BRPI0614943A2 - combinação de um agente hipnótico e composto de bisarila e heteroarila substituìdo e aplicação terapêutica da mesma - Google Patents

Info

Publication number

BRPI0614943A2

BRPI0614943A2 BRPI0614943-0A BRPI0614943A BRPI0614943A2 BR PI0614943 A2 BRPI0614943 A2 BR PI0614943A2 BR PI0614943 A BRPI0614943 A BR PI0614943A BR PI0614943 A2 BRPI0614943 A2 BR PI0614943A2

Authority

BR

Brazil

Prior art keywords

alkyl

formula

compound

fluoro

sleep

Prior art date

2005-08-19

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003326 hypnotic agent Substances 0.000 title claims abstract description 114
• -1 heteroaryl compound Chemical class 0.000 title claims description 221
• 230000001225 therapeutic effect Effects 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 120
• 208000019116 sleep disease Diseases 0.000 claims abstract description 40
• 239000000203 mixture Substances 0.000 claims description 105
• 125000000217 alkyl group Chemical group 0.000 claims description 97
• 239000008188 pellet Substances 0.000 claims description 72
• 239000003826 tablet Substances 0.000 claims description 72
• 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 67
• 150000003839 salts Chemical class 0.000 claims description 36
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 35
• 229960001475 zolpidem Drugs 0.000 claims description 35
• ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 claims description 35
• 206010022437 insomnia Diseases 0.000 claims description 34
• 239000002775 capsule Substances 0.000 claims description 33
• 230000003111 delayed effect Effects 0.000 claims description 33
• 125000000623 heterocyclic group Chemical group 0.000 claims description 32
• 239000010410 layer Substances 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 32
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 239000003795 chemical substances by application Substances 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 30
• 125000001424 substituent group Chemical group 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 238000002360 preparation method Methods 0.000 claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 208000020685 sleep-wake disease Diseases 0.000 claims description 21
• 239000001257 hydrogen Substances 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 230000000147 hypnotic effect Effects 0.000 claims description 20
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
• 239000000126 substance Substances 0.000 claims description 19
• 229910052717 sulfur Inorganic materials 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
• 208000035475 disorder Diseases 0.000 claims description 14
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 150000002367 halogens Chemical class 0.000 claims description 11
• 239000007950 delayed release tablet Substances 0.000 claims description 10
• 229940049706 benzodiazepine Drugs 0.000 claims description 9
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 9
• 208000001797 obstructive sleep apnea Diseases 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 239000012453 solvate Substances 0.000 claims description 9
• 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 claims description 8
• 125000002619 bicyclic group Chemical group 0.000 claims description 8
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
• GBBSUAFBMRNDJC-MRXNPFEDSA-N (5R)-zopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-MRXNPFEDSA-N 0.000 claims description 7
• 125000003342 alkenyl group Chemical group 0.000 claims description 7
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
• 239000011247 coating layer Substances 0.000 claims description 7
• 229960001578 eszopiclone Drugs 0.000 claims description 7
• GBBSUAFBMRNDJC-INIZCTEOSA-N eszopiclone Chemical compound C1CN(C)CCN1C(=O)O[C@H]1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-INIZCTEOSA-N 0.000 claims description 7
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 7
• DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical class COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 7
• 125000002950 monocyclic group Chemical group 0.000 claims description 7
• 229960000820 zopiclone Drugs 0.000 claims description 7
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• 125000003282 alkyl amino group Chemical group 0.000 claims description 6
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 5
• UMSGKTJDUHERQW-UHFFFAOYSA-N Brotizolam Chemical compound C1=2C=C(Br)SC=2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl UMSGKTJDUHERQW-UHFFFAOYSA-N 0.000 claims description 5
• 102000004300 GABA-A Receptors Human genes 0.000 claims description 5
• 108090000839 GABA-A Receptors Proteins 0.000 claims description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 5
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
• 229960003051 brotizolam Drugs 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 5
• 238000004904 shortening Methods 0.000 claims description 5
• JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 claims description 5
• 229960003386 triazolam Drugs 0.000 claims description 5
• HUNXMJYCHXQEGX-UHFFFAOYSA-N zaleplon Chemical compound CCN(C(C)=O)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C#N)=C1 HUNXMJYCHXQEGX-UHFFFAOYSA-N 0.000 claims description 5
• 229960004010 zaleplon Drugs 0.000 claims description 5
• YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 4
• YLXDSYKOBKBWJQ-LBPRGKRZSA-N N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e]benzofuran-8-yl]ethyl]propanamide Chemical compound C1=C2OCCC2=C2[C@H](CCNC(=O)CC)CCC2=C1 YLXDSYKOBKBWJQ-LBPRGKRZSA-N 0.000 claims description 4
• 229960003987 melatonin Drugs 0.000 claims description 4
• 229960001150 ramelteon Drugs 0.000 claims description 4
• 239000002974 melatonin derivative Substances 0.000 claims description 3
• VMZUTJCNQWMAGF-UHFFFAOYSA-N Etizolam Chemical compound S1C(CC)=CC2=C1N1C(C)=NN=C1CN=C2C1=CC=CC=C1Cl VMZUTJCNQWMAGF-UHFFFAOYSA-N 0.000 claims description 2
• 229960004404 etizolam Drugs 0.000 claims description 2
• 229910052751 metal Inorganic materials 0.000 claims description 2
• 239000002184 metal Substances 0.000 claims description 2
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
• CBIAWPMZSFFRGN-UHFFFAOYSA-N Indiplon Chemical compound CC(=O)N(C)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C(=O)C=2SC=CC=2)=C1 CBIAWPMZSFFRGN-UHFFFAOYSA-N 0.000 claims 3
• 150000002431 hydrogen Chemical class 0.000 claims 3
• 229950003867 indiplon Drugs 0.000 claims 3
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims 2
• 229940121723 Melatonin receptor agonist Drugs 0.000 claims 2
• 229940075993 receptor modulator Drugs 0.000 claims 2
• 239000000969 carrier Substances 0.000 claims 1
• 239000002662 enteric coated tablet Substances 0.000 claims 1
• 230000007958 sleep Effects 0.000 description 109
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
• 238000000034 method Methods 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 32
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
• 239000002904 solvent Substances 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
• VXRDAMSNTXUHFX-CEAXSRTFSA-N zolpidem tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1.N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 VXRDAMSNTXUHFX-CEAXSRTFSA-N 0.000 description 22
