water by type Substances 0.000 description 7
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 6
- BTGHXCBKXUBEIA-UHFFFAOYSA-N 3-(2,5-dimethylfuran-3-yl)-3-oxopropanenitrile Chemical compound CC1=CC(C(=O)CC#N)=C(C)O1 BTGHXCBKXUBEIA-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 208000004454 Hyperalgesia Diseases 0.000 description 6
- 206010020751 Hypersensitivity Diseases 0.000 description 6
- 208000026935 allergic disease Diseases 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000001201 calcium accumulation Effects 0.000 description 6
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
- 230000004064 dysfunction Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 201000001119 neuropathy Diseases 0.000 description 6
- 230000007823 neuropathy Effects 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 208000033808 peripheral neuropathy Diseases 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 description 5
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 208000004296 neuralgia Diseases 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 206010002383 Angina Pectoris Diseases 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- 208000035154 Hyperesthesia Diseases 0.000 description 4
- 206010021067 Hypopituitarism Diseases 0.000 description 4
- 208000019695 Migraine disease Diseases 0.000 description 4
- 229940123730 Orexin receptor antagonist Drugs 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000009610 hypersensitivity Effects 0.000 description 4
- 230000002267 hypothalamic effect Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- SMCVPMKCDDNUCQ-UHFFFAOYSA-N methyl 3,3-dimethoxypropanoate Chemical compound COC(OC)CC(=O)OC SMCVPMKCDDNUCQ-UHFFFAOYSA-N 0.000 description 4
- 206010027599 migraine Diseases 0.000 description 4
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000007958 sleep Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 4
- IACWJZMJRQJJSI-UHFFFAOYSA-N 1-hydroxybenzotriazole;trihydrate Chemical compound O.O.O.C1=CC=C2N(O)N=NC2=C1 IACWJZMJRQJJSI-UHFFFAOYSA-N 0.000 description 3
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 3
- MAYUDEQHQBXSCY-UHFFFAOYSA-N 2-[3-(3,5-dimethoxyphenyl)-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl]oxyacetic acid Chemical compound COC1=CC(OC)=CC(C=2C3=C(C)C=C(OCC(O)=O)N=C3N(C)N=2)=C1 MAYUDEQHQBXSCY-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 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 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 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
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- CBDPWKVOPADMJC-UHFFFAOYSA-N ethyl 4,4-difluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)F CBDPWKVOPADMJC-UHFFFAOYSA-N 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 238000009499 grossing Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 201000003631 narcolepsy Diseases 0.000 description 3
- 208000021722 neuropathic pain Diseases 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- JTDGKQNNPKXKII-ZETCQYMHSA-N (1s)-1-(4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C([C@H](C)N)C=C1 JTDGKQNNPKXKII-ZETCQYMHSA-N 0.000 description 2
- OAXSTMJSFUYCIP-UHFFFAOYSA-N (2,6-dichloropyridin-3-yl)-phenylmethanone Chemical compound ClC1=NC(Cl)=CC=C1C(=O)C1=CC=CC=C1 OAXSTMJSFUYCIP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- NGQLGTPUCYNRQI-UHFFFAOYSA-N 1-methyl-3-phenyl-7H-pyrazolo[3,4-b]pyridin-6-one Chemical compound C1=2C=CC(=O)NC=2N(C)N=C1C1=CC=CC=C1 NGQLGTPUCYNRQI-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
- DUPAJBWOMRGFBC-INIZCTEOSA-N 2-(1-methyl-3-phenylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-[(1s)-1-phenylethyl]acetamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)COC(N=C1N(C)N=2)=CC=C1C=2C1=CC=CC=C1 DUPAJBWOMRGFBC-INIZCTEOSA-N 0.000 description 2
- QTKMVSBSYZESBS-UHFFFAOYSA-N 2-(3-chloro-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxyacetic acid Chemical compound CC1=CC(OCC(O)=O)=NC2=C1C(Cl)=NN2C QTKMVSBSYZESBS-UHFFFAOYSA-N 0.000 description 2
