BRPI0616609A2 - compostos que têm atividade no receptor m1, composição farmacêutica contendo tais compostos, processo para preparação dos mesmos, bem como seus usos em medicina - Google Patents
compostos que têm atividade no receptor m1, composição farmacêutica contendo tais compostos, processo para preparação dos mesmos, bem como seus usos em medicina Download PDFInfo
- Publication number
- BRPI0616609A2 BRPI0616609A2 BRPI0616609-1A BRPI0616609A BRPI0616609A2 BR PI0616609 A2 BRPI0616609 A2 BR PI0616609A2 BR PI0616609 A BRPI0616609 A BR PI0616609A BR PI0616609 A2 BRPI0616609 A2 BR PI0616609A2
- Authority
- BR
- Brazil
- Prior art keywords
- formula
- group
- compound
- convertible
- original document
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 242
- 230000000694 effects Effects 0.000 title claims abstract description 31
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
- 238000000034 method Methods 0.000 title claims description 71
- 239000003814 drug Substances 0.000 title claims description 43
- 230000008569 process Effects 0.000 title claims description 38
- 238000002360 preparation method Methods 0.000 title claims description 18
- 102000005962 receptors Human genes 0.000 title claims description 12
- 108020003175 receptors Proteins 0.000 title claims description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 62
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 58
- 239000012453 solvate Substances 0.000 claims abstract description 51
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 38
- 239000001257 hydrogen Substances 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 claims abstract description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 36
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 23
- 239000011737 fluorine Substances 0.000 claims abstract description 21
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 21
- 208000028698 Cognitive impairment Diseases 0.000 claims abstract description 19
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 17
- 238000004519 manufacturing process Methods 0.000 claims abstract description 17
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 15
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract 3
- -1 tetrahydro-2H-pyran-4-yl Chemical group 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 239000000460 chlorine Chemical group 0.000 claims description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 22
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 17
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
- 238000005804 alkylation reaction Methods 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 230000029936 alkylation Effects 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 229910052763 palladium Inorganic materials 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 8
- 230000008484 agonism Effects 0.000 claims description 8
- 230000008878 coupling Effects 0.000 claims description 8
- 238000010168 coupling process Methods 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- 239000012442 inert solvent Substances 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 238000006969 Curtius rearrangement reaction Methods 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 239000010949 copper Substances 0.000 claims description 5
- 229910052802 copper Inorganic materials 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 230000003551 muscarinic effect Effects 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 claims 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims 1
- 238000003747 Grignard reaction Methods 0.000 claims 1
- 102000007207 Muscarinic M1 Receptor Human genes 0.000 claims 1
- 108010008406 Muscarinic M1 Receptor Proteins 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 112
- 239000000203 mixture Substances 0.000 description 94
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 48
- 230000001225 therapeutic effect Effects 0.000 description 46
- 239000002249 anxiolytic agent Substances 0.000 description 36
- 230000000949 anxiolytic effect Effects 0.000 description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 36
- 239000000164 antipsychotic agent Substances 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- 208000035475 disorder Diseases 0.000 description 31
- 239000007787 solid Substances 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 239000000935 antidepressant agent Substances 0.000 description 24
- 229940079593 drug Drugs 0.000 description 24
- 229940005513 antidepressants Drugs 0.000 description 23
- 239000000543 intermediate Substances 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000004480 active ingredient Substances 0.000 description 22
- 239000002475 cognitive enhancer Substances 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 230000001430 anti-depressive effect Effects 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 239000004050 mood stabilizer Substances 0.000 description 20
- 229940127237 mood stabilizer Drugs 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 14
- 239000005557 antagonist Substances 0.000 description 14
- 230000000147 hypnotic effect Effects 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 13
- 208000019901 Anxiety disease Diseases 0.000 description 13
- 229940025084 amphetamine Drugs 0.000 description 13
- 239000000932 sedative agent Substances 0.000 description 13
- 230000001624 sedative effect Effects 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- 206010012218 Delirium Diseases 0.000 description 12
- 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 12
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 11
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 208000019116 sleep disease Diseases 0.000 description 11
- 208000019022 Mood disease Diseases 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 230000035987 intoxication Effects 0.000 description 10
- 231100000566 intoxication Toxicity 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 9
- 230000002085 persistent effect Effects 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 206010012289 Dementia Diseases 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 201000001880 Sexual dysfunction Diseases 0.000 description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 150000002513 isocyanates Chemical class 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 231100000872 sexual dysfunction Toxicity 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 8
- 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 7
- 206010026749 Mania Diseases 0.000 description 7
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 239000000380 hallucinogen Substances 0.000 description 7
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 7
- 229950010883 phencyclidine Drugs 0.000 description 7
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 208000020685 sleep-wake disease Diseases 0.000 description 7
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 7
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 6
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 6
- 239000003693 atypical antipsychotic agent Substances 0.000 description 6
- 229940127236 atypical antipsychotics Drugs 0.000 description 6
- 229960003920 cocaine Drugs 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- YQZBAXDVDZTKEQ-UHFFFAOYSA-N loxapine succinate Chemical compound [H+].[H+].[O-]C(=O)CCC([O-])=O.C1CN(C)CCN1C1=NC2=CC=CC=C2OC2=CC=C(Cl)C=C12 YQZBAXDVDZTKEQ-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 5
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 5
- JCNSWCZJWGOGNR-UHFFFAOYSA-N 6,7-difluoro-5-methyl-3-piperidin-4-yl-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.O=C1NC=2C(F)=C(F)C(C)=CC=2N1C1CCNCC1 JCNSWCZJWGOGNR-UHFFFAOYSA-N 0.000 description 5
- KRRSQJOVDWYKHH-UHFFFAOYSA-N 7-fluoro-5-methyl-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound C12=CC(C)=CC(F)=C2NC(=O)N1C(CC1)CCN1C1CCOCC1 KRRSQJOVDWYKHH-UHFFFAOYSA-N 0.000 description 5