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
• 238000006243 chemical reaction Methods 0.000 description 21
• 239000000243 solution Substances 0.000 description 21
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
• 239000002585 base Substances 0.000 description 20
• 125000001544 thienyl group Chemical group 0.000 description 20
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 19
• 125000002541 furyl group Chemical group 0.000 description 19
• 239000008187 granular material Substances 0.000 description 19
• 125000004076 pyridyl group Chemical group 0.000 description 19
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
• 125000001207 fluorophenyl group Chemical group 0.000 description 17
• 230000000694 effects Effects 0.000 description 16
• 239000000047 product Substances 0.000 description 16
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000002253 acid Substances 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• 238000000576 coating method Methods 0.000 description 15
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
• WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 13
• 239000004480 active ingredient Substances 0.000 description 13
• 238000007906 compression Methods 0.000 description 13
• 230000006835 compression Effects 0.000 description 13
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 13
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 150000001299 aldehydes Chemical class 0.000 description 12
• 230000014759 maintenance of location Effects 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• 150000001412 amines Chemical class 0.000 description 11
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 11
• 125000004193 piperazinyl group Chemical group 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• 239000011248 coating agent Substances 0.000 description 10
• 238000004090 dissolution Methods 0.000 description 10
• 125000003373 pyrazinyl group Chemical group 0.000 description 10
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 9
• QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical group C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 9
• GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 9
• 239000011159 matrix material Substances 0.000 description 9
• 125000003386 piperidinyl group Chemical group 0.000 description 9
• 229920000642 polymer Polymers 0.000 description 9
• 230000037322 slow-wave sleep Effects 0.000 description 9
• 239000007787 solid Substances 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• 229920003134 Eudragit® polymer Polymers 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 125000000068 chlorophenyl group Chemical group 0.000 description 8
• 238000005859 coupling reaction Methods 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 150000002148 esters Chemical class 0.000 description 8
• 235000019439 ethyl acetate Nutrition 0.000 description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 7
• 150000001557 benzodiazepines Chemical class 0.000 description 7
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
• 201000010099 disease Diseases 0.000 description 7
• 125000001153 fluoro group Chemical group F* 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 208000020016 psychiatric disease Diseases 0.000 description 7
• 238000005160 1H NMR spectroscopy Methods 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 229910000024 caesium carbonate Inorganic materials 0.000 description 6
• 239000000460 chlorine Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 229910052731 fluorine Inorganic materials 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 230000001965 increasing effect Effects 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• 235000019341 magnesium sulphate Nutrition 0.000 description 6
• 238000012423 maintenance Methods 0.000 description 6
• 238000002156 mixing Methods 0.000 description 6
• 239000003960 organic solvent Substances 0.000 description 6
• 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 6
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 5
• 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
• 229920003084 Avicel® PH-102 Polymers 0.000 description 5
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
• 206010041349 Somnolence Diseases 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 239000003638 chemical reducing agent Substances 0.000 description 5
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
• 238000010828 elution Methods 0.000 description 5
• 239000012530 fluid Substances 0.000 description 5
• 239000011737 fluorine Substances 0.000 description 5
• 230000014509 gene expression Effects 0.000 description 5
• 239000002117 illicit drug Substances 0.000 description 5
• 150000002500 ions Chemical class 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 150000007524 organic acids Chemical class 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• 230000001766 physiological effect Effects 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 238000005932 reductive alkylation reaction Methods 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 229940076279 serotonin Drugs 0.000 description 5
• 208000022925 sleep disturbance Diseases 0.000 description 5
• 229940086542 triethylamine Drugs 0.000 description 5
• 208000021500 Breathing-related sleep disease Diseases 0.000 description 4
• 239000007821 HATU Substances 0.000 description 4
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• 208000006199 Parasomnias Diseases 0.000 description 4
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 229920001577 copolymer Polymers 0.000 description 4
• SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 4
• 230000006378 damage Effects 0.000 description 4
• 230000003247 decreasing effect Effects 0.000 description 4
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 230000003287 optical effect Effects 0.000 description 4
• 150000003254 radicals Chemical class 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 230000003860 sleep quality Effects 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000008107 starch Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 4
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 3
• XWSCOGPKWVNQSV-UHFFFAOYSA-N 5-bromo-2,3-dichloropyridine Chemical compound ClC1=CC(Br)=CN=C1Cl XWSCOGPKWVNQSV-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 3
• 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• 229930195725 Mannitol Natural products 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• 208000032140 Sleepiness Diseases 0.000 description 3
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 208000008784 apnea Diseases 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• 239000007891 compressed tablet Substances 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
• 239000012153 distilled water Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 230000004064 dysfunction Effects 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 125000006332 fluoro benzoyl group Chemical group 0.000 description 3
• 125000004175 fluorobenzyl group Chemical group 0.000 description 3
• 239000008240 homogeneous mixture Substances 0.000 description 3
