TW201402116A - （２ｓ，３ｒ）-ｎ-（２-（（３-吡啶基）甲基）-１-氮雜雙環〔２．２．２〕辛-３-基）苯并呋喃-２-甲醯胺，其新穎鹽形式及使用方法 - Google Patents

Info

Publication number

TW201402116A

TW201402116A TW102135271A TW102135271A TW201402116A TW 201402116 A TW201402116 A TW 201402116A TW 102135271 A TW102135271 A TW 102135271A TW 102135271 A TW102135271 A TW 102135271A TW 201402116 A TW201402116 A TW 201402116A

Authority

TW

Taiwan

Prior art keywords

azabicyclo

pyridyl

methyl

oct

benzofuran

Prior art date

2007-08-02

Links

• Espacenet
• Global Dossier
• Discuss

• 150000003839 salts Chemical group 0.000 title claims abstract description 58
• 238000000034 method Methods 0.000 title claims abstract description 47
• OXKRFEWMSWPKKV-GHTZIAJQSA-N n-[(2s,3r)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound C([C@@H]1N2CCC(CC2)[C@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 OXKRFEWMSWPKKV-GHTZIAJQSA-N 0.000 title description 18
• 238000006243 chemical reaction Methods 0.000 claims description 55
• 238000004458 analytical method Methods 0.000 claims description 16
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
• 238000006268 reductive amination reaction Methods 0.000 claims description 3
• 230000000707 stereoselective effect Effects 0.000 claims description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 47
• -1 (2S,3R)-N-(2-((3-pyridyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamidine Amines Chemical class 0.000 abstract description 28
• 210000003169 central nervous system Anatomy 0.000 abstract description 23
• 238000002360 preparation method Methods 0.000 abstract description 9
• 239000000543 intermediate Substances 0.000 abstract description 4
• 231100000877 autonomic nervous system dysfunction Toxicity 0.000 abstract description 2
• 150000001875 compounds Chemical class 0.000 description 114
• 239000000203 mixture Substances 0.000 description 87
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
• 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 59
• 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 59
• 230000000694 effects Effects 0.000 description 55
• 239000000523 sample Substances 0.000 description 53
• 239000007787 solid Substances 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• 239000000243 solution Substances 0.000 description 50
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
• 201000000980 schizophrenia Diseases 0.000 description 37
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• 229940126062 Compound A Drugs 0.000 description 34
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 34
• 102000005962 receptors Human genes 0.000 description 34
• 108020003175 receptors Proteins 0.000 description 34
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
• 210000004027 cell Anatomy 0.000 description 29
• 238000011282 treatment Methods 0.000 description 28
• QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 description 27
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• 230000015572 biosynthetic process Effects 0.000 description 27
• 201000010099 disease Diseases 0.000 description 26
• 238000003786 synthesis reaction Methods 0.000 description 26
• 239000011541 reaction mixture Substances 0.000 description 25
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 24
• 229960004373 acetylcholine Drugs 0.000 description 24
• 208000015114 central nervous system disease Diseases 0.000 description 24
• 208000010877 cognitive disease Diseases 0.000 description 23
• 208000024827 Alzheimer disease Diseases 0.000 description 22
• 239000003814 drug Substances 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 238000005481 NMR spectroscopy Methods 0.000 description 20
• 239000000556 agonist Substances 0.000 description 20
• 208000035475 disorder Diseases 0.000 description 20
• 206010012289 Dementia Diseases 0.000 description 19
• 239000002253 acid Substances 0.000 description 19
• 239000008194 pharmaceutical composition Substances 0.000 description 19
• 235000019439 ethyl acetate Nutrition 0.000 description 18
• 208000024891 symptom Diseases 0.000 description 18
• 208000012902 Nervous system disease Diseases 0.000 description 16
• 208000002193 Pain Diseases 0.000 description 16
• 239000011521 glass Substances 0.000 description 16
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 15
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 15
• 206010028980 Neoplasm Diseases 0.000 description 15
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 15
• 239000013078 crystal Substances 0.000 description 15
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 14
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 14
• 239000010410 layer Substances 0.000 description 14
• 210000000287 oocyte Anatomy 0.000 description 14
• 241000700159 Rattus Species 0.000 description 13
• 230000027455 binding Effects 0.000 description 13
• 230000006870 function Effects 0.000 description 13
• 239000002904 solvent Substances 0.000 description 13
• 239000000126 substance Substances 0.000 description 13
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
• GMODWNYTPWWCCD-GHTZIAJQSA-N C1CN2CCC1[C@H]([C@@H]2CC3=CN=CC=C3)N=C(C4=CC5=CC=CC=C5O4)N Chemical compound C1CN2CCC1[C@H]([C@@H]2CC3=CN=CC=C3)N=C(C4=CC5=CC=CC=C5O4)N GMODWNYTPWWCCD-GHTZIAJQSA-N 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• 206010057190 Respiratory tract infections Diseases 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 238000000634 powder X-ray diffraction Methods 0.000 description 12
• 230000001225 therapeutic effect Effects 0.000 description 12
• 206010061218 Inflammation Diseases 0.000 description 11
• 239000005557 antagonist Substances 0.000 description 11
• 238000001816 cooling Methods 0.000 description 11
• 230000004054 inflammatory process Effects 0.000 description 11
• 230000005764 inhibitory process Effects 0.000 description 11
• 239000012453 solvate Substances 0.000 description 11
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 239000012065 filter cake Substances 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• 239000000463 material Substances 0.000 description 10
• 229960002715 nicotine Drugs 0.000 description 10
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 10
• 230000002265 prevention Effects 0.000 description 10
• 230000004044 response Effects 0.000 description 10
• 238000002390 rotary evaporation Methods 0.000 description 10
• 206010029113 Neovascularisation Diseases 0.000 description 9
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 9