- NHKDZRLVFDFWKF-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-(5-methoxy-2,3-dihydro-1h-inden-1-yl)acetamide Chemical compound C1CC2=CC(OC)=CC=C2C1NC(=O)COC(N=C1N(C)N=2)=CC(C)=C1C=2C1CC1 NHKDZRLVFDFWKF-UHFFFAOYSA-N 0.000 description 2
- INWNZPNJUVSFJR-UHFFFAOYSA-N 2-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrrolo[2,3-b]pyridin-6-yl]oxyacetic acid Chemical compound C12=C(C(F)(F)F)C=C(OCC(O)=O)N=C2N(C)C=C1C1=CC=CC=C1 INWNZPNJUVSFJR-UHFFFAOYSA-N 0.000 description 2
- YNRCUKRDBBARTQ-UHFFFAOYSA-N 2-[3-(2,5-dimethylfuran-3-yl)-1-methyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxyacetic acid Chemical compound O1C(C)=CC(C=2C3=C(C=C(OCC(O)=O)N=C3N(C)N=2)C(F)(F)F)=C1C YNRCUKRDBBARTQ-UHFFFAOYSA-N 0.000 description 2
- ZNASAJGWPUTONJ-AWEZNQCLSA-N 2-[3-(2-fluorophenyl)-1-methyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxy-n-[(1s)-1-phenylethyl]acetamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)COC(N=C1N(C)N=2)=CC(C(F)(F)F)=C1C=2C1=CC=CC=C1F ZNASAJGWPUTONJ-AWEZNQCLSA-N 0.000 description 2
- VHPHJZXOLJJSPJ-INIZCTEOSA-N 2-[3-(3-fluoropyridin-2-yl)-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl]oxy-n-[(1s)-1-(4-methylphenyl)ethyl]acetamide Chemical compound N([C@@H](C)C=1C=CC(C)=CC=1)C(=O)COC(N=C1N(C)N=2)=CC(C)=C1C=2C1=NC=CC=C1F VHPHJZXOLJJSPJ-INIZCTEOSA-N 0.000 description 2
- WNPREEFBUPFVNG-UHFFFAOYSA-N 2-[4-(difluoromethyl)-3-(2,5-dimethylfuran-3-yl)-1-methylpyrazolo[3,4-b]pyridin-6-yl]oxyacetic acid Chemical compound O1C(C)=CC(C=2C3=C(C(F)F)C=C(OCC(O)=O)N=C3N(C)N=2)=C1C WNPREEFBUPFVNG-UHFFFAOYSA-N 0.000 description 2
- XCGOFXSJHBHNTE-HNNXBMFYSA-N 2-[[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]amino]-n-[(1s)-1-phenylethyl]acetamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)CNC(N=C1N(C)N=2)=CC(C(F)(F)F)=C1C=2C1=CC=CC=C1 XCGOFXSJHBHNTE-HNNXBMFYSA-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
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- DCDIARHGQXJUCG-UHFFFAOYSA-N 5-(3,5-dimethoxyphenyl)-2-methylpyrazol-3-amine Chemical compound COC1=CC(OC)=CC(C2=NN(C)C(N)=C2)=C1 DCDIARHGQXJUCG-UHFFFAOYSA-N 0.000 description 2
- CSKGTUGORXMNNS-UHFFFAOYSA-N 5-chloro-2-methylpyrazole-3-carboxylic acid Chemical compound CN1N=C(Cl)C=C1C(O)=O CSKGTUGORXMNNS-UHFFFAOYSA-N 0.000 description 2
- YAPIAFFFLXKOFJ-UHFFFAOYSA-N 6-chloro-1-methyl-3-phenylpyrazolo[3,4-b]pyridine Chemical compound C12=CC=C(Cl)N=C2N(C)N=C1C1=CC=CC=C1 YAPIAFFFLXKOFJ-UHFFFAOYSA-N 0.000 description 2
- WHTJBSBJQBIBOM-UHFFFAOYSA-N 6-methoxy-3-phenyl-4-(trifluoromethyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1NC2=NC(OC)=CC(C(F)(F)F)=C2C=1C1=CC=CC=C1 WHTJBSBJQBIBOM-UHFFFAOYSA-N 0.000 description 2
- 206010000599 Acromegaly Diseases 0.000 description 2
- 208000003200 Adenoma Diseases 0.000 description 2
- 206010001233 Adenoma benign Diseases 0.000 description 2
- 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 2
- 201000000736 Amenorrhea Diseases 0.000 description 2
- 206010001928 Amenorrhoea Diseases 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- 208000027559 Appetite disease Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 201000009586 Basophil Adenoma Diseases 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010007556 Cardiac failure acute Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 2
- 208000033054 Cushing disease Diseases 0.000 description 2
- 208000014311 Cushing syndrome Diseases 0.000 description 2
- 206010012218 Delirium Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010058359 Hypogonadism Diseases 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 208000028482 Hypothalamic disease Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000001456 Jet Lag Syndrome Diseases 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 208000019022 Mood disease Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- 206010034010 Parkinsonism Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 2