• 229920001477 hydrophilic polymer Polymers 0.000 description 3
• 230000001771 impaired effect Effects 0.000 description 3
• 239000000411 inducer Substances 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 229960001375 lactose Drugs 0.000 description 3
• 239000003509 long acting drug Substances 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 208000024714 major depressive disease Diseases 0.000 description 3
• 239000000594 mannitol Substances 0.000 description 3
• 235000010355 mannitol Nutrition 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 description 3
• 239000008108 microcrystalline cellulose Substances 0.000 description 3
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
• 229940016286 microcrystalline cellulose Drugs 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 201000003631 narcolepsy Diseases 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 230000000414 obstructive effect Effects 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 239000002831 pharmacologic agent Substances 0.000 description 3
• 239000002464 receptor antagonist Substances 0.000 description 3
• 229940044551 receptor antagonist Drugs 0.000 description 3
• 238000006268 reductive amination reaction Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 230000037321 sleepiness Effects 0.000 description 3
• 238000005507 spraying Methods 0.000 description 3
• 230000002195 synergetic effect Effects 0.000 description 3
• 239000003039 volatile agent Substances 0.000 description 3
• 230000002618 waking effect Effects 0.000 description 3
• 229960005111 zolpidem tartrate Drugs 0.000 description 3
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 2
• CRKJYSGULUUTIV-UHFFFAOYSA-N 6-bromo-3-trityl-1,3-benzoxazol-2-one Chemical compound O=C1OC2=CC(Br)=CC=C2N1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 CRKJYSGULUUTIV-UHFFFAOYSA-N 0.000 description 2
• 208000000884 Airway Obstruction Diseases 0.000 description 2
• 208000019901 Anxiety disease Diseases 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 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
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
• OMPIYDSYGYKWSG-UHFFFAOYSA-N Citronensaeure-alpha-aethylester Natural products CCOC(=O)CC(O)(C(O)=O)CC(O)=O OMPIYDSYGYKWSG-UHFFFAOYSA-N 0.000 description 2
• 208000028698 Cognitive impairment Diseases 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• 206010012218 Delirium Diseases 0.000 description 2
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
• ZXRVKCBLGJOCEE-UHFFFAOYSA-N Gaboxadol Chemical compound C1NCCC2=C1ONC2=O ZXRVKCBLGJOCEE-UHFFFAOYSA-N 0.000 description 2
• 208000011688 Generalised anxiety disease Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 208000010340 Sleep Deprivation Diseases 0.000 description 2
• 206010041235 Snoring Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
• ZZHLYYDVIOPZBE-UHFFFAOYSA-N Trimeprazine Chemical compound C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 ZZHLYYDVIOPZBE-UHFFFAOYSA-N 0.000 description 2
• 206010063968 Upper airway resistance syndrome Diseases 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
• 238000007259 addition reaction Methods 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 230000004520 agglutination Effects 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 2
• 239000003420 antiserotonin agent Substances 0.000 description 2
• 230000036506 anxiety Effects 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 150000003934 aromatic aldehydes Chemical class 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 150000001793 charged compounds Chemical class 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• DDNKJFBQMQOIKI-UHFFFAOYSA-N cincreasin Chemical compound BrC1=CC=C2NC(=O)OC2=C1 DDNKJFBQMQOIKI-UHFFFAOYSA-N 0.000 description 2
• DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 2
• 229960003120 clonazepam Drugs 0.000 description 2
• 208000010877 cognitive disease Diseases 0.000 description 2
• 239000007822 coupling agent Substances 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 125000006333 difluoro benzoyl group Chemical group 0.000 description 2
• 229960003638 dopamine Drugs 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 229940057975 ethyl citrate Drugs 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 238000001125 extrusion Methods 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 239000001530 fumaric acid Substances 0.000 description 2
• 229950004346 gaboxadol Drugs 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 208000029364 generalized anxiety disease Diseases 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N hexanedioic acid Natural products OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 2
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
• 206010020765 hypersomnia Diseases 0.000 description 2
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 239000004310 lactic acid Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 238000005461 lubrication Methods 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000011976 maleic acid Substances 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 239000002808 molecular sieve Substances 0.000 description 2
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
• 125000002524 organometallic group Chemical group 0.000 description 2
• 150000002941 palladium compounds Chemical class 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 229940127557 pharmaceutical product Drugs 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
• IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
• 229940069328 povidone Drugs 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 2
• 229960001233 pregabalin Drugs 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 230000000241 respiratory effect Effects 0.000 description 2
• 230000029058 respiratory gaseous exchange Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 201000000980 schizophrenia Diseases 0.000 description 2
• 239000002400 serotonin 2A antagonist Substances 0.000 description 2
• 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 2
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 201000002859 sleep apnea Diseases 0.000 description 2
• 210000000813 small intestine Anatomy 0.000 description 2
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000011975 tartaric acid Substances 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
• CAQGDWLRIQCXSP-UHFFFAOYSA-N tert-butyl 5-bromoindazole-1-carboxylate Chemical compound BrC1=CC=C2N(C(=O)OC(C)(C)C)N=CC2=C1 CAQGDWLRIQCXSP-UHFFFAOYSA-N 0.000 description 2
• 238000004809 thin layer chromatography Methods 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
• 239000003053 toxin Substances 0.000 description 2
• 231100000765 toxin Toxicity 0.000 description 2
• 235000013769 triethyl citrate Nutrition 0.000 description 2
• PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 2
• 229940094989 trimethylsilane Drugs 0.000 description 2
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
• LINQCVKFKXQJJS-UHFFFAOYSA-N 1-(1-ethylpyrrolidin-2-yl)-n-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methyl]methanamine Chemical compound CCN1CCCC1CNCC1=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1F LINQCVKFKXQJJS-UHFFFAOYSA-N 0.000 description 1