• 208000018737 Parkinson disease Diseases 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 230000008859 change Effects 0.000 description 9
• 239000012458 free base Substances 0.000 description 9
• 238000004128 high performance liquid chromatography Methods 0.000 description 9
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 9
• 239000003446 ligand Substances 0.000 description 9
• 208000004296 neuralgia Diseases 0.000 description 9
• 208000020016 psychiatric disease Diseases 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 208000019901 Anxiety disease Diseases 0.000 description 8
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 8
• 206010026749 Mania Diseases 0.000 description 8
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• 238000002441 X-ray diffraction Methods 0.000 description 8
• 239000012298 atmosphere Substances 0.000 description 8
• 206010013932 dyslexia Diseases 0.000 description 8
• 239000006260 foam Substances 0.000 description 8
• 230000036961 partial effect Effects 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 238000000967 suction filtration Methods 0.000 description 8
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
• 206010034010 Parkinsonism Diseases 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 230000036506 anxiety Effects 0.000 description 7
• 230000001149 cognitive effect Effects 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
• 230000001404 mediated effect Effects 0.000 description 7
• 229910052757 nitrogen Inorganic materials 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 239000004031 partial agonist Substances 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 208000011117 substance-related disease Diseases 0.000 description 7
• 208000011580 syndromic disease Diseases 0.000 description 7
• 229940124597 therapeutic agent Drugs 0.000 description 7
• OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 6
• KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 6
• 208000035143 Bacterial infection Diseases 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• 208000028698 Cognitive impairment Diseases 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• 230000033115 angiogenesis Effects 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 208000022362 bacterial infectious disease Diseases 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 230000003993 interaction Effects 0.000 description 6
• 208000027061 mild cognitive impairment Diseases 0.000 description 6
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
• 239000003039 volatile agent Substances 0.000 description 6
• ZUCBDKDJRQVFNO-QWHCGFSZSA-N (2s,3r)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-amine Chemical compound C([C@@H]1N2CCC(CC2)[C@H]1N)C1=CC=CN=C1 ZUCBDKDJRQVFNO-QWHCGFSZSA-N 0.000 description 5
• 206010065040 AIDS dementia complex Diseases 0.000 description 5
• 201000011240 Frontotemporal dementia Diseases 0.000 description 5
• 206010065390 Inflammatory pain Diseases 0.000 description 5
• 208000009829 Lewy Body Disease Diseases 0.000 description 5
• 201000002832 Lewy body dementia Diseases 0.000 description 5
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
• 208000036142 Viral infection Diseases 0.000 description 5
• 210000004556 brain Anatomy 0.000 description 5
• 201000011510 cancer Diseases 0.000 description 5
• 229960001270 d- tartaric acid Drugs 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 210000000609 ganglia Anatomy 0.000 description 5
• 230000002757 inflammatory effect Effects 0.000 description 5
• 238000007912 intraperitoneal administration Methods 0.000 description 5
• 150000002500 ions Chemical class 0.000 description 5
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 5
• 229940011051 isopropyl acetate Drugs 0.000 description 5
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
• 239000011976 maleic acid Substances 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 210000003205 muscle Anatomy 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 208000019906 panic disease Diseases 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 230000006977 prepulse inhibition Effects 0.000 description 5
• 210000002027 skeletal muscle Anatomy 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 238000002411 thermogravimetry Methods 0.000 description 5
• 239000003053 toxin Substances 0.000 description 5
• 231100000765 toxin Toxicity 0.000 description 5
• 108700012359 toxins Proteins 0.000 description 5
• 238000012546 transfer Methods 0.000 description 5
• IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 4
• 208000000094 Chronic Pain Diseases 0.000 description 4
• 102000004127 Cytokines Human genes 0.000 description 4
• 108090000695 Cytokines Proteins 0.000 description 4
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• 208000003098 Ganglion Cysts Diseases 0.000 description 4
• 208000023105 Huntington disease Diseases 0.000 description 4
• 208000004454 Hyperalgesia Diseases 0.000 description 4
• 206010020651 Hyperkinesia Diseases 0.000 description 4
• 208000000269 Hyperkinesis Diseases 0.000 description 4
• 208000026139 Memory disease Diseases 0.000 description 4
• 208000019022 Mood disease Diseases 0.000 description 4
• 208000025966 Neurological disease Diseases 0.000 description 4
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 4
• 206010036790 Productive cough Diseases 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• 208000005400 Synovial Cyst Diseases 0.000 description 4
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
• 241000269370 Xenopus <genus> Species 0.000 description 4
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
• VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 4
• 229960004046 apomorphine Drugs 0.000 description 4
• 230000001580 bacterial effect Effects 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 206010008118 cerebral infarction Diseases 0.000 description 4
• 230000007278 cognition impairment Effects 0.000 description 4
• 230000009850 completed effect Effects 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 230000003111 delayed effect Effects 0.000 description 4
• 238000004090 dissolution Methods 0.000 description 4
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
• 238000001035 drying Methods 0.000 description 4
• 230000004064 dysfunction Effects 0.000 description 4
• 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 4
• 230000002996 emotional effect Effects 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• 229910052739 hydrogen Inorganic materials 0.000 description 4
