NZ539848A - Substituted 1,4-di-piperidin-4-YL-piperazine derivatives and their use as neurokinin antagonists - Google Patents

Info

Publication number

NZ539848A

NZ539848A NZ539848A NZ53984803A NZ539848A NZ 539848 A NZ539848 A NZ 539848A NZ 539848 A NZ539848 A NZ 539848A NZ 53984803 A NZ53984803 A NZ 53984803A NZ 539848 A NZ539848 A NZ 539848A

Authority

NZ

New Zealand

Prior art keywords

formula

alkyl

compound

group

alk

Prior art date

2002-10-08

Links

• Espacenet
• Global Dossier
• Discuss

• 239000005557 antagonist Substances 0.000 title description 23
• TYYZPUUMIWNDKS-UHFFFAOYSA-N 1,4-di(piperidin-4-yl)piperazine Chemical class C1CNCCC1N1CCN(C2CCNCC2)CC1 TYYZPUUMIWNDKS-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 186
• 238000011282 treatment Methods 0.000 claims abstract description 40
• 206010047700 Vomiting Diseases 0.000 claims abstract description 35
• 208000002551 irritable bowel syndrome Diseases 0.000 claims abstract description 20
• 208000002193 Pain Diseases 0.000 claims abstract description 16
• 208000019901 Anxiety disease Diseases 0.000 claims abstract description 15
• 230000036407 pain Effects 0.000 claims abstract description 14
• 206010033645 Pancreatitis Diseases 0.000 claims abstract description 10
• 230000001404 mediated effect Effects 0.000 claims abstract description 9
• 208000021891 Micturition disease Diseases 0.000 claims abstract description 4
• 206010020853 Hypertonic bladder Diseases 0.000 claims abstract 2
• 208000009722 Overactive Urinary Bladder Diseases 0.000 claims abstract 2
• 208000020629 overactive bladder Diseases 0.000 claims abstract 2
• -1 cyano, hydroxy, formyl Chemical group 0.000 claims description 93
• 239000000203 mixture Substances 0.000 claims description 68
• 239000002904 solvent Substances 0.000 claims description 52
• 238000002360 preparation method Methods 0.000 claims description 46
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 41
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 35
• 239000002253 acid Substances 0.000 claims description 34
• 125000000217 alkyl group Chemical group 0.000 claims description 34
• 239000002585 base Substances 0.000 claims description 33
• 229910001868 water Inorganic materials 0.000 claims description 31
• 239000000243 solution Substances 0.000 claims description 30
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
• 125000004432 carbon atom Chemical group C* 0.000 claims description 27
• 238000006243 chemical reaction Methods 0.000 claims description 27
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• 125000005843 halogen group Chemical group 0.000 claims description 24
• 239000003814 drug Substances 0.000 claims description 21
• 238000000034 method Methods 0.000 claims description 17
• 229940002612 prodrug Drugs 0.000 claims description 17
• 239000000651 prodrug Substances 0.000 claims description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
• 125000003545 alkoxy group Chemical group 0.000 claims description 14
• 229930195734 saturated hydrocarbon Natural products 0.000 claims description 14
• 125000004122 cyclic group Chemical group 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 125000004076 pyridyl group Chemical group 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 12
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 12
• 238000003756 stirring Methods 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 125000001544 thienyl group Chemical group 0.000 claims description 11
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
• 239000003638 chemical reducing agent Substances 0.000 claims description 10
• 239000012442 inert solvent Substances 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000003386 piperidinyl group Chemical group 0.000 claims description 9
• 230000008569 process Effects 0.000 claims description 9
• 229920006395 saturated elastomer Polymers 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
• 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 8
• 239000004480 active ingredient Substances 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 7
• 125000004043 oxo group Chemical group O=* 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 230000002829 reductive effect Effects 0.000 claims description 7
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
• 125000002883 imidazolyl group Chemical group 0.000 claims description 6
• 125000001041 indolyl group Chemical group 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 6
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
• 125000000335 thiazolyl group Chemical group 0.000 claims description 6
• 238000005804 alkylation reaction Methods 0.000 claims description 5
• 125000001246 bromo group Chemical group Br* 0.000 claims description 5
• 238000002347 injection Methods 0.000 claims description 5
• 239000007924 injection Substances 0.000 claims description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 4
• 239000002202 Polyethylene glycol Substances 0.000 claims description 4
• 125000003118 aryl group Chemical group 0.000 claims description 4
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• 229930195733 hydrocarbon Natural products 0.000 claims description 4
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 4
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 125000002971 oxazolyl group Chemical group 0.000 claims description 4
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 229920001223 polyethylene glycol Polymers 0.000 claims description 4
• 239000000725 suspension Substances 0.000 claims description 4
• 239000004215 Carbon black (E152) Substances 0.000 claims description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 3
• 239000003513 alkali Substances 0.000 claims description 3
• 230000029936 alkylation Effects 0.000 claims description 3
• 125000004429 atom Chemical group 0.000 claims description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