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• YLRAWICLSSHTJH-UHFFFAOYSA-N 2-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound NC(=O)C1=CC=CC=C1CCN1CCCC1 YLRAWICLSSHTJH-UHFFFAOYSA-N 0.000 description 1
• NNEKEQRIVLVCKR-UHFFFAOYSA-N 2-fluoro-4-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)benzaldehyde Chemical compound O1C(C)(C)C(C)(C)OC1C1=CC=C(C=O)C(F)=C1 NNEKEQRIVLVCKR-UHFFFAOYSA-N 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• PKRSYEPBQPFNRB-UHFFFAOYSA-N 2-phenoxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CC=CC=C1 PKRSYEPBQPFNRB-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
• QKEKUZYEHOVYSN-UHFFFAOYSA-N 3-(1h-indol-5-yl)benzaldehyde Chemical compound O=CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 QKEKUZYEHOVYSN-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 239000003148 4 aminobutyric acid receptor blocking agent Substances 0.000 description 1
• QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 description 1
• QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
• MRGBBKQOSUHKPF-UHFFFAOYSA-N 4-bromofuran-2-carbaldehyde Chemical compound BrC1=COC(C=O)=C1 MRGBBKQOSUHKPF-UHFFFAOYSA-N 0.000 description 1
• YFQFIPQQCGDESN-UHFFFAOYSA-N 4-chloro-n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzothiazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=C(Cl)C=C1 YFQFIPQQCGDESN-UHFFFAOYSA-N 0.000 description 1
• DFSFDJWPILSHHC-UHFFFAOYSA-N 4-chloro-n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=C(Cl)C=C1 DFSFDJWPILSHHC-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• HTCWMWGQTZLIIX-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-3-yl)benzamide Chemical compound C1N(C)CCCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CC=C1F HTCWMWGQTZLIIX-UHFFFAOYSA-N 0.000 description 1
• BHRCOVLBWBPNGM-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CC=C1F BHRCOVLBWBPNGM-UHFFFAOYSA-N 0.000 description 1
• DQUUDWQTMYMNNL-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-3-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=C(C(F)=CC=1)C(F)(F)F)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F DQUUDWQTMYMNNL-UHFFFAOYSA-N 0.000 description 1
• YARYXWNULHXGCT-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F YARYXWNULHXGCT-UHFFFAOYSA-N 0.000 description 1
• HSKVFCUSNYYKBX-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2C=CNC2=CC=1)F)CCN1CCCC1 HSKVFCUSNYYKBX-UHFFFAOYSA-N 0.000 description 1
• RGSJEKWEARVCBT-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-pyrrolo[2,3-c]pyridin-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1N=CC=2NC=CC=2C=1)F)CCN1CCCC1 RGSJEKWEARVCBT-UHFFFAOYSA-N 0.000 description 1
• UWLSAXUNLOGZKG-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(1h-pyrrolo[3,2-b]pyridin-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1N=C2C=CNC2=CC=1)F)CCN1CCCC1 UWLSAXUNLOGZKG-UHFFFAOYSA-N 0.000 description 1
• MMLOGCJLVYBGMT-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=C1F MMLOGCJLVYBGMT-UHFFFAOYSA-N 0.000 description 1
• VXJWXSCPMIQSMI-UHFFFAOYSA-N 4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2OC(=O)NC2=CC=1)F)CCN1CCCC1 VXJWXSCPMIQSMI-UHFFFAOYSA-N 0.000 description 1
• XJNQGSDHNHZIJS-UHFFFAOYSA-N 4-fluoro-n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 XJNQGSDHNHZIJS-UHFFFAOYSA-N 0.000 description 1
• YEGQCJSXNDCXJQ-UHFFFAOYSA-N 4-fluoro-n-[[4-(1h-indazol-5-yl)furan-2-yl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CO1 YEGQCJSXNDCXJQ-UHFFFAOYSA-N 0.000 description 1
• FRHCJJWSMXDBKW-UHFFFAOYSA-N 4-fluoro-n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CO1 FRHCJJWSMXDBKW-UHFFFAOYSA-N 0.000 description 1
• VRWQGLFKUQTKQC-UHFFFAOYSA-N 4-fluoro-n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C=C(C(F)=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 VRWQGLFKUQTKQC-UHFFFAOYSA-N 0.000 description 1
• XTAMTJXBUKKGSM-UHFFFAOYSA-N 4-fluoro-n-[[5-(1h-indol-5-yl)pyridin-3-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C=C(C=NC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 XTAMTJXBUKKGSM-UHFFFAOYSA-N 0.000 description 1
• YYNCJJLOAKQESC-UHFFFAOYSA-N 4-fluoro-n-[[5-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1SC(=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 YYNCJJLOAKQESC-UHFFFAOYSA-N 0.000 description 1
• BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
• SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 description 1
• PNEOKAGWIFEWNK-UHFFFAOYSA-N 5-[3-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-1h-indole Chemical compound C1CN(C)CCCN1CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 PNEOKAGWIFEWNK-UHFFFAOYSA-N 0.000 description 1
• IIZXKGJRAXFWTJ-UHFFFAOYSA-N 5-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound C1CN(C)CCN1CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 IIZXKGJRAXFWTJ-UHFFFAOYSA-N 0.000 description 1
• HAAPQNSHWVROTN-UHFFFAOYSA-N 5-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-2h-benzotriazole Chemical compound C1CN(C)CCN1CC1=CC=CC(C=2C=C3N=NNC3=CC=2)=C1 HAAPQNSHWVROTN-UHFFFAOYSA-N 0.000 description 1
• UIHVZHGNGWCBFR-UHFFFAOYSA-N 5-[3-[[2-(dimethylamino)ethyl-[(4-fluorophenyl)methyl]amino]methyl]-4-fluorophenyl]-1h-indole-3-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C(C=2C=C3C(C#N)=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)CC1=CC=C(F)C=C1 UIHVZHGNGWCBFR-UHFFFAOYSA-N 0.000 description 1
• CAKWHMWWQGQGJS-UHFFFAOYSA-N 5-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-1,3-dihydrobenzimidazol-2-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3NC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 CAKWHMWWQGQGJS-UHFFFAOYSA-N 0.000 description 1
• CBGLMQWHEAXZDJ-UHFFFAOYSA-N 5-[4-fluoro-3-[(4-methyl-2-pyridin-4-ylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=NC=C1 CBGLMQWHEAXZDJ-UHFFFAOYSA-N 0.000 description 1
• WZNQSOMASICACW-UHFFFAOYSA-N 5-[4-fluoro-3-[(4-methylpiperazin-1-yl)methyl]phenyl]-2h-benzotriazole Chemical compound C1CN(C)CCN1CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F WZNQSOMASICACW-UHFFFAOYSA-N 0.000 description 1
• CYPMENQZAYYMTF-UHFFFAOYSA-N 5-[4-fluoro-3-[[2-(4-fluorophenyl)-4-methylpiperazin-1-yl]methyl]phenyl]-1h-pyrrolo[3,2-b]pyridine Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2N=C3C=CNC3=CC=2)F)C1C1=CC=C(F)C=C1 CYPMENQZAYYMTF-UHFFFAOYSA-N 0.000 description 1
• MNGZJBFTHGLPQE-UHFFFAOYSA-N 5-[4-fluoro-3-[[2-(furan-2-yl)-4-methylpiperazin-1-yl]methyl]phenyl]-1h-indole Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=CO1 MNGZJBFTHGLPQE-UHFFFAOYSA-N 0.000 description 1
• GQFXAFQSILNKAW-UHFFFAOYSA-N 5-[4-fluoro-3-[[4-methyl-2-[4-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]phenyl]-1h-indole Chemical compound C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=C(C(F)(F)F)C=C1 GQFXAFQSILNKAW-UHFFFAOYSA-N 0.000 description 1
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• STVHMYNPQCLUNJ-UHFFFAOYSA-N 5-bromo-1h-indazole Chemical compound BrC1=CC=C2NN=CC2=C1 STVHMYNPQCLUNJ-UHFFFAOYSA-N 0.000 description 1
• VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
• MIYODQRDAPJMKK-UHFFFAOYSA-N 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-trityl-1,3-benzoxazol-2-one Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N(C(=O)O2)C(C=3C=CC=CC=3)(C=3C=CC=CC=3)C=3C=CC=CC=3)C2=C1 MIYODQRDAPJMKK-UHFFFAOYSA-N 0.000 description 1