- KWBOEFVUJIZJDY-UHFFFAOYSA-N 7-fluoro-5-methyl-3-piperidin-4-yl-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.C12=CC(C)=CC(F)=C2NC(=O)N1C1CCNCC1 KWBOEFVUJIZJDY-UHFFFAOYSA-N 0.000 description 5
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 5
- 208000020925 Bipolar disease Diseases 0.000 description 5
- 206010013654 Drug abuse Diseases 0.000 description 5
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000006555 catalytic reaction Methods 0.000 description 5
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 150000003840 hydrochlorides Chemical class 0.000 description 5
- 239000012948 isocyanate Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 208000024714 major depressive disease Diseases 0.000 description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 230000002093 peripheral effect Effects 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 208000020016 psychiatric disease Diseases 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 5
- 239000012047 saturated solution Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- YNHSGDUOWUPKKQ-UHFFFAOYSA-N 1,3-difluoro-5-methoxy-2-nitrobenzene Chemical compound COC1=CC(F)=C([N+]([O-])=O)C(F)=C1 YNHSGDUOWUPKKQ-UHFFFAOYSA-N 0.000 description 4
- HMDHQYKNBZEFTH-UHFFFAOYSA-N 2,3-difluoro-4-methylaniline Chemical compound CC1=CC=C(N)C(F)=C1F HMDHQYKNBZEFTH-UHFFFAOYSA-N 0.000 description 4
- ZAJBUIBKJUTUIT-UHFFFAOYSA-N 2,3-difluoro-6-iodo-4-methylaniline Chemical compound CC1=CC(I)=C(N)C(F)=C1F ZAJBUIBKJUTUIT-UHFFFAOYSA-N 0.000 description 4
- WAGLGQXOHWSQOD-UHFFFAOYSA-N 2-fluoro-6-iodo-4-methylaniline Chemical compound CC1=CC(F)=C(N)C(I)=C1 WAGLGQXOHWSQOD-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 241000218236 Cannabis Species 0.000 description 4
- DCNLAFXMGQNPKQ-UHFFFAOYSA-N Cc1cc(F)c2[nH]c(=O)n(C3CCN(CC3)C(O)=O)c2c1 Chemical compound Cc1cc(F)c2[nH]c(=O)n(C3CCN(CC3)C(O)=O)c2c1 DCNLAFXMGQNPKQ-UHFFFAOYSA-N 0.000 description 4
- 208000022497 Cocaine-Related disease Diseases 0.000 description 4
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- GUTXTARXLVFHDK-UHFFFAOYSA-N Haloperidol decanoate Chemical compound C1CC(OC(=O)CCCCCCCCC)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 GUTXTARXLVFHDK-UHFFFAOYSA-N 0.000 description 4
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 208000003863 Marijuana Abuse Diseases 0.000 description 4
- KLPWJLBORRMFGK-UHFFFAOYSA-N Molindone Chemical compound O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 KLPWJLBORRMFGK-UHFFFAOYSA-N 0.000 description 4
- 208000026251 Opioid-Related disease Diseases 0.000 description 4
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 4
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
- 229960004373 acetylcholine Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000003109 amnesic effect Effects 0.000 description 4
- 229940005530 anxiolytics Drugs 0.000 description 4
- 239000003125 aqueous solvent Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 229960001948 caffeine Drugs 0.000 description 4
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 230000001713 cholinergic effect Effects 0.000 description 4
- 229960004170 clozapine Drugs 0.000 description 4
- 150000004985 diamines Chemical class 0.000 description 4
- 235000014632 disordered eating Nutrition 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 206010022437 insomnia Diseases 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 229960005017 olanzapine Drugs 0.000 description 4
- 208000022821 personality disease Diseases 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 229960003770 reboxetine Drugs 0.000 description 4
- CBQGYUDMJHNJBX-RTBURBONSA-N reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229960001534 risperidone Drugs 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- MWRDGYGQIVGWTB-UHFFFAOYSA-N tert-butyl 4-(6-chloro-4-fluoro-2-oxo-3h-benzimidazol-1-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)NC2=C(F)C=C(Cl)C=C21 MWRDGYGQIVGWTB-UHFFFAOYSA-N 0.000 description 4
- SLBZPKSUFGWJSZ-UHFFFAOYSA-N tert-butyl 4-[(2-bromo-4-chloro-6-fluorophenyl)carbamoylamino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC(=O)NC1=C(F)C=C(Cl)C=C1Br SLBZPKSUFGWJSZ-UHFFFAOYSA-N 0.000 description 4
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 4
- 229960000604 valproic acid Drugs 0.000 description 4
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 4
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 3
- WSPOMRSOLSGNFJ-AUWJEWJLSA-N (Z)-chlorprothixene Chemical compound C1=C(Cl)C=C2C(=C/CCN(C)C)\C3=CC=CC=C3SC2=C1 WSPOMRSOLSGNFJ-AUWJEWJLSA-N 0.000 description 3
- BWMNOFXLNWSOMU-UHFFFAOYSA-N 1-fluoro-3-iodo-2-isocyanato-5-methylbenzene Chemical compound CC1=CC(F)=C(N=C=O)C(I)=C1 BWMNOFXLNWSOMU-UHFFFAOYSA-N 0.000 description 3
- QVECFWRRZNGQDO-UHFFFAOYSA-N 2-bromo-6-fluoro-4-methylaniline Chemical compound CC1=CC(F)=C(N)C(Br)=C1 QVECFWRRZNGQDO-UHFFFAOYSA-N 0.000 description 3
- DDNBXAHODWXJKM-UHFFFAOYSA-N 3,5-difluoro-4-nitrophenol Chemical compound OC1=CC(F)=C([N+]([O-])=O)C(F)=C1 DDNBXAHODWXJKM-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- ABAGKHWCTWMUDH-UHFFFAOYSA-N 5-bromo-1,3-difluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(F)C=C(Br)C=C1F ABAGKHWCTWMUDH-UHFFFAOYSA-N 0.000 description 3
- DASKXADFUYTWTK-UHFFFAOYSA-N 5-chloro-7-fluoro-3-piperidin-4-yl-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.O=C1NC=2C(F)=CC(Cl)=CC=2N1C1CCNCC1 DASKXADFUYTWTK-UHFFFAOYSA-N 0.000 description 3
- UJCASPHRCDNOAI-UHFFFAOYSA-N 6,7-difluoro-5-methyl-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.O=C1NC=2C(F)=C(F)C(C)=CC=2N1C(CC1)CCN1C1CCOCC1 UJCASPHRCDNOAI-UHFFFAOYSA-N 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 208000029197 Amphetamine-Related disease Diseases 0.000 description 3
- 102000017926 CHRM2 Human genes 0.000 description 3
- 101150012960 Chrm2 gene Proteins 0.000 description 3
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 3
- 208000030814 Eating disease Diseases 0.000 description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 description 3
- 208000004230 Gender Dysphoria Diseases 0.000 description 3
- 208000004547 Hallucinations Diseases 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000006199 Parasomnias Diseases 0.000 description 3
- 208000005374 Poisoning Diseases 0.000 description 3
- ZGUGWUXLJSTTMA-UHFFFAOYSA-N Promazinum Chemical compound C1=CC=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZGUGWUXLJSTTMA-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 229960000276 acetophenazine Drugs 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 229960003036 amisulpride Drugs 0.000 description 3
- NTJOBXMMWNYJFB-UHFFFAOYSA-N amisulpride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(N)C=C1OC NTJOBXMMWNYJFB-UHFFFAOYSA-N 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 3
- 229960001076 chlorpromazine Drugs 0.000 description 3
- 229960001552 chlorprothixene Drugs 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
- 230000006999 cognitive decline Effects 0.000 description 3
- 230000001149 cognitive effect Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 3
- 229960003878 haloperidol Drugs 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 206010020765 hypersomnia Diseases 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229960001848 lamotrigine Drugs 0.000 description 3
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 3
- 229940089527 loxitane Drugs 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229960002715 nicotine Drugs 0.000 description 3
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 3
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 3
- 231100000572 poisoning Toxicity 0.000 description 3
- 230000000607 poisoning effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229960004431 quetiapine Drugs 0.000 description 3
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 201000009032 substance abuse Diseases 0.000 description 3