• 235000014655 lactic acid Nutrition 0.000 claims description 3
• 230000009466 transformation Effects 0.000 claims description 3
• 150000003855 acyl compounds Chemical class 0.000 claims description 2
• 230000010933 acylation Effects 0.000 claims description 2
• 238000005917 acylation reaction Methods 0.000 claims description 2
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
• 238000009835 boiling Methods 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• 230000003197 catalytic effect Effects 0.000 claims description 2
• 239000011248 coating agent Substances 0.000 claims description 2
• 238000000576 coating method Methods 0.000 claims description 2
• 238000001816 cooling Methods 0.000 claims description 2
• 125000005883 dithianyl group Chemical group 0.000 claims description 2
• 238000001914 filtration Methods 0.000 claims description 2
• 239000012458 free base Substances 0.000 claims description 2
• 235000011187 glycerol Nutrition 0.000 claims description 2
• 125000002636 imidazolinyl group Chemical group 0.000 claims description 2
• 125000002346 iodo group Chemical group I* 0.000 claims description 2
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
• 239000004310 lactic acid Substances 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 2
• 238000005935 nucleophilic addition reaction Methods 0.000 claims description 2
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 2
• 229960003415 propylparaben Drugs 0.000 claims description 2
• 125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
• 125000004306 triazinyl group Chemical group 0.000 claims description 2
• 125000001425 triazolyl group Chemical group 0.000 claims description 2
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 3
• PINRUEQFGKWBTO-UHFFFAOYSA-N 3-methyl-5-phenyl-1,3-oxazolidin-2-imine Chemical compound O1C(=N)N(C)CC1C1=CC=CC=C1 PINRUEQFGKWBTO-UHFFFAOYSA-N 0.000 claims 2
• 239000001856 Ethyl cellulose Substances 0.000 claims 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims 1
• 238000005576 amination reaction Methods 0.000 claims 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 1
• 150000002148 esters Chemical class 0.000 claims 1
• 235000019325 ethyl cellulose Nutrition 0.000 claims 1
• 229920001249 ethyl cellulose Polymers 0.000 claims 1
• 229940102223 injectable solution Drugs 0.000 claims 1
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 1
• 229920000609 methyl cellulose Polymers 0.000 claims 1
• 239000001923 methylcellulose Substances 0.000 claims 1
• 235000010981 methylcellulose Nutrition 0.000 claims 1
• 239000008215 water for injection Substances 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
• 239000000543 intermediate Substances 0.000 description 46
• 108020003175 receptors Proteins 0.000 description 32
• 102000005962 receptors Human genes 0.000 description 32
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
• 150000003254 radicals Chemical class 0.000 description 23
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 22
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
• 230000002265 prevention Effects 0.000 description 20
• 239000003054 catalyst Substances 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 19
• QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 18
• 102100024304 Protachykinin-1 Human genes 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 101800003906 Substance P Proteins 0.000 description 18
• 229940125782 compound 2 Drugs 0.000 description 18
• 208000035475 disorder Diseases 0.000 description 18
• 238000004440 column chromatography Methods 0.000 description 17
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• 229960001866 silicon dioxide Drugs 0.000 description 17
• 239000003480 eluent Substances 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• 229940079593 drug Drugs 0.000 description 14
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 12
• 239000000126 substance Substances 0.000 description 12
• 230000001154 acute effect Effects 0.000 description 11
• 230000003111 delayed effect Effects 0.000 description 11
• 241000282414 Homo sapiens Species 0.000 description 10
• 239000000935 antidepressant agent Substances 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• 229940005513 antidepressants Drugs 0.000 description 9
• 208000028017 Psychotic disease Diseases 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 208000024714 major depressive disease Diseases 0.000 description 8
• 239000012071 phase Substances 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
• 206010012289 Dementia Diseases 0.000 description 7
• 208000020401 Depressive disease Diseases 0.000 description 7
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 7
• 208000019022 Mood disease Diseases 0.000 description 7
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• 230000036506 anxiety Effects 0.000 description 7
• 230000000949 anxiolytic effect Effects 0.000 description 7
• 201000006549 dyspepsia Diseases 0.000 description 7
• 208000022821 personality disease Diseases 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 230000004044 response Effects 0.000 description 7
• 230000035882 stress Effects 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• 230000001225 therapeutic effect Effects 0.000 description 7
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 6
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
• 206010028980 Neoplasm Diseases 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 6
• 229940125773 compound 10 Drugs 0.000 description 6
• 108010037444 diisopropylglutathione ester Proteins 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 6
• 150000002576 ketones Chemical class 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 238000002844 melting Methods 0.000 description 6
• 230000008018 melting Effects 0.000 description 6
• 229930192474 thiophene Natural products 0.000 description 6
• 208000009935 visceral pain Diseases 0.000 description 6