• REPHVNGRWIFVMJ-UHFFFAOYSA-N 6-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCN1CC1=CC=CC(C=2C=C3OC(=O)NC3=CC=2)=C1 REPHVNGRWIFVMJ-UHFFFAOYSA-N 0.000 description 1
• CLAHVIWPABLYNF-UHFFFAOYSA-N 6-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-3-methyl-1h-quinazoline-2,4-dione;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3C(=O)N(C)C(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 CLAHVIWPABLYNF-UHFFFAOYSA-N 0.000 description 1
• JLMVYNXQXVHUDX-UHFFFAOYSA-N 6-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-3h-1,3-benzothiazol-2-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 JLMVYNXQXVHUDX-UHFFFAOYSA-N 0.000 description 1
• JJPMWPVVCZNYSC-UHFFFAOYSA-N 6-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-3h-1,3-benzoxazol-2-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 JJPMWPVVCZNYSC-UHFFFAOYSA-N 0.000 description 1
• BYNVFXLKWAWEFK-UHFFFAOYSA-N 6-[4-fluoro-3-[(2-thiophen-2-ylpiperazin-1-yl)methyl]phenyl]-3h-1,3-benzoxazol-2-one Chemical compound FC1=CC=C(C=2C=C3OC(=O)NC3=CC=2)C=C1CN1CCNCC1C1=CC=CS1 BYNVFXLKWAWEFK-UHFFFAOYSA-N 0.000 description 1
• FTLJTVKXADVTQC-UHFFFAOYSA-N 6-[4-fluoro-3-[[(4-fluorophenyl)methyl-(1-methylpiperidin-4-yl)amino]methyl]phenyl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2OC(=O)NC2=CC=1)F)CC1=CC=C(F)C=C1 FTLJTVKXADVTQC-UHFFFAOYSA-N 0.000 description 1
• IKFVERNEDYZIRR-UHFFFAOYSA-N 6-[5-[[(4-fluorophenyl)methyl-(1-methylpiperidin-4-yl)amino]methyl]furan-3-yl]-3h-1,3-benzoxazol-2-one Chemical compound C1CN(C)CCC1N(CC=1C=CC(F)=CC=1)CC1=CC(C=2C=C3OC(=O)NC3=CC=2)=CO1 IKFVERNEDYZIRR-UHFFFAOYSA-N 0.000 description 1
• QCPQMQBXFGUSQZ-UHFFFAOYSA-N 6-[5-[[2-(4-fluorophenyl)-4-methylpiperazin-1-yl]methyl]furan-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1N(C)CCN(CC=2OC=C(C=2)C=2C=C3OC(=O)NC3=CC=2)C1C1=CC=C(F)C=C1 QCPQMQBXFGUSQZ-UHFFFAOYSA-N 0.000 description 1
• DXBFXQJNQZFORV-UHFFFAOYSA-N 6-[5-[[2-(dimethylamino)ethyl-[(4-fluorophenyl)methyl]amino]methyl]furan-3-yl]-3h-1,3-benzoxazol-2-one Chemical compound C=1C(C=2C=C3OC(=O)NC3=CC=2)=COC=1CN(CCN(C)C)CC1=CC=C(F)C=C1 DXBFXQJNQZFORV-UHFFFAOYSA-N 0.000 description 1
• HBINRFRIDMACKS-UHFFFAOYSA-N 6-[5-[[2-(dimethylamino)ethyl-[(4-fluorophenyl)methyl]amino]methyl]pyridin-3-yl]-3h-1,3-benzoxazol-2-one Chemical compound C=1N=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=C(F)C=C1 HBINRFRIDMACKS-UHFFFAOYSA-N 0.000 description 1
• MHRWDIMYIWMUOS-UHFFFAOYSA-N 7-[3-[[benzyl-[2-(dimethylamino)ethyl]amino]methyl]phenyl]-4h-pyrido[3,2-b][1,4]oxazin-3-one;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OCC(=O)NC3=NC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 MHRWDIMYIWMUOS-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 239000005541 ACE inhibitor Substances 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
• JYMAYABXQDQNHV-UHFFFAOYSA-N CN(CC1)CCC1NCC(C=C(C=C1)C2=CC=C3NC=CC3=C2)=C1F.OC(C(C=C1)=CC2=C1OCCO2)=O Chemical compound CN(CC1)CCC1NCC(C=C(C=C1)C2=CC=C3NC=CC3=C2)=C1F.OC(C(C=C1)=CC2=C1OCCO2)=O JYMAYABXQDQNHV-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 208000003417 Central Sleep Apnea Diseases 0.000 description 1
• 206010008589 Choking Diseases 0.000 description 1
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
• 241000640885 Dysonia Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 229940098788 GABA receptor antagonist Drugs 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
• 208000017657 Menopausal disease Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 206010027590 Middle insomnia Diseases 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
• NZGZNNPUIKUMJG-UHFFFAOYSA-N N-[[5-(2H-benzotriazol-5-yl)-2-fluorophenyl]methyl]-N-(2-pyrrolidin-1-ylethyl)thiophene-2-carboxamide hydrochloride Chemical compound Cl.FC1=CC=C(C=2C=C3N=NNC3=CC=2)C=C1CN(C(=O)C=1SC=CC=1)CCN1CCCC1 NZGZNNPUIKUMJG-UHFFFAOYSA-N 0.000 description 1
• 229910003204 NH2 Inorganic materials 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229920001774 Perfluoroether Polymers 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• 206010062519 Poor quality sleep Diseases 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 206010038743 Restlessness Diseases 0.000 description 1
• 206010039897 Sedation Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 231100000643 Substance intoxication Toxicity 0.000 description 1
• SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 1
• UNRBEYYLYRXYCG-ZETCQYMHSA-N [(2s)-1-ethylpyrrolidin-2-yl]methanamine Chemical compound CCN1CCC[C@H]1CN UNRBEYYLYRXYCG-ZETCQYMHSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• SJFFDJGHUDCLNC-UHFFFAOYSA-N acetic acid;5-[4-fluoro-3-[(4-methyl-2-pyridin-2-ylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound CC(O)=O.C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=CC=N1 SJFFDJGHUDCLNC-UHFFFAOYSA-N 0.000 description 1
• ZATHGVHUMFFOPY-UHFFFAOYSA-N acetic acid;5-[4-fluoro-3-[(4-methyl-2-pyridin-3-ylpiperazin-1-yl)methyl]phenyl]-1h-indole Chemical compound CC(O)=O.C1N(C)CCN(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C1C1=CC=CN=C1 ZATHGVHUMFFOPY-UHFFFAOYSA-N 0.000 description 1
• WHSAOBZVNVTBQH-UHFFFAOYSA-N acetic acid;n'-[(4-fluorophenyl)methyl]-n'-[[5-(1h-indazol-5-yl)pyridin-3-yl]methyl]-n,n-dimethylethane-1,2-diamine Chemical compound CC(O)=O.C=1N=CC(C=2C=C3C=NNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=C(F)C=C1 WHSAOBZVNVTBQH-UHFFFAOYSA-N 0.000 description 1
• AJXIDXPJRCDQNV-UHFFFAOYSA-N acetic acid;n-(1-azabicyclo[2.2.2]octan-4-ylmethyl)-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-1-(4-fluorophenyl)methanamine Chemical compound CC(O)=O.C1=CC(F)=CC=C1CN(CC12CCN(CC1)CC2)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F AJXIDXPJRCDQNV-UHFFFAOYSA-N 0.000 description 1
• NNEUDDYXKARJJP-UHFFFAOYSA-N acetic acid;n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethoxy)benzamide Chemical compound CC(O)=O.C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CC(OC(F)(F)F)=CC=1)CCN1CCCC1 NNEUDDYXKARJJP-UHFFFAOYSA-N 0.000 description 1
• 229960000669 acetylleucine Drugs 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 208000012826 adjustment disease Diseases 0.000 description 1
• 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 229960003790 alimemazine Drugs 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 125000005037 alkyl phenyl group Chemical group 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000001430 anti-depressive effect Effects 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 239000002249 anxiolytic agent Substances 0.000 description 1
• 230000000949 anxiolytic effect Effects 0.000 description 1
• 229940005530 anxiolytics Drugs 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 125000005418 aryl aryl group Chemical group 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• 238000006254 arylation reaction Methods 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 125000003725 azepanyl group Chemical group 0.000 description 1
• 125000004069 aziridinyl 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
• 125000005605 benzo group Chemical group 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000005347 biaryls Chemical group 0.000 description 1