• 208000015181 infectious disease Diseases 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• ULAHIHHGQVIRTO-UHFFFAOYSA-N methanesulfonic acid;4-methylbenzenesulfonic acid Chemical compound CS(O)(=O)=O.CC1=CC=C(S(O)(=O)=O)C=C1 ULAHIHHGQVIRTO-UHFFFAOYSA-N 0.000 description 4
• ISPRRZDPZDVHLE-OZYANKIXSA-N n-[(2s,3r)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide;hydrochloride Chemical compound Cl.C([C@@H]1N2CCC(CC2)[C@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 ISPRRZDPZDVHLE-OZYANKIXSA-N 0.000 description 4
• 230000001537 neural effect Effects 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
• 230000000750 progressive effect Effects 0.000 description 4
• 238000000926 separation method Methods 0.000 description 4
• 238000001179 sorption measurement Methods 0.000 description 4
• 208000024794 sputum Diseases 0.000 description 4
• 238000004809 thin layer chromatography Methods 0.000 description 4
• 102000003390 tumor necrosis factor Human genes 0.000 description 4
• 230000003936 working memory Effects 0.000 description 4
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• XRHGYUZYPHTUJZ-UHFFFAOYSA-M 4-chlorobenzoate Chemical compound [O-]C(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-M 0.000 description 3
• XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 241000894006 Bacteria Species 0.000 description 3
• 206010010904 Convulsion Diseases 0.000 description 3
• RGHNJXZEOKUKBD-MGCNEYSASA-N D-galactonic acid Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-MGCNEYSASA-N 0.000 description 3
• 208000037487 Endotoxemia Diseases 0.000 description 3
• 206010017533 Fungal infection Diseases 0.000 description 3
• 208000011688 Generalised anxiety disease Diseases 0.000 description 3
• 201000005569 Gout Diseases 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• 208000035154 Hyperesthesia Diseases 0.000 description 3
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 3
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 3
• 208000031888 Mycoses Diseases 0.000 description 3
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
• 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 206010033799 Paralysis Diseases 0.000 description 3
• 201000004681 Psoriasis Diseases 0.000 description 3
• 206010040070 Septic Shock Diseases 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
• 208000030886 Traumatic Brain injury Diseases 0.000 description 3
• 239000008186 active pharmaceutical agent Substances 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 230000002411 adverse Effects 0.000 description 3
• 230000008484 agonism Effects 0.000 description 3
• 230000000202 analgesic effect Effects 0.000 description 3
• 230000008485 antagonism Effects 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• 239000002026 chloroform extract Substances 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 230000008025 crystallization Effects 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• 238000000113 differential scanning calorimetry Methods 0.000 description 3
• 229940000406 drug candidate Drugs 0.000 description 3
• 229940088679 drug related substance Drugs 0.000 description 3
• 239000003596 drug target Substances 0.000 description 3
• 238000011156 evaluation Methods 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• TVFIYRKPCACCNL-UHFFFAOYSA-N furan-2-carboxamide Chemical compound NC(=O)C1=CC=CO1 TVFIYRKPCACCNL-UHFFFAOYSA-N 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 208000029364 generalized anxiety disease Diseases 0.000 description 3
• 238000003384 imaging method Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 3
• 238000004255 ion exchange chromatography Methods 0.000 description 3
• 208000028867 ischemia Diseases 0.000 description 3
• 208000030159 metabolic disease Diseases 0.000 description 3
• 229940098779 methanesulfonic acid Drugs 0.000 description 3
• 229960000485 methotrexate Drugs 0.000 description 3
• 230000007576 microinfarct Effects 0.000 description 3
• 238000000386 microscopy Methods 0.000 description 3
• OXKRFEWMSWPKKV-UHFFFAOYSA-N n-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical class C=1C2=CC=CC=C2OC=1C(=O)NC1C(CC2)CCN2C1CC1=CC=CN=C1 OXKRFEWMSWPKKV-UHFFFAOYSA-N 0.000 description 3
• 230000009826 neoplastic cell growth Effects 0.000 description 3
• 208000021722 neuropathic pain Diseases 0.000 description 3
• 230000003957 neurotransmitter release Effects 0.000 description 3
• 238000010606 normalization Methods 0.000 description 3
• 201000008482 osteoarthritis Diseases 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 238000010926 purge Methods 0.000 description 3
• 230000005855 radiation Effects 0.000 description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 229940076279 serotonin Drugs 0.000 description 3
• 208000019116 sleep disease Diseases 0.000 description 3
• 239000002002 slurry Substances 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 230000009870 specific binding Effects 0.000 description 3
• 210000003802 sputum Anatomy 0.000 description 3
• 230000004936 stimulating effect Effects 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 239000011550 stock solution Substances 0.000 description 3
• 229960001367 tartaric acid Drugs 0.000 description 3
• 235000002906 tartaric acid Nutrition 0.000 description 3
• 239000011975 tartaric acid Substances 0.000 description 3
• 229940095064 tartrate Drugs 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 230000009529 traumatic brain injury Effects 0.000 description 3
• 230000009385 viral infection Effects 0.000 description 3
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
• RFDPHKHXPMDJJD-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-one;hydron;chloride Chemical compound Cl.C1CC2C(=O)CN1CC2 RFDPHKHXPMDJJD-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• ZUCBDKDJRQVFNO-UHFFFAOYSA-N 2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-amine Chemical compound NC1C(CC2)CCN2C1CC1=CC=CN=C1 ZUCBDKDJRQVFNO-UHFFFAOYSA-N 0.000 description 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 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
• 208000020925 Bipolar disease Diseases 0.000 description 2
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
• 208000032841 Bulimia Diseases 0.000 description 2
• 206010006550 Bulimia nervosa Diseases 0.000 description 2
• 206010006895 Cachexia Diseases 0.000 description 2
• 206010007134 Candida infections Diseases 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 241000282693 Cercopithecidae Species 0.000 description 2
