RU2369599C2 - Амиды 3-замещенной 5- и 6-аминоалкилиндол-2-карбоновой кислоты и родственные аналоги как ингибиторы казеинкиназы iε - Google Patents

Info

Publication number

RU2369599C2

RU2369599C2 RU2007109783/04A RU2007109783A RU2369599C2 RU 2369599 C2 RU2369599 C2 RU 2369599C2 RU 2007109783/04 A RU2007109783/04 A RU 2007109783/04A RU 2007109783 A RU2007109783 A RU 2007109783A RU 2369599 C2 RU2369599 C2 RU 2369599C2

Authority

RU

Russia

Prior art keywords

indole

carboxylic acid

phenylsulfanyl

alkyl

amide

Prior art date

2004-08-19

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001408 amides Chemical class 0.000 title claims description 142
• 102000005403 Casein Kinases Human genes 0.000 title claims description 30
• 108010031425 Casein Kinases Proteins 0.000 title claims description 30
• 239000003112 inhibitor Substances 0.000 title claims description 14
• -1 methylenedioxy Chemical group 0.000 claims abstract description 215
• 150000001875 compounds Chemical class 0.000 claims abstract description 142
• 125000003118 aryl group Chemical group 0.000 claims abstract description 103
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 93
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 44
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 40
• 230000000694 effects Effects 0.000 claims abstract description 35
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 31
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 31
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
• 150000003839 salts Chemical class 0.000 claims abstract description 22
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 20
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 15
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
• 150000002367 halogens Chemical class 0.000 claims abstract description 13
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 12
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 11
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 10
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 9
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 6
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims abstract description 5
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 5
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 5
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims abstract description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 46
• 230000027288 circadian rhythm Effects 0.000 claims description 33
• 230000007958 sleep Effects 0.000 claims description 33
• 208000019116 sleep disease Diseases 0.000 claims description 33
• 230000002060 circadian Effects 0.000 claims description 32
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 239000002904 solvent Substances 0.000 claims description 29
• 208000020925 Bipolar disease Diseases 0.000 claims description 24
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• 208000035475 disorder Diseases 0.000 claims description 23
• 201000010099 disease Diseases 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 208000019022 Mood disease Diseases 0.000 claims description 16
• 208000011580 syndromic disease Diseases 0.000 claims description 16
• 208000020401 Depressive disease Diseases 0.000 claims description 14
• 230000005764 inhibitory process Effects 0.000 claims description 13
• 238000011282 treatment Methods 0.000 claims description 12
• 208000020685 sleep-wake disease Diseases 0.000 claims description 11
• 239000003937 drug carrier Substances 0.000 claims description 10
• 125000002252 acyl group Chemical group 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• 230000033764 rhythmic process Effects 0.000 claims description 9
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• 230000010006 flight Effects 0.000 claims description 7
• JLYRSHVVQADSID-UHFFFAOYSA-N 3-phenylsulfanyl-5-(propylaminomethyl)-1h-indole-2-carboxamide Chemical compound C12=CC(CNCCC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 JLYRSHVVQADSID-UHFFFAOYSA-N 0.000 claims description 6
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 5
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
• 230000002028 premature Effects 0.000 claims description 5
• ZRSYJRIKLSTZMT-UHFFFAOYSA-N 5-(aminomethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CN)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 ZRSYJRIKLSTZMT-UHFFFAOYSA-N 0.000 claims description 4
• TZYCYPZBYDYRQB-UHFFFAOYSA-N 5-(methylaminomethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 TZYCYPZBYDYRQB-UHFFFAOYSA-N 0.000 claims description 4
• 235000013922 glutamic acid Nutrition 0.000 claims description 4
• HDHLISZWASJGHT-UHFFFAOYSA-N 1-[(2-bicyclo[2.2.1]heptanylamino)methyl]-3-phenylsulfanylindole-2-carboxamide Chemical compound C12=CC=CC=C2N(CNC2C3CCC(C3)C2)C(C(=O)N)=C1SC1=CC=CC=C1 HDHLISZWASJGHT-UHFFFAOYSA-N 0.000 claims description 3
• 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 3
• PHTVYNGDFBACTF-UHFFFAOYSA-N 3-(3-chlorophenyl)sulfanyl-5-(methylaminomethyl)-1h-indole-2-carboxamide Chemical compound C12=CC(CNC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC(Cl)=C1 PHTVYNGDFBACTF-UHFFFAOYSA-N 0.000 claims description 3
• OJFWSLXLAIEZSO-UHFFFAOYSA-N 3-(3-fluorophenyl)sulfanyl-5-(methylaminomethyl)-1h-indole-2-carboxamide Chemical compound C12=CC(CNC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC(F)=C1 OJFWSLXLAIEZSO-UHFFFAOYSA-N 0.000 claims description 3
• BXJWUHNROITKOB-UHFFFAOYSA-N 3-phenylsulfanyl-5-(piperidin-1-ylmethyl)-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN1CCCCC1 BXJWUHNROITKOB-UHFFFAOYSA-N 0.000 claims description 3
• JUQZGNJVJIHARC-UHFFFAOYSA-N 3-phenylsulfanyl-5-[(propan-2-ylamino)methyl]-1h-indole-2-carboxamide Chemical compound C12=CC(CNC(C)C)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 JUQZGNJVJIHARC-UHFFFAOYSA-N 0.000 claims description 3
• PQWRIVOWPXRRJX-UHFFFAOYSA-N 3-phenylsulfanyl-5-[(quinolin-6-ylamino)methyl]-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC=C(CNC=3C=C4C=CC=NC4=CC=3)C=C2C=1SC1=CC=CC=C1 PQWRIVOWPXRRJX-UHFFFAOYSA-N 0.000 claims description 3
• SHKMPRXGCZCJQL-UHFFFAOYSA-N 5-(1,4-diazepan-1-ylmethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN1CCCNCC1 SHKMPRXGCZCJQL-UHFFFAOYSA-N 0.000 claims description 3
• UDUXBKHRALVKNO-UHFFFAOYSA-N 5-(butylaminomethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNCCCC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 UDUXBKHRALVKNO-UHFFFAOYSA-N 0.000 claims description 3
• HLZRKWABRSXWTB-UHFFFAOYSA-N 5-(ethylaminomethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNCC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 HLZRKWABRSXWTB-UHFFFAOYSA-N 0.000 claims description 3
• XLAUWVOGJHPJML-UHFFFAOYSA-N 5-(morpholin-4-ylmethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN1CCOCC1 XLAUWVOGJHPJML-UHFFFAOYSA-N 0.000 claims description 3
• LARCNPWNXCRVKY-UHFFFAOYSA-N 5-[(3-carbamoylpiperidin-1-yl)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1C(C(=O)N)CCCN1CC1=CC=C(NC(C(N)=O)=C2SC=3C=CC=CC=3)C2=C1 LARCNPWNXCRVKY-UHFFFAOYSA-N 0.000 claims description 3
• IPEWRCABZMBLLR-UHFFFAOYSA-N 5-[(benzylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CNCC1=CC=CC=C1 IPEWRCABZMBLLR-UHFFFAOYSA-N 0.000 claims description 3
• DAAPUDXKYYZXKS-UHFFFAOYSA-N 5-[(heptylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNCCCCCCC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 DAAPUDXKYYZXKS-UHFFFAOYSA-N 0.000 claims description 3
• OCICEAWBXNDPAL-UHFFFAOYSA-N 5-[(pentylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNCCCCC)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 OCICEAWBXNDPAL-UHFFFAOYSA-N 0.000 claims description 3
• BSOFVACFRCOLPE-UHFFFAOYSA-N 5-[[2-(hydroxymethyl)pyrrolidin-1-yl]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN1CCCC1CO BSOFVACFRCOLPE-UHFFFAOYSA-N 0.000 claims description 3
• BKPVPPGKGHXIJE-UHFFFAOYSA-N 5-[[4-(3-phenylprop-1-enyl)piperazin-1-yl]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN(CC1)CCN1C=CCC1=CC=CC=C1 BKPVPPGKGHXIJE-UHFFFAOYSA-N 0.000 claims description 3