• 230000000035 biogenic effect Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 150000001639 boron compounds Chemical class 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
• YAGCIXJCAUGCGI-UHFFFAOYSA-N butoxycarbonyl butyl carbonate Chemical compound CCCCOC(=O)OC(=O)OCCCC YAGCIXJCAUGCGI-UHFFFAOYSA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910001424 calcium ion Inorganic materials 0.000 description 1
• 125000001589 carboacyl group Chemical group 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 230000002060 circadian Effects 0.000 description 1
• 230000027288 circadian rhythm Effects 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002131 composite material Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000006837 decompression Effects 0.000 description 1
• 238000007872 degassing Methods 0.000 description 1
• 239000012024 dehydrating agents‎ Substances 0.000 description 1
• 238000002242 deionisation method Methods 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 230000000881 depressing effect Effects 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 239000011903 deuterated solvents‎ Substances 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 125000005959 diazepanyl group Chemical group 0.000 description 1
• ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
• 238000007907 direct compression Methods 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000012738 dissolution medium Substances 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 208000024732 dysthymic disease Diseases 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• MEEWSBNOBXBASQ-UHFFFAOYSA-M fluoromethanesulfonate Chemical compound [O-]S(=O)(=O)[CH]F MEEWSBNOBXBASQ-UHFFFAOYSA-M 0.000 description 1
• 238000005755 formation reaction Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 230000003371 gabaergic effect Effects 0.000 description 1
• 230000005021 gait Effects 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 229940053999 hypnotics and sedatives melatonin receptor agonists Drugs 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 150000005232 imidazopyridines Chemical class 0.000 description 1
• 201000001881 impotence Diseases 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 230000035987 intoxication Effects 0.000 description 1
• 231100000566 intoxication Toxicity 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• 150000002513 isocyanates Chemical class 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960001021 lactose monohydrate Drugs 0.000 description 1
• 239000007942 layered tablet Substances 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 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
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229940057948 magnesium stearate Drugs 0.000 description 1
• MSWIFFGHKBTPMY-VFUQPONKSA-L magnesium;(e)-4-octadecoxy-4-oxobut-2-enoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O.CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O MSWIFFGHKBTPMY-VFUQPONKSA-L 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 229960001855 mannitol Drugs 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• FRQMUZJSZHZSGN-HBNHAYAOSA-N medroxyprogesterone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FRQMUZJSZHZSGN-HBNHAYAOSA-N 0.000 description 1
• 229960004616 medroxyprogesterone Drugs 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting 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
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 230000004973 motor coordination Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• NORFKNIONUICLG-UHFFFAOYSA-N n'-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n'-[(4-fluorophenyl)methyl]-n-methylethane-1,2-diamine Chemical compound C=1C(C=2C=C3C=NNC3=CC=2)=CC=C(F)C=1CN(CCNC)CC1=CC=C(F)C=C1 NORFKNIONUICLG-UHFFFAOYSA-N 0.000 description 1
• DPKOENODKZISQV-UHFFFAOYSA-N n'-[[3-(2h-benzotriazol-5-yl)phenyl]methyl]-n'-benzyl-n,n-dimethylpropane-1,3-diamine Chemical compound C=1C=CC(C=2C=C3N=NNC3=CC=2)=CC=1CN(CCCN(C)C)CC1=CC=CC=C1 DPKOENODKZISQV-UHFFFAOYSA-N 0.000 description 1
• VPEYZBPHUGTNEJ-UHFFFAOYSA-N n'-[[3-(3h-benzimidazol-5-yl)phenyl]methyl]-n'-benzyl-n,n-dimethylethane-1,2-diamine;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3N=CNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 VPEYZBPHUGTNEJ-UHFFFAOYSA-N 0.000 description 1
• RBHFMNPEVIQOAQ-UHFFFAOYSA-N n'-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n'-[(4-fluorophenyl)methyl]-n-methylethane-1,2-diamine Chemical compound C=1C(C=2C=C3N=NNC3=CC=2)=CC=C(F)C=1CN(CCNC)CC1=CC=C(F)C=C1 RBHFMNPEVIQOAQ-UHFFFAOYSA-N 0.000 description 1
• CLRXDNKIZRKYCU-UHFFFAOYSA-N n'-benzyl-n'-[[3-(1h-indazol-5-yl)phenyl]methyl]-n,n-dimethylethane-1,2-diamine;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3C=NNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 CLRXDNKIZRKYCU-UHFFFAOYSA-N 0.000 description 1
• JSCTYNKYJGSRJV-UHFFFAOYSA-N n'-benzyl-n'-[[3-(1h-indol-5-yl)phenyl]methyl]-n,n-dimethylethane-1,2-diamine Chemical compound C=1C=CC(C=2C=C3C=CNC3=CC=2)=CC=1CN(CCN(C)C)CC1=CC=CC=C1 JSCTYNKYJGSRJV-UHFFFAOYSA-N 0.000 description 1
• KWTRAOYWRQCOTR-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-4-fluoro-n-[[2-fluoro-5-(1-tritylbenzotriazol-5-yl)phenyl]methyl]benzamide Chemical compound CCN1CCCC1CN(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3N=NN(C3=CC=2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1F KWTRAOYWRQCOTR-UHFFFAOYSA-N 0.000 description 1
• BPOOZSRHPOZVSF-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide Chemical compound CCN1CCCC1CN(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=C1F BPOOZSRHPOZVSF-UHFFFAOYSA-N 0.000 description 1
• MQHOLIFSZFIBGH-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-n-[[4-(1h-indazol-5-yl)furan-2-yl]methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1N(CC=1C=CC(F)=CC=1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CO1 MQHOLIFSZFIBGH-UHFFFAOYSA-N 0.000 description 1
• JYWGKSVZWUYLJD-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]benzamide Chemical compound C=1C(C=2C=C3C=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 JYWGKSVZWUYLJD-UHFFFAOYSA-N 0.000 description 1
• NKFKIKMCCXYSCY-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[2-fluoro-5-(2-methyl-1h-indol-5-yl)phenyl]methyl]benzamide Chemical compound C=1C(C=2C=C3C=C(C)NC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 NKFKIKMCCXYSCY-UHFFFAOYSA-N 0.000 description 1
• ZOMCDVCZLMXNCC-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[2-fluoro-5-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide Chemical compound C=1C(C=2C=C3OC(=O)NC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 ZOMCDVCZLMXNCC-UHFFFAOYSA-N 0.000 description 1
• NIPWIQYSANKKFM-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-fluoro-n-[[5-(1h-indol-5-yl)pyridin-3-yl]methyl]benzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1N=CC(C=2C=C3C=CNC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 NIPWIQYSANKKFM-UHFFFAOYSA-N 0.000 description 1
• NSJJGGIMSVSOJR-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]thiophene-2-carboxamide Chemical compound C=1C(C=2C=C3C=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=CS1 NSJJGGIMSVSOJR-UHFFFAOYSA-N 0.000 description 1