- 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 2
- 208000004550 Postoperative Pain Diseases 0.000 description 2
- 206010036832 Prolactinoma Diseases 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 208000005793 Restless legs syndrome Diseases 0.000 description 2
- 208000036623 Severe mental retardation Diseases 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 206010046555 Urinary retention Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 206010053552 allodynia Diseases 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 231100000540 amenorrhea Toxicity 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- ZJRCIQAMTAINCB-UHFFFAOYSA-N benzoylacetonitrile Chemical compound N#CCC(=O)C1=CC=CC=C1 ZJRCIQAMTAINCB-UHFFFAOYSA-N 0.000 description 2
- 208000028683 bipolar I disease Diseases 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000006172 buffering agent Substances 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
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 230000003001 depressive effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- PRUOKQGCHFIEND-UHFFFAOYSA-N ethyl 2-(3-chloro-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxyacetate Chemical compound CCOC(=O)COC1=CC(C)=C2C(Cl)=NN(C)C2=N1 PRUOKQGCHFIEND-UHFFFAOYSA-N 0.000 description 2
- 206010016165 failure to thrive Diseases 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 208000031424 hyperprolactinemia Diseases 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 208000003532 hypothyroidism Diseases 0.000 description 2
- 230000002989 hypothyroidism Effects 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000010829 isocratic elution Methods 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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
- 229960002510 mandelic acid Drugs 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 201000000585 muscular atrophy Diseases 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 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 2
- 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 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 208000030062 persistent idiopathic facial pain Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 2
- 208000030153 prolactin-producing pituitary gland adenoma Diseases 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000008786 sensory perception of smell Effects 0.000 description 2
- 201000002859 sleep apnea Diseases 0.000 description 2
- 208000020685 sleep-wake disease Diseases 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 201000009032 substance abuse Diseases 0.000 description 2
- 231100000736 substance abuse Toxicity 0.000 description 2
- 201000006152 substance dependence Diseases 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000004808 supercritical fluid chromatography Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- QZGMVMPHSSPPJN-UHFFFAOYSA-N tert-butyl n-(5-chloro-2-methylpyrazol-3-yl)carbamate Chemical compound CN1N=C(Cl)C=C1NC(=O)OC(C)(C)C QZGMVMPHSSPPJN-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical class 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
- 231100000397 ulcer Toxicity 0.000 description 2
- 206010046494 urge incontinence Diseases 0.000 description 2
- 208000009935 visceral pain Diseases 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
- AXORVIZLPOGIRG-MRVPVSSYSA-N (2s)-2-phenylpropan-1-amine Chemical compound NC[C@@H](C)C1=CC=CC=C1 AXORVIZLPOGIRG-MRVPVSSYSA-N 0.000 description 1
- 125000006569 (C5-C6) heterocyclic 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
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BDDVQOCZUMFMRH-UHFFFAOYSA-N 1-(3,5-dimethyl-1h-pyrazol-4-yl)ethanamine Chemical compound CC(N)C=1C(C)=NNC=1C BDDVQOCZUMFMRH-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- JRLPEMVDPFPYPJ-UHFFFAOYSA-N 1-ethyl-4-methylbenzene Chemical compound CCC1=CC=C(C)C=C1 JRLPEMVDPFPYPJ-UHFFFAOYSA-N 0.000 description 1