• CWKFMXVKGKBRJP-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN(CC1)CCN1C1=CC=C(F)C=C1 CWKFMXVKGKBRJP-UHFFFAOYSA-N 0.000 claims description 3
• NNXGDKGCTQFQHZ-UHFFFAOYSA-N 6-[[(2-methoxyphenyl)methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound COC1=CC=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(N)=O)C2=C1 NNXGDKGCTQFQHZ-UHFFFAOYSA-N 0.000 claims description 3
• PFWZZDJRMHSJHV-UHFFFAOYSA-N BrC1=C(OC)C(OC)=CC(CNCC=2C=C3NC(=C(SC=4C=CC=CC=4)C3=CC=2)C(O)=O)=C1 Chemical compound BrC1=C(OC)C(OC)=CC(CNCC=2C=C3NC(=C(SC=4C=CC=CC=4)C3=CC=2)C(O)=O)=C1 PFWZZDJRMHSJHV-UHFFFAOYSA-N 0.000 claims description 3
• WIOXGFLODZHVOT-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CN(CC=1OC(=CC=1)[N+]([O-])=O)CC1=CC=C([N+]([O-])=O)O1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CN(CC=1OC(=CC=1)[N+]([O-])=O)CC1=CC=C([N+]([O-])=O)O1 WIOXGFLODZHVOT-UHFFFAOYSA-N 0.000 claims description 3
• YQDYCJYMHWHRHW-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC(C=1)=CC=CC=1OC1=CC=CC=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC(C=1)=CC=CC=1OC1=CC=CC=C1 YQDYCJYMHWHRHW-UHFFFAOYSA-N 0.000 claims description 3
• NOUXSSPHKDTDLH-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=C(F)C=CC=C1C(F)(F)F Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=C(F)C=CC=C1C(F)(F)F NOUXSSPHKDTDLH-UHFFFAOYSA-N 0.000 claims description 3
• ANOIXNIRUZMARF-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C([N+]([O-])=O)O1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C([N+]([O-])=O)O1 ANOIXNIRUZMARF-UHFFFAOYSA-N 0.000 claims description 3
• DUUOHBIOELUIOW-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C([N+]([O-])=O)S1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C([N+]([O-])=O)S1 DUUOHBIOELUIOW-UHFFFAOYSA-N 0.000 claims description 3
• JWRHJPWFVCJJBQ-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=CC(C(F)(F)F)=C1F Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=CC(C(F)(F)F)=C1F JWRHJPWFVCJJBQ-UHFFFAOYSA-N 0.000 claims description 3
• DISCJKOBBJRYBX-UHFFFAOYSA-N CC1=CC=CC(CNCC=2C=C3NC(=C(SC=4C=CC=CC=4)C3=CC=2)C(O)=O)=C1 Chemical compound CC1=CC=CC(CNCC=2C=C3NC(=C(SC=4C=CC=CC=4)C3=CC=2)C(O)=O)=C1 DISCJKOBBJRYBX-UHFFFAOYSA-N 0.000 claims description 3
• BUYZBZRKEWWFTN-UHFFFAOYSA-N COC1=CC(OC)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 Chemical compound COC1=CC(OC)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 BUYZBZRKEWWFTN-UHFFFAOYSA-N 0.000 claims description 3
• VSNAOCNBXTWWFG-UHFFFAOYSA-N ClC1=C2C=CC=CC2=C(C2=CC=CC=C12)CNCC1=CC=C2C(=C(NC2=C1)C(=O)O)SC1=CC=CC=C1 Chemical compound ClC1=C2C=CC=CC2=C(C2=CC=CC=C12)CNCC1=CC=C2C(=C(NC2=C1)C(=O)O)SC1=CC=CC=C1 VSNAOCNBXTWWFG-UHFFFAOYSA-N 0.000 claims description 3
• OICCTERCOZFKED-UHFFFAOYSA-N OC(=O)C=1NC2=CC(CNC(=O)C(N)C(C)CC)=CC=C2C=1SC1=CC=CC=C1 Chemical compound OC(=O)C=1NC2=CC(CNC(=O)C(N)C(C)CC)=CC=C2C=1SC1=CC=CC=C1 OICCTERCOZFKED-UHFFFAOYSA-N 0.000 claims description 3
• IQBZHVDCHNVQLZ-UHFFFAOYSA-N OC(=O)C=1NC2=CC(CNC(=O)C(N)CCSC)=CC=C2C=1SC1=CC=CC=C1 Chemical compound OC(=O)C=1NC2=CC(CNC(=O)C(N)CCSC)=CC=C2C=1SC1=CC=CC=C1 IQBZHVDCHNVQLZ-UHFFFAOYSA-N 0.000 claims description 3
• XDRXCWMFSJLTPU-UHFFFAOYSA-N OC(=O)C=1NC2=CC(CNC(=O)CN)=CC=C2C=1SC1=CC=CC=C1 Chemical compound OC(=O)C=1NC2=CC(CNC(=O)CN)=CC=C2C=1SC1=CC=CC=C1 XDRXCWMFSJLTPU-UHFFFAOYSA-N 0.000 claims description 3
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 3
• NBWPZQRXZKZWTG-UHFFFAOYSA-N methyl 4-[[(2-carbamoyl-3-phenylsulfanyl-1h-indol-6-yl)methylamino]methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(N)=O)C2=C1 NBWPZQRXZKZWTG-UHFFFAOYSA-N 0.000 claims description 3
• SYZDABMIUZMPPL-UHFFFAOYSA-N 5-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylmethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN(CC1)CCC21OCCO2 SYZDABMIUZMPPL-UHFFFAOYSA-N 0.000 claims description 2
• VIQIAMCXYSBYQY-UHFFFAOYSA-N 5-[(1-hydroxypropan-2-ylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNC(CO)C)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 VIQIAMCXYSBYQY-UHFFFAOYSA-N 0.000 claims description 2
• RYWSGPKTJTWPJH-UHFFFAOYSA-N 5-[(2,3-dihydroxypropylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC=C(CNCC(O)CO)C=C2C=1SC1=CC=CC=C1 RYWSGPKTJTWPJH-UHFFFAOYSA-N 0.000 claims description 2
• LCFUECWRWISTPP-UHFFFAOYSA-N 5-[(2-cyano-4,5-dimethoxyanilino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C(OC)C(OC)=CC(NCC=2C=C3C(SC=4C=CC=CC=4)=C(C(N)=O)NC3=CC=2)=C1C#N LCFUECWRWISTPP-UHFFFAOYSA-N 0.000 claims description 2
• WWFKUELLAFXIEG-UHFFFAOYSA-N 5-[(2-fluoroanilino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CNC1=CC=CC=C1F WWFKUELLAFXIEG-UHFFFAOYSA-N 0.000 claims description 2
• WVKHZVHKRFIYHU-UHFFFAOYSA-N 5-[(3-methoxyanilino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound COC1=CC=CC(NCC=2C=C3C(SC=4C=CC=CC=4)=C(C(N)=O)NC3=CC=2)=C1 WVKHZVHKRFIYHU-UHFFFAOYSA-N 0.000 claims description 2
• VRUDQDCPQOQGDE-UHFFFAOYSA-N 5-[(4-butylanilino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=CC(CCCC)=CC=C1NCC1=CC=C(NC(C(N)=O)=C2SC=3C=CC=CC=3)C2=C1 VRUDQDCPQOQGDE-UHFFFAOYSA-N 0.000 claims description 2
• BBVKPLPOVHBJGO-UHFFFAOYSA-N 5-[[(1,3-dihydroxy-2-methylpropan-2-yl)amino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNC(CO)(CO)C)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 BBVKPLPOVHBJGO-UHFFFAOYSA-N 0.000 claims description 2
• CCUHUKCNAKYYIH-UHFFFAOYSA-N 5-[[(1-amino-1-oxopropan-2-yl)amino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C12=CC(CNC(C)C(N)=O)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 CCUHUKCNAKYYIH-UHFFFAOYSA-N 0.000 claims description 2
• ROEZJVSADVPLTJ-UHFFFAOYSA-N 5-[[4-(hydroxymethyl)piperidin-1-yl]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN1CCC(CO)CC1 ROEZJVSADVPLTJ-UHFFFAOYSA-N 0.000 claims description 2
• NLWLOSBVSVYELF-UHFFFAOYSA-N 6-[(2,6-diaminohexanoylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC(CNC(=O)C(N)CCCCN)=CC=C2C=1SC1=CC=CC=C1 NLWLOSBVSVYELF-UHFFFAOYSA-N 0.000 claims description 2
• WEQYXTUOZWXXHA-UHFFFAOYSA-N 6-[[(2-amino-3-phenylpropanoyl)amino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(N)=O)NC2=CC=1CNC(=O)C(N)CC1=CC=CC=C1 WEQYXTUOZWXXHA-UHFFFAOYSA-N 0.000 claims description 2
• ZWFRLZNZMVFECA-UHFFFAOYSA-N CC1=CC=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 Chemical compound CC1=CC=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 ZWFRLZNZMVFECA-UHFFFAOYSA-N 0.000 claims description 2
• NSEDAQCRZGKEMB-UHFFFAOYSA-N CN1C(=C(C2=CC(=CC=C12)CNC)SC1=CC=CC=C1)C(=O)O Chemical compound CN1C(=C(C2=CC(=CC=C12)CNC)SC1=CC=CC=C1)C(=O)O NSEDAQCRZGKEMB-UHFFFAOYSA-N 0.000 claims description 2
• 229940122537 Casein kinase inhibitor Drugs 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• VMPJTEFACVOVJN-UHFFFAOYSA-N tert-butyl 4-[(2-carbamoyl-3-phenylsulfanyl-1h-indol-5-yl)methyl]-1,4-diazepane-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCCN1CC1=CC=C(NC(C(N)=O)=C2SC=3C=CC=CC=3)C2=C1 VMPJTEFACVOVJN-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims 5
• PEIUTXYUTPXDCK-UHFFFAOYSA-N 6-[[[5-(2-chlorophenyl)furan-2-yl]methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=1CNCC(O1)=CC=C1C1=CC=CC=C1Cl PEIUTXYUTPXDCK-UHFFFAOYSA-N 0.000 claims 1
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 claims 1
• 239000000126 substance Substances 0.000 abstract description 10
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 19
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 2
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
• 102000008122 Casein Kinase I Human genes 0.000 abstract 1
• 108010049812 Casein Kinase I Proteins 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 308
• 238000000034 method Methods 0.000 description 113
• 238000006243 chemical reaction Methods 0.000 description 61
• 239000011541 reaction mixture Substances 0.000 description 54
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 52
• 239000012458 free base Substances 0.000 description 51
• 150000003840 hydrochlorides Chemical class 0.000 description 50
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
• 239000000243 solution Substances 0.000 description 41