• NKYLVIKUMDSXAE-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzothiazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=CC=C1 NKYLVIKUMDSXAE-UHFFFAOYSA-N 0.000 description 1
• KUXBBRSOZSVBLV-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[[3-(2-oxo-3h-1,3-benzoxazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3OC(=O)NC3=CC=2)=CC=1CN(CCN(C)C)C(=O)C1=CC=CC=C1 KUXBBRSOZSVBLV-UHFFFAOYSA-N 0.000 description 1
• UAVIRLMJQFOHCI-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-n-[[3-(2-oxo-3h-1,3-benzothiazol-6-yl)phenyl]methyl]benzamide;hydrochloride Chemical compound Cl.C=1C=CC(C=2C=C3SC(=O)NC3=CC=2)=CC=1CN(CCCN(C)C)C(=O)C1=CC=CC=C1 UAVIRLMJQFOHCI-UHFFFAOYSA-N 0.000 description 1
• KADBQUJLPKMWCL-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-(1-methylpyrrolidin-3-yl)-4-(trifluoromethyl)benzamide Chemical compound C1N(C)CCC1N(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CC1=CC(C=2C=C3C=NNC3=CC=2)=CC=C1F KADBQUJLPKMWCL-UHFFFAOYSA-N 0.000 description 1
• SHHRTUXBEDCURH-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-[(4-fluorophenyl)methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2C=NNC2=CC=1)F)CC1=CC=C(F)C=C1 SHHRTUXBEDCURH-UHFFFAOYSA-N 0.000 description 1
• WRTMCHZDWZBKEX-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indazol-5-yl)phenyl]methyl]-n-[(4-fluorophenyl)methyl]piperidin-4-amine Chemical compound C1=CC(F)=CC=C1CN(C1CCNCC1)CC1=CC(C=2C=C3C=NNC3=CC=2)=CC=C1F WRTMCHZDWZBKEX-UHFFFAOYSA-N 0.000 description 1
• KTNIQNANOUEQKT-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1NCC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F KTNIQNANOUEQKT-UHFFFAOYSA-N 0.000 description 1
• OVVKQDMOZMPOLX-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-3-(trifluoromethoxy)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=C(OC(F)(F)F)C=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F OVVKQDMOZMPOLX-UHFFFAOYSA-N 0.000 description 1
• CCYBEFNZYMOGBN-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-3-propan-2-yloxybenzamide Chemical compound CC(C)OC1=CC=CC(C(=O)N(CC=2C(=CC=C(C=2)C=2C=C3C=CNC3=CC=2)F)C2CCN(C)CC2)=C1 CCYBEFNZYMOGBN-UHFFFAOYSA-N 0.000 description 1
• DPHQJISNFIGVKI-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-4-(trifluoromethoxy)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(OC(F)(F)F)=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F DPHQJISNFIGVKI-UHFFFAOYSA-N 0.000 description 1
• LLLHDFLJXAIDBE-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-4-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F LLLHDFLJXAIDBE-UHFFFAOYSA-N 0.000 description 1
• PKFQTSKCDVPHJQ-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyrazine-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CC=NC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F PKFQTSKCDVPHJQ-UHFFFAOYSA-N 0.000 description 1
• AHDUMCHMYSFHIU-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridazine-3-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=NC=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F AHDUMCHMYSFHIU-UHFFFAOYSA-N 0.000 description 1
• SPAYHXLHIKDLME-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridazine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=NN=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F SPAYHXLHIKDLME-UHFFFAOYSA-N 0.000 description 1
• CDOHEHXGAQIAPA-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CC=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F CDOHEHXGAQIAPA-UHFFFAOYSA-N 0.000 description 1
• DPFXEHRVNPYVOK-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CN=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F DPFXEHRVNPYVOK-UHFFFAOYSA-N 0.000 description 1
• IVNGUWJYSQCFEP-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyrimidine-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CC=CN=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F IVNGUWJYSQCFEP-UHFFFAOYSA-N 0.000 description 1
• PHWDKOGPGBMXBK-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyrimidine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1N=CN=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F PHWDKOGPGBMXBK-UHFFFAOYSA-N 0.000 description 1
• YPMFOVMXSKGTSS-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)thiophene-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1SC=CC=1)CC1=CC(C=2C=C3C=CNC3=CC=2)=CC=C1F YPMFOVMXSKGTSS-UHFFFAOYSA-N 0.000 description 1
• DLFONWAJSZOKII-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound FC1=CC=C(C=2C=C3C=CNC3=CC=2)C=C1CN(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CCN1CCCC1 DLFONWAJSZOKII-UHFFFAOYSA-N 0.000 description 1
• GHKZCYUPGIOECR-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound FC1=CC=C(C=2C=C3C=CNC3=CC=2)C=C1CN(C(=O)C=1C=CN=CC=1)CCN1CCCC1 GHKZCYUPGIOECR-UHFFFAOYSA-N 0.000 description 1
• PLMOMLSRTDHBEA-UHFFFAOYSA-N n-[[2-fluoro-5-(1h-indol-5-yl)phenyl]methyl]-n-[(4-fluorophenyl)methyl]-1-methylpiperidin-4-amine Chemical compound C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2C=CNC2=CC=1)F)CC1=CC=C(F)C=C1 PLMOMLSRTDHBEA-UHFFFAOYSA-N 0.000 description 1
• XMKVXVQEBWOGDB-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)-4-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 XMKVXVQEBWOGDB-UHFFFAOYSA-N 0.000 description 1
• UHRYIQCHOOCYHR-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)pyridine-4-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CN=CC=1)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 UHRYIQCHOOCYHR-UHFFFAOYSA-N 0.000 description 1
• JEPATVHORFCQTI-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(1-methylpiperidin-4-yl)thiophene-2-carboxamide Chemical compound C1CN(C)CCC1N(C(=O)C=1SC=CC=1)CC1=CC=CC(C=2C=C3C=CNC3=CC=2)=C1 JEPATVHORFCQTI-UHFFFAOYSA-N 0.000 description 1
• BUPSNLWDMCEPMU-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 BUPSNLWDMCEPMU-UHFFFAOYSA-N 0.000 description 1
• WOGYNPXAPRCMRZ-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 WOGYNPXAPRCMRZ-UHFFFAOYSA-N 0.000 description 1
• WXHGDNBVTXGJQI-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 WXHGDNBVTXGJQI-UHFFFAOYSA-N 0.000 description 1
• HEIAVMHOQKGYKI-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 HEIAVMHOQKGYKI-UHFFFAOYSA-N 0.000 description 1
• DYFGGUFRZROJMX-UHFFFAOYSA-N n-[[3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1C=C(C=CC=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 DYFGGUFRZROJMX-UHFFFAOYSA-N 0.000 description 1
• CWLGPJRYTWNWLZ-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 CWLGPJRYTWNWLZ-UHFFFAOYSA-N 0.000 description 1
• WIQSUHUOXHJYDP-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 WIQSUHUOXHJYDP-UHFFFAOYSA-N 0.000 description 1
• MYFMPMMPCJUFDW-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 MYFMPMMPCJUFDW-UHFFFAOYSA-N 0.000 description 1
• OVCJQDAKFFGOCX-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 OVCJQDAKFFGOCX-UHFFFAOYSA-N 0.000 description 1
• QQRSLCPFFHYMTJ-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)furan-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1OC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 QQRSLCPFFHYMTJ-UHFFFAOYSA-N 0.000 description 1
• PIYMZBQSRQXRDX-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCN1CCCC1 PIYMZBQSRQXRDX-UHFFFAOYSA-N 0.000 description 1