- 208000011117 substance-related disease Diseases 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- JTXUYROQJKQWLS-UHFFFAOYSA-N tert-butyl 4-(6-cyclopropyl-4-fluoro-2-oxo-3h-benzimidazol-1-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)NC2=C(F)C=C(C3CC3)C=C21 JTXUYROQJKQWLS-UHFFFAOYSA-N 0.000 description 3
- SKGBPPYCDJEMIE-UHFFFAOYSA-N tert-butyl 4-[(2,3-difluoro-6-iodo-4-methylphenyl)carbamoylamino]piperidine-1-carboxylate Chemical compound FC1=C(F)C(C)=CC(I)=C1NC(=O)NC1CCN(C(=O)OC(C)(C)C)CC1 SKGBPPYCDJEMIE-UHFFFAOYSA-N 0.000 description 3
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 3
- 238000003828 vacuum filtration Methods 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- 229960000607 ziprasidone Drugs 0.000 description 3
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 2
- GJJFMKBJSRMPLA-HIFRSBDPSA-N (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenyl-1-cyclopropanecarboxamide Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)N(CC)CC)C[C@@H]1CN GJJFMKBJSRMPLA-HIFRSBDPSA-N 0.000 description 2
- DIWRORZWFLOCLC-HNNXBMFYSA-N (3s)-7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(Cl)C=C11)=O)O)=C1C1=CC=CC=C1Cl DIWRORZWFLOCLC-HNNXBMFYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 2
- 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 2
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- RCDKCOBKMXBXAU-UHFFFAOYSA-N 1,3-difluoro-5-methyl-2-nitrobenzene Chemical compound CC1=CC(F)=C([N+]([O-])=O)C(F)=C1 RCDKCOBKMXBXAU-UHFFFAOYSA-N 0.000 description 2
- XGLFBUVWWKDQKP-UHFFFAOYSA-N 2-(3,5-difluoro-4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC(F)=C([N+]([O-])=O)C(F)=C1 XGLFBUVWWKDQKP-UHFFFAOYSA-N 0.000 description 2
- ZQEXBVHABAJPHJ-UHFFFAOYSA-N 2-fluoro-4-methylaniline Chemical compound CC1=CC=C(N)C(F)=C1 ZQEXBVHABAJPHJ-UHFFFAOYSA-N 0.000 description 2
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 2
- MGOCSCHYSUUUMG-UHFFFAOYSA-N 3,4-difluoro-1-iodo-2-isocyanato-5-methylbenzene Chemical compound CC1=CC(I)=C(N=C=O)C(F)=C1F MGOCSCHYSUUUMG-UHFFFAOYSA-N 0.000 description 2
- CMAUNVCQJBNTDY-UHFFFAOYSA-N 3-fluoro-5-methyl-1-n-[1-(oxan-4-yl)piperidin-4-yl]benzene-1,2-diamine Chemical compound CC1=CC(F)=C(N)C(NC2CCN(CC2)C2CCOCC2)=C1 CMAUNVCQJBNTDY-UHFFFAOYSA-N 0.000 description 2
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
- AXXFKJZRMQNHPU-UHFFFAOYSA-N 5-chloro-7-fluoro-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.O=C1NC=2C(F)=CC(Cl)=CC=2N1C(CC1)CCN1C1CCOCC1 AXXFKJZRMQNHPU-UHFFFAOYSA-N 0.000 description 2
- FEOCDVZPUFNULB-UHFFFAOYSA-N 5-cyclopropyl-7-fluoro-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.O=C1NC=2C(F)=CC(C3CC3)=CC=2N1C(CC1)CCN1C1CCOCC1 FEOCDVZPUFNULB-UHFFFAOYSA-N 0.000 description 2
- FYSPFNKQWVTUKI-UHFFFAOYSA-N 5-cyclopropyl-7-fluoro-3-piperidin-4-yl-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.O=C1NC=2C(F)=CC(C3CC3)=CC=2N1C1CCNCC1 FYSPFNKQWVTUKI-UHFFFAOYSA-N 0.000 description 2
- XKFPYPQQHFEXRZ-UHFFFAOYSA-N 5-methyl-N'-(phenylmethyl)-3-isoxazolecarbohydrazide Chemical compound O1C(C)=CC(C(=O)NNCC=2C=CC=CC=2)=N1 XKFPYPQQHFEXRZ-UHFFFAOYSA-N 0.000 description 2
- FJYKBJUHMMQVPU-UHFFFAOYSA-N 7-fluoro-5-methoxy-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.C12=CC(OC)=CC(F)=C2NC(=O)N1C(CC1)CCN1C1CCOCC1 FJYKBJUHMMQVPU-UHFFFAOYSA-N 0.000 description 2
- ITOSOZSWRKORAW-UHFFFAOYSA-N 7-fluoro-5-methoxy-3-piperidin-4-yl-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.C12=CC(OC)=CC(F)=C2NC(=O)N1C1CCNCC1 ITOSOZSWRKORAW-UHFFFAOYSA-N 0.000 description 2
- FDACQSJDRGVKFF-UHFFFAOYSA-N 7-fluoro-5-methyl-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one;hydrochloride Chemical compound Cl.C12=CC(C)=CC(F)=C2NC(=O)N1C(CC1)CCN1C1CCOCC1 FDACQSJDRGVKFF-UHFFFAOYSA-N 0.000 description 2
- 208000008811 Agoraphobia Diseases 0.000 description 2
- 206010001605 Alcohol poisoning Diseases 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 208000027448 Attention Deficit and Disruptive Behavior disease Diseases 0.000 description 2
- 208000020706 Autistic disease Diseases 0.000 description 2
- 102000017925 CHRM3 Human genes 0.000 description 2
- 101150060249 CHRM3 gene Proteins 0.000 description 2
- 102000017924 CHRM4 Human genes 0.000 description 2
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 2
- 208000017781 Cocaine intoxication Diseases 0.000 description 2
- 206010012239 Delusion Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 206010016754 Flashback Diseases 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 208000029810 Gender identity disease Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 2
- 238000006751 Mitsunobu reaction Methods 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 2
- 206010033888 Paraphilia Diseases 0.000 description 2
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 2
- RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 2
- 208000020186 Schizophreniform disease Diseases 0.000 description 2
- 206010041250 Social phobia Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 208000011962 Substance-induced mood disease Diseases 0.000 description 2
- 231100000395 Substance-induced mood disorder Toxicity 0.000 description 2
- 208000011963 Substance-induced psychotic disease Diseases 0.000 description 2
- 231100000393 Substance-induced psychotic disorder Toxicity 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GFBKORZTTCHDGY-UWVJOHFNSA-N Thiothixene Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2\C1=C\CCN1CCN(C)CC1 GFBKORZTTCHDGY-UWVJOHFNSA-N 0.000 description 2
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 101100107916 Xenopus laevis chrm4 gene Proteins 0.000 description 2
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 2
- WNTYBHLDCKXEOT-UHFFFAOYSA-N acetophenazine Chemical compound C12=CC(C(=O)C)=CC=C2SC2=CC=CC=C2N1CCCN1CCN(CCO)CC1 WNTYBHLDCKXEOT-UHFFFAOYSA-N 0.000 description 2
- 238000011360 adjunctive therapy Methods 0.000 description 2
- 239000004479 aerosol dispenser Substances 0.000 description 2
- 208000028505 alcohol-related disease Diseases 0.000 description 2
- 229960004538 alprazolam Drugs 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 229960000959 amineptine Drugs 0.000 description 2
- VDPUXONTAVMIKZ-UHFFFAOYSA-N amineptine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2C([NH2+]CCCCCCC(=O)O)C2=CC=CC=C21 VDPUXONTAVMIKZ-UHFFFAOYSA-N 0.000 description 2
- 229960000836 amitriptyline Drugs 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000000561 anti-psychotic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 2
- 229960001058 bupropion Drugs 0.000 description 2
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
- 201000001843 cannabis dependence Diseases 0.000 description 2
- 229960000623 carbamazepine Drugs 0.000 description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 229960001653 citalopram Drugs 0.000 description 2
- 229960004606 clomipramine Drugs 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 231100000868 delusion Toxicity 0.000 description 2
- 230000003001 depressive effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 208000035548 disruptive behavior disease Diseases 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 229960000394 droperidol Drugs 0.000 description 2
- RMEDXOLNCUSCGS-UHFFFAOYSA-N droperidol Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CC=C(N2C(NC3=CC=CC=C32)=O)CC1 RMEDXOLNCUSCGS-UHFFFAOYSA-N 0.000 description 2
- 206010013663 drug dependence Diseases 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 229960002866 duloxetine Drugs 0.000 description 2
- 229960004341 escitalopram Drugs 0.000 description 2
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 229950003930 femoxetine Drugs 0.000 description 2
- OJSFTALXCYKKFQ-YLJYHZDGSA-N femoxetine Chemical compound C1=CC(OC)=CC=C1OC[C@@H]1[C@@H](C=2C=CC=CC=2)CCN(C)C1 OJSFTALXCYKKFQ-YLJYHZDGSA-N 0.000 description 2
- 229960002464 fluoxetine Drugs 0.000 description 2
- 229960004038 fluvoxamine Drugs 0.000 description 2
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 2