• 238000007429 general method Methods 0.000 description 40
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
• HGBOPPKVQTVZHH-UHFFFAOYSA-N 5-formyl-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC=C(C=O)C=C2C=1SC1=CC=CC=C1 HGBOPPKVQTVZHH-UHFFFAOYSA-N 0.000 description 34
• 239000007787 solid Substances 0.000 description 33
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• 239000000203 mixture Substances 0.000 description 32
• FLDSMVTWEZKONL-AWEZNQCLSA-N 5,5-dimethyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,4,7,8-tetrahydrooxepino[4,5-c]pyrazole-3-carboxamide Chemical compound CC1(CC2=C(NN=C2C(=O)N[C@@H]2C(N(C3=C(OC2)C=CC=C3)C)=O)CCO1)C FLDSMVTWEZKONL-AWEZNQCLSA-N 0.000 description 31
• 108090000623 proteins and genes Proteins 0.000 description 29
• 210000004027 cell Anatomy 0.000 description 27
• 238000001308 synthesis method Methods 0.000 description 23
• 238000004587 chromatography analysis Methods 0.000 description 20
• 235000019439 ethyl acetate Nutrition 0.000 description 20
• 238000004809 thin layer chromatography Methods 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
• 239000000543 intermediate Substances 0.000 description 19
• 239000000047 product Substances 0.000 description 19
• 235000018102 proteins Nutrition 0.000 description 18
• 102000004169 proteins and genes Human genes 0.000 description 18
• 239000002244 precipitate Substances 0.000 description 17
• 238000002360 preparation method Methods 0.000 description 17
• HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 16
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 15
• 125000001931 aliphatic group Chemical group 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 206010022437 insomnia Diseases 0.000 description 15
• 239000012071 phase Substances 0.000 description 15
• 102100037398 Casein kinase I isoform epsilon Human genes 0.000 description 14
• 101001026376 Homo sapiens Casein kinase I isoform epsilon Proteins 0.000 description 14
• VZSOXWAHGVEQOT-UHFFFAOYSA-N ethyl 5-cyano-1h-indole-2-carboxylate Chemical compound N#CC1=CC=C2NC(C(=O)OCC)=CC2=C1 VZSOXWAHGVEQOT-UHFFFAOYSA-N 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• 238000001914 filtration Methods 0.000 description 13
• 208000024714 major depressive disease Diseases 0.000 description 13
• 150000003141 primary amines Chemical class 0.000 description 13
• 208000022925 sleep disturbance Diseases 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 238000004458 analytical method Methods 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
• 125000002947 alkylene group Chemical group 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• 239000011347 resin Substances 0.000 description 11
• 229920005989 resin Polymers 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• 102100037402 Casein kinase I isoform delta Human genes 0.000 description 10
• 101000579484 Homo sapiens Period circadian protein homolog 1 Proteins 0.000 description 10
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 10
• 241001465754 Metazoa Species 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• 150000001299 aldehydes Chemical class 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• 239000012141 concentrate Substances 0.000 description 10
• 235000008504 concentrate Nutrition 0.000 description 10
• 125000001033 ether group Chemical group 0.000 description 10
• IUCDNWPSPSMAPS-UHFFFAOYSA-N ethyl 6-cyano-1h-indole-2-carboxylate Chemical compound C1=C(C#N)C=C2NC(C(=O)OCC)=CC2=C1 IUCDNWPSPSMAPS-UHFFFAOYSA-N 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• 239000011550 stock solution Substances 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• SHBJKZBTLKRLSE-UHFFFAOYSA-N 3-(aminomethyl)-1h-indole-2-carboxamide Chemical class C1=CC=C2C(CN)=C(C(N)=O)NC2=C1 SHBJKZBTLKRLSE-UHFFFAOYSA-N 0.000 description 9
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 9
• 102100028293 Period circadian protein homolog 1 Human genes 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 125000004430 oxygen atom Chemical group O* 0.000 description 9
• 230000026731 phosphorylation Effects 0.000 description 9
• 238000006366 phosphorylation reaction Methods 0.000 description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• 229910004298 SiO 2 Inorganic materials 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 239000001257 hydrogen Substances 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
• 101001026336 Homo sapiens Casein kinase I isoform delta Proteins 0.000 description 7
• 101001073216 Homo sapiens Period circadian protein homolog 2 Proteins 0.000 description 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
• 102100035787 Period circadian protein homolog 2 Human genes 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 230000006870 function Effects 0.000 description 7
• 210000002569 neuron Anatomy 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 230000001932 seasonal effect Effects 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 7
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 6
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 6
• UAYYSAPJTRVEQA-UHFFFAOYSA-N 1h-indol-5-ylmethanamine Chemical compound NCC1=CC=C2NC=CC2=C1 UAYYSAPJTRVEQA-UHFFFAOYSA-N 0.000 description 6
• FURRUNQWZZOXOT-UHFFFAOYSA-N 1h-indol-6-ylmethanamine Chemical compound NCC1=CC=C2C=CNC2=C1 FURRUNQWZZOXOT-UHFFFAOYSA-N 0.000 description 6
• VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• 108010047048 Casein Kinase Idelta Proteins 0.000 description 6
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 108060001084 Luciferase Proteins 0.000 description 6
• 239000005089 Luciferase Substances 0.000 description 6
• 241000124008 Mammalia Species 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 229910000564 Raney nickel Inorganic materials 0.000 description 6
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 235000001014 amino acid Nutrition 0.000 description 6
• 229940024606 amino acid Drugs 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 230000036760 body temperature Effects 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 230000008632 circadian clock Effects 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 239000003814 drug Substances 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 150000004702 methyl esters Chemical class 0.000 description 6
• 238000001126 phototherapy Methods 0.000 description 6
• 239000002798 polar solvent Substances 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 235000011181 potassium carbonates Nutrition 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 238000006268 reductive amination reaction Methods 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• LJIOTBMDLVHTBO-CUYJMHBOSA-N (2s)-2-amino-n-[(1r,2r)-1-cyano-2-[4-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]phenyl]cyclopropyl]butanamide Chemical compound CC[C@H](N)C(=O)N[C@]1(C#N)C[C@@H]1C1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)C=C1 LJIOTBMDLVHTBO-CUYJMHBOSA-N 0.000 description 5
• WAZBRNASBVLCNU-UHFFFAOYSA-N 5-cyano-1h-indole-2-carboxamide Chemical class N#CC1=CC=C2NC(C(=O)N)=CC2=C1 WAZBRNASBVLCNU-UHFFFAOYSA-N 0.000 description 5
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 5
• 241000700159 Rattus Species 0.000 description 5
• 108010084455 Zeocin Proteins 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 230000006399 behavior Effects 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 230000008859 change Effects 0.000 description 5
• 239000007795 chemical reaction product Substances 0.000 description 5
• 239000003638 chemical reducing agent Substances 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 208000037765 diseases and disorders Diseases 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 5
• 210000002950 fibroblast Anatomy 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 description 5
• 230000000737 periodic effect Effects 0.000 description 5
• CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 5