- KCYRMURRLLYLPU-UHFFFAOYSA-N 1-methyl-3-phenyl-1H-pyrazol-5-amine Chemical compound C1=C(N)N(C)N=C1C1=CC=CC=C1 KCYRMURRLLYLPU-UHFFFAOYSA-N 0.000 description 1
- HQGCHPGWVCTYIF-UHFFFAOYSA-N 1-methyl-3-phenyl-4-(trifluoromethyl)-7h-pyrrolo[2,3-b]pyridin-6-one Chemical compound C1=2C(C(F)(F)F)=CC(=O)NC=2N(C)C=C1C1=CC=CC=C1 HQGCHPGWVCTYIF-UHFFFAOYSA-N 0.000 description 1
- JKZWEWZMYSBQME-UHFFFAOYSA-N 1-methylpyrazolidin-3-one Chemical compound CN1CCC(=O)N1 JKZWEWZMYSBQME-UHFFFAOYSA-N 0.000 description 1
- 150000005258 1H-pyrrolo(2,3-b)pyridines Chemical class 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 description 1
- MRSFJNIJUNFZEB-UHFFFAOYSA-N 2-(1-methyl-3-phenylpyrazolo[3,4-b]pyridin-6-yl)oxyacetic acid Chemical compound C12=CC=C(OCC(O)=O)N=C2N(C)N=C1C1=CC=CC=C1 MRSFJNIJUNFZEB-UHFFFAOYSA-N 0.000 description 1
- KFFXDDXSMBVGNP-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxyacetic acid Chemical compound C1=2C(C)=CC(OCC(O)=O)=NC=2N(C)N=C1C1CC1 KFFXDDXSMBVGNP-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- HYQGCUGXXGKSFM-MRXNPFEDSA-N 2-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxy-n-[(2s)-2-phenylpropyl]acetamide Chemical compound C([C@@H](C)C=1C=CC=CC=1)NC(=O)COC(N=C1N(C)N=2)=CC(C(F)(F)F)=C1C=2C1=CC=CC=C1 HYQGCUGXXGKSFM-MRXNPFEDSA-N 0.000 description 1
- NGJOXNMJGOVFGZ-UHFFFAOYSA-N 2-[3-(2-fluorophenyl)-1-methyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxyacetic acid Chemical compound C12=C(C(F)(F)F)C=C(OCC(O)=O)N=C2N(C)N=C1C1=CC=CC=C1F NGJOXNMJGOVFGZ-UHFFFAOYSA-N 0.000 description 1
- ATDRTNDYIVXCCF-KRWDZBQOSA-N 2-[3-(3,5-dimethoxyphenyl)-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl]oxy-n-[(1s)-1-(4-methoxyphenyl)ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1[C@H](C)NC(=O)COC1=CC(C)=C(C(=NN2C)C=3C=C(OC)C=C(OC)C=3)C2=N1 ATDRTNDYIVXCCF-KRWDZBQOSA-N 0.000 description 1
- BEZZNQFBPGIIIH-INIZCTEOSA-N 2-[3-cyclopropyl-4-(difluoromethyl)-1-methylpyrazolo[3,4-b]pyridin-6-yl]oxy-n-[(5s)-2-methyl-6,7-dihydro-5h-cyclopenta[b]pyridin-5-yl]acetamide Chemical compound N([C@@H]1C2=CC=C(N=C2CC1)C)C(=O)COC(N=C1N(C)N=2)=CC(C(F)F)=C1C=2C1CC1 BEZZNQFBPGIIIH-INIZCTEOSA-N 0.000 description 1
- KFURFMNSOHTOGE-UHFFFAOYSA-N 2-[3-cyclopropyl-4-(difluoromethyl)-1-methylpyrazolo[3,4-b]pyridin-6-yl]oxyacetic acid Chemical compound C12=C(C(F)F)C=C(OCC(O)=O)N=C2N(C)N=C1C1CC1 KFURFMNSOHTOGE-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- WNDLOBWBYQHDQY-UHFFFAOYSA-N 3-(2-fluorophenyl)-3-oxopropanenitrile Chemical compound FC1=CC=CC=C1C(=O)CC#N WNDLOBWBYQHDQY-UHFFFAOYSA-N 0.000 description 1
- UORRVNNABUGIMI-UHFFFAOYSA-N 3-(3,5-dimethoxyphenyl)-1,4-dimethyl-7H-pyrazolo[3,4-b]pyridin-6-one Chemical compound COC1=CC(OC)=CC(C=2C=3C(C)=CC(=O)NC=3N(C)N=2)=C1 UORRVNNABUGIMI-UHFFFAOYSA-N 0.000 description 1
- LKMXJVUYRSDTPZ-UHFFFAOYSA-N 3-(3,5-dimethoxyphenyl)-3-oxopropanenitrile Chemical compound COC1=CC(OC)=CC(C(=O)CC#N)=C1 LKMXJVUYRSDTPZ-UHFFFAOYSA-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
- SDARMQNRQJBGQE-UHFFFAOYSA-N 3-cyclopropyl-3-oxopropanenitrile Chemical compound N#CCC(=O)C1CC1 SDARMQNRQJBGQE-UHFFFAOYSA-N 0.000 description 1
- VDTQDPLTAAQUMT-UHFFFAOYSA-N 3-methyl-5,6-dihydrocyclopenta[b]pyridin-7-one Chemical compound CC1=CN=C2C(=O)CCC2=C1 VDTQDPLTAAQUMT-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- VKZGTORDNRVMIN-UHFFFAOYSA-N 4-methyl-3-oxopentanenitrile Chemical compound CC(C)C(=O)CC#N VKZGTORDNRVMIN-UHFFFAOYSA-N 0.000 description 1
- JDOZUYVDIAKODH-SNAWJCMRSA-N 4-o-ethyl 1-o-methyl (e)-but-2-enedioate Chemical compound CCOC(=O)\C=C\C(=O)OC JDOZUYVDIAKODH-SNAWJCMRSA-N 0.000 description 1
- PMFJDFRZFOSMSM-UHFFFAOYSA-N 5,6-dimethoxy-2,3-dihydro-1h-inden-1-amine Chemical compound C1=C(OC)C(OC)=CC2=C1C(N)CC2 PMFJDFRZFOSMSM-UHFFFAOYSA-N 0.000 description 1
- LCPUQZNJLLPNCJ-UHFFFAOYSA-N 5-(2-fluorophenyl)-2-methylpyrazol-3-amine Chemical compound C1=C(N)N(C)N=C1C1=CC=CC=C1F LCPUQZNJLLPNCJ-UHFFFAOYSA-N 0.000 description 1