• 102000009660 Cholinergic Receptors Human genes 0.000 description 2
• 108010009685 Cholinergic Receptors Proteins 0.000 description 2
• 206010009900 Colitis ulcerative Diseases 0.000 description 2
• 229920000742 Cotton Polymers 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 2
• 206010012335 Dependence Diseases 0.000 description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
• 208000035895 Guillain-Barré syndrome Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 description 2
• 206010049567 Miller Fisher syndrome Diseases 0.000 description 2
• 208000026072 Motor neurone disease Diseases 0.000 description 2
• 208000001089 Multiple system atrophy Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 208000005890 Neuroma Diseases 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 208000007027 Oral Candidiasis Diseases 0.000 description 2
• 206010033128 Ovarian cancer Diseases 0.000 description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
• 206010034912 Phobia Diseases 0.000 description 2
• 208000002389 Pouchitis Diseases 0.000 description 2
• 208000028017 Psychotic disease Diseases 0.000 description 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• 206010040047 Sepsis Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• 241000287411 Turdidae Species 0.000 description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 description 2
• 206010046543 Urinary incontinence Diseases 0.000 description 2
• 201000004810 Vascular dementia Diseases 0.000 description 2
• MIOPJNTWMNEORI-MHPPCMCBSA-N [(4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-MHPPCMCBSA-N 0.000 description 2
• BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
• 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 2
• 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 2
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 201000010312 acute cholangitis Diseases 0.000 description 2
• 230000007000 age related cognitive decline Effects 0.000 description 2
• 230000036626 alertness Effects 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 208000022531 anorexia Diseases 0.000 description 2
• 230000000561 anti-psychotic effect Effects 0.000 description 2
• 230000001147 anti-toxic effect Effects 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 229940034982 antineoplastic agent Drugs 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• 239000000164 antipsychotic agent Substances 0.000 description 2
• 239000002249 anxiolytic agent Substances 0.000 description 2
• 230000000949 anxiolytic effect Effects 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 210000001367 artery Anatomy 0.000 description 2
• 230000003935 attention Effects 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 230000006399 behavior Effects 0.000 description 2
• 230000003542 behavioural effect Effects 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 125000005605 benzo group Chemical group 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
• 238000004364 calculation method Methods 0.000 description 2
• 201000003984 candidiasis Diseases 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 230000037410 cognitive enhancement Effects 0.000 description 2
• 239000012141 concentrate Substances 0.000 description 2
• 235000008504 concentrate Nutrition 0.000 description 2
• 230000036461 convulsion Effects 0.000 description 2
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
• 206010061428 decreased appetite Diseases 0.000 description 2
• 230000007547 defect Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
• 229960003638 dopamine Drugs 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 206010015037 epilepsy Diseases 0.000 description 2
• 238000011067 equilibration Methods 0.000 description 2
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 239000003777 experimental drug Substances 0.000 description 2
• 230000005714 functional activity Effects 0.000 description 2
• 230000002538 fungal effect Effects 0.000 description 2
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• 239000010439 graphite Substances 0.000 description 2
• 229910002804 graphite Inorganic materials 0.000 description 2
• LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
• 230000000971 hippocampal effect Effects 0.000 description 2
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
• 208000013403 hyperactivity Diseases 0.000 description 2
• BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 2
• 229960004801 imipramine Drugs 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 230000004968 inflammatory condition Effects 0.000 description 2
• 230000028709 inflammatory response Effects 0.000 description 2
• 230000010365 information processing Effects 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• 230000013016 learning Effects 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• 206010025135 lupus erythematosus Diseases 0.000 description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
• 229960002510 mandelic acid Drugs 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 230000015654 memory Effects 0.000 description 2
• 239000011859 microparticle Substances 0.000 description 2
• 239000004005 microsphere Substances 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• 208000005264 motor neuron disease Diseases 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• OXKRFEWMSWPKKV-WIYYLYMNSA-N n-[(2r,3r)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound C([C@H]1N2CCC(CC2)[C@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 OXKRFEWMSWPKKV-WIYYLYMNSA-N 0.000 description 2
• 201000003631 narcolepsy Diseases 0.000 description 2
• 210000005036 nerve Anatomy 0.000 description 2
• 208000007538 neurilemmoma Diseases 0.000 description 2
• 230000002232 neuromuscular Effects 0.000 description 2
• 239000002858 neurotransmitter agent Substances 0.000 description 2
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 201000002528 pancreatic cancer Diseases 0.000 description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 210000001428 peripheral nervous system Anatomy 0.000 description 2
• 208000022821 personality disease Diseases 0.000 description 2
• JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 239000002504 physiological saline solution Substances 0.000 description 2
• 230000036470 plasma concentration Effects 0.000 description 2
• 229910052697 platinum Inorganic materials 0.000 description 2
• 230000008092 positive effect Effects 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 2