• 150000003140 primary amides Chemical class 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 208000020016 psychiatric disease Diseases 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 210000000221 suprachiasmatic nucleus Anatomy 0.000 description 5
• 238000013518 transcription Methods 0.000 description 5
• 230000035897 transcription Effects 0.000 description 5
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 4
• 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 4
• 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 4
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
• GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 4
• 101000882920 Drosophila melanogaster Circadian locomoter output cycles protein kaput Proteins 0.000 description 4
• DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 4
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• 101000579486 Mus musculus Period circadian protein homolog 1 Proteins 0.000 description 4
• 101001073214 Mus musculus Period circadian protein homolog 2 Proteins 0.000 description 4
• HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 239000004743 Polypropylene Substances 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 230000009435 amidation Effects 0.000 description 4
• 238000007112 amidation reaction Methods 0.000 description 4
• 150000001413 amino acids Chemical class 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• VQYOKDLEFVOVEV-UHFFFAOYSA-L bis(2,6-diphenylphenoxy)-methylalumane Chemical compound [Al+2]C.[O-]C1=C(C=2C=CC=CC=2)C=CC=C1C1=CC=CC=C1.[O-]C1=C(C=2C=CC=CC=2)C=CC=C1C1=CC=CC=C1 VQYOKDLEFVOVEV-UHFFFAOYSA-L 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 150000001735 carboxylic acids Chemical class 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 239000001963 growth medium Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 238000002955 isolation Methods 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 229920001155 polypropylene Polymers 0.000 description 4
• 235000011118 potassium hydroxide Nutrition 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 208000012672 seasonal affective disease Diseases 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 235000011121 sodium hydroxide Nutrition 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 125000004434 sulfur atom Chemical group 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
• RNAODKZCUVVPEN-UHFFFAOYSA-N 1h-indol-2-ylmethanamine Chemical compound C1=CC=C2NC(CN)=CC2=C1 RNAODKZCUVVPEN-UHFFFAOYSA-N 0.000 description 3
• IHVNKSXTJZNBQA-UHFFFAOYSA-N 3-methyl-4-nitrobenzonitrile Chemical class CC1=CC(C#N)=CC=C1[N+]([O-])=O IHVNKSXTJZNBQA-UHFFFAOYSA-N 0.000 description 3
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
• 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 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
• 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• 239000006145 Eagle's minimal essential medium Substances 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 101000601274 Homo sapiens Period circadian protein homolog 3 Proteins 0.000 description 3
• 101001126582 Homo sapiens Post-GPI attachment to proteins factor 3 Proteins 0.000 description 3
• 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 3
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
• 238000007126 N-alkylation reaction Methods 0.000 description 3
• 102100037630 Period circadian protein homolog 3 Human genes 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• 239000004793 Polystyrene Substances 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 150000001350 alkyl halides Chemical class 0.000 description 3
• 150000001371 alpha-amino acids Chemical class 0.000 description 3
• 235000008206 alpha-amino acids Nutrition 0.000 description 3
• 230000006793 arrhythmia Effects 0.000 description 3
• 206010003119 arrhythmia Diseases 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 229940125797 compound 12 Drugs 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 238000006471 dimerization reaction Methods 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• QQXQAEWRSVZPJM-UHFFFAOYSA-N ethyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1 QQXQAEWRSVZPJM-UHFFFAOYSA-N 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 239000007943 implant Substances 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 125000001041 indolyl group Chemical group 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 238000004949 mass spectrometry Methods 0.000 description 3
• 238000001819 mass spectrum Methods 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 229920002223 polystyrene Polymers 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000001681 protective effect Effects 0.000 description 3
• 230000002285 radioactive effect Effects 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 238000006722 reduction reaction Methods 0.000 description 3
• 238000012216 screening Methods 0.000 description 3
• 150000003335 secondary amines Chemical class 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 229960005322 streptomycin Drugs 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 230000001360 synchronised effect Effects 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
• SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• LWRSYTXEQUUTKW-UHFFFAOYSA-N 2,4-dimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1 LWRSYTXEQUUTKW-UHFFFAOYSA-N 0.000 description 2
• PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
• 239000001431 2-methylbenzaldehyde Substances 0.000 description 2
• YNWVKDDJHOXFNS-UHFFFAOYSA-N 3-(aminomethyl)-1h-indole-2-carboxylic acid Chemical class C1=CC=C2C(CN)=C(C(O)=O)NC2=C1 YNWVKDDJHOXFNS-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 2
• YUDYVWVBVNISFO-UHFFFAOYSA-N 3-phenylsulfanyl-5-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1h-indole-2-carboxamide Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=C1CN(CC1)CCN1C1=NC=CC=N1 YUDYVWVBVNISFO-UHFFFAOYSA-N 0.000 description 2
• KOFBNBCOGKLUOM-UHFFFAOYSA-N 4-methyl-3-nitrobenzonitrile Chemical class CC1=CC=C(C#N)C=C1[N+]([O-])=O KOFBNBCOGKLUOM-UHFFFAOYSA-N 0.000 description 2
• ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 2
• RUUKYBVLFFMPAQ-UHFFFAOYSA-N 5-(methylamino)-1h-indole-2-carboxylic acid Chemical compound CNC1=CC=C2NC(C(O)=O)=CC2=C1 RUUKYBVLFFMPAQ-UHFFFAOYSA-N 0.000 description 2
• SXINBFXPADXIEY-UHFFFAOYSA-N 5-Nitrofurfural Chemical compound [O-][N+](=O)C1=CC=C(C=O)O1 SXINBFXPADXIEY-UHFFFAOYSA-N 0.000 description 2
• BELDOPKTGBSVCA-UHFFFAOYSA-N 5-formyl-1-methyl-3-phenylsulfanylindole-2-carboxamide Chemical compound C12=CC(C=O)=CC=C2N(C)C(C(N)=O)=C1SC1=CC=CC=C1 BELDOPKTGBSVCA-UHFFFAOYSA-N 0.000 description 2
• UMNAHFVVEYZBSQ-UHFFFAOYSA-N 5-formyl-1h-indole-2-carboxamide Chemical class O=CC1=CC=C2NC(C(=O)N)=CC2=C1 UMNAHFVVEYZBSQ-UHFFFAOYSA-N 0.000 description 2
• GKLVGVOVOMDNTG-UHFFFAOYSA-N 6-(aminomethyl)-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC(CN)=CC=C2C=1SC1=CC=CC=C1 GKLVGVOVOMDNTG-UHFFFAOYSA-N 0.000 description 2
• FPICROACQHOCMQ-UHFFFAOYSA-N 6-[(benzylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=1CNCC1=CC=CC=C1 FPICROACQHOCMQ-UHFFFAOYSA-N 0.000 description 2
• ICOFFQSMCNAVEO-UHFFFAOYSA-N 6-[[[5-(2-chlorophenyl)furan-2-yl]methylamino]methyl]-3-phenylsulfanyl-1H-indole-2-carboxylic acid Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC(O1)=CC=C1C1=CC=CC=C1Cl ICOFFQSMCNAVEO-UHFFFAOYSA-N 0.000 description 2
• RGYZFLITNHXGMM-UHFFFAOYSA-N 6-cyano-1h-indole-2-carboxamide Chemical compound C1=C(C#N)C=C2NC(C(=O)N)=CC2=C1 RGYZFLITNHXGMM-UHFFFAOYSA-N 0.000 description 2
• 102000008867 ARNTL Transcription Factors Human genes 0.000 description 2
• 108010088547 ARNTL Transcription Factors Proteins 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
• GSLAVVXFDUQWPJ-UHFFFAOYSA-N C1=CC(C)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 Chemical compound C1=CC(C)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 GSLAVVXFDUQWPJ-UHFFFAOYSA-N 0.000 description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
• IALUTRZVZBGCNS-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC(C=C1)=CC=C1C1=CC=CC=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC(C=C1)=CC=C1C1=CC=CC=C1 IALUTRZVZBGCNS-UHFFFAOYSA-N 0.000 description 2