- 229960002870 gabapentin Drugs 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229940095895 haldol Drugs 0.000 description 2
- 229960005007 haloperidol decanoate Drugs 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 229960004801 imipramine Drugs 0.000 description 2
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 2
- 229950002473 indalpine Drugs 0.000 description 2
- SADQVAVFGNTEOD-UHFFFAOYSA-N indalpine Chemical compound C=1NC2=CC=CC=C2C=1CCC1CCNCC1 SADQVAVFGNTEOD-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229960002672 isocarboxazid Drugs 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229960004391 lorazepam Drugs 0.000 description 2
- 229960000423 loxapine Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960004090 maprotiline Drugs 0.000 description 2
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229940042053 methotrimeprazine Drugs 0.000 description 2
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 2
- 229960004503 metoclopramide Drugs 0.000 description 2
- 229960003955 mianserin Drugs 0.000 description 2
- 229960000600 milnacipran Drugs 0.000 description 2
- 229960001785 mirtazapine Drugs 0.000 description 2
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229940028394 moban Drugs 0.000 description 2
- YHXISWVBGDMDLQ-UHFFFAOYSA-N moclobemide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCCN1CCOCC1 YHXISWVBGDMDLQ-UHFFFAOYSA-N 0.000 description 2
- 229960004644 moclobemide Drugs 0.000 description 2
- 229960004938 molindone Drugs 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229960001158 nortriptyline Drugs 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N o-aminobenzenecarboxylic acid Natural products NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 229950009875 osanetant Drugs 0.000 description 2
- DZOJBGLFWINFBF-UMSFTDKQSA-N osanetant Chemical compound C([C@](C1)(CCCN2CCC(CC2)(N(C(C)=O)C)C=2C=CC=CC=2)C=2C=C(Cl)C(Cl)=CC=2)CCN1C(=O)C1=CC=CC=C1 DZOJBGLFWINFBF-UMSFTDKQSA-N 0.000 description 2
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 2
- 229960001816 oxcarbazepine Drugs 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 229960002296 paroxetine Drugs 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 2
- 229960000762 perphenazine Drugs 0.000 description 2
- 229960000964 phenelzine Drugs 0.000 description 2
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
- 229960003634 pimozide Drugs 0.000 description 2
- YVUQSNJEYSNKRX-UHFFFAOYSA-N pimozide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 YVUQSNJEYSNKRX-UHFFFAOYSA-N 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229960003111 prochlorperazine Drugs 0.000 description 2
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 229950010561 radafaxine Drugs 0.000 description 2
- RCOBKSKAZMVBHT-TVQRCGJNSA-N radafaxine Chemical compound C[C@@H]1NC(C)(C)CO[C@@]1(O)C1=CC=CC(Cl)=C1 RCOBKSKAZMVBHT-TVQRCGJNSA-N 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 2
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
- 239000000952 serotonin receptor agonist Substances 0.000 description 2
- GZKLJWGUPQBVJQ-UHFFFAOYSA-N sertindole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Cl)C=C2C(C2CCN(CCN3C(NCC3)=O)CC2)=C1 GZKLJWGUPQBVJQ-UHFFFAOYSA-N 0.000 description 2
- 229960002073 sertraline Drugs 0.000 description 2
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 2
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- OHLUOLTYTMEECV-UHFFFAOYSA-N tert-butyl 2-(3,5-difluoro-4-nitrophenyl)acetate Chemical compound CC(C)(C)OC(=O)CC1=CC(F)=C([N+]([O-])=O)C(F)=C1 OHLUOLTYTMEECV-UHFFFAOYSA-N 0.000 description 2
- URZMJJACYUGKRT-UHFFFAOYSA-N tert-butyl 4-(4,5-difluoro-6-methyl-2-oxo-3h-benzimidazol-1-yl)piperidine-1-carboxylate Chemical compound O=C1NC=2C(F)=C(F)C(C)=CC=2N1C1CCN(C(=O)OC(C)(C)C)CC1 URZMJJACYUGKRT-UHFFFAOYSA-N 0.000 description 2
- MUNHANZLYUCPKU-UHFFFAOYSA-N tert-butyl 4-(4-fluoro-6-methoxy-2-oxo-3h-benzimidazol-1-yl)piperidine-1-carboxylate Chemical compound C12=CC(OC)=CC(F)=C2NC(=O)N1C1CCN(C(=O)OC(C)(C)C)CC1 MUNHANZLYUCPKU-UHFFFAOYSA-N 0.000 description 2
- ZVHOWAPFATVRBO-UHFFFAOYSA-N tert-butyl 4-(4-fluoro-6-methyl-2-oxo-3h-benzimidazol-1-yl)piperidine-1-carboxylate Chemical compound C12=CC(C)=CC(F)=C2NC(=O)N1C1CCN(C(=O)OC(C)(C)C)CC1 ZVHOWAPFATVRBO-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229960002784 thioridazine Drugs 0.000 description 2
- 229960004394 topiramate Drugs 0.000 description 2
- 229960003991 trazodone Drugs 0.000 description 2
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 2
- 229960002324 trifluoperazine Drugs 0.000 description 2
- BXDAOUXDMHXPDI-UHFFFAOYSA-N trifluoperazine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 BXDAOUXDMHXPDI-UHFFFAOYSA-N 0.000 description 2
- 229960002431 trimipramine Drugs 0.000 description 2
- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 2
- 229940102566 valproate Drugs 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960004688 venlafaxine Drugs 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 2
- 229960000317 yohimbine Drugs 0.000 description 2
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 2
- 229960002791 zimeldine Drugs 0.000 description 2
- OYPPVKRFBIWMSX-SXGWCWSVSA-N zimeldine Chemical compound C=1C=CN=CC=1C(=C/CN(C)C)\C1=CC=C(Br)C=C1 OYPPVKRFBIWMSX-SXGWCWSVSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 description 1
- RTGAJOPJZJDWAX-XVGSOSPHSA-N (1e,4e)-1,5-bis(3,5-dimethoxyphenyl)penta-1,4-dien-3-one;palladium Chemical compound [Pd].COC1=CC(OC)=CC(\C=C\C(=O)\C=C\C=2C=C(OC)C=C(OC)C=2)=C1.COC1=CC(OC)=CC(\C=C\C(=O)\C=C\C=2C=C(OC)C=C(OC)C=2)=C1 RTGAJOPJZJDWAX-XVGSOSPHSA-N 0.000 description 1
- WYDUSKDSKCASEF-LJQANCHMSA-N (1s)-1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol Chemical compound C([C@](O)(C1CCCCC1)C=1C=CC=CC=1)CN1CCCC1 WYDUSKDSKCASEF-LJQANCHMSA-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
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- IFLZPECPTYCEBR-VIEYUMQNSA-N (z)-but-2-enedioic acid;(2r)-3-(2-methoxyphenothiazin-10-yl)-n,n,2-trimethylpropan-1-amine Chemical compound OC(=O)\C=C/C(O)=O.C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1 IFLZPECPTYCEBR-VIEYUMQNSA-N 0.000 description 1
- ARCACZWMYGILNI-UHFFFAOYSA-N 1,2,3-trifluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1F ARCACZWMYGILNI-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- ODMLBEQUDLHJMW-UHFFFAOYSA-N 1,2-difluoro-3-methyl-4-nitrobenzene Chemical compound CC1=C(F)C(F)=CC=C1[N+]([O-])=O ODMLBEQUDLHJMW-UHFFFAOYSA-N 0.000 description 1
- SSNCMIDZGFCTST-UHFFFAOYSA-N 1,3-difluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(F)C=CC=C1F SSNCMIDZGFCTST-UHFFFAOYSA-N 0.000 description 1
- DKMFBWQBDIGMHM-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-(4-methyl-1-piperidinyl)-1-butanone Chemical compound C1CC(C)CCN1CCCC(=O)C1=CC=C(F)C=C1 DKMFBWQBDIGMHM-UHFFFAOYSA-N 0.000 description 1
- MQHYXXIJLKFQGY-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-(4-methylpiperidin-1-ium-1-yl)butan-1-one;chloride Chemical compound [Cl-].C1CC(C)CC[NH+]1CCCC(=O)C1=CC=C(F)C=C1 MQHYXXIJLKFQGY-UHFFFAOYSA-N 0.000 description 1
- BFEWWTCNTUFKDX-UHFFFAOYSA-N 1-(oxan-4-yl)piperidin-4-amine Chemical compound C1CC(N)CCN1C1CCOCC1 BFEWWTCNTUFKDX-UHFFFAOYSA-N 0.000 description 1
- HYXJEJRVAXONMK-UHFFFAOYSA-N 1-(oxan-4-yl)piperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(N)CCN1C1CCOCC1 HYXJEJRVAXONMK-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- KZNVCGPCWKYPKD-UHFFFAOYSA-N 2-(2,3-difluoro-6-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=C(F)C(F)=CC=C1[N+]([O-])=O KZNVCGPCWKYPKD-UHFFFAOYSA-N 0.000 description 1
- XZXYQEHISUMZAT-UHFFFAOYSA-N 2-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol Chemical compound CC1=CC=C(O)C(CC=2C(=CC=C(C)C=2)O)=C1 XZXYQEHISUMZAT-UHFFFAOYSA-N 0.000 description 1
- BKYUJVHOWQZPQD-UHFFFAOYSA-N 2-[4-[3-(2-chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethanol;3-(5,6-dihydrodibenzo[2,1-b:2',1'-f][7]annulen-11-ylidene)-n,n-dimethylpropan-1-amine;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21.C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 BKYUJVHOWQZPQD-UHFFFAOYSA-N 0.000 description 1