• 238000011002 quantification Methods 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 238000013341 scale-up Methods 0.000 description 2
• 208000022610 schizoaffective disease Diseases 0.000 description 2
• 230000001953 sensory effect Effects 0.000 description 2
• BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
• 230000007958 sleep Effects 0.000 description 2
• 239000012086 standard solution Substances 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• 239000012258 stirred mixture Substances 0.000 description 2
• 230000035882 stress Effects 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 201000009032 substance abuse Diseases 0.000 description 2
• 201000006152 substance dependence Diseases 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-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
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 1
• ZUCBDKDJRQVFNO-OLZOCXBDSA-N (2r,3s)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-amine Chemical compound C([C@H]1N2CCC(CC2)[C@@H]1N)C1=CC=CN=C1 ZUCBDKDJRQVFNO-OLZOCXBDSA-N 0.000 description 1
• METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
• RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
• IWYDHOAUDWTVEP-SSDOTTSWSA-M (R)-mandelate Chemical compound [O-]C(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-M 0.000 description 1
• ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
• VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
• QCIUVDYZQNETIG-UHFFFAOYSA-N 2-(pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-one Chemical compound O=C1C(CC2)CCN2C1=CC1=CC=CN=C1 QCIUVDYZQNETIG-UHFFFAOYSA-N 0.000 description 1
• SHXWCVYOXRDMCX-UHFFFAOYSA-N 3,4-methylenedioxymethamphetamine Chemical compound CNC(C)CC1=CC=C2OCOC2=C1 SHXWCVYOXRDMCX-UHFFFAOYSA-N 0.000 description 1
• MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• YDJXUVIIXSFVOJ-OZYANKIXSA-N 4-methylbenzenesulfonic acid;n-[(2s,3r)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C([C@@H]1N2CCC(CC2)[C@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 YDJXUVIIXSFVOJ-OZYANKIXSA-N 0.000 description 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 206010001513 AIDS related complex Diseases 0.000 description 1
• 208000004998 Abdominal Pain Diseases 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 208000017194 Affective disease Diseases 0.000 description 1
• 208000007848 Alcoholism Diseases 0.000 description 1
• 229910000809 Alumel Inorganic materials 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 208000027448 Attention Deficit and Disruptive Behavior disease Diseases 0.000 description 1
• 206010003805 Autism Diseases 0.000 description 1
• 208000020706 Autistic disease Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 241000193738 Bacillus anthracis Species 0.000 description 1
• 206010004663 Biliary colic Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 241001674044 Blattodea Species 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 208000003508 Botulism Diseases 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• GMODWNYTPWWCCD-WIYYLYMNSA-N C1CN2CCC1[C@H]([C@H]2CC3=CN=CC=C3)N=C(C4=CC5=CC=CC=C5O4)N Chemical compound C1CN2CCC1[C@H]([C@H]2CC3=CN=CC=C3)N=C(C4=CC5=CC=CC=C5O4)N GMODWNYTPWWCCD-WIYYLYMNSA-N 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 108091006146 Channels Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 206010008690 Chondrocalcinosis pyrophosphate Diseases 0.000 description 1
• 206010008748 Chorea Diseases 0.000 description 1
• 208000006332 Choriocarcinoma Diseases 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
• 208000022497 Cocaine-Related disease Diseases 0.000 description 1
• 208000002881 Colic Diseases 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 206010010774 Constipation Diseases 0.000 description 1
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
• 229910016523 CuKa Inorganic materials 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 1
• WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
• 206010012239 Delusion Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• 208000012239 Developmental disease Diseases 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• 208000035240 Disease Resistance Diseases 0.000 description 1
• 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 208000005171 Dysmenorrhea Diseases 0.000 description 1
• 208000030814 Eating disease Diseases 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
• 240000001414 Eucalyptus viminalis Species 0.000 description 1
• 208000019454 Feeding and Eating disease Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
• 229940123457 Free radical scavenger Drugs 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
• 241000237858 Gastropoda Species 0.000 description 1
• 208000021309 Germ cell tumor Diseases 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 206010018634 Gouty Arthritis Diseases 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 206010021042 Hypopharyngeal cancer Diseases 0.000 description 1
• 206010056305 Hypopharyngeal neoplasm 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
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
• 208000008930 Low Back Pain Diseases 0.000 description 1
• 208000004852 Lung Injury Diseases 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 208000005777 Lupus Nephritis Diseases 0.000 description 1
• 239000006091 Macor Substances 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000003863 Marijuana Abuse Diseases 0.000 description 1
• 208000015021 Meningeal Neoplasms Diseases 0.000 description 1
• 201000009906 Meningitis Diseases 0.000 description 1
• 208000036626 Mental retardation Diseases 0.000 description 1
• 208000019896 Motor Skills disease Diseases 0.000 description 1
• 208000010428 Muscle Weakness Diseases 0.000 description 1
• 206010028372 Muscular weakness Diseases 0.000 description 1
• 206010028424 Myasthenic syndrome Diseases 0.000 description 1
• 102000006386 Myelin Proteins Human genes 0.000 description 1
• 108010083674 Myelin Proteins Proteins 0.000 description 1
• 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
• 102000003945 NF-kappa B Human genes 0.000 description 1
• 108010057466 NF-kappa B Proteins 0.000 description 1
• 102000014649 NMDA glutamate receptor activity proteins Human genes 0.000 description 1
• 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 244000061176 Nicotiana tabacum Species 0.000 description 1
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
• 208000014060 Niemann-Pick disease Diseases 0.000 description 1