• POEPJRWUMCICEZ-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC(F)=CC(C(F)(F)F)=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC(F)=CC(C(F)(F)F)=C1 POEPJRWUMCICEZ-UHFFFAOYSA-N 0.000 description 2
• FRHHNGKUKVDUEB-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C(Br)C=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C(Br)C=C1 FRHHNGKUKVDUEB-UHFFFAOYSA-N 0.000 description 2
• AFRDKGXNBFNUOC-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C([N+]([O-])=O)C=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C([N+]([O-])=O)C=C1 AFRDKGXNBFNUOC-UHFFFAOYSA-N 0.000 description 2
• DDJXODPKMBOWAV-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=CC([N+]([O-])=O)=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=CC([N+]([O-])=O)=C1 DDJXODPKMBOWAV-UHFFFAOYSA-N 0.000 description 2
• UUKNPLRYUNREPR-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=CC=C1[N+]([O-])=O Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=CC=C1[N+]([O-])=O UUKNPLRYUNREPR-UHFFFAOYSA-N 0.000 description 2
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 102000011632 Caseins Human genes 0.000 description 2
• 108010076119 Caseins Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 2
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
• QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 2
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 2
• 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 2
• 108700017648 Drosophila tim Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 2
• 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 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 2
• 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 2
• 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 2
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 206010026749 Mania Diseases 0.000 description 2
• 101000601275 Mus musculus Period circadian protein homolog 3 Proteins 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 206010062519 Poor quality sleep Diseases 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 238000005903 acid hydrolysis reaction Methods 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 125000005466 alkylenyl group Chemical group 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
• 238000004364 calculation method Methods 0.000 description 2
• 125000005242 carbamoyl alkyl group Chemical group 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 239000005018 casein Substances 0.000 description 2
• 235000021240 caseins Nutrition 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 150000001793 charged compounds Chemical class 0.000 description 2
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 229940126543 compound 14 Drugs 0.000 description 2
• WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 2
• 125000004990 dihydroxyalkyl group Chemical group 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 206010020765 hypersomnia Diseases 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 238000004811 liquid chromatography Methods 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
• 206010025482 malaise Diseases 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
• 230000036651 mood Effects 0.000 description 2
• 125000002560 nitrile group Chemical group 0.000 description 2
• 150000002829 nitrogen Chemical class 0.000 description 2
• BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 2
• 101150008094 per1 gene Proteins 0.000 description 2
• 230000010363 phase shift Effects 0.000 description 2
• 230000035479 physiological effects, processes and functions Effects 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• PYNUOAIJIQGACY-UHFFFAOYSA-N propylazanium;chloride Chemical compound Cl.CCCN PYNUOAIJIQGACY-UHFFFAOYSA-N 0.000 description 2
• 230000004224 protection Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000001020 rhythmical effect Effects 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 238000003153 stable transfection Methods 0.000 description 2
• 150000003463 sulfur Chemical class 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 238000003419 tautomerization reaction Methods 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• GXSKHMNBZZVSSQ-UHFFFAOYSA-N tert-butyl n-[(2-carbamoyl-3-phenylsulfanyl-1h-indol-5-yl)methyl]carbamate Chemical compound C12=CC(CNC(=O)OC(C)(C)C)=CC=C2NC(C(N)=O)=C1SC1=CC=CC=C1 GXSKHMNBZZVSSQ-UHFFFAOYSA-N 0.000 description 2
• HORQAWFOJKHFQG-UHFFFAOYSA-N tert-butyl n-[(2-carbamoyl-3-phenylsulfanyl-1h-indol-6-yl)methyl]carbamate Chemical compound NC(=O)C=1NC2=CC(CNC(=O)OC(C)(C)C)=CC=C2C=1SC1=CC=CC=C1 HORQAWFOJKHFQG-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 230000002103 transcriptional effect Effects 0.000 description 2
• 238000005809 transesterification reaction Methods 0.000 description 2
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
• 230000003827 upregulation Effects 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• IQVLXQGNLCPZCL-ZDUSSCGKSA-N (2,5-dioxopyrrolidin-1-yl) (2s)-2,6-bis[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate Chemical compound CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O IQVLXQGNLCPZCL-ZDUSSCGKSA-N 0.000 description 1
• NHUCANAMPJGMQL-ZDUSSCGKSA-N (2,5-dioxopyrrolidin-1-yl) (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(CCC1=O)=O)C1=CC=CC=C1 NHUCANAMPJGMQL-ZDUSSCGKSA-N 0.000 description 1
• PCZJWSPKNYONIM-VIFPVBQESA-N (2,5-dioxopyrrolidin-1-yl) (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoate Chemical compound CC(C)(C)OC(=O)N[C@@H](CCSC)C(=O)ON1C(=O)CCC1=O PCZJWSPKNYONIM-VIFPVBQESA-N 0.000 description 1
• COMUWNFVTWKSDT-ZETCQYMHSA-N (2,5-dioxopyrrolidin-1-yl) (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)ON1C(=O)CCC1=O COMUWNFVTWKSDT-ZETCQYMHSA-N 0.000 description 1
• CPJXMXQYRHNIFU-HNNXBMFYSA-N (2,5-dioxopyrrolidin-1-yl) (2s)-3-(1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound O=C([C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)OC(C)(C)C)ON1C(=O)CCC1=O CPJXMXQYRHNIFU-HNNXBMFYSA-N 0.000 description 1
• WWXJEZQDOXUDOV-QMMMGPOBSA-N (2,5-dioxopyrrolidin-1-yl) (2s)-5-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate Chemical compound CC(C)(C)OC(=O)N[C@@H](CCC(N)=O)C(=O)ON1C(=O)CCC1=O WWXJEZQDOXUDOV-QMMMGPOBSA-N 0.000 description 1
• FATJLEZSGFVHQA-CABZTGNLSA-N (2,5-dioxopyrrolidin-1-yl) (2s,3s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate Chemical compound CC(C)(C)OC(=O)N[C@@H]([C@@H](C)CC)C(=O)ON1C(=O)CCC1=O FATJLEZSGFVHQA-CABZTGNLSA-N 0.000 description 1
• LJCWRJYVPJJTMB-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound CC(C)(C)OC(=O)NCC(=O)ON1C(=O)CCC1=O LJCWRJYVPJJTMB-UHFFFAOYSA-N 0.000 description 1
• FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 1
• MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 1
• IBTAWDHGKXYPHI-UHFFFAOYSA-N 1-(3-phenylprop-1-enyl)piperazine Chemical compound C=1C=CC=CC=1CC=CN1CCNCC1 IBTAWDHGKXYPHI-UHFFFAOYSA-N 0.000 description 1
• AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 1
• XZMIDORMXBMWTQ-UHFFFAOYSA-N 1-(benzenesulfonyl)pyrrole-2-carbaldehyde Chemical compound O=CC1=CC=CN1S(=O)(=O)C1=CC=CC=C1 XZMIDORMXBMWTQ-UHFFFAOYSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• MNCMBBIFTVWHIP-UHFFFAOYSA-N 1-anthracen-9-yl-2,2,2-trifluoroethanone Chemical group C1=CC=C2C(C(=O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 MNCMBBIFTVWHIP-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• OLOYVIPZMIIGOH-UHFFFAOYSA-N 1-chloro-3-[(3-chlorophenyl)disulfanyl]benzene Chemical compound ClC1=CC=CC(SSC=2C=C(Cl)C=CC=2)=C1 OLOYVIPZMIIGOH-UHFFFAOYSA-N 0.000 description 1
• LFVFHTBHAIVNJQ-UHFFFAOYSA-N 1-fluoro-3-[(3-fluorophenyl)disulfanyl]benzene Chemical compound FC1=CC=CC(SSC=2C=C(F)C=CC=2)=C1 LFVFHTBHAIVNJQ-UHFFFAOYSA-N 0.000 description 1
• 125000006039 1-hexenyl group Chemical group 0.000 description 1
• 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
• 125000006019 1-methyl-1-propenyl group Chemical group 0.000 description 1