- VRFJLUHAQPBTLE-UHFFFAOYSA-N 2-aminopiperidine-1-carboxylic acid Chemical compound NC1CCCCN1C(O)=O VRFJLUHAQPBTLE-UHFFFAOYSA-N 0.000 description 1
- HBHBARSMRVAINH-UHFFFAOYSA-N 2-bromo-4-chloro-6-fluoroaniline Chemical compound NC1=C(F)C=C(Cl)C=C1Br HBHBARSMRVAINH-UHFFFAOYSA-N 0.000 description 1
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 1
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
- UBWBVRSSIHWAQL-UHFFFAOYSA-N 2-tert-butylpiperidine-1-carboxylic acid Chemical compound CC(C)(C)C1CCCCN1C(O)=O UBWBVRSSIHWAQL-UHFFFAOYSA-N 0.000 description 1
- HJSSBIMVTMYKPD-UHFFFAOYSA-N 3,5-difluorophenol Chemical compound OC1=CC(F)=CC(F)=C1 HJSSBIMVTMYKPD-UHFFFAOYSA-N 0.000 description 1
- FEBOTPHFXYHVPL-UHFFFAOYSA-N 3-[1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidinyl]-1H-benzimidazol-2-one Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 FEBOTPHFXYHVPL-UHFFFAOYSA-N 0.000 description 1
- BIAVGWDGIJKWRM-FQEVSTJZSA-N 3-hydroxy-2-phenyl-n-[(1s)-1-phenylpropyl]quinoline-4-carboxamide Chemical compound N([C@@H](CC)C=1C=CC=CC=1)C(=O)C(C1=CC=CC=C1N=1)=C(O)C=1C1=CC=CC=C1 BIAVGWDGIJKWRM-FQEVSTJZSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QWEIQKPHTLTIBG-UHFFFAOYSA-N 4-(4,5-difluoro-6-methyl-2-oxo-3H-benzimidazol-1-yl)piperidine-1-carboxylic acid Chemical compound Cc1cc2n(C3CCN(CC3)C(O)=O)c(=O)[nH]c2c(F)c1F QWEIQKPHTLTIBG-UHFFFAOYSA-N 0.000 description 1
- UYBYDTOXYQFZAH-UHFFFAOYSA-N 4-[(2-bromo-6-fluoro-4-methylphenyl)carbamoylamino]piperidine-1-carboxylic acid Chemical compound Cc1cc(F)c(NC(=O)NC2CCN(CC2)C(O)=O)c(Br)c1 UYBYDTOXYQFZAH-UHFFFAOYSA-N 0.000 description 1
- BFQSQUAVMNHOEF-UHFFFAOYSA-N 4-bromo-2,6-difluoroaniline Chemical compound NC1=C(F)C=C(Br)C=C1F BFQSQUAVMNHOEF-UHFFFAOYSA-N 0.000 description 1
- 229940127239 5 Hydroxytryptamine receptor antagonist Drugs 0.000 description 1
- 229940124801 5-HT6 antagonist Drugs 0.000 description 1
- DSUMPQPZYPXTND-UHFFFAOYSA-N 5-chloro-7-fluoro-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound O=C1NC=2C(F)=CC(Cl)=CC=2N1C(CC1)CCN1C1CCOCC1 DSUMPQPZYPXTND-UHFFFAOYSA-N 0.000 description 1
- KHAFQDDIUWMYAT-UHFFFAOYSA-N 5-chloro-7-fluoro-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound O=C1NC=2C(F)=CC(Cl)=CC=2N1C1CCNCC1 KHAFQDDIUWMYAT-UHFFFAOYSA-N 0.000 description 1
- IRGBOMFFIWQHOO-UHFFFAOYSA-N 5-cyclopropyl-1,3-difluoro-2-nitrobenzene Chemical compound C1=C(F)C([N+](=O)[O-])=C(F)C=C1C1CC1 IRGBOMFFIWQHOO-UHFFFAOYSA-N 0.000 description 1
- YFCGENMQCIXTNC-UHFFFAOYSA-N 5-cyclopropyl-7-fluoro-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound O=C1NC=2C(F)=CC(C3CC3)=CC=2N1C(CC1)CCN1C1CCOCC1 YFCGENMQCIXTNC-UHFFFAOYSA-N 0.000 description 1
- NCIMFRCDQMTAFP-UHFFFAOYSA-N 7-fluoro-5-methoxy-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound C12=CC(OC)=CC(F)=C2NC(=O)N1C(CC1)CCN1C1CCOCC1 NCIMFRCDQMTAFP-UHFFFAOYSA-N 0.000 description 1
- DQSNUMFLMIZQFH-UHFFFAOYSA-N 7-fluoro-5-methyl-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C12=CC(C)=CC(F)=C2NC(=O)N1C(CC1)CCN1C1CCOCC1 DQSNUMFLMIZQFH-UHFFFAOYSA-N 0.000 description 1
- KJCKZWGVZMJOCI-UHFFFAOYSA-N 7-fluoro-5-methyl-3-[1-(oxan-4-yl)piperidin-4-yl]-1h-benzimidazol-2-one;methanesulfonic acid Chemical compound CS(O)(=O)=O.C12=CC(C)=CC(F)=C2NC(=O)N1C(CC1)CCN1C1CCOCC1 KJCKZWGVZMJOCI-UHFFFAOYSA-N 0.000 description 1
- YCJKQIOJATYMNT-UHFFFAOYSA-N 7-fluoro-5-methyl-3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound C12=CC(C)=CC(F)=C2NC(=O)N1C1CCNCC1 YCJKQIOJATYMNT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JSXBVMKACNEMKY-UHFFFAOYSA-N 8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine;hydron;chloride Chemical compound Cl.C1CN(C)CCN1C1=NC2=CC=CC=C2OC2=CC=C(Cl)C=C12 JSXBVMKACNEMKY-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 206010002859 Anxiety disorder due to a general medical condition Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 208000021500 Breathing-related sleep disease Diseases 0.000 description 1
- 208000021465 Brief psychotic disease Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 102000017923 CHRM5 Human genes 0.000 description 1
- 101150064612 CHRM5 gene Proteins 0.000 description 1
- 101150071146 COX2 gene Proteins 0.000 description 1
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 1
- 206010008027 Cerebellar atrophy Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000027691 Conduct disease Diseases 0.000 description 1
- 241001480079 Corymbia calophylla Species 0.000 description 1
- 208000024254 Delusional disease Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 208000004483 Dyspareunia Diseases 0.000 description 1
- 208000026097 Factitious disease Diseases 0.000 description 1
- 208000021663 Female sexual arousal disease Diseases 0.000 description 1
- MBHNWCYEGXQEIT-UHFFFAOYSA-N Fluphenazine hydrochloride Chemical compound Cl.Cl.C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 MBHNWCYEGXQEIT-UHFFFAOYSA-N 0.000 description 1
- 208000010235 Food Addiction Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 206010017389 Frotteurism Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000016619 Histrionic personality disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000016588 Idiopathic hypersomnia Diseases 0.000 description 1
- 208000001271 Inhalant Abuse Diseases 0.000 description 1
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-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
- 208000020358 Learning disease Diseases 0.000 description 1
- 206010024419 Libido decreased Diseases 0.000 description 1
- 235000006552 Liquidambar styraciflua Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000030431 Male orgasmic disease Diseases 0.000 description 1
- 206010026864 Masochism Diseases 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 description 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GQWNECFJGBQMBO-UHFFFAOYSA-N Molindone hydrochloride Chemical compound Cl.O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 GQWNECFJGBQMBO-UHFFFAOYSA-N 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000027120 Narcissistic personality disease Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 208000000224 Night Terrors Diseases 0.000 description 1
- 206010029412 Nightmare Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 229940087098 Oxidase inhibitor Drugs 0.000 description 1
- 101150000187 PTGS2 gene Proteins 0.000 description 1
- 206010033664 Panic attack Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 206010034018 Parosmia Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000032769 Pedophilia Diseases 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- 206010034912 Phobia Diseases 0.000 description 1
- 208000007222 Physiological Sexual Dysfunction Diseases 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000034592 Polysubstance dependence Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 206010052276 Pseudodementia Diseases 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 206010039367 Sadism Diseases 0.000 description 1
- 208000024791 Schizotypal Personality disease Diseases 0.000 description 1
- 208000029901 Sexual arousal disease Diseases 0.000 description 1
- 208000029899 Sexual aversion 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
- 206010063910 Sleep disorder due to a general medical condition Diseases 0.000 description 1
- 206010041010 Sleep terror Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 102100023145 Sodium- and chloride-dependent glycine transporter 1 Human genes 0.000 description 1
- 101710083171 Sodium- and chloride-dependent glycine transporter 1 Proteins 0.000 description 1
- 206010041347 Somnambulism Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 231100000643 Substance intoxication Toxicity 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000005386 Transient Global Amnesia Diseases 0.000 description 1