• 206010029412 Nightmare Diseases 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 239000005480 Olmesartan Substances 0.000 description 1
• 208000026251 Opioid-Related disease Diseases 0.000 description 1
• 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
• 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 238000012879 PET imaging Methods 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 208000017787 Paraneoplastic neurologic syndrome Diseases 0.000 description 1
• 206010033864 Paranoia Diseases 0.000 description 1
• 208000027099 Paranoid disease Diseases 0.000 description 1
• 208000006199 Parasomnias Diseases 0.000 description 1
• 208000007542 Paresis Diseases 0.000 description 1
• 208000027089 Parkinsonian disease Diseases 0.000 description 1
• AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 208000007452 Plasmacytoma Diseases 0.000 description 1
• 206010035737 Pneumonia viral Diseases 0.000 description 1
• 208000005374 Poisoning Diseases 0.000 description 1
• 206010036105 Polyneuropathy Diseases 0.000 description 1
• 208000004550 Postoperative Pain Diseases 0.000 description 1
• 206010036618 Premenstrual syndrome Diseases 0.000 description 1
• 208000024777 Prion disease Diseases 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 208000005793 Restless legs syndrome Diseases 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 206010053879 Sepsis syndrome Diseases 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• 206010041250 Social phobia Diseases 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 206010041347 Somnambulism Diseases 0.000 description 1
• 206010041349 Somnolence Diseases 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 1
• 208000004760 Tenosynovitis Diseases 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 206010057644 Testis cancer Diseases 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
• 208000000323 Tourette Syndrome Diseases 0.000 description 1
• 208000016620 Tourette disease Diseases 0.000 description 1
• 206010044248 Toxic shock syndrome Diseases 0.000 description 1
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
• 206010069363 Traumatic lung injury Diseases 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 208000025865 Ulcer Diseases 0.000 description 1
• LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
• TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000006593 Urologic Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 206010047139 Vasoconstriction Diseases 0.000 description 1
• 206010047141 Vasodilatation Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 241000269368 Xenopus laevis Species 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 229960004150 aciclovir Drugs 0.000 description 1
• MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 206010051895 acute chest syndrome Diseases 0.000 description 1
• 208000038016 acute inflammation Diseases 0.000 description 1
• 230000006022 acute inflammation Effects 0.000 description 1
• 208000005298 acute pain Diseases 0.000 description 1
• 208000026345 acute stress disease Diseases 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000001919 adrenal effect Effects 0.000 description 1
• 201000005188 adrenal gland cancer Diseases 0.000 description 1
• 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
• 229940009456 adriamycin Drugs 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 238000005054 agglomeration Methods 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000007605 air drying Methods 0.000 description 1
• 239000000956 alloy Substances 0.000 description 1
• 229910045601 alloy Inorganic materials 0.000 description 1
• 229960004538 alprazolam Drugs 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 229940035674 anesthetics Drugs 0.000 description 1
• 230000002491 angiogenic effect Effects 0.000 description 1
• 230000006481 angiogenic pathway Effects 0.000 description 1
• 230000006427 angiogenic response Effects 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 230000000118 anti-neoplastic effect Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 230000001754 anti-pyretic effect Effects 0.000 description 1
• 239000012296 anti-solvent Substances 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 229940125681 anticonvulsant agent Drugs 0.000 description 1
• 239000001961 anticonvulsive agent Substances 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229960005475 antiinfective agent Drugs 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 229940005529 antipsychotics Drugs 0.000 description 1
• 239000002221 antipyretic Substances 0.000 description 1
• 229940125716 antipyretic agent Drugs 0.000 description 1
• 239000003699 antiulcer agent Substances 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 229940121357 antivirals Drugs 0.000 description 1
• 229940005530 anxiolytics Drugs 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 229960004372 aripiprazole Drugs 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 208000011775 arteriosclerosis disease Diseases 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 229960002274 atenolol Drugs 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 230000002238 attenuated effect Effects 0.000 description 1
• 239000003693 atypical antipsychotic agent Substances 0.000 description 1
• 229940127236 atypical antipsychotics Drugs 0.000 description 1
• 210000003403 autonomic nervous system Anatomy 0.000 description 1
• 208000008233 autosomal dominant nocturnal frontal lobe epilepsy Diseases 0.000 description 1
• 210000003050 axon Anatomy 0.000 description 1
• QHYIGPGWXQQZSA-UHFFFAOYSA-N azane;methanesulfonic acid Chemical compound [NH4+].CS([O-])(=O)=O QHYIGPGWXQQZSA-UHFFFAOYSA-N 0.000 description 1
• 210000004227 basal ganglia Anatomy 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 208000028683 bipolar I disease Diseases 0.000 description 1
• 208000025307 bipolar depression Diseases 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 230000036772 blood pressure Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 206010006007 bone sarcoma Diseases 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 208000029028 brain injury Diseases 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• 150000001649 bromium compounds Chemical class 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 229960002495 buspirone Drugs 0.000 description 1
• QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 1
• IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 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