• ZRUUVAXNJWUIJO-UHFFFAOYSA-N 1-methyl-5-(methylaminomethyl)-3-phenylsulfanylindole-2-carboxamide Chemical compound C12=CC(CNC)=CC=C2N(C)C(C(N)=O)=C1SC1=CC=CC=C1 ZRUUVAXNJWUIJO-UHFFFAOYSA-N 0.000 description 1
• 125000006018 1-methyl-ethenyl group Chemical group 0.000 description 1
• XIVDZBIBWGQOTI-UHFFFAOYSA-N 1-methylindole-5-carbaldehyde Chemical compound O=CC1=CC=C2N(C)C=CC2=C1 XIVDZBIBWGQOTI-UHFFFAOYSA-N 0.000 description 1
• AJFSBYJNTNGKJS-UHFFFAOYSA-N 1-phenylsulfanylindole-2-carboxylic acid Chemical compound OC(=O)c1cc2ccccc2n1Sc1ccccc1 AJFSBYJNTNGKJS-UHFFFAOYSA-N 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
• SHYBXXMECBHHFH-UHFFFAOYSA-N 10-chloroanthracene-9-carbaldehyde Chemical compound C1=CC=C2C(Cl)=C(C=CC=C3)C3=C(C=O)C2=C1 SHYBXXMECBHHFH-UHFFFAOYSA-N 0.000 description 1
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
• SBNOTUDDIXOFSN-UHFFFAOYSA-N 1h-indole-2-carbaldehyde Chemical compound C1=CC=C2NC(C=O)=CC2=C1 SBNOTUDDIXOFSN-UHFFFAOYSA-N 0.000 description 1
• VSPBWOAEHQDXRD-UHFFFAOYSA-N 1h-indole-6-carbaldehyde Chemical compound O=CC1=CC=C2C=CNC2=C1 VSPBWOAEHQDXRD-UHFFFAOYSA-N 0.000 description 1
• SZSZDBFJCQKTRG-UHFFFAOYSA-N 1h-indole-6-carbonitrile Chemical compound N#CC1=CC=C2C=CNC2=C1 SZSZDBFJCQKTRG-UHFFFAOYSA-N 0.000 description 1
• UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
• VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 description 1
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
• ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 1
• 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
• UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical compound OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 description 1
• BJAYMNUBIULRMF-UHFFFAOYSA-N 2-amino-4,5-dimethoxybenzonitrile Chemical compound COC1=CC(N)=C(C#N)C=C1OC BJAYMNUBIULRMF-UHFFFAOYSA-N 0.000 description 1
• QZXIXSZVEYUCGM-UHFFFAOYSA-N 2-aminopropan-2-ol Chemical compound CC(C)(N)O QZXIXSZVEYUCGM-UHFFFAOYSA-N 0.000 description 1
• HQMLIDZJXVVKCW-UHFFFAOYSA-N 2-aminopropanamide Chemical compound CC(N)C(N)=O HQMLIDZJXVVKCW-UHFFFAOYSA-N 0.000 description 1
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• XDMZVNQKVMTCSP-UHFFFAOYSA-N 2-fluoro-3-(trifluoromethyl)benzaldehyde Chemical compound FC1=C(C=O)C=CC=C1C(F)(F)F XDMZVNQKVMTCSP-UHFFFAOYSA-N 0.000 description 1
• FAKUGVHRTLCKHB-UHFFFAOYSA-N 2-fluoro-6-(trifluoromethyl)benzaldehyde Chemical compound FC1=CC=CC(C(F)(F)F)=C1C=O FAKUGVHRTLCKHB-UHFFFAOYSA-N 0.000 description 1
• FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 description 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• 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 description 1
• YIQGLTKAOHRZOL-UHFFFAOYSA-N 2-methoxynaphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(C=O)C(OC)=CC=C21 YIQGLTKAOHRZOL-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
• 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
• 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
• CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
• 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
• 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
• 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
• 125000006024 2-pentenyl group Chemical group 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000006494 2-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 description 1
• FABVMBDCVAJXMB-UHFFFAOYSA-N 3,5-dichloro-2-hydroxybenzaldehyde Chemical compound OC1=C(Cl)C=C(Cl)C=C1C=O FABVMBDCVAJXMB-UHFFFAOYSA-N 0.000 description 1
• VZIRCHXYMBFNFD-HNQUOIGGSA-N 3-(2-Furanyl)-2-propenal Chemical compound O=C\C=C\C1=CC=CO1 VZIRCHXYMBFNFD-HNQUOIGGSA-N 0.000 description 1
• GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
• VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 1
• CTBWWPIIRKWDDL-UHFFFAOYSA-N 3-amino-n,n-diethylbenzenesulfonamide Chemical compound CCN(CC)S(=O)(=O)C1=CC=CC(N)=C1 CTBWWPIIRKWDDL-UHFFFAOYSA-N 0.000 description 1
• ICVODPFGWCUVJC-UHFFFAOYSA-N 3-bromo-4,5-dimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(Br)=C1OC ICVODPFGWCUVJC-UHFFFAOYSA-N 0.000 description 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• UZZYXZWSOWQPIS-UHFFFAOYSA-N 3-fluoro-5-(trifluoromethyl)benzaldehyde Chemical compound FC1=CC(C=O)=CC(C(F)(F)F)=C1 UZZYXZWSOWQPIS-UHFFFAOYSA-N 0.000 description 1
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
• AARAIFZDFDNWOI-UHFFFAOYSA-N 3-methoxy-4-phenoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OC1=CC=CC=C1 AARAIFZDFDNWOI-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
• 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
• ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
• MRLGCTNJRREZHZ-UHFFFAOYSA-N 3-phenoxybenzaldehyde Chemical compound O=CC1=CC=CC(OC=2C=CC=CC=2)=C1 MRLGCTNJRREZHZ-UHFFFAOYSA-N 0.000 description 1
• 125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 description 1
• BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
• BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
• ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
• 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
• OGIQUQKNJJTLSZ-UHFFFAOYSA-N 4-butylaniline Chemical compound CCCCC1=CC=C(N)C=C1 OGIQUQKNJJTLSZ-UHFFFAOYSA-N 0.000 description 1
• AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
• 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• 125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
• VQVQZFHUXRSRBZ-UHFFFAOYSA-N 4-methoxy-3-phenylmethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1OCC1=CC=CC=C1 VQVQZFHUXRSRBZ-UHFFFAOYSA-N 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
• BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
• PIITZDSTZQZNQH-JTQLQIEISA-N 4-o-tert-butyl 1-o-(2,5-dioxopyrrolidin-1-yl) (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioate Chemical compound CC(C)(C)OC(=O)C[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O PIITZDSTZQZNQH-JTQLQIEISA-N 0.000 description 1
• 125000006189 4-phenyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
• ONQOZTFAOFZDFK-UHFFFAOYSA-N 5-(2-chlorophenyl)furan-2-carbaldehyde Chemical compound ClC1=CC=CC=C1C1=CC=C(C=O)O1 ONQOZTFAOFZDFK-UHFFFAOYSA-N 0.000 description 1
• UFPYLZCAXXJSIQ-UHFFFAOYSA-N 5-(methylaminomethyl)-1h-indole-2-carboxamide Chemical compound CNCC1=CC=C2NC(C(N)=O)=CC2=C1 UFPYLZCAXXJSIQ-UHFFFAOYSA-N 0.000 description 1
• AXAUNIVIEFHPSY-UHFFFAOYSA-N 5-cyano-1h-indole-2-carboxylic acid Chemical compound N#CC1=CC=C2NC(C(=O)O)=CC2=C1 AXAUNIVIEFHPSY-UHFFFAOYSA-N 0.000 description 1
• HLCZXPWKRBNEAT-UHFFFAOYSA-N 5-cyano-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC=C(C#N)C=C2C=1SC1=CC=CC=C1 HLCZXPWKRBNEAT-UHFFFAOYSA-N 0.000 description 1
• WFPYGZLPEVJECK-UHFFFAOYSA-N 6-(aminomethyl)-3-phenylsulfanyl-1H-indole-2-carboxamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=O)C=1NC2=CC(CN)=CC=C2C=1SC1=CC=CC=C1 WFPYGZLPEVJECK-UHFFFAOYSA-N 0.000 description 1
• LUMOFRIFMDHOOY-UHFFFAOYSA-N 6-[(2-aminopropanoylamino)methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC(CNC(=O)C(N)C)=CC=C2C=1SC1=CC=CC=C1 LUMOFRIFMDHOOY-UHFFFAOYSA-N 0.000 description 1
• MKIJAGJRNHRXFV-UHFFFAOYSA-N 6-[[(3,5-dichloro-2-hydroxyphenyl)methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=1CNCC1=CC(Cl)=CC(Cl)=C1O MKIJAGJRNHRXFV-UHFFFAOYSA-N 0.000 description 1
• GESOVJVFJICPLO-UHFFFAOYSA-N 6-[[(3-methoxy-4-phenylmethoxyphenyl)methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(OC)=CC=1CNCC(C=C1NC=2C(N)=O)=CC=C1C=2SC1=CC=CC=C1 GESOVJVFJICPLO-UHFFFAOYSA-N 0.000 description 1
• VUJXYLNLAYONKC-UHFFFAOYSA-N 6-[[(3-methoxyphenyl)methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound COC1=CC=CC(CNCC=2C=C3NC(=C(SC=4C=CC=CC=4)C3=CC=2)C(N)=O)=C1 VUJXYLNLAYONKC-UHFFFAOYSA-N 0.000 description 1
• LKBQWPLEIQKZIG-UHFFFAOYSA-N 6-[[(4-chlorophenyl)methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=1CNCC1=CC=C(Cl)C=C1 LKBQWPLEIQKZIG-UHFFFAOYSA-N 0.000 description 1
• NKYALTYFEFDZFM-UHFFFAOYSA-N 6-[[(4-methoxy-3-phenylmethoxyphenyl)methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=C(OCC=2C=CC=CC=2)C(OC)=CC=C1CNCC(C=C1NC=2C(N)=O)=CC=C1C=2SC1=CC=CC=C1 NKYALTYFEFDZFM-UHFFFAOYSA-N 0.000 description 1