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 5
• 150000001204 N-oxides Chemical group 0.000 description 5
• 208000007920 Neurogenic Inflammation Diseases 0.000 description 5
• 201000001880 Sexual dysfunction Diseases 0.000 description 5
• 208000012826 adjustment disease Diseases 0.000 description 5
• 239000000556 agonist Substances 0.000 description 5
• 230000003042 antagnostic effect Effects 0.000 description 5
• 239000002249 anxiolytic agent Substances 0.000 description 5
• ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 description 5
• 208000010668 atopic eczema Diseases 0.000 description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
• 210000004556 brain Anatomy 0.000 description 5
• 210000003169 central nervous system Anatomy 0.000 description 5
• 238000002512 chemotherapy Methods 0.000 description 5
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 5
• 229960004316 cisplatin Drugs 0.000 description 5
• 229940125797 compound 12 Drugs 0.000 description 5
• 229940126214 compound 3 Drugs 0.000 description 5
• 229940125898 compound 5 Drugs 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• 239000003208 petroleum Substances 0.000 description 5
• 231100000872 sexual dysfunction Toxicity 0.000 description 5
• 210000003491 skin Anatomy 0.000 description 5
• 208000019116 sleep disease Diseases 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 4
• 102000009493 Neurokinin receptors Human genes 0.000 description 4
• 108050000302 Neurokinin receptors Proteins 0.000 description 4
• 206010033647 Pancreatitis acute Diseases 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 201000003229 acute pancreatitis Diseases 0.000 description 4
• 230000000172 allergic effect Effects 0.000 description 4
• 230000008485 antagonism Effects 0.000 description 4
• 230000001430 anti-depressive effect Effects 0.000 description 4
• 230000003474 anti-emetic effect Effects 0.000 description 4
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• 229940125904 compound 1 Drugs 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 208000024798 heartburn Diseases 0.000 description 4
• 230000004968 inflammatory condition Effects 0.000 description 4
• 239000012528 membrane Substances 0.000 description 4
• 229940043265 methyl isobutyl ketone Drugs 0.000 description 4
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
• 229940005483 opioid analgesics Drugs 0.000 description 4
• 230000000144 pharmacologic effect Effects 0.000 description 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
• 239000002287 radioligand Substances 0.000 description 4
• 230000000306 recurrent effect Effects 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 230000020341 sensory perception of pain Effects 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 241000700198 Cavia Species 0.000 description 3
• 206010012374 Depressed mood Diseases 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• 208000030814 Eating disease Diseases 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 208000019454 Feeding and Eating disease Diseases 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 241000699694 Gerbillinae Species 0.000 description 3
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
• 206010061218 Inflammation Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 241000282339 Mustela Species 0.000 description 3
• 108090000189 Neuropeptides Proteins 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 206010034010 Parkinsonism Diseases 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 239000002246 antineoplastic agent Substances 0.000 description 3
• 229940005530 anxiolytics Drugs 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• 230000000903 blocking effect Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 239000007795 chemical reaction product Substances 0.000 description 3
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 230000027288 circadian rhythm Effects 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 229960003920 cocaine Drugs 0.000 description 3
• 208000010877 cognitive disease Diseases 0.000 description 3
• 229940125877 compound 31 Drugs 0.000 description 3
• 235000014632 disordered eating Nutrition 0.000 description 3
• 208000024732 dysthymic disease Diseases 0.000 description 3
• 230000002526 effect on cardiovascular system Effects 0.000 description 3
• 230000005176 gastrointestinal motility Effects 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 239000008103 glucose Substances 0.000 description 3
• 239000000380 hallucinogen Substances 0.000 description 3
• 238000005984 hydrogenation reaction Methods 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 206010025482 malaise Diseases 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 125000005948 methanesulfonyloxy group Chemical group 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 208000004296 neuralgia Diseases 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 201000001119 neuropathy Diseases 0.000 description 3
• 230000007823 neuropathy Effects 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 208000033808 peripheral neuropathy Diseases 0.000 description 3
• 229950010883 phencyclidine Drugs 0.000 description 3
• JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 3
• 239000002574 poison Substances 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000000069 prophylactic effect Effects 0.000 description 3
• 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 239000003890 substance P antagonist Substances 0.000 description 3
• 208000011117 substance-related disease Diseases 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 239000003053 toxin Substances 0.000 description 3
• 231100000765 toxin Toxicity 0.000 description 3
• 108700012359 toxins Proteins 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 230000000472 traumatic effect Effects 0.000 description 3
• 230000008673 vomiting Effects 0.000 description 3