• 239000007894 caplet Substances 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 239000000544 cholinesterase inhibitor Substances 0.000 description 1
• 208000002849 chondrocalcinosis Diseases 0.000 description 1
• 208000012601 choreatic disease Diseases 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 229960002896 clonidine Drugs 0.000 description 1
• 229960004170 clozapine Drugs 0.000 description 1
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 230000003920 cognitive function Effects 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 230000000112 colonic effect Effects 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 208000030251 communication disease Diseases 0.000 description 1
• 230000009137 competitive binding Effects 0.000 description 1
• 230000001054 cortical effect Effects 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 229910052593 corundum Inorganic materials 0.000 description 1
• 239000010431 corundum Substances 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 238000012864 cross contamination Methods 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 238000013480 data collection Methods 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 231100000868 delusion Toxicity 0.000 description 1
• 208000017004 dementia pugilistica Diseases 0.000 description 1
• 230000000994 depressogenic effect Effects 0.000 description 1
• 201000001981 dermatomyositis Diseases 0.000 description 1
• 238000003795 desorption Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 239000002027 dichloromethane extract Substances 0.000 description 1
• CURUTKGFNZGFSE-UHFFFAOYSA-N dicyclomine Chemical compound C1CCCCC1C1(C(=O)OCCN(CC)CC)CCCCC1 CURUTKGFNZGFSE-UHFFFAOYSA-N 0.000 description 1
• 229960002777 dicycloverine Drugs 0.000 description 1
• 239000012470 diluted sample Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 235000014632 disordered eating Nutrition 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• LBOJYSIDWZQNJS-CVEARBPZSA-N dizocilpine Chemical compound C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 LBOJYSIDWZQNJS-CVEARBPZSA-N 0.000 description 1
• 229950004794 dizocilpine Drugs 0.000 description 1
• 229960003530 donepezil Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 206010013663 drug dependence Diseases 0.000 description 1
• 229960002866 duloxetine Drugs 0.000 description 1
• 208000024732 dysthymic disease Diseases 0.000 description 1
• 235000005686 eating Nutrition 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000008144 emollient laxative Substances 0.000 description 1
• 230000008451 emotion Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 229960004341 escitalopram Drugs 0.000 description 1
• WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
• SUBDBMMJDZJVOS-DEOSSOPVSA-N esomeprazole Chemical compound C([S@](=O)C1=NC2=CC=C(C=C2N1)OC)C1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-DEOSSOPVSA-N 0.000 description 1
• 229960004770 esomeprazole Drugs 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 208000024519 eye neoplasm Diseases 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000005002 female reproductive tract Anatomy 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 229960002464 fluoxetine Drugs 0.000 description 1
• 230000003325 follicular Effects 0.000 description 1
• 239000013022 formulation composition Substances 0.000 description 1
• 238000002546 full scan Methods 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 229960003883 furosemide Drugs 0.000 description 1
• 229960002870 gabapentin Drugs 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 150000008195 galaktosides Chemical class 0.000 description 1
• 229960003980 galantamine Drugs 0.000 description 1
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
• 201000010175 gallbladder cancer Diseases 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 239000003193 general anesthetic agent Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 208000003884 gestational trophoblastic disease Diseases 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 229960003878 haloperidol Drugs 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• 210000000777 hematopoietic system Anatomy 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 230000000887 hydrating effect Effects 0.000 description 1
• 229960000890 hydrocortisone Drugs 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 201000001421 hyperglycemia Diseases 0.000 description 1
• 201000006866 hypopharynx cancer Diseases 0.000 description 1
• 239000012216 imaging agent Substances 0.000 description 1
• 238000007654 immersion Methods 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 230000006872 improvement Effects 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
• 239000012678 infectious agent Substances 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000015788 innate immune response Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 208000003243 intestinal obstruction Diseases 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 229940102253 isopropanolamine Drugs 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 239000008141 laxative Substances 0.000 description 1
• 229940125722 laxative agent Drugs 0.000 description 1
• 201000003723 learning disability Diseases 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 230000006742 locomotor activity Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 231100000515 lung injury Toxicity 0.000 description 1
• 208000037841 lung tumor Diseases 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 208000024714 major depressive disease Diseases 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 210000005001 male reproductive tract Anatomy 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 206010027175 memory impairment Diseases 0.000 description 1
• 206010027191 meningioma Diseases 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000000897 modulatory effect Effects 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000002864 mononuclear phagocyte Anatomy 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 230000037023 motor activity Effects 0.000 description 1
• 230000007659 motor function Effects 0.000 description 1
• 230000003551 muscarinic effect Effects 0.000 description 1
• 210000005012 myelin Anatomy 0.000 description 1
• 210000001087 myotubule Anatomy 0.000 description 1
• OXKRFEWMSWPKKV-NQIIRXRSSA-N n-[(2r,3s)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide Chemical compound C([C@H]1N2CCC(CC2)[C@@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 OXKRFEWMSWPKKV-NQIIRXRSSA-N 0.000 description 1
• 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 230000010004 neural pathway Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000002981 neuropathic effect Effects 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 239000004090 neuroprotective agent Substances 0.000 description 1
• 230000000324 neuroprotective effect Effects 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 230000036963 noncompetitive effect Effects 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
• 229940127073 nucleoside analogue Drugs 0.000 description 1
• 239000002417 nutraceutical Substances 0.000 description 1
• 235000021436 nutraceutical agent Nutrition 0.000 description 1
• 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 1
• 201000008106 ocular cancer Diseases 0.000 description 1
• 229960005017 olanzapine Drugs 0.000 description 1
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
• VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 1
• 229960005117 olmesartan Drugs 0.000 description 1
• 208000024196 oppositional defiant disease Diseases 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 201000006958 oropharynx cancer Diseases 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 229960002296 paroxetine Drugs 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 229950010883 phencyclidine Drugs 0.000 description 1
• 229960002036 phenytoin Drugs 0.000 description 1
• 208000028591 pheochromocytoma Diseases 0.000 description 1
• 208000019899 phobic disease Diseases 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000008288 physiological mechanism Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 201000002511 pituitary cancer Diseases 0.000 description 1
• 231100000572 poisoning Toxicity 0.000 description 1
• 230000000607 poisoning effect Effects 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 230000007824 polyneuropathy Effects 0.000 description 1
• 230000002980 postoperative effect Effects 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
• 229960001289 prazosin Drugs 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 230000004224 protection Effects 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 230000004800 psychological effect Effects 0.000 description 1
• 238000005086 pumping Methods 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 229960004431 quetiapine Drugs 0.000 description 1
• URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
• SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
• 239000002516 radical scavenger Substances 0.000 description 1
• 238000000163 radioactive labelling Methods 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 230000036647 reaction Effects 0.000 description 1
• 230000003134 recirculating effect Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• 206010039667 schwannoma Diseases 0.000 description 1
• 210000003497 sciatic nerve Anatomy 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 210000001625 seminal vesicle Anatomy 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 229960002073 sertraline Drugs 0.000 description 1
• VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
• 229960003310 sildenafil Drugs 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 201000002314 small intestine cancer Diseases 0.000 description 1
• 239000000779 smoke Substances 0.000 description 1
• 230000000391 smoking effect Effects 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 201000001716 specific phobia Diseases 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000012899 standard injection Substances 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 238000011916 stereoselective reduction Methods 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 231100000736 substance abuse Toxicity 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000013595 supernatant sample Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 208000006379 syphilis Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000007474 system interaction Effects 0.000 description 1
• 229910052715 tantalum Inorganic materials 0.000 description 1
• GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
• WNAHEVXTGAEKIY-ZDUSSCGKSA-N tert-butyl n-[(2r)-1-phenylbut-3-en-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C=C)CC1=CC=CC=C1 WNAHEVXTGAEKIY-ZDUSSCGKSA-N 0.000 description 1
• 239000012085 test solution Substances 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000167 toxic agent Toxicity 0.000 description 1
• 239000003440 toxic substance Substances 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 206010044412 transitional cell carcinoma Diseases 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• ZMCBYSBVJIMENC-UHFFFAOYSA-N tricaine Chemical compound CCOC(=O)C1=CC=CC(N)=C1 ZMCBYSBVJIMENC-UHFFFAOYSA-N 0.000 description 1
• 206010044652 trigeminal neuralgia Diseases 0.000 description 1
• JLEXUIVKURIPFI-UHFFFAOYSA-N tris phosphate Chemical compound OP(O)(O)=O.OCC(N)(CO)CO JLEXUIVKURIPFI-UHFFFAOYSA-N 0.000 description 1
• 208000013706 tumor of meninges Diseases 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 231100000397 ulcer Toxicity 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 239000013026 undiluted sample Substances 0.000 description 1
• 229940116269 uric acid Drugs 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 210000001186 vagus nerve Anatomy 0.000 description 1
• 229940102566 valproate Drugs 0.000 description 1
• JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
• 229960004751 varenicline Drugs 0.000 description 1
• 230000025033 vasoconstriction Effects 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 229940124549 vasodilator Drugs 0.000 description 1
• 239000003071 vasodilator agent Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 229960004688 venlafaxine Drugs 0.000 description 1
• PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
• 229960001722 verapamil Drugs 0.000 description 1
• 238000012795 verification Methods 0.000 description 1
• 201000010653 vesiculitis Diseases 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 208000009421 viral pneumonia Diseases 0.000 description 1
• 239000000304 virulence factor Substances 0.000 description 1
• 230000007923 virulence factor Effects 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 229960005080 warfarin Drugs 0.000 description 1
• PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
• 229960002555 zidovudine Drugs 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1