• RIUGQEZGFSVYQB-UHFFFAOYSA-N 6-[[(4-methoxyphenyl)methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C1=CC(OC)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(N)=O)C2=C1 RIUGQEZGFSVYQB-UHFFFAOYSA-N 0.000 description 1
• AMHXEZXPHPSVPE-UHFFFAOYSA-N 6-[[[1-(benzenesulfonyl)pyrrol-2-yl]methylamino]methyl]-3-phenylsulfanyl-1H-indole-2-carboxylic acid Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=CN1S(=O)(=O)C1=CC=CC=C1 AMHXEZXPHPSVPE-UHFFFAOYSA-N 0.000 description 1
• YSYBLLPQACHVMA-UHFFFAOYSA-N 6-[[[4-(2-phenylethenyl)phenyl]methylamino]methyl]-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)N)NC2=CC=1CNCC(C=C1)=CC=C1C=CC1=CC=CC=C1 YSYBLLPQACHVMA-UHFFFAOYSA-N 0.000 description 1
• DZAGFMALIIXWPO-UHFFFAOYSA-N 6-cyano-1h-indole-2-carboxylic acid Chemical compound C1=C(C#N)C=C2NC(C(=O)O)=CC2=C1 DZAGFMALIIXWPO-UHFFFAOYSA-N 0.000 description 1
• MDGHBCQNNSTDPV-UHFFFAOYSA-N 6-cyano-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC(C#N)=CC=C2C=1SC1=CC=CC=C1 MDGHBCQNNSTDPV-UHFFFAOYSA-N 0.000 description 1
• PWCVXLWGYDLWHF-UHFFFAOYSA-N 6-formyl-3-phenylsulfanyl-1h-indole-2-carboxamide Chemical class NC(=O)C=1NC2=CC(C=O)=CC=C2C=1SC1=CC=CC=C1 PWCVXLWGYDLWHF-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 206010002199 Anaphylactic shock Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 102100030907 Aryl hydrocarbon receptor nuclear translocator Human genes 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• AEJFESLQMBXXBT-UHFFFAOYSA-N C(#N)C=1C=CC(=C(C1)CC(C(=O)O)=O)[N+](=O)[O-] Chemical compound C(#N)C=1C=CC(=C(C1)CC(C(=O)O)=O)[N+](=O)[O-] AEJFESLQMBXXBT-UHFFFAOYSA-N 0.000 description 1
• BUEIBCUABJPEIS-UHFFFAOYSA-N C12=CC(CNC(CO)C)=CC=C2NC(C(O)=O)=C1SC1=CC=CC=C1 Chemical compound C12=CC(CNC(CO)C)=CC=C2NC(C(O)=O)=C1SC1=CC=CC=C1 BUEIBCUABJPEIS-UHFFFAOYSA-N 0.000 description 1
• OYUATTCDRIBQKC-UHFFFAOYSA-N C1=C(OC)C(OC)=CC(NCC=2C=C3C(SC=4C=CC=CC=4)=C(C(O)=O)NC3=CC=2)=C1C#N Chemical compound C1=C(OC)C(OC)=CC(NCC=2C=C3C(SC=4C=CC=CC=4)=C(C(O)=O)NC3=CC=2)=C1C#N OYUATTCDRIBQKC-UHFFFAOYSA-N 0.000 description 1
• IAFWBFYYXSYFKY-UHFFFAOYSA-N C1=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=C1CNC1=CC=CC(C(F)(F)F)=C1 Chemical compound C1=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=C1CNC1=CC=CC(C(F)(F)F)=C1 IAFWBFYYXSYFKY-UHFFFAOYSA-N 0.000 description 1
• MSLGXCZMQZTOMI-UHFFFAOYSA-N C1=CC(N(C)C)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 Chemical compound C1=CC(N(C)C)=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 MSLGXCZMQZTOMI-UHFFFAOYSA-N 0.000 description 1
• OMCXITMZQPBEIE-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C(Cl)C=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(=O)O)NC2=CC=1CNCC1=CC=C(Cl)C=C1 OMCXITMZQPBEIE-UHFFFAOYSA-N 0.000 description 1
• QSXLLSWCYJQKSC-UHFFFAOYSA-N C=1C=C2C(SC=3C=CC=CC=3)=C(C(O)=O)NC2=CC=1CNC(=O)C(N)CC1=CC=CC=C1 Chemical compound C=1C=C2C(SC=3C=CC=CC=3)=C(C(O)=O)NC2=CC=1CNC(=O)C(N)CC1=CC=CC=C1 QSXLLSWCYJQKSC-UHFFFAOYSA-N 0.000 description 1
• 102000008025 CLOCK Proteins Human genes 0.000 description 1
• 108010075228 CLOCK Proteins Proteins 0.000 description 1
• IANCSEWWSMKGDL-UHFFFAOYSA-N COC1=CC=CC(NCC=2C=C3C(SC=4C=CC=CC=4)=C(C(O)=O)NC3=CC=2)=C1 Chemical compound COC1=CC=CC(NCC=2C=C3C(SC=4C=CC=CC=4)=C(C(O)=O)NC3=CC=2)=C1 IANCSEWWSMKGDL-UHFFFAOYSA-N 0.000 description 1
• RLNWVLPIRCOEPF-UHFFFAOYSA-N COC1=CC=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 Chemical compound COC1=CC=CC=C1CNCC1=CC=C(C(SC=2C=CC=CC=2)=C(N2)C(O)=O)C2=C1 RLNWVLPIRCOEPF-UHFFFAOYSA-N 0.000 description 1
• GSYTVXOARWSQSV-BYPYZUCNSA-N CSCC[C@@H](C(N)=O)N Chemical compound CSCC[C@@H](C(N)=O)N GSYTVXOARWSQSV-BYPYZUCNSA-N 0.000 description 1
• 101150047910 CSNK1D gene Proteins 0.000 description 1
• 101000690445 Caenorhabditis elegans Aryl hydrocarbon receptor nuclear translocator homolog Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
• 235000005979 Citrus limon Nutrition 0.000 description 1
• 244000131522 Citrus pyriformis Species 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
• 206010054089 Depressive symptom Diseases 0.000 description 1
• 208000012239 Developmental disease Diseases 0.000 description 1
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
• 108700013908 Drosophila PER Proteins 0.000 description 1
• 241000255601 Drosophila melanogaster Species 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
• RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• WJYIASZWHGOTOU-UHFFFAOYSA-N Heptylamine Chemical compound CCCCCCCN WJYIASZWHGOTOU-UHFFFAOYSA-N 0.000 description 1
• 101000793115 Homo sapiens Aryl hydrocarbon receptor nuclear translocator Proteins 0.000 description 1
• 101000882921 Homo sapiens Circadian locomoter output cycles protein kaput Proteins 0.000 description 1
• 206010020710 Hyperphagia Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010021030 Hypomania Diseases 0.000 description 1
• 206010022998 Irritability Diseases 0.000 description 1
• VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 244000246386 Mentha pulegium Species 0.000 description 1
• 235000016257 Mentha pulegium Nutrition 0.000 description 1
• 235000004357 Mentha x piperita Nutrition 0.000 description 1
• 241000699673 Mesocricetus auratus Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 108090000143 Mouse Proteins Proteins 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 101000831245 Mus musculus Protein timeless homolog Proteins 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
• 108020004485 Nonsense Codon Proteins 0.000 description 1
• DFORUDLSMOBTNJ-UHFFFAOYSA-N OC(=O)C=1NC2=CC(CNC(=O)C(N)CCCCN)=CC=C2C=1SC1=CC=CC=C1 Chemical compound OC(=O)C=1NC2=CC(CNC(=O)C(N)CCCCN)=CC=C2C=1SC1=CC=CC=C1 DFORUDLSMOBTNJ-UHFFFAOYSA-N 0.000 description 1
• 241000283283 Orcinus orca Species 0.000 description 1
• 208000025174 PANDAS Diseases 0.000 description 1
• 102000002131 PAS domains Human genes 0.000 description 1
• 108050009469 PAS domains Proteins 0.000 description 1
• 101150074181 PER2 gene Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000021155 Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection Diseases 0.000 description 1
• 240000000220 Panda oleosa Species 0.000 description 1
• 235000016496 Panda oleosa Nutrition 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
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 241000382353 Pupa Species 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• 108700008625 Reporter Genes Proteins 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 206010041349 Somnolence Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 238000000692 Student's t-test Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 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
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 241000255588 Tephritidae Species 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 208000021017 Weight Gain Diseases 0.000 description 1
• YTAHJIFKAKIKAV-XNMGPUDCSA-N [(1R)-3-morpholin-4-yl-1-phenylpropyl] N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate Chemical compound O=C1[C@H](N=C(C2=C(N1)C=CC=C2)C1=CC=CC=C1)NC(O[C@H](CCN1CCOCC1)C1=CC=CC=C1)=O YTAHJIFKAKIKAV-XNMGPUDCSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000003302 alkenyloxy group Chemical group 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• 125000005133 alkynyloxy group Chemical group 0.000 description 1
• 125000003275 alpha amino acid group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 238000000540 analysis of variance Methods 0.000 description 1
• 208000003455 anaphylaxis Diseases 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000037037 animal physiology Effects 0.000 description 1
• 210000001971 anterior hypothalamus Anatomy 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000001430 anti-depressive effect Effects 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 239000000305 astragalus gummifer gum Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 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