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
• XPNMCDYOYIKVGB-CONSDPRKSA-N (2s,3s)-2-benzhydryl-n-[(2-methoxy-5-propan-2-ylphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine Chemical compound COC1=CC=C(C(C)C)C=C1CN[C@@H]1[C@H](C(C=2C=CC=CC=2)C=2C=CC=CC=2)N2CCC1CC2 XPNMCDYOYIKVGB-CONSDPRKSA-N 0.000 description 2
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 2
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 2
• 208000030507 AIDS Diseases 0.000 description 2
• 208000008811 Agoraphobia Diseases 0.000 description 2
• 206010002383 Angina Pectoris Diseases 0.000 description 2
• 208000000103 Anorexia Nervosa Diseases 0.000 description 2
• 206010002660 Anoxia Diseases 0.000 description 2
• 241000976983 Anoxia Species 0.000 description 2
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
• 206010006550 Bulimia nervosa Diseases 0.000 description 2
• 241000218236 Cannabis Species 0.000 description 2
• 108010078791 Carrier Proteins Proteins 0.000 description 2
• 206010064012 Central pain syndrome Diseases 0.000 description 2
• 208000000094 Chronic Pain Diseases 0.000 description 2
• 208000027932 Collagen disease Diseases 0.000 description 2
• 208000027691 Conduct disease Diseases 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
• 206010015866 Extravasation Diseases 0.000 description 2
• 208000001640 Fibromyalgia Diseases 0.000 description 2
• 230000005526 G1 to G0 transition Effects 0.000 description 2
• 208000018522 Gastrointestinal disease Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 206010021143 Hypoxia Diseases 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 208000019695 Migraine disease Diseases 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• 206010028813 Nausea Diseases 0.000 description 2
• HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 2
• 101800000399 Neurokinin A Proteins 0.000 description 2
• 102400000097 Neurokinin A Human genes 0.000 description 2
• NHXYSAFTNPANFK-HDMCBQFHSA-N Neurokinin B Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC(O)=O)C1=CC=CC=C1 NHXYSAFTNPANFK-HDMCBQFHSA-N 0.000 description 2
• 102000046798 Neurokinin B Human genes 0.000 description 2
• 101800002813 Neurokinin-B Proteins 0.000 description 2
• 208000027089 Parkinsonian disease Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 208000003251 Pruritus Diseases 0.000 description 2
• 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 2
• 208000001431 Psychomotor Agitation Diseases 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 208000025747 Rheumatic disease Diseases 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• 206010041250 Social phobia Diseases 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 208000026345 acute stress disease Diseases 0.000 description 2
• 239000004411 aluminium Substances 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
• 230000003109 amnesic effect Effects 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 230000007953 anoxia Effects 0.000 description 2
• 239000002111 antiemetic agent Substances 0.000 description 2
• 229960001372 aprepitant Drugs 0.000 description 2
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 2
• 230000003542 behavioural effect Effects 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 230000005540 biological transmission Effects 0.000 description 2
• 208000028683 bipolar I disease Diseases 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229960001948 caffeine Drugs 0.000 description 2
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 206010007776 catatonia Diseases 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 230000003412 degenerative effect Effects 0.000 description 2
• 230000000994 depressogenic effect Effects 0.000 description 2
• 229960003957 dexamethasone Drugs 0.000 description 2
• 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 2
• 239000002895 emetic Substances 0.000 description 2
• 230000008451 emotion Effects 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 230000036251 extravasation Effects 0.000 description 2
• 239000001530 fumaric acid Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 150000002431 hydrogen Chemical class 0.000 description 2
• 239000003326 hypnotic agent Substances 0.000 description 2
• 230000000147 hypnotic effect Effects 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• 206010027599 migraine Diseases 0.000 description 2
• 229960005181 morphine Drugs 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• DYGBNAYFDZEYBA-UHFFFAOYSA-N n-(cyclopropylmethyl)-2-[4-(4-methoxybenzoyl)piperidin-1-yl]-n-[(4-oxo-1,5,7,8-tetrahydropyrano[4,3-d]pyrimidin-2-yl)methyl]acetamide Chemical compound C1=CC(OC)=CC=C1C(=O)C1CCN(CC(=O)N(CC2CC2)CC=2NC(=O)C=3COCCC=3N=2)CC1 DYGBNAYFDZEYBA-UHFFFAOYSA-N 0.000 description 2
• 230000008693 nausea Effects 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 229960002715 nicotine Drugs 0.000 description 2
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 230000001473 noxious effect Effects 0.000 description 2
• 229940100688 oral solution Drugs 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 208000019906 panic disease Diseases 0.000 description 2
• 150000002978 peroxides Chemical class 0.000 description 2
• 230000035479 physiological effects, processes and functions Effects 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 229960005235 piperonyl butoxide Drugs 0.000 description 2
• 208000028173 post-traumatic stress disease Diseases 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 2
• DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 2
• 229960003081 probenecid Drugs 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 208000020016 psychiatric disease Diseases 0.000 description 2
• 239000008213 purified water Substances 0.000 description 2