• YZCCXNKYEHALHU-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)-4-(trifluoromethyl)benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 YZCCXNKYEHALHU-UHFFFAOYSA-N 0.000 description 1
• JLLLXEFQWHSKHC-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 JLLLXEFQWHSKHC-UHFFFAOYSA-N 0.000 description 1
• QFSMXEBVMOQSNT-UHFFFAOYSA-N n-[[4-(1h-indol-5-yl)thiophen-2-yl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C=1C=NC=CC=1C(=O)N(CC=1SC=C(C=1)C=1C=C2C=CNC2=CC=1)CCCN1CCCC1 QFSMXEBVMOQSNT-UHFFFAOYSA-N 0.000 description 1
• PCFIHKBUEKEQGD-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)-4-(trifluoromethyl)benzamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CC(=CC=1)C(F)(F)F)CCN1CCCC1 PCFIHKBUEKEQGD-UHFFFAOYSA-N 0.000 description 1
• PARQLKCEFTVVPF-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CN=CC=1)CCN1CCCC1 PARQLKCEFTVVPF-UHFFFAOYSA-N 0.000 description 1
• OTDQLXGENODYNT-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-2-carboxamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1N=CC=CC=1)CCCN1CCCC1 OTDQLXGENODYNT-UHFFFAOYSA-N 0.000 description 1
• UDFOJJRJSZPOPQ-UHFFFAOYSA-N n-[[4-fluoro-3-(1h-indol-5-yl)phenyl]methyl]-n-(3-pyrrolidin-1-ylpropyl)pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3C=CNC3=CC=2)C(F)=CC=C1CN(C(=O)C=1C=CN=CC=1)CCCN1CCCC1 UDFOJJRJSZPOPQ-UHFFFAOYSA-N 0.000 description 1
• BPIPIBXGOHQVAI-UHFFFAOYSA-N n-[[5-(2,3-dihydro-1h-indol-5-yl)-2-fluorophenyl]methyl]-n-[2-(dimethylamino)ethyl]-4-fluorobenzamide Chemical compound C=1C(C=2C=C3CCNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 BPIPIBXGOHQVAI-UHFFFAOYSA-N 0.000 description 1
• ALGRRZXZWPBSSM-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-2,4-difluoro-n-(2-pyrrolidin-1-ylethyl)benzamide;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2N=NNC2=CC=1)F)CCN1CCCC1 ALGRRZXZWPBSSM-UHFFFAOYSA-N 0.000 description 1
• WSPPLTHLDDBMBV-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F WSPPLTHLDDBMBV-UHFFFAOYSA-N 0.000 description 1
• KRBDRYLXOICLQH-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-(1-propan-2-ylpiperidin-4-yl)benzamide Chemical compound C1CN(C(C)C)CCC1N(C(=O)C=1C=CC(F)=CC=1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F KRBDRYLXOICLQH-UHFFFAOYSA-N 0.000 description 1
• YDVLMPIGLAODFV-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(CC=1C(=CC=C(C=1)C=1C=C2N=NNC2=CC=1)F)CCN1CCCC1 YDVLMPIGLAODFV-UHFFFAOYSA-N 0.000 description 1
• IFPYUMUOSRWJPM-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-4-fluoro-n-piperidin-4-ylbenzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(C1CCNCC1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F IFPYUMUOSRWJPM-UHFFFAOYSA-N 0.000 description 1
• ZKLWBLVHYUYTIU-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-(1-cyclopropylpiperidin-4-yl)-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(=O)N(C1CCN(CC1)C1CC1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F ZKLWBLVHYUYTIU-UHFFFAOYSA-N 0.000 description 1
• SFIIUXLAGNDLGX-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-(thiophen-2-ylmethyl)piperidin-4-amine Chemical compound FC1=CC=C(C=2C=C3N=NNC3=CC=2)C=C1CN(C1CCNCC1)CC1=CC=CS1 SFIIUXLAGNDLGX-UHFFFAOYSA-N 0.000 description 1
• RXJNOKWXAVVCGR-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-[(4-fluorophenyl)methyl]-1-methylpiperidin-4-amine;hydrochloride Chemical compound Cl.C1CN(C)CCC1N(CC=1C(=CC=C(C=1)C=1C=C2N=NNC2=CC=1)F)CC1=CC=C(F)C=C1 RXJNOKWXAVVCGR-UHFFFAOYSA-N 0.000 description 1
• MWBKYWAJVNXSPQ-UHFFFAOYSA-N n-[[5-(2h-benzotriazol-5-yl)-2-fluorophenyl]methyl]-n-[(4-fluorophenyl)methyl]piperidin-4-amine Chemical compound C1=CC(F)=CC=C1CN(C1CCNCC1)CC1=CC(C=2C=C3N=NNC3=CC=2)=CC=C1F MWBKYWAJVNXSPQ-UHFFFAOYSA-N 0.000 description 1
• ZSZBDOJQRFGYBF-UHFFFAOYSA-N n-[[5-(3-cyano-1h-indol-5-yl)-2-fluorophenyl]methyl]-n-[2-(dimethylamino)ethyl]-4-fluorobenzamide Chemical compound C=1C(C=2C=C3C(C#N)=CNC3=CC=2)=CC=C(F)C=1CN(CCN(C)C)C(=O)C1=CC=C(F)C=C1 ZSZBDOJQRFGYBF-UHFFFAOYSA-N 0.000 description 1
• LLSJAFHDYCTFCM-UHFFFAOYSA-N n-benzyl-n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCNCC1=CC=CC=C1 LLSJAFHDYCTFCM-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000003887 narcotic antagonist Substances 0.000 description 1
• 229960002715 nicotine Drugs 0.000 description 1
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
• 150000002828 nitro derivatives Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 230000037053 non-rapid eye movement Effects 0.000 description 1
• 125000005246 nonafluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
• 229960002748 norepinephrine Drugs 0.000 description 1
• 229940005483 opioid analgesics Drugs 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000006194 pentinyl group Chemical group 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 239000003444 phase transfer catalyst Substances 0.000 description 1
• 150000002990 phenothiazines Chemical class 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
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920002959 polymer blend Polymers 0.000 description 1
• 239000013047 polymeric layer Substances 0.000 description 1
• 235000011056 potassium acetate Nutrition 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
• 239000008057 potassium phosphate buffer Substances 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• HHAVHBDPWSUKHZ-UHFFFAOYSA-N propan-2-ol;propan-2-one Chemical compound CC(C)O.CC(C)=O HHAVHBDPWSUKHZ-UHFFFAOYSA-N 0.000 description 1
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
• 229960002601 protriptyline Drugs 0.000 description 1
• 239000004089 psychotropic agent Substances 0.000 description 1
• 150000005229 pyrazolopyridines Chemical class 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 239000012429 reaction media Substances 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000036280 sedation Effects 0.000 description 1
• 229940125723 sedative agent Drugs 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 230000004799 sedative–hypnotic effect Effects 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 239000003727 serotonin 1A antagonist Substances 0.000 description 1
• 239000003215 serotonin 5-HT2 receptor antagonist Substances 0.000 description 1
• 239000002356 single layer Substances 0.000 description 1
• 230000004620 sleep latency Effects 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 229960002920 sorbitol Drugs 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 238000005563 spheronization Methods 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 208000011117 substance-related disease Diseases 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
• 229960003188 temazepam Drugs 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• UBAZQJTUNPKEGK-UHFFFAOYSA-N tert-butyl 5-(4-fluoro-3-formylphenyl)indazole-1-carboxylate Chemical compound C=1C=C2N(C(=O)OC(C)(C)C)N=CC2=CC=1C1=CC=C(F)C(C=O)=C1 UBAZQJTUNPKEGK-UHFFFAOYSA-N 0.000 description 1
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 238000009423 ventilation Methods 0.000 description 1
• 230000003519 ventilatory effect Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 238000005550 wet granulation Methods 0.000 description 1