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000013547 bright light therapy Methods 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 125000005997 bromomethyl group Chemical group 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 235000011116 calcium hydroxide Nutrition 0.000 description 1
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 238000000451 chemical ionisation Methods 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 235000017803 cinnamon Nutrition 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 238000012761 co-transfection Methods 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940125890 compound Ia Drugs 0.000 description 1
• DKZBBWMURDFHNE-NSCUHMNNSA-N coniferyl aldehyde Chemical compound COC1=CC(\C=C\C=O)=CC=C1O DKZBBWMURDFHNE-NSCUHMNNSA-N 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 229920006237 degradable polymer Polymers 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 150000002019 disulfides Chemical class 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
• 230000002222 downregulating effect Effects 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 208000024732 dysthymic disease Diseases 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• MQUUSXJLDZMUFK-UHFFFAOYSA-N ethyl 3-(4-cyano-2-nitrophenyl)-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CC1=CC=C(C#N)C=C1[N+]([O-])=O MQUUSXJLDZMUFK-UHFFFAOYSA-N 0.000 description 1
• WBVPBHUKCRDTRZ-UHFFFAOYSA-N ethyl 3-(5-cyano-2-nitrophenyl)-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CC1=CC(C#N)=CC=C1[N+]([O-])=O WBVPBHUKCRDTRZ-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 125000005290 ethynyloxy group Chemical group C(#C)O* 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000005281 excited state Effects 0.000 description 1
• 239000010685 fatty oil Substances 0.000 description 1
• 238000000855 fermentation Methods 0.000 description 1
• 230000004151 fermentation Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 125000001153 fluoro group Chemical group F* 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
• 239000008369 fruit flavor Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 238000002695 general anesthesia Methods 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000012447 hatching Effects 0.000 description 1
• 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 230000003284 homeostatic effect Effects 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 235000001050 hortel pimenta Nutrition 0.000 description 1
• 102000051667 human CLOCK Human genes 0.000 description 1
• 102000044565 human PER1 Human genes 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 230000009848 hypophosphorylation Effects 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000008676 import Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229940030980 inova Drugs 0.000 description 1
• 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 229960003299 ketamine Drugs 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
• 229910000103 lithium hydride Inorganic materials 0.000 description 1
• 230000006742 locomotor activity Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
• OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 1
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical class [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 235000012254 magnesium hydroxide Nutrition 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• NQPIEWBAWBFGOB-UHFFFAOYSA-N methyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OC)=CC2=C1 NQPIEWBAWBFGOB-UHFFFAOYSA-N 0.000 description 1
• FEIOASZZURHTHB-UHFFFAOYSA-N methyl 4-formylbenzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 1
• UEDIACVNFFMSHB-UHFFFAOYSA-N methyl 5-cyano-1h-indole-2-carboxylate Chemical compound N#CC1=CC=C2NC(C(=O)OC)=CC2=C1 UEDIACVNFFMSHB-UHFFFAOYSA-N 0.000 description 1
• VDOVWALYWVUEQR-UHFFFAOYSA-N methyl 6-cyano-1h-indole-2-carboxylate Chemical compound C1=C(C#N)C=C2NC(C(=O)OC)=CC2=C1 VDOVWALYWVUEQR-UHFFFAOYSA-N 0.000 description 1
• 229960001047 methyl salicylate Drugs 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 238000007479 molecular analysis Methods 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 230000008450 motivation Effects 0.000 description 1
• ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 201000003631 narcolepsy Diseases 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
• BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 230000037434 nonsense mutation Effects 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 230000003534 oscillatory effect Effects 0.000 description 1
• 235000020830 overeating Nutrition 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
• 150000002926 oxygen Chemical class 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
• ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• SEVSMVUOKAMPDO-UHFFFAOYSA-N para-Acetoxybenzaldehyde Natural products CC(=O)OC1=CC=C(C=O)C=C1 SEVSMVUOKAMPDO-UHFFFAOYSA-N 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 238000005192 partition Methods 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000037361 pathway Effects 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
• 229940100684 pentylamine Drugs 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 238000011458 pharmacological treatment Methods 0.000 description 1
• 238000001050 pharmacotherapy Methods 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• 125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000006 phenylethylthio group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])S* 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
• NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000002574 poison Substances 0.000 description 1
• 231100000614 poison Toxicity 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000015497 potassium bicarbonate Nutrition 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• HVVNJUAVDAZWCB-UHFFFAOYSA-N prolinol Chemical compound OCC1CCCN1 HVVNJUAVDAZWCB-UHFFFAOYSA-N 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 230000009822 protein phosphorylation Effects 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 150000003216 pyrazines Chemical class 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• RJSRSRITMWVIQT-UHFFFAOYSA-N quinolin-6-amine Chemical compound N1=CC=CC2=CC(N)=CC=C21 RJSRSRITMWVIQT-UHFFFAOYSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000021907 regulation of circadian rhythm Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 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
• 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 238000004904 shortening Methods 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 230000004622 sleep time Effects 0.000 description 1
• 230000005061 slumber Effects 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 229960001922 sodium perborate Drugs 0.000 description 1
• YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• PXMWRAAMGAHXFZ-UHFFFAOYSA-N tert-butyl 1h-1,4-diazepine-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=CC=CN1 PXMWRAAMGAHXFZ-UHFFFAOYSA-N 0.000 description 1
• HEZMSIJTFGHAKX-UHFFFAOYSA-N tert-butyl 2-(aminomethyl)-1h-indole-6-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=C2C=C(CN)NC2=C1 HEZMSIJTFGHAKX-UHFFFAOYSA-N 0.000 description 1
• DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical compound C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
• KPOWODVZVBAOQC-UHFFFAOYSA-N tert-butyl n-[(2-carbamoyl-1h-indol-6-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C2C=C(C(N)=O)NC2=C1 KPOWODVZVBAOQC-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
• DKZBBWMURDFHNE-UHFFFAOYSA-N trans-coniferylaldehyde Natural products COC1=CC(C=CC=O)=CC=C1O DKZBBWMURDFHNE-UHFFFAOYSA-N 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 239000013598 vector Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 230000004584 weight gain Effects 0.000 description 1
• 235000019786 weight gain Nutrition 0.000 description 1
• BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1