• JADFCQKRKICRKI-UHFFFAOYSA-N quinoline;sulfane Chemical compound S.N1=CC=CC2=CC=CC=C21 JADFCQKRKICRKI-UHFFFAOYSA-N 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• LMHHRCOWPQNFTF-UHFFFAOYSA-N s-propan-2-yl azepane-1-carbothioate Chemical compound CC(C)SC(=O)N1CCCCCC1 LMHHRCOWPQNFTF-UHFFFAOYSA-N 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 208000022610 schizoaffective disease Diseases 0.000 description 2
• 229940125723 sedative agent Drugs 0.000 description 2
• 239000000932 sedative agent Substances 0.000 description 2
• 208000017520 skin disease Diseases 0.000 description 2
• 230000016160 smooth muscle contraction Effects 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 2
• CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 2
• 239000010936 titanium Substances 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 230000002455 vasospastic effect Effects 0.000 description 2
• 230000009278 visceral effect Effects 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• 238000004260 weight control Methods 0.000 description 2
• FCDRFVCGMLUYPG-ROUUACIJSA-N (2S,3S)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](NCCC2)C=2C=CC=CC=2)=C1 FCDRFVCGMLUYPG-ROUUACIJSA-N 0.000 description 1
• FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 1
• NRQHBNNTBIDSRK-YRNVUSSQSA-N (4e)-4-[(4-methoxyphenyl)methylidene]-2-methyl-1,3-oxazol-5-one Chemical compound C1=CC(OC)=CC=C1\C=C\1C(=O)OC(C)=N/1 NRQHBNNTBIDSRK-YRNVUSSQSA-N 0.000 description 1
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-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
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 101150072531 10 gene Proteins 0.000 description 1
• KRTMDCMRXQPVAZ-UHFFFAOYSA-N 2-(chloromethyl)-6-methylpyridin-3-ol Chemical compound CC1=CC=C(O)C(CCl)=N1 KRTMDCMRXQPVAZ-UHFFFAOYSA-N 0.000 description 1
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
• 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 1
• FCAFIWSACLLPGG-UHFFFAOYSA-N 2-chloro-1-morpholin-4-yl-2-phenylethanone Chemical compound C=1C=CC=CC=1C(Cl)C(=O)N1CCOCC1 FCAFIWSACLLPGG-UHFFFAOYSA-N 0.000 description 1
• GSVQWRYRPRJOIM-UHFFFAOYSA-N 2-methylpropan-2-ol;sodium Chemical compound [Na].CC(C)(C)O GSVQWRYRPRJOIM-UHFFFAOYSA-N 0.000 description 1
• SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
• WAKMMQSMEDJRRI-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC(C(Cl)=O)=CC(C(F)(F)F)=C1 WAKMMQSMEDJRRI-UHFFFAOYSA-N 0.000 description 1
• ZJIOBDJEKDUUCI-UHFFFAOYSA-N 3,5-dimethylbenzoyl chloride Chemical compound CC1=CC(C)=CC(C(Cl)=O)=C1 ZJIOBDJEKDUUCI-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• 102000035037 5-HT3 receptors Human genes 0.000 description 1
• 108091005477 5-HT3 receptors Proteins 0.000 description 1
• VQBXUKGMJCPBMF-UHFFFAOYSA-N 5-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC=1ON=CC=1C(O)=O VQBXUKGMJCPBMF-UHFFFAOYSA-N 0.000 description 1
• GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
• 206010000234 Abortion spontaneous Diseases 0.000 description 1
• 206010001297 Adjustment disorder with depressed mood Diseases 0.000 description 1
• 208000017194 Affective disease Diseases 0.000 description 1
• 206010001540 Akathisia Diseases 0.000 description 1
• 206010001541 Akinesia Diseases 0.000 description 1
• 208000007848 Alcoholism Diseases 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 206010002859 Anxiety disorder due to a general medical condition Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 208000025978 Athletic injury Diseases 0.000 description 1
• 206010063659 Aversion Diseases 0.000 description 1
• 208000000412 Avitaminosis Diseases 0.000 description 1
• 208000008035 Back Pain Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 208000020925 Bipolar disease Diseases 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 208000021465 Brief psychotic disease Diseases 0.000 description 1
• 206010006458 Bronchitis chronic Diseases 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
• 208000001387 Causalgia Diseases 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• 206010008748 Chorea Diseases 0.000 description 1
• 208000000668 Chronic Pancreatitis Diseases 0.000 description 1
• 208000006561 Cluster Headache Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
• 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• 108010092160 Dactinomycin Proteins 0.000 description 1
• 206010012225 Delirium tremens Diseases 0.000 description 1
• 208000024254 Delusional disease Diseases 0.000 description 1
• 208000016192 Demyelinating disease Diseases 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
• 201000010374 Down Syndrome Diseases 0.000 description 1
• 206010013654 Drug abuse Diseases 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 208000012661 Dyskinesia Diseases 0.000 description 1
• 208000005171 Dysmenorrhea Diseases 0.000 description 1
• 208000014094 Dystonic disease Diseases 0.000 description 1
• OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 201000011240 Frontotemporal dementia Diseases 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 206010017964 Gastrointestinal infection Diseases 0.000 description 1
• 206010017999 Gastrointestinal pain Diseases 0.000 description 1
• 208000011688 Generalised anxiety disease Diseases 0.000 description 1
• 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
• 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 description 1
• ATFVTAOSZBVGHC-UHFFFAOYSA-N Glycolaldehyde dimer Chemical compound OC1COC(O)CO1 ATFVTAOSZBVGHC-UHFFFAOYSA-N 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 238000007341 Heck reaction Methods 0.000 description 1
• GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
• 208000000903 Herpes simplex encephalitis Diseases 0.000 description 1
• 206010063491 Herpes zoster oticus Diseases 0.000 description 1
• 208000016619 Histrionic personality disease Diseases 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
• 208000004454 Hyperalgesia Diseases 0.000 description 1
• 206010020601 Hyperchlorhydria Diseases 0.000 description 1