- 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- NUKVZKPNSKJGBK-SPIKMXEPSA-N acetophenazine dimaleate Chemical compound [H+].[H+].[H+].[H+].[O-]C(=O)\C=C/C([O-])=O.[O-]C(=O)\C=C/C([O-])=O.C12=CC(C(=O)C)=CC=C2SC2=CC=CC=C2N1CCCN1CCN(CCO)CC1 NUKVZKPNSKJGBK-SPIKMXEPSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000026345 acute stress disease Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000007000 age related cognitive decline Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 208000029650 alcohol withdrawal Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000008055 alkyl aryl sulfonates Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940107816 ammonium iodide Drugs 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 201000002472 amphetamine abuse Diseases 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940070021 anabolic steroids Drugs 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 208000024823 antisocial personality disease Diseases 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000022804 avoidant personality disease Diseases 0.000 description 1
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 229960002507 benperidol Drugs 0.000 description 1
- GIJXKZJWITVLHI-PMOLBWCYSA-N benzatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(C=1C=CC=CC=1)C1=CC=CC=C1 GIJXKZJWITVLHI-PMOLBWCYSA-N 0.000 description 1
- 229960001081 benzatropine Drugs 0.000 description 1
- MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical compound C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 description 1
- 150000008316 benzisoxazoles Chemical class 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 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 1
- 230000004071 biological effect Effects 0.000 description 1
- YSXKPIUOCJLQIE-UHFFFAOYSA-N biperiden Chemical compound C1C(C=C2)CC2C1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 YSXKPIUOCJLQIE-UHFFFAOYSA-N 0.000 description 1
- 229960003003 biperiden Drugs 0.000 description 1
- 208000030963 borderline personality disease Diseases 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical class CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 230000028956 calcium-mediated signaling Effects 0.000 description 1
- 201000009322 cannabis abuse Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- WUTYZMFRCNBCHQ-PSASIEDQSA-N cevimeline Chemical compound C1S[C@H](C)O[C@]21C(CC1)CCN1C2 WUTYZMFRCNBCHQ-PSASIEDQSA-N 0.000 description 1
- 229960001314 cevimeline Drugs 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- NJMYODHXAKYRHW-DVZOWYKESA-N cis-flupenthixol Chemical compound C1CN(CCO)CCN1CC\C=C\1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C2/1 NJMYODHXAKYRHW-DVZOWYKESA-N 0.000 description 1
- 229940068796 clozaril Drugs 0.000 description 1
- 201000001272 cocaine abuse Diseases 0.000 description 1
- 201000006145 cocaine dependence Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000011340 continuous therapy Methods 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 208000030964 dependent personality disease Diseases 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- 150000008533 dibenzodiazepines Chemical class 0.000 description 1
- 150000008509 dibenzothiazepines Chemical class 0.000 description 1
- SEESNIHRBOITKW-UHFFFAOYSA-N diethyl 2-(2,3-difluoro-4-nitrophenyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=CC=C([N+]([O-])=O)C(F)=C1F SEESNIHRBOITKW-UHFFFAOYSA-N 0.000 description 1
- MSOQCNAFADYWFJ-UHFFFAOYSA-N diethyl 2-(2,3-difluoro-6-nitrophenyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=C(F)C(F)=CC=C1[N+]([O-])=O MSOQCNAFADYWFJ-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000142 dyskinetic effect Effects 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical compound CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- 229940103472 etrafon Drugs 0.000 description 1
- 208000003481 exhibitionism Diseases 0.000 description 1
- 210000003499 exocrine gland Anatomy 0.000 description 1
- 208000014840 female orgasmic disease Diseases 0.000 description 1
- 206010016531 fetishism Diseases 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 229960002419 flupentixol Drugs 0.000 description 1
- VIQCGTZFEYDQMR-UHFFFAOYSA-N fluphenazine decanoate Chemical compound C1CN(CCOC(=O)CCCCCCCCC)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 VIQCGTZFEYDQMR-UHFFFAOYSA-N 0.000 description 1
- 229960001374 fluphenazine decanoate Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 229940003380 geodon Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides 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
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000003400 hallucinatory effect Effects 0.000 description 1
- 201000002270 hallucinogen abuse Diseases 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 208000017020 hypoactive sexual desire disease Diseases 0.000 description 1
- 229960003162 iloperidone Drugs 0.000 description 1
- XMXHEBAFVSFQEX-UHFFFAOYSA-N iloperidone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 150000008624 imidazolidinones Chemical class 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 201000004197 inhibited female orgasm Diseases 0.000 description 1
- 201000000068 inhibited male orgasm Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229940047507 ioxapine Drugs 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000008449 language Effects 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 229960004990 loxapine hydrochloride Drugs 0.000 description 1
- 229960000589 loxapine succinate Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 208000015421 male orgasm disease Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960001861 melperone Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003695 memory enhancer Substances 0.000 description 1
- SLVMESMUVMCQIY-UHFFFAOYSA-N mesoridazine Chemical compound CN1CCCCC1CCN1C2=CC(S(C)=O)=CC=C2SC2=CC=CC=C21 SLVMESMUVMCQIY-UHFFFAOYSA-N 0.000 description 1
- 229960000300 mesoridazine Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- VRQVVMDWGGWHTJ-CQSZACIVSA-N methotrimeprazine Chemical compound C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1 VRQVVMDWGGWHTJ-CQSZACIVSA-N 0.000 description 1
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229960004684 molindone hydrochloride Drugs 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 239000000472 muscarinic agonist Substances 0.000 description 1
- SBPSKOUVCKNGSB-UHFFFAOYSA-N n-(3-fluoro-5-methyl-2-nitrophenyl)-1-(oxan-4-yl)piperidin-4-amine Chemical compound CC1=CC(F)=C([N+]([O-])=O)C(NC2CCN(CC2)C2CCOCC2)=C1 SBPSKOUVCKNGSB-UHFFFAOYSA-N 0.000 description 1
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229960001800 nefazodone Drugs 0.000 description 1
- VRBKIVRKKCLPHA-UHFFFAOYSA-N nefazodone Chemical compound O=C1N(CCOC=2C=CC=CC=2)C(CC)=NN1CCCN(CC1)CCN1C1=CC=CC(Cl)=C1 VRBKIVRKKCLPHA-UHFFFAOYSA-N 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229940127221 norepinephrine reuptake inhibitor Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 208000030459 obsessive-compulsive personality disease Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960005343 ondansetron Drugs 0.000 description 1
- 201000000988 opioid abuse Diseases 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 208000024817 paranoid personality disease Diseases 0.000 description 1
- 208000002851 paranoid schizophrenia Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960002195 perazine Drugs 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 208000007100 phencyclidine abuse Diseases 0.000 description 1
- 150000002990 phenothiazines Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- LYYSMBDYBWUXFG-UHFFFAOYSA-N piperazine;triazine Chemical compound C1CNCCN1.C1=CN=NN=C1 LYYSMBDYBWUXFG-UHFFFAOYSA-N 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 229940068151 pipothiazine Drugs 0.000 description 1