- NGBFVEOMCMLCJX-UHFFFAOYSA-N 5-chloro-2-methylpyrazol-3-amine Chemical compound CN1N=C(Cl)C=C1N NGBFVEOMCMLCJX-UHFFFAOYSA-N 0.000 description 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
- OCKMEQGLPHSFCD-UHFFFAOYSA-N 6-methoxy-1-methyl-3-phenyl-4-(trifluoromethyl)pyrrolo[2,3-b]pyridine Chemical compound C=1N(C)C2=NC(OC)=CC(C(F)(F)F)=C2C=1C1=CC=CC=C1 OCKMEQGLPHSFCD-UHFFFAOYSA-N 0.000 description 1
- HCQHCLNFZJUQSP-UHFFFAOYSA-N 6-methoxy-n-(2-phenylethylideneamino)-4-(trifluoromethyl)pyridin-2-amine Chemical compound COC1=CC(C(F)(F)F)=CC(NN=CCC=2C=CC=CC=2)=N1 HCQHCLNFZJUQSP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000017164 Chronobiology disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 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 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
- 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 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000014094 Dystonic disease Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 241000282326 Felis catus Species 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
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
- UKERDACREYXSIV-UHFFFAOYSA-N N-methoxy-N-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=CC=C1 UKERDACREYXSIV-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000006199 Parasomnias Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000025371 Taste disease Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DITTYRBIXKVOTK-UHFFFAOYSA-N [1,2]oxazolo[5,4-b]pyridine Chemical class C1=CC=C2C=NOC2=N1 DITTYRBIXKVOTK-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- QLDHWVVRQCGZLE-UHFFFAOYSA-N acetyl cyanide Chemical compound CC(=O)C#N QLDHWVVRQCGZLE-UHFFFAOYSA-N 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 201000007034 advanced sleep phase syndrome Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 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
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000003181 co-melting Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229940097362 cyclodextrins Drugs 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
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 201000001098 delayed sleep phase syndrome Diseases 0.000 description 1
- 208000033921 delayed sleep phase type circadian rhythm sleep disease Diseases 0.000 description 1
- 230000036576 dermal application Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- 229960004419 dimethyl fumarate Drugs 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
- 230000006806 disease prevention Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- MONPWSFULSPMCQ-UHFFFAOYSA-N ethyl 2-(1-methyl-3-phenylpyrazolo[3,4-b]pyridin-6-yl)oxyacetate Chemical compound N=1N(C)C2=NC(OCC(=O)OCC)=CC=C2C=1C1=CC=CC=C1 MONPWSFULSPMCQ-UHFFFAOYSA-N 0.000 description 1
- FNENWZWNOPCZGK-UHFFFAOYSA-N ethyl 2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(C)=O FNENWZWNOPCZGK-UHFFFAOYSA-N 0.000 description 1
- VVCYNVCCODBCOE-UHFFFAOYSA-N ethyl 2-methyl-3-oxopropanoate Chemical compound CCOC(=O)C(C)C=O VVCYNVCCODBCOE-UHFFFAOYSA-N 0.000 description 1
- XCLDSQRVMMXWMS-UHFFFAOYSA-N ethyl 4-methyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)C XCLDSQRVMMXWMS-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 230000004634 feeding behavior Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000011888 foil 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
- 238000004108 freeze drying 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
- 238000007306 functionalization reaction Methods 0.000 description 1
- 150000002244 furazanes Chemical class 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- XBFMJHQFVWWFLA-UHFFFAOYSA-N hexane;pentane Chemical compound CCCCC.CCCCCC XBFMJHQFVWWFLA-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 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