• 208000035154 Hyperesthesia Diseases 0.000 description 1
• 206010020710 Hyperphagia Diseases 0.000 description 1
• 208000013016 Hypoglycemia Diseases 0.000 description 1
• 206010021135 Hypovitaminosis Diseases 0.000 description 1
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000027601 Inner ear disease Diseases 0.000 description 1
• 206010049949 Intercostal neuralgia Diseases 0.000 description 1
• 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
• 206010022773 Intracranial pressure increased Diseases 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 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 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
• 208000008930 Low Back Pain Diseases 0.000 description 1
• 208000004852 Lung Injury Diseases 0.000 description 1
• 241000763212 Lype Species 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 206010026749 Mania Diseases 0.000 description 1
• 102100027373 Melanin-concentrating hormone receptor 2 Human genes 0.000 description 1
• 101710089759 Melanin-concentrating hormone receptor 2 Proteins 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 208000027530 Meniere disease Diseases 0.000 description 1
• 201000009906 Meningitis Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• 208000001089 Multiple system atrophy Diseases 0.000 description 1
• 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
• 208000002033 Myoclonus Diseases 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• 229910017974 NH40H Inorganic materials 0.000 description 1
• 208000027120 Narcissistic personality disease Diseases 0.000 description 1
• 229940127387 Neurokinin 1 Antagonists Drugs 0.000 description 1
• 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
• 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000001294 Nociceptive Pain Diseases 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
• 206010068106 Occipital neuralgia Diseases 0.000 description 1
• 206010033649 Pancreatitis chronic Diseases 0.000 description 1
• 102000008080 Pancreatitis-Associated Proteins Human genes 0.000 description 1
• 108010074467 Pancreatitis-Associated Proteins Proteins 0.000 description 1
• 206010033664 Panic attack Diseases 0.000 description 1
• 206010033668 Panic disorder without agoraphobia Diseases 0.000 description 1
• 208000006199 Parasomnias Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 1
• 208000004983 Phantom Limb Diseases 0.000 description 1
• 206010056238 Phantom pain Diseases 0.000 description 1
• 206010034912 Phobia Diseases 0.000 description 1
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
• 208000036757 Postencephalitic parkinsonism Diseases 0.000 description 1
• 208000004550 Postoperative Pain Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
• 206010067171 Regurgitation Diseases 0.000 description 1
• 206010038743 Restlessness Diseases 0.000 description 1
• 206010038776 Retching Diseases 0.000 description 1
• 235000002357 Ribes grossularia Nutrition 0.000 description 1
• 244000171263 Ribes grossularia Species 0.000 description 1
• 240000007651 Rubus glaucus Species 0.000 description 1
• 235000011034 Rubus glaucus Nutrition 0.000 description 1
• 235000009122 Rubus idaeus Nutrition 0.000 description 1
• 206010049002 Scar pain Diseases 0.000 description 1
• 208000030988 Schizoid Personality disease Diseases 0.000 description 1
• 208000036750 Schizophrenia, residual type Diseases 0.000 description 1
• 208000020186 Schizophreniform disease Diseases 0.000 description 1
• 208000008765 Sciatica Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 208000029901 Sexual arousal disease Diseases 0.000 description 1
• 208000030047 Sexual desire disease Diseases 0.000 description 1
• 208000019568 Shared Paranoid disease Diseases 0.000 description 1
• 208000028810 Shared psychotic disease Diseases 0.000 description 1
• 206010040744 Sinus headache Diseases 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• 206010063910 Sleep disorder due to a general medical condition Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 208000027520 Somatoform disease Diseases 0.000 description 1
• 206010041738 Sports injury Diseases 0.000 description 1
• 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
• 208000011962 Substance-induced mood disease Diseases 0.000 description 1
• 231100000395 Substance-induced mood disorder Toxicity 0.000 description 1
• 208000011963 Substance-induced psychotic disease Diseases 0.000 description 1
• 231100000393 Substance-induced psychotic disorder Toxicity 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 206010042496 Sunburn Diseases 0.000 description 1
• 102000003141 Tachykinin Human genes 0.000 description 1
• 206010043269 Tension headache Diseases 0.000 description 1
• 208000008548 Tension-Type Headache Diseases 0.000 description 1
• 244000299461 Theobroma cacao Species 0.000 description 1
• 235000009470 Theobroma cacao Nutrition 0.000 description 1
• RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
• LCKIEQZJEYYRIY-UHFFFAOYSA-N Titanium ion Chemical compound [Ti+4] LCKIEQZJEYYRIY-UHFFFAOYSA-N 0.000 description 1
• 208000000323 Tourette Syndrome Diseases 0.000 description 1
• 208000016620 Tourette disease Diseases 0.000 description 1
• 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
• 206010069363 Traumatic lung injury Diseases 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010044688 Trisomy 21 Diseases 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
• 208000024780 Urticaria Diseases 0.000 description 1
• 208000001407 Vascular Headaches Diseases 0.000 description 1
• 201000004810 Vascular dementia Diseases 0.000 description 1
• 208000012886 Vertigo Diseases 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• NEOQCQIBCCRRPO-FCHUYYIVSA-N [(2r,4s)-2-benzyl-4-piperazin-1-ylpiperidin-1-yl]-[3,5-bis(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C(=O)N2[C@@H](C[C@H](CC2)N2CCNCC2)CC=2C=CC=CC=2)=C1 NEOQCQIBCCRRPO-FCHUYYIVSA-N 0.000 description 1
• 206010000210 abortion Diseases 0.000 description 1
• 231100000176 abortion Toxicity 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000002730 additional effect Effects 0.000 description 1
• 210000003766 afferent neuron Anatomy 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 206010001584 alcohol abuse Diseases 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 208000025746 alcohol use disease Diseases 0.000 description 1
• 208000006246 alcohol withdrawal delirium Diseases 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 208000008445 altitude sickness Diseases 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 210000004727 amygdala Anatomy 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 230000000454 anti-cipatory effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 238000011394 anticancer treatment Methods 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003972 antineoplastic antibiotic Substances 0.000 description 1
• 230000000338 anxiogenic effect Effects 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 206010003074 arachnoiditis Diseases 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 230000002567 autonomic effect Effects 0.000 description 1
• 208000022804 avoidant personality disease Diseases 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 201000002922 basal ganglia calcification Diseases 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 229940049706 benzodiazepine Drugs 0.000 description 1
• 150000001557 benzodiazepines Chemical class 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• 230000002146 bilateral effect Effects 0.000 description 1
• 208000016791 bilateral striopallidodentate calcinosis Diseases 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 208000022257 bipolar II disease Diseases 0.000 description 1
• 208000025307 bipolar depression Diseases 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 208000030963 borderline personality disease Diseases 0.000 description 1
• 210000003461 brachial plexus Anatomy 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 229960005243 carmustine Drugs 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 229940044683 chemotherapy drug Drugs 0.000 description 1
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• 208000012601 choreatic disease Diseases 0.000 description 1
• 208000007451 chronic bronchitis Diseases 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 208000018912 cluster headache syndrome Diseases 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
• 238000011970 concomitant therapy Methods 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 230000036461 convulsion Effects 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 208000026725 cyclothymic disease Diseases 0.000 description 1
• 201000003146 cystitis Diseases 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 229960003901 dacarbazine Drugs 0.000 description 1
• 229960000640 dactinomycin Drugs 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 239000012024 dehydrating agents‎ Substances 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 208000030964 dependent personality disease Diseases 0.000 description 1
• 230000003001 depressive effect Effects 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 229960002069 diamorphine Drugs 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 208000019836 digestive system infectious disease Diseases 0.000 description 1
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
• 230000009429 distress Effects 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 208000010118 dystonia Diseases 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 230000004970 emotional disturbance Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 201000003104 endogenous depression Diseases 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002327 eosinophilic effect Effects 0.000 description 1
• 230000001667 episodic effect Effects 0.000 description 1
• 210000000981 epithelium Anatomy 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 229950000331 ezlopitant Drugs 0.000 description 1
• 208000006275 fascioliasis Diseases 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 238000011832 ferret model Methods 0.000 description 1
• 239000007941 film coated tablet Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 238000002073 fluorescence micrograph Methods 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• 229960002464 fluoxetine Drugs 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
• 238000012224 gene deletion Methods 0.000 description 1
• 208000029364 generalized anxiety disease Diseases 0.000 description 1
• 201000011349 geniculate herpes zoster Diseases 0.000 description 1
• 201000005442 glossopharyngeal neuralgia Diseases 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 229960004275 glycolic acid Drugs 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 1
• 229960003727 granisetron Drugs 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 229960001330 hydroxycarbamide Drugs 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000002218 hypoglycaemic effect Effects 0.000 description 1
• 210000003016 hypothalamus Anatomy 0.000 description 1
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
• 229960004801 imipramine Drugs 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000001965 increasing effect Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 208000001286 intracranial vasospasm Diseases 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 238000011813 knockout mouse model Methods 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 208000010325 limbic encephalitis Diseases 0.000 description 1
• 210000003715 limbic system Anatomy 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 229960002247 lomustine Drugs 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
• 229960001571 loperamide Drugs 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 231100000515 lung injury Toxicity 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 210000004086 maxillary sinus Anatomy 0.000 description 1
• 235000012054 meals Nutrition 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 206010027175 memory impairment Diseases 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 150000004972 metal peroxides Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
• 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 208000015994 miscarriage Diseases 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 201000003152 motion sickness Diseases 0.000 description 1
• 208000005264 motor neuron disease Diseases 0.000 description 1
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
• 201000003631 narcolepsy Diseases 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 208000019382 nerve compression syndrome Diseases 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 208000025319 neurotic depression Diseases 0.000 description 1
• 208000015238 neurotic disease Diseases 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 230000000422 nocturnal effect Effects 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
• 235000020824 obesity Nutrition 0.000 description 1
• 208000030459 obsessive-compulsive personality disease Diseases 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 229960005343 ondansetron Drugs 0.000 description 1
• 239000000014 opioid analgesic Substances 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 229940098462 oral drops Drugs 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000001451 organic peroxides Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 235000020830 overeating Nutrition 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 208000027753 pain disease Diseases 0.000 description 1
• 230000037324 pain perception Effects 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 208000024817 paranoid personality disease Diseases 0.000 description 1
• 208000002851 paranoid schizophrenia Diseases 0.000 description 1
• 210000005034 parasympathetic neuron Anatomy 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 239000003961 penetration enhancing agent Substances 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 206010034674 peritonitis Diseases 0.000 description 1
• 150000004965 peroxy acids Chemical class 0.000 description 1
• XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical class OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 231100000614 poison Toxicity 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 208000000170 postencephalitic Parkinson disease Diseases 0.000 description 1
• 230000002980 postoperative effect Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 108010041634 preprotachykinin Proteins 0.000 description 1
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
• 229960000624 procarbazine Drugs 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000012429 reaction media Substances 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000008327 renal blood flow Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 206010039083 rhinitis Diseases 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 230000001932 seasonal effect Effects 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 230000004799 sedative–hypnotic effect Effects 0.000 description 1
• 238000010956 selective crystallization Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000001953 sensory effect Effects 0.000 description 1
• 210000001044 sensory neuron Anatomy 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 201000002859 sleep apnea Diseases 0.000 description 1
• 208000020685 sleep-wake disease Diseases 0.000 description 1
• MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
• PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
• 210000001679 solitary nucleus Anatomy 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 201000001716 specific phobia Diseases 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 208000005198 spinal stenosis Diseases 0.000 description 1
• 208000000995 spontaneous abortion Diseases 0.000 description 1
• 239000004544 spot-on Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 230000024188 startle response Effects 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
• 201000009032 substance abuse Diseases 0.000 description 1
• 201000006152 substance dependence Diseases 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002889 sympathetic effect Effects 0.000 description 1
• 230000005062 synaptic transmission Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229940037128 systemic glucocorticoids Drugs 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 108060008037 tachykinin Proteins 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 210000003478 temporal lobe Anatomy 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical group 0.000 description 1
• 235000019157 thiamine Nutrition 0.000 description 1
• 239000011721 thiamine Substances 0.000 description 1
• QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 229910052719 titanium Inorganic materials 0.000 description 1
• 208000004371 toothache Diseases 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000017105 transposition Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 206010044652 trigeminal neuralgia Diseases 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229960004441 tyrosine Drugs 0.000 description 1
• 206010046494 urge incontinence Diseases 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 230000024883 vasodilation Effects 0.000 description 1
• 231100000889 vertigo Toxicity 0.000 description 1
• 208000027491 vestibular disease Diseases 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 208000030401 vitamin deficiency disease Diseases 0.000 description 1
• 235000012431 wafers Nutrition 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1