- JOMHSQGEWSNUKU-UHFFFAOYSA-N pipotiazine Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2N1CCCN1CCC(CCO)CC1 JOMHSQGEWSNUKU-UHFFFAOYSA-N 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical compound O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000002442 prefrontal cortex Anatomy 0.000 description 1
- 206010036596 premature ejaculation Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960005253 procyclidine Drugs 0.000 description 1
- HKJYVRJHDIPMQB-UHFFFAOYSA-N propan-1-olate;titanium(4+) Chemical compound CCCO[Ti](OCCC)(OCCC)OCCC HKJYVRJHDIPMQB-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZTHJULTYCAQOIJ-WXXKFALUSA-N quetiapine fumarate Chemical compound [H+].[H+].[O-]C(=O)\C=C\C([O-])=O.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 ZTHJULTYCAQOIJ-WXXKFALUSA-N 0.000 description 1
- 229960005197 quetiapine fumarate Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 229940106887 risperdal Drugs 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000005488 sandblasting Methods 0.000 description 1
- 208000022610 schizoaffective disease Diseases 0.000 description 1
- 229940035004 seroquel Drugs 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 229960000652 sertindole Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 201000005814 sexual masochism Diseases 0.000 description 1
- 208000027599 sexual masochism disease Diseases 0.000 description 1
- 201000005841 sexual sadism Diseases 0.000 description 1
- 208000027596 sexual sadism disease Diseases 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical class [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- OXRILMCCGJTGOH-UHFFFAOYSA-M sodium;ethyl sulfite Chemical compound [Na+].CCOS([O-])=O OXRILMCCGJTGOH-UHFFFAOYSA-M 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 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
- 229960001685 tacrine Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 229950011332 talnetant Drugs 0.000 description 1
- 210000001587 telencephalon Anatomy 0.000 description 1
- KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 1
- VPWMYWZWIPSPIZ-UHFFFAOYSA-N tert-butyl 4-(2-amino-3-fluoro-5-methoxyanilino)piperidine-1-carboxylate Chemical compound COC1=CC(F)=C(N)C(NC2CCN(CC2)C(=O)OC(C)(C)C)=C1 VPWMYWZWIPSPIZ-UHFFFAOYSA-N 0.000 description 1
- YZBQMSPKOMUXBY-UHFFFAOYSA-N tert-butyl 4-(2-amino-5-cyclopropyl-3-fluoroanilino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=CC(C2CC2)=CC(F)=C1N YZBQMSPKOMUXBY-UHFFFAOYSA-N 0.000 description 1
- XGYUUVSXTLOGJO-UHFFFAOYSA-N tert-butyl 4-(5-cyclopropyl-3-fluoro-2-nitroanilino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=CC(C2CC2)=CC(F)=C1[N+]([O-])=O XGYUUVSXTLOGJO-UHFFFAOYSA-N 0.000 description 1
- JHXBVBXTYSGILK-UHFFFAOYSA-N tert-butyl 4-[(2-fluoro-6-iodo-4-methylphenyl)carbamoylamino]piperidine-1-carboxylate Chemical compound IC1=CC(C)=CC(F)=C1NC(=O)NC1CCN(C(=O)OC(C)(C)C)CC1 JHXBVBXTYSGILK-UHFFFAOYSA-N 0.000 description 1
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229960000882 thiothixene hydrochloride Drugs 0.000 description 1
- 150000005075 thioxanthenes Chemical class 0.000 description 1
- 208000016686 tic disease Diseases 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 201000005142 transvestism Diseases 0.000 description 1
- 229960003741 tranylcypromine Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 206010046947 vaginismus Diseases 0.000 description 1
- 208000008918 voyeurism Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000012991 xanthate Substances 0.000 description 1
- 229940039925 zyprexa Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0519950.0 | 2005-09-30 | ||
| GBGB0519950.0A GB0519950D0 (en) | 2005-09-30 | 2005-09-30 | Compounds |
| GB0602040A GB0602040D0 (en) | 2006-02-01 | 2006-02-01 | Compounds |
| GB0602040.8 | 2006-02-01 | ||
| PCT/GB2006/003590 WO2007036715A2 (en) | 2005-09-30 | 2006-09-27 | Compounds which have activity at m1 receptor and their uses in medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0616609A2 true BRPI0616609A2 (pt) | 2011-06-28 |
Family
ID=37598231
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0616609-1A BRPI0616609A2 (pt) | 2005-09-30 | 2006-09-27 | compostos que têm atividade no receptor m1, composição farmacêutica contendo tais compostos, processo para preparação dos mesmos, bem como seus usos em medicina |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US8283364B2 (enExample) |
| EP (1) | EP1943230B1 (enExample) |
| JP (1) | JP5209480B2 (enExample) |
| KR (2) | KR101374458B1 (enExample) |
| CN (1) | CN101321736B (enExample) |
| AR (1) | AR056103A1 (enExample) |
| AT (1) | ATE492537T1 (enExample) |
| AU (1) | AU2006296369B2 (enExample) |
| BR (1) | BRPI0616609A2 (enExample) |
| CA (1) | CA2624504C (enExample) |
| CR (1) | CR9904A (enExample) |
| DE (1) | DE602006019119D1 (enExample) |
| EA (1) | EA016286B1 (enExample) |
| IL (1) | IL190219A (enExample) |
| JO (1) | JO2634B1 (enExample) |
| MA (1) | MA29849B1 (enExample) |
| MY (1) | MY148504A (enExample) |
| NO (1) | NO20081945L (enExample) |
| NZ (1) | NZ566508A (enExample) |
| PE (1) | PE20070490A1 (enExample) |
| TW (1) | TWI389905B (enExample) |
| UA (1) | UA101299C2 (enExample) |
| WO (1) | WO2007036715A2 (enExample) |
| ZA (1) | ZA200802167B (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007036715A2 (en) | 2005-09-30 | 2007-04-05 | Glaxo Group Limited | Compounds which have activity at m1 receptor and their uses in medicine |
| US8288413B2 (en) * | 2005-09-30 | 2012-10-16 | Glaxo Group Limited | Benzimidazolones which have activity at M1 receptor |
| WO2007036718A2 (en) * | 2005-09-30 | 2007-04-05 | Glaxo Group Limited | Compounds which have activity at m1 receptor and their uses in medicine |
| US7766829B2 (en) * | 2005-11-04 | 2010-08-03 | Abbott Diabetes Care Inc. | Method and system for providing basal profile modification in analyte monitoring and management systems |
| GB0605785D0 (en) * | 2006-03-22 | 2006-05-03 | Glaxo Group Ltd | Compounds |
| GB0706170D0 (en) * | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706165D0 (en) * | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706174D0 (en) * | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706164D0 (en) * | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0718415D0 (en) | 2007-09-20 | 2007-10-31 | Glaxo Group Ltd | Compounds |
| WO2009124882A1 (en) * | 2008-04-09 | 2009-10-15 | H. Lundbeck A/S | Novel piperidinyl-1,3-dihydro-benzoimidazol-2-ones as m1 agonists |
| GB0817982D0 (en) | 2008-10-01 | 2008-11-05 | Glaxo Group Ltd | Compounds |
| US20170333407A1 (en) * | 2014-11-03 | 2017-11-23 | William Beaumont Hospital | Method for treating underactive bladder syndrome |
| US10604484B2 (en) * | 2015-04-29 | 2020-03-31 | Janssen Pharmaceutica Nv | Indolone compounds and their use as AMPA receptor modulators |
| ES2865330T3 (es) | 2015-04-29 | 2021-10-15 | Janssen Pharmaceutica Nv | Azabenzimidazoles y su uso como moduladores del receptor AMPA |
| WO2017044693A1 (en) | 2015-09-11 | 2017-03-16 | Chase Pharmaceuticals Corporation | Muscarinic combination and its use for combating hypocholinergic disorders of the central nervous system |
| CN107673994A (zh) * | 2017-04-27 | 2018-02-09 | 联化科技股份有限公司 | 一种芳基甲烷类化合物的制备方法 |
| CN107739342B (zh) * | 2017-11-29 | 2020-01-10 | 华南理工大学 | 一种一步合成5-二芳氨基苯并咪唑酮衍生物的方法 |
| CN117049938B (zh) * | 2023-06-20 | 2024-06-14 | 山东轩德医药科技有限公司 | 一种6-溴-2,3-二氟甲苯的制备方法 |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3161645A (en) * | 1962-12-18 | 1964-12-15 | Res Lab Dr C Janssen N V | 1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds |
| US3989707A (en) * | 1974-06-21 | 1976-11-02 | Janssen Pharmaceutica N.V. | Benzimidazolinone derivatives |
| US4292321A (en) | 1979-05-24 | 1981-09-29 | Warner-Lambert Company | 1,3,8-Triazaspirodecane-4-ones, pharmaceutical compositions thereof and method of use thereof |
| DE3124366A1 (de) | 1981-06-20 | 1982-12-30 | Hoechst Ag, 6000 Frankfurt | N-oxacyclyl-alkylpiperidin-derivate, verfahren zu ihrer herstellung, sie enthaltende pharmazeutische praeparate und deren verwendung |