- 238000002955 isolation Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 210000003796 lateral hypothalamic area Anatomy 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- HZZOEADXZLYIHG-UHFFFAOYSA-N magnesiomagnesium Chemical compound [Mg][Mg] HZZOEADXZLYIHG-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000001055 magnesium Nutrition 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- VUMAKGCUBLVHCE-UHFFFAOYSA-N methyl 2-[[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]amino]acetate Chemical compound N=1N(C)C2=NC(NCC(=O)OC)=CC(C(F)(F)F)=C2C=1C1=CC=CC=C1 VUMAKGCUBLVHCE-UHFFFAOYSA-N 0.000 description 1
- JTZFGJRGEJCKEP-UHFFFAOYSA-N methyl 5-chloro-2-methyl-3,4-dihydropyrazole-3-carboxylate Chemical compound COC(=O)C1CC(Cl)=NN1C JTZFGJRGEJCKEP-UHFFFAOYSA-N 0.000 description 1
- HXVYKJUTAPFZGY-UHFFFAOYSA-N methyl 5-chloro-2-methylpyrazole-3-carboxylate Chemical compound COC(=O)C1=CC(Cl)=NN1C HXVYKJUTAPFZGY-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- GUDQJFKBBOAOIC-HNNXBMFYSA-N n-[(1s)-1-(4-methoxyphenyl)ethyl]-2-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxyacetamide Chemical compound C1=CC(OC)=CC=C1[C@H](C)NC(=O)COC1=CC(C(F)(F)F)=C(C(=NN2C)C=3C=CC=CC=3)C2=N1 GUDQJFKBBOAOIC-HNNXBMFYSA-N 0.000 description 1
- NXYUYYGDODQELZ-IBGZPJMESA-N n-[(1s)-2,3-dihydro-1h-inden-1-yl]-2-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxyacetamide Chemical compound C12=C(C(F)(F)F)C=C(OCC(=O)N[C@@H]3C4=CC=CC=C4CC3)N=C2N(C)N=C1C1=CC=CC=C1 NXYUYYGDODQELZ-IBGZPJMESA-N 0.000 description 1
- ZYDUGRWINUBOPL-UHFFFAOYSA-N n-[2-(4-methylphenyl)propan-2-yl]acetamide Chemical compound CC(=O)NC(C)(C)C1=CC=C(C)C=C1 ZYDUGRWINUBOPL-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WLECPEWQOMTQOI-UHFFFAOYSA-N n-ethyl-n-(4-methylphenyl)acetamide Chemical compound CCN(C(C)=O)C1=CC=C(C)C=C1 WLECPEWQOMTQOI-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000018791 negative regulation of catalytic activity Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- XNYFAJZQMFNULQ-UHFFFAOYSA-N pyridin-1-ium-3-amine;chloride Chemical compound Cl.NC1=CC=CN=C1 XNYFAJZQMFNULQ-UHFFFAOYSA-N 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
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 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
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 235000019669 taste disorders Nutrition 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 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
- 239000012443 tonicity enhancing agent Substances 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- NXAOTUZKJHXTSD-UHFFFAOYSA-N tributyl-(3-fluoropyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CC=C1F NXAOTUZKJHXTSD-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- 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
- A61P25/20—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
- A61P25/28—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
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Anesthesiology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2664DE2009 | 2009-12-21 | ||
| IN2664/DEL/2009 | 2009-12-21 | ||
| PCT/EP2010/070260 WO2011076744A1 (en) | 2009-12-21 | 2010-12-20 | Disubstituted heteroaryl-fused pyridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013515032A true JP2013515032A (ja) | 2013-05-02 |
| JP2013515032A5 JP2013515032A5 (cg-RX-API-DMAC7.html) | 2014-01-30 |
Family
ID=43640661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012545276A Pending JP2013515032A (ja) | 2009-12-21 | 2010-12-20 | 二置換ヘテロアリール縮合ピリジン類 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8742106B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2516437B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2013515032A (cg-RX-API-DMAC7.html) |
| CN (1) | CN102762560A (cg-RX-API-DMAC7.html) |
| ES (1) | ES2460915T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2011076744A1 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022504780A (ja) * | 2018-10-18 | 2022-01-13 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 光学活性１－シクロプロピルアルキル－１－アミンのスケーラブルな合成 |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013119639A1 (en) | 2012-02-07 | 2013-08-15 | Eolas Therapeutics, Inc. | Substituted prolines / piperidines as orexin receptor antagonists |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| BR102012024778A2 (pt) | 2012-09-28 | 2014-08-19 | Cristalia Prod Quimicos Farm | Compostos heteroaromáticos; processo para preparar os compostos, composições farmacêuticas, usos e método de tratamento para as dores aguda e crônica |
| US10221170B2 (en) | 2014-08-13 | 2019-03-05 | Eolas Therapeutics, Inc. | Difluoropyrrolidines as orexin receptor modulators |
| ES3042832T3 (en) | 2014-12-29 | 2025-11-24 | Us Health | Small molecule inhibitors of lactate dehydrogenase and methods of use thereof |
| CN105541719B (zh) * | 2016-02-03 | 2018-06-29 | 安徽工业大学 | 一种以乳清酸为原料制备5-氨基-1,2二氢吡唑-3-酮的方法 |
| DK3414241T3 (da) | 2016-02-12 | 2022-08-01 | Astrazeneca Ab | Halogensubstituerede piperidiner som orexinreceptormodulatorer |
| WO2018054832A1 (en) | 2016-09-22 | 2018-03-29 | Bayer Cropscience Aktiengesellschaft | Novel triazole derivatives |
| US20190281828A1 (en) | 2016-09-22 | 2019-09-19 | Bayer Cropscience Aktiengesellschaft | Novel triazole derivatives |
| CA3038362A1 (en) | 2016-09-29 | 2018-04-05 | Bayer Cropscience Aktiengesellschaft | 5-substituted imidazolylmethyldioxolane derivatives as fungiciides |
| WO2018060091A1 (en) | 2016-09-29 | 2018-04-05 | Bayer Cropscience Aktiengesellschaft | Novel 5-substituted imidazolylmethyl derivatives |
| EP3580218A1 (en) | 2017-02-08 | 2019-12-18 | Bayer CropScience Aktiengesellschaft | Novel triazole derivatives |
| CN110267952A (zh) | 2017-02-08 | 2019-09-20 | 拜耳公司 | 三唑硫酮衍生物 |
| BR112019016241A2 (pt) | 2017-02-08 | 2020-04-07 | Bayer Cropscience Ag | derivados de triazol e seu uso como fungicidas |
| AU2018217749A1 (en) | 2017-02-10 | 2019-08-01 | Bayer Aktiengesellschaft | Composition for controlling harmful microorganisms comprising 1 -(phenoxy-pyridinyl)-2-(1,2,4-triazol-1 -yl)-ethanol derivatives |
| WO2020020816A1 (en) | 2018-07-26 | 2020-01-30 | Bayer Aktiengesellschaft | Novel triazole derivatives |
| WO2022094012A1 (en) * | 2020-11-02 | 2022-05-05 | Merck Sharp & Dohme Corp. | Macrocyclic urea orexin receptor agonists |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001098301A1 (en) * | 2000-06-20 | 2001-12-27 | Japan Tobacco Inc. | Pyrazolopyridine compounds and use thereof as drugs |
| WO2009003993A1 (en) * | 2007-07-03 | 2009-01-08 | Glaxo Group Limited | Piperidine derivatives useful as orexin receptor antagonists |
| WO2009017848A1 (en) * | 2007-03-05 | 2009-02-05 | Proteo Tech Inc. | Compounds, compositions, and methods for the treatment of amyloid diseases such as systemic aa amyloidosis |
| JP2009535324A (ja) * | 2006-04-26 | 2009-10-01 | アクテリオン ファーマシューティカルズ リミテッド | 新規なピラゾロ−テトラヒドロピリジン誘導体 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2232038A1 (de) | 1972-06-30 | 1974-01-10 | Hoechst Ag | 3-amino-1h-pyrazolo eckige klammer auf 3,4-b eckige klammer zu pyridine, ihre herstellung und verwendung |
| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| US6670364B2 (en) | 2001-01-31 | 2003-12-30 | Telik, Inc. | Antagonists of MCP-1 function and methods of use thereof |
| US6962926B2 (en) | 2001-01-31 | 2005-11-08 | Telik, Inc. | Antagonist of MCP-1 function, and compositions and methods of use thereof |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| DE102004061288A1 (de) | 2004-12-14 | 2006-06-29 | Schering Ag | 3-Amino-Pyrazolo[3,4b]pyridine als Inhibitoren von Proteintyrosinkinasen, deren Herstellung und Verwendung als Arzneimittel |
| AR057455A1 (es) | 2005-07-22 | 2007-12-05 | Merck & Co Inc | Inhibidores de la transcriptasa reversa de vih y composicion farmaceutica |
| EP1764099A3 (en) | 2005-09-17 | 2007-05-09 | Speedel Experimenta AG | Diaminoalcohol derivatives for the treatment of Alzheimer, malaria, HIV |
| JP2007099640A (ja) | 2005-09-30 | 2007-04-19 | Tsumura & Co | 含窒素複素環化合物、その製造方法およびそれを用いた医薬組成物 |
| TW200815438A (en) | 2006-06-13 | 2008-04-01 | Bayer Schering Pharma Ag | Substituted pyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| EP1870410A1 (en) | 2006-06-13 | 2007-12-26 | Bayer Schering Pharma Aktiengesellschaft | Substituted arylpyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| GB0617161D0 (en) | 2006-08-31 | 2006-10-11 | Vernalis R&D Ltd | Enzyme inhibitors |
-
2010
- 2010-12-20 JP JP2012545276A patent/JP2013515032A/ja active Pending
- 2010-12-20 US US13/517,115 patent/US8742106B2/en not_active Expired - Fee Related
- 2010-12-20 CN CN2010800643114A patent/CN102762560A/zh active Pending
- 2010-12-20 WO PCT/EP2010/070260 patent/WO2011076744A1/en not_active Ceased
- 2010-12-20 ES ES10805785.2T patent/ES2460915T3/es active Active
- 2010-12-20 EP EP10805785.2A patent/EP2516437B1/en not_active Not-in-force
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001098301A1 (en) * | 2000-06-20 | 2001-12-27 | Japan Tobacco Inc. | Pyrazolopyridine compounds and use thereof as drugs |
| JP2009535324A (ja) * | 2006-04-26 | 2009-10-01 | アクテリオン ファーマシューティカルズ リミテッド | 新規なピラゾロ−テトラヒドロピリジン誘導体 |
| WO2009017848A1 (en) * | 2007-03-05 | 2009-02-05 | Proteo Tech Inc. | Compounds, compositions, and methods for the treatment of amyloid diseases such as systemic aa amyloidosis |
| WO2009003993A1 (en) * | 2007-07-03 | 2009-01-08 | Glaxo Group Limited | Piperidine derivatives useful as orexin receptor antagonists |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022504780A (ja) * | 2018-10-18 | 2022-01-13 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 光学活性１－シクロプロピルアルキル－１－アミンのスケーラブルな合成 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102762560A (zh) | 2012-10-31 |
| EP2516437B1 (en) | 2014-01-29 |
| WO2011076744A1 (en) | 2011-06-30 |
| EP2516437A1 (en) | 2012-10-31 |
| ES2460915T3 (es) | 2014-05-16 |
| US20120258973A1 (en) | 2012-10-11 |
| US8742106B2 (en) | 2014-06-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2516437B1 (en) | Disubstituted heteroaryl-fused pyridines | |
| EP2516439B1 (en) | Diaza-spiro[5.5]undecanes as orexin receptor antagonists | |
| KR102549952B1 (ko) | 키나제 억제제로서의 아미노트리아졸로피리딘 | |
| US8492378B2 (en) | GSK-3β inhibitor | |
| CN107406426B (zh) | 作为rock抑制剂的环状脲类 | |
| CA2691776C (en) | Substituted imidazoheterocycles | |
| TWI378098B (en) | Hydroxymethyl pyrrolidines as beta 3 adrenergic receptor agonists | |
| JP6716711B2 (ja) | Ａｐｊアゴニストとしての６−ヒドロキシ−４−オキソ−１，４−ジヒドロピリミジン−５−カルボキシアミド | |
| US20080113967A1 (en) | Enzyme modulators and treatments | |
| US20120165331A1 (en) | Di/tri-aza-spiro-C9-C11alkanes | |
| RS57332B1 (sr) | Heterociklični amidi kao inhibitori kinaze | |
| KR20090096636A (ko) | Ｄｄｐ-ｉｖ 억제제로서의 1-아미노메틸-ｌ-페닐-시클로헥산 유도체 | |
| EA029312B1 (ru) | Производные имидазопирролидинона и их применение при лечении заболеваний | |
| WO2011073316A1 (en) | 4-aryl-butane-1,3-diamides | |
| CN110072850A (zh) | 3-磺酰基-5-氨基吡啶-2,4-二醇apj激动剂 | |
| JP2022519770A (ja) | ファルネソイドｘ受容体モジュレータとしての置換二環式化合物 | |
| AU2013214226A1 (en) | Fused pyrroledicarboxamides and their use as pharmaceuticals | |
| CN105814051A (zh) | 用作tnf活性调节剂的四氢咪唑并吡啶衍生物 | |
| US20100222396A1 (en) | 4-aryl-butane-1,3-diamides | |
| CN109195968A (zh) | 作为tnf活性调节剂的稠合五环咪唑衍生物 | |
| JP2016510810A (ja) | オレキシン受容体アンタゴニストとしてのアゼチジンアミド誘導体 | |
| WO2012055888A1 (en) | Diaza-spiro[5.5]undecanes useful as orexin receptor antagonists | |
| EA047337B1 (ru) | Замещенные бициклические соединения в качестве модуляторов фарнезоидного х-рецептора | |
| OA18099A (en) | 2-Amino-6-Methyl-4,4a,5,6-Tetrahydropyrano[3,4-d][1,3]Thiazin-8a(8H)-YL-1,3Thiazol4-YL Amides | |
| HK1167386A (en) | Metabotropic glutamate receptor modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131203 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131203 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140818 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20140902 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150324 |