| DE4040300A1 (de) | 1990-12-17 | 1992-07-02 | Leifeld Gmbh & Co | Drueckmaschine mit wenigstens einem rollenhalter |
| JP3916093B2 (ja) * | 1993-09-17 | 2007-05-16 | 杏林製薬株式会社 | 光学活性イミダゾリジノン誘導体とその製造方法 |
| US5574044A (en) | 1994-10-27 | 1996-11-12 | Merck & Co., Inc. | Muscarine antagonists |
| US5691323A (en) * | 1995-05-12 | 1997-11-25 | Merck & Co., Inc. | Muscarine antagonists |
| EP0786997A4 (en) * | 1994-10-27 | 1998-03-11 | Merck & Co Inc | MUSCARINE ANTAGONISTS |
| AU7478396A (en) | 1995-10-31 | 1997-05-22 | Merck & Co., Inc. | Muscarine agonists |
| US5718912A (en) | 1996-10-28 | 1998-02-17 | Merck & Co., Inc. | Muscarine agonists |
| US5977134A (en) | 1996-12-05 | 1999-11-02 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US6465484B1 (en) | 1997-09-26 | 2002-10-15 | Merck & Co., Inc. | Angiogenesis inhibitors |
| US6162804A (en) | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| AU2307999A (en) * | 1997-12-23 | 1999-07-12 | Alcon Laboratories, Inc. | Muscarinic agents and use thereof to treat glaucoma, myopia and various other conditions |
| DE60013464T2 (de) | 1999-10-13 | 2005-09-15 | Banyu Pharmaceutical Co., Ltd. | Substituierte imidazolin-derivate |
| SE9904652D0 (sv) | 1999-12-17 | 1999-12-17 | Astra Pharma Prod | Novel Compounds |
| EP1263754A1 (en) | 2000-02-01 | 2002-12-11 | Millennium Pharmaceuticals, Inc. | INDALONE AND BENZIMIDAZOLONE INHIBITORS OF FACTOR Xa |
| EP1975164B1 (en) | 2001-04-18 | 2010-01-27 | Euro-Celtique S.A. | Octahydrobenzimidazolone compounds as analgetics |
| US7164024B2 (en) * | 2001-04-20 | 2007-01-16 | Banyu Pharmaceutical Co., Ltd. | Benzimidazolone derivatives |
| KR100809569B1 (ko) | 2001-10-02 | 2008-03-04 | 아카디아 파마슈티칼스 인코포레이티드 | 무스카린 제제로서 벤즈이미다졸리디논 유도체 |
| WO2004089942A2 (en) * | 2001-10-02 | 2004-10-21 | Acadia Pharmaceuticals Inc. | Benzimidazolidinone derivatives as muscarinic agents |
| US6951849B2 (en) | 2001-10-02 | 2005-10-04 | Acadia Pharmaceuticals Inc. | Benzimidazolidinone derivatives as muscarinic agents |
| US7244744B2 (en) | 2001-11-01 | 2007-07-17 | Icagen, Inc. | Piperidines |
| US7566728B2 (en) | 2002-03-29 | 2009-07-28 | Mitsubishi Tanabe Pharma Corporation | Remedy for sleep disturbance |
| JP2005532361A (ja) | 2002-06-17 | 2005-10-27 | メルク エンド カムパニー インコーポレーテッド | 高眼圧症の治療用の眼科用組成物 |
| CN1744899A (zh) | 2002-12-13 | 2006-03-08 | 史密丝克莱恩比彻姆公司 | 作为ccr5拮抗剂的哌啶衍生物 |
| JP2005102133A (ja) | 2003-04-28 | 2005-04-14 | Ricoh Co Ltd | 画像形成装置及び宛先情報参照方法 |
| BRPI0412809A (pt) | 2003-07-23 | 2006-09-26 | Wyeth Corp | compostos de sulfonildihidrobenzimidazolona como ligantes a 5-hidróxitriptamina-6 |
| OA13248A (en) | 2003-09-03 | 2007-01-31 | Pfizer | Benzimidazolone coumpounds having 5-HT4 receptor agonistic activity. |
| ES2318556T3 (es) | 2004-11-02 | 2009-05-01 | Pfizer, Inc. | Derivados de sulfonil bencimidazol. |
| US7300947B2 (en) | 2005-07-13 | 2007-11-27 | Banyu Pharmaceutical Co., Ltd. | N-dihydroxyalkyl-substituted 2-oxo-imidazole derivatives |
| WO2007036715A2 (en) | 2005-09-30 | 2007-04-05 | Glaxo Group Limited | Compounds which have activity at m1 receptor and their uses in medicine |
| WO2007036718A2 (en) | 2005-09-30 | 2007-04-05 | Glaxo Group Limited | Compounds which have activity at m1 receptor and their uses in medicine |
| US8288413B2 (en) | 2005-09-30 | 2012-10-16 | Glaxo Group Limited | Benzimidazolones which have activity at M1 receptor |
| CN101511222B (zh) | 2006-09-08 | 2012-11-14 | 吉莱特公司 | 具有多种刷毛状态的牙刷 |
| GB0706187D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706168D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706170D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706190D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706188D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706165D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706167D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706173D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706189D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706174D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
| GB0706164D0 (en) | 2007-03-29 | 2007-05-09 | Glaxo Group Ltd | Compounds |
-
2006
- 2006-09-27 WO PCT/GB2006/003590 patent/WO2007036715A2/en not_active Ceased
- 2006-09-27 MY MYPI20080901A patent/MY148504A/en unknown
- 2006-09-27 BR BRPI0616609-1A patent/BRPI0616609A2/pt not_active IP Right Cessation
- 2006-09-27 AU AU2006296369A patent/AU2006296369B2/en not_active Ceased
- 2006-09-27 DE DE602006019119T patent/DE602006019119D1/de active Active
- 2006-09-27 EA EA200801001A patent/EA016286B1/ru not_active IP Right Cessation
- 2006-09-27 CA CA2624504A patent/CA2624504C/en not_active Expired - Fee Related
- 2006-09-27 KR KR1020087007797A patent/KR101374458B1/ko not_active Expired - Fee Related
- 2006-09-27 CN CN2006800451692A patent/CN101321736B/zh not_active Expired - Fee Related
- 2006-09-27 EP EP06794584A patent/EP1943230B1/en active Active
- 2006-09-27 NZ NZ566508A patent/NZ566508A/en not_active IP Right Cessation
- 2006-09-27 KR KR1020137020049A patent/KR20130091791A/ko not_active Ceased
- 2006-09-27 UA UAA200803937A patent/UA101299C2/uk unknown
- 2006-09-27 US US12/088,465 patent/US8283364B2/en not_active Expired - Fee Related
- 2006-09-27 AT AT06794584T patent/ATE492537T1/de not_active IP Right Cessation
- 2006-09-27 JP JP2008532866A patent/JP5209480B2/ja not_active Expired - Fee Related
- 2006-09-28 JO JO2006342A patent/JO2634B1/en active
- 2006-09-28 AR ARP060104268A patent/AR056103A1/es unknown
- 2006-09-28 TW TW095135887A patent/TWI389905B/zh not_active IP Right Cessation
- 2006-09-28 PE PE2006001183A patent/PE20070490A1/es not_active Application Discontinuation
-
2007
- 2007-09-10 US US11/852,455 patent/US8481566B2/en not_active Expired - Fee Related
-
2008
- 2008-03-17 IL IL190219A patent/IL190219A/en not_active IP Right Cessation
- 2008-04-04 MA MA30812A patent/MA29849B1/fr unknown
- 2008-04-18 CR CR9904A patent/CR9904A/es unknown
- 2008-04-23 NO NO20081945A patent/NO20081945L/no not_active Application Discontinuation
-
2009
- 2009-03-07 ZA ZA200802167A patent/ZA200802167B/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8481566B2 (en) | Compounds which have activity at M1 receptor and their uses in medicine | |
| BRPI0708999A2 (pt) | benzimidazóis que têm atividade em receptor m1 e seus usos em medicina | |
| ES2391107T3 (es) | Compuestos que tienen actividad en el receptor M1 y sus usos en medicina | |
| JP5256189B2 (ja) | M1受容体で活性を有するベンズイミダゾールおよび医薬におけるその使用 | |
| WO2008119720A1 (en) | 1-(1-cyclobutyl-4-piperidinyl)-1,3-dihydro-2h-benzimidazol-2-one derivatives which have activity on the m1 receptor and their use in medicine | |
| JP5256188B2 (ja) | M1受容体で活性を有するベンズイミダゾールおよび医薬におけるその使用 | |
| JP5209479B2 (ja) | M1受容体にて活性を有するベンゾイミダゾロン類 | |
| WO2008119718A1 (en) | Compounds which have activity at m1 receptor and their uses in medicine | |
| WO2008119717A1 (en) | Compounds which have activity at m1 receptor and their uses in medicine | |
| WO2008119721A1 (en) | Compounds which have activity at m1 receptor and their uses in medicine | |
| WO2008119715A1 (en) | 1- (1-cyclohexyl-4-piperidinyl) -1, 3-dihydro-2h-benzimidazol-2-one derivatives which have activity on the m1 receptor and their use in medicine | |
| WO2008119711A1 (en) | Substituted benzimidazolone compounds which have activity at m1 receptor and their uses in medicine | |
| WO2008119719A1 (en) | 1- (1-cyclohexyl-4-piperidinyl) -1, 3-dihydro-2h-benzimidazol-2-one derivatives which have activity on the m1 receptor and their use in medicine | |
| ES2357970T3 (es) | Compuestos que tienen actividad en el receptor m1 y sus usos en medicina. | |
| EP2344483B1 (en) | Compounds which have activity at m1 receptor and their uses in medicine | |
| US8344000B2 (en) | Compounds which have activity at M1 receptor and their uses in medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] | ||
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 12A ANUIDADE. |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2481 DE 24-07-2018 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |