AU2012356885B2 - Quinoline derivatives as PDE10A enzyme inhibitors - Google Patents
Quinoline derivatives as PDE10A enzyme inhibitors Download PDFInfo
- Publication number
- AU2012356885B2 AU2012356885B2 AU2012356885A AU2012356885A AU2012356885B2 AU 2012356885 B2 AU2012356885 B2 AU 2012356885B2 AU 2012356885 A AU2012356885 A AU 2012356885A AU 2012356885 A AU2012356885 A AU 2012356885A AU 2012356885 B2 AU2012356885 B2 AU 2012356885B2
- Authority
- AU
- Australia
- Prior art keywords
- triazolo
- dimethyl
- pyrazin
- quinoline
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 239000002532 enzyme inhibitor Substances 0.000 title abstract description 8
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title abstract description 4
- 101001072037 Homo sapiens cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Proteins 0.000 title abstract description 3
- 102100036377 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Human genes 0.000 title abstract 2
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 86
- 238000000034 method Methods 0.000 claims abstract description 80
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 17
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 13
- 230000000626 neurodegenerative effect Effects 0.000 claims abstract description 8
- -1 triazolo[1,5-a]pyrazin-2-yl Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 15
- 239000003085 diluting agent Substances 0.000 claims description 13
- 208000028017 Psychotic disease Diseases 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 8
- 201000000980 schizophrenia Diseases 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000022610 schizoaffective disease Diseases 0.000 claims description 5
- AOLYXBUFENUNSR-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-6-fluoroquinoline Chemical compound C1=C(F)C=CC2=NC(CCC3=NN4C(C)=CN=C(C4=N3)C)=CC=C21 AOLYXBUFENUNSR-UHFFFAOYSA-N 0.000 claims description 3
- VOASYVQFJORMOW-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-7-fluoroquinoline Chemical compound Cc1ncc(C)n2nc(CCc3ccc4ccc(F)cc4n3)nc12 VOASYVQFJORMOW-UHFFFAOYSA-N 0.000 claims description 3
- 208000020186 Schizophreniform disease Diseases 0.000 claims description 3
- 206010007776 catatonia Diseases 0.000 claims description 3
- 230000003001 depressive effect Effects 0.000 claims description 3
- ACHLOAIBOBHNHG-UHFFFAOYSA-N 6-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-[1,3]dioxolo[4,5-g]quinolin-2-one Chemical compound CC1=CN=C(C=2N1N=C(N=2)CCC1=NC=2C=C3C(=CC=2C=C1)OC(O3)=O)C ACHLOAIBOBHNHG-UHFFFAOYSA-N 0.000 claims description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims 2
- LPLFYRHICYZTLZ-UHFFFAOYSA-N [1,4]dioxino[2,3-g]quinolin-2-one Chemical compound C1=CC=C2C=C(OC(=O)CO3)C3=CC2=N1 LPLFYRHICYZTLZ-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 22
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 55
- 210000002569 neuron Anatomy 0.000 description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 12
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 11
- 101150049660 DRD2 gene Proteins 0.000 description 10
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 10
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 206010013663 drug dependence Diseases 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 7
- 230000008485 antagonism Effects 0.000 description 7
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 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 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 229940123773 Phosphodiesterase 10A inhibitor Drugs 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 229910052801 chlorine Chemical group 0.000 description 5
- 239000000460 chlorine Chemical group 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 230000004899 motility Effects 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 208000011117 substance-related disease Diseases 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 229920002554 vinyl polymer Polymers 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 229940025084 amphetamine Drugs 0.000 description 4
- 230000000561 anti-psychotic effect Effects 0.000 description 4
- 239000000164 antipsychotic agent Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 239000003176 neuroleptic agent Substances 0.000 description 4
- 230000000926 neurological effect Effects 0.000 description 4
- 210000001010 olfactory tubercle Anatomy 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 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 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
- WJYVVSXHXZHVBM-SOFGYWHQSA-N 2-[(e)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethenyl]quinoline-6-carbonitrile Chemical compound C1=C(C#N)C=CC2=NC(/C=C/C=3N=C4C(C)=NC=C(N4N=3)C)=CC=C21 WJYVVSXHXZHVBM-SOFGYWHQSA-N 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 229960003920 cocaine Drugs 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 229960003878 haloperidol Drugs 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 208000013403 hyperactivity Diseases 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 229960001789 papaverine Drugs 0.000 description 3
- 150000004714 phosphonium salts Chemical class 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- BUZRLKAAOKGUPS-UHFFFAOYSA-N (5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl-triphenylphosphanium Chemical compound N=1N2C(C)=CN=C(C)C2=NC=1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BUZRLKAAOKGUPS-UHFFFAOYSA-N 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- OLFBFKVOGRBSGB-SOFGYWHQSA-N 2-[(e)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethenyl]-6-(trifluoromethyl)quinoline Chemical compound C1=C(C(F)(F)F)C=CC2=NC(/C=C/C3=NN4C(C)=CN=C(C4=N3)C)=CC=C21 OLFBFKVOGRBSGB-SOFGYWHQSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- OBKFPUPSZAQTJF-UHFFFAOYSA-N 6-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-[1,3]dioxolo[4,5-g]quinoline Chemical compound C1=C2OCOC2=CC2=NC(CCC=3N=C4C(C)=NC=C(N4N=3)C)=CC=C21 OBKFPUPSZAQTJF-UHFFFAOYSA-N 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- 208000029197 Amphetamine-Related disease Diseases 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000022497 Cocaine-Related disease Diseases 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 2
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 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 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 208000026251 Opioid-Related disease Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 201000006145 cocaine dependence Diseases 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000011461 current therapy Methods 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002537 isoquinolines Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 210000001009 nucleus accumben Anatomy 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
- 201000005040 opiate dependence Diseases 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000002524 organometallic group Chemical group 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
- 229950009875 osanetant Drugs 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- 208000022821 personality disease Diseases 0.000 description 2
- 229950010883 phencyclidine Drugs 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 229960004431 quetiapine Drugs 0.000 description 2
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229960001534 risperidone Drugs 0.000 description 2
- 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 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
- 229960000652 sertindole Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 229960000607 ziprasidone Drugs 0.000 description 2
- 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 2
- AUEKAKHRRYWONI-UHFFFAOYSA-N 1-(4,4-diphenylbutyl)piperidine Chemical class C1CCCCN1CCCC(C=1C=CC=CC=1)C1=CC=CC=C1 AUEKAKHRRYWONI-UHFFFAOYSA-N 0.000 description 1
- VCJQMIGZVTVBKJ-MDZDMXLPSA-N 2-[(e)-2-(5,7-dimethylimidazo[1,2-a]pyrimidin-2-yl)ethenyl]quinoline Chemical compound C1=CC=CC2=NC(/C=C/C3=CN4C(C)=CC(=NC4=N3)C)=CC=C21 VCJQMIGZVTVBKJ-MDZDMXLPSA-N 0.000 description 1
- UBXXVGJHVGSWFK-CSKARUKUSA-N 2-[(e)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethenyl]-5-methoxyquinoline Chemical compound N1=C2C(C)=NC=C(C)N2N=C1/C=C/C1=CC=C2C(OC)=CC=CC2=N1 UBXXVGJHVGSWFK-CSKARUKUSA-N 0.000 description 1
- UNADFJGCAZZCNL-VMPITWQZSA-N 2-[(e)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethenyl]-6-(trifluoromethoxy)quinoline Chemical compound C1=C(OC(F)(F)F)C=CC2=NC(/C=C/C=3N=C4C(C)=NC=C(N4N=3)C)=CC=C21 UNADFJGCAZZCNL-VMPITWQZSA-N 0.000 description 1
- ULQILZNVSXQNAJ-BQYQJAHWSA-N 2-[(e)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethenyl]-7-(trifluoromethyl)quinoline Chemical compound C1=CC(C(F)(F)F)=CC2=NC(/C=C/C3=NN4C(C)=CN=C(C4=N3)C)=CC=C21 ULQILZNVSXQNAJ-BQYQJAHWSA-N 0.000 description 1
- IQHHSWDAHJQZSL-VQHVLOKHSA-N 2-[(e)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethenyl]-7-methoxyquinoline Chemical compound N1=C2C(C)=NC=C(C)N2N=C1/C=C/C1=NC2=CC(OC)=CC=C2C=C1 IQHHSWDAHJQZSL-VQHVLOKHSA-N 0.000 description 1
- WULZGMJESGYPSN-UHFFFAOYSA-N 2-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)ethyl]-6-methoxyquinoline Chemical compound N1=C2N=C(C)C=C(C)N2N=C1CCC1=NC2=CC=C(OC)C=C2C=C1 WULZGMJESGYPSN-UHFFFAOYSA-N 0.000 description 1
- UNWOJSIARZYPLQ-UHFFFAOYSA-N 2-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)ethyl]quinoline Chemical compound C1=CC=CC2=NC(CCC3=NN4C(C)=CC(=NC4=N3)C)=CC=C21 UNWOJSIARZYPLQ-UHFFFAOYSA-N 0.000 description 1
- VCJQMIGZVTVBKJ-UHFFFAOYSA-N 2-[2-(5,7-dimethylimidazo[1,2-a]pyrimidin-2-yl)ethenyl]quinoline Chemical compound Cc1cc(C)n2cc(C=Cc3ccc4ccccc4n3)nc2n1 VCJQMIGZVTVBKJ-UHFFFAOYSA-N 0.000 description 1
- DXCCBCLBIKQMTN-UHFFFAOYSA-N 2-[2-(5,7-dimethylimidazo[1,2-a]pyrimidin-2-yl)ethyl]quinoline Chemical compound C1=CC=CC2=NC(CCC3=CN4C(C)=CC(=NC4=N3)C)=CC=C21 DXCCBCLBIKQMTN-UHFFFAOYSA-N 0.000 description 1
- GIJZZVQFLNFTDQ-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-4-fluoroquinoline Chemical compound C1=CC=CC2=NC(CCC3=NN4C(C)=CN=C(C4=N3)C)=CC(F)=C21 GIJZZVQFLNFTDQ-UHFFFAOYSA-N 0.000 description 1
- UCAZEKFQHOQZAC-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-4-methoxyquinoline Chemical compound C1=CC=C2C(OC)=CC(CCC3=NN4C(C)=CN=C(C)C4=N3)=NC2=C1 UCAZEKFQHOQZAC-UHFFFAOYSA-N 0.000 description 1
- IJLDUWNLOVNMEI-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-4-methylquinoline Chemical compound CC1=CN=C(C=2N1N=C(N2)CCC2=NC1=CC=CC=C1C(=C2)C)C IJLDUWNLOVNMEI-UHFFFAOYSA-N 0.000 description 1
- FXBMVZKKWQDMJE-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-5,6,8-trifluoroquinoline Chemical compound FC1=C(F)C=C(F)C2=NC(CCC3=NN4C(C)=CN=C(C4=N3)C)=CC=C21 FXBMVZKKWQDMJE-UHFFFAOYSA-N 0.000 description 1
- OSGRTQNTMWQYTB-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-5,7-difluoroquinoline Chemical compound FC1=CC(F)=CC2=NC(CCC3=NN4C(C)=CN=C(C4=N3)C)=CC=C21 OSGRTQNTMWQYTB-UHFFFAOYSA-N 0.000 description 1
- YCQZMYCKKNSEKA-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-5-fluoroquinoline Chemical compound Cc1ncc(C)n2nc(CCc3ccc4c(F)cccc4n3)nc12 YCQZMYCKKNSEKA-UHFFFAOYSA-N 0.000 description 1
- JJLJRBJEYATBDV-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-6,8-difluoroquinoline Chemical compound CC1=CN=C(C=2N1N=C(N2)CCC2=NC1=C(C=C(C=C1C=C2)F)F)C JJLJRBJEYATBDV-UHFFFAOYSA-N 0.000 description 1
- UAZUUNMDIYLHLR-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-6-fluoro-1h-quinolin-4-one Chemical compound FC1=CC=C2NC(CCC=3N=C4C(C)=NC=C(N4N=3)C)=CC(=O)C2=C1 UAZUUNMDIYLHLR-UHFFFAOYSA-N 0.000 description 1
- RVNLAISERMFIRL-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-6-fluoro-4-methoxyquinoline Chemical compound C1=C(F)C=C2C(OC)=CC(CCC3=NN4C(C)=CN=C(C)C4=N3)=NC2=C1 RVNLAISERMFIRL-UHFFFAOYSA-N 0.000 description 1
- IDJOPFLFODQPJY-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-6-fluoro-7-methylquinoline Chemical compound N1=C2C(C)=NC=C(C)N2N=C1CCC1=CC=C(C=C(C(C)=C2)F)C2=N1 IDJOPFLFODQPJY-UHFFFAOYSA-N 0.000 description 1
- IYYHXWQTNJZSKX-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-6-fluoro-8-methylquinoline Chemical compound Cc1ncc(C)n2nc(CCc3ccc4cc(F)cc(C)c4n3)nc12 IYYHXWQTNJZSKX-UHFFFAOYSA-N 0.000 description 1
- HWPNBMFXBLZFQW-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-7-(trifluoromethyl)quinoline Chemical compound Cc1ncc(C)n2nc(CCc3ccc4ccc(cc4n3)C(F)(F)F)nc12 HWPNBMFXBLZFQW-UHFFFAOYSA-N 0.000 description 1
- GCGYJTLJUUHVRD-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-7-fluoro-1h-quinolin-4-one Chemical compound C1=C(F)C=C2NC(CCC=3N=C4C(C)=NC=C(N4N=3)C)=CC(=O)C2=C1 GCGYJTLJUUHVRD-UHFFFAOYSA-N 0.000 description 1
- NHIURNUYBMWWBY-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-7-fluoro-4-methoxyquinoline Chemical compound FC1=CC=C2C(OC)=CC(CCC3=NN4C(C)=CN=C(C)C4=N3)=NC2=C1 NHIURNUYBMWWBY-UHFFFAOYSA-N 0.000 description 1
- HFJAJRSXGFHBJL-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]quinoline Chemical compound C1=CC=CC2=NC(CCC3=NN4C(C)=CN=C(C4=N3)C)=CC=C21 HFJAJRSXGFHBJL-UHFFFAOYSA-N 0.000 description 1
- YBBKCQFKMXFXOD-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]quinoline Chemical compound CC1=CC=C(C=2N1N=C(N2)CCC2=NC1=CC=CC=C1C=C2)C YBBKCQFKMXFXOD-UHFFFAOYSA-N 0.000 description 1
- WZMWOURTNFNVJV-UHFFFAOYSA-N 2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)ethyl]-6-propan-2-ylquinoline Chemical compound CC1=NC=C(C=2N1N=C(N2)CCC2=NC1=CC=C(C=C1C=C2)C(C)C)C WZMWOURTNFNVJV-UHFFFAOYSA-N 0.000 description 1
- SISLFPKXUFKGCB-UHFFFAOYSA-N 2-[2-(6-fluoroquinolin-2-yl)ethyl]-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-ol Chemical compound C1=C(F)C=CC2=NC(CCC=3N=C4C(O)=CC=C(N4N=3)C)=CC=C21 SISLFPKXUFKGCB-UHFFFAOYSA-N 0.000 description 1
- CPPUIDGHVWWSII-UHFFFAOYSA-N 2-[2-(8-ethyl-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]-6-fluoroquinoline Chemical compound C1=C(F)C=CC2=NC(CCC3=NN4C(C)=CC=C(C4=N3)CC)=CC=C21 CPPUIDGHVWWSII-UHFFFAOYSA-N 0.000 description 1
- MYSKWDGTGRORPM-UHFFFAOYSA-N 2-[2-(8-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]-4-methylquinoline Chemical compound COC=1C=2N(C(=CC1)C)N=C(N2)CCC2=NC1=CC=CC=C1C(=C2)C MYSKWDGTGRORPM-UHFFFAOYSA-N 0.000 description 1
- KMIUVXMJAFUCJW-UHFFFAOYSA-N 2-[2-(8-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]quinoline Chemical compound C1=CC=CC2=NC(CCC3=NN4C(C)=CC=C(C4=N3)OC)=CC=C21 KMIUVXMJAFUCJW-UHFFFAOYSA-N 0.000 description 1
- AOZLWNFMUCPBJA-UHFFFAOYSA-N 2-formylquinoline-6-carbonitrile Chemical compound C1=C(C#N)C=CC2=NC(C=O)=CC=C21 AOZLWNFMUCPBJA-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- IGJRVXPXQLTRFL-VQHVLOKHSA-N 4-chloro-8-fluoro-2-[(e)-2-(8-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethenyl]quinoline Chemical compound C1=CC=C(F)C2=NC(/C=C/C3=NN4C(C)=CC=C(C4=N3)OC)=CC(Cl)=C21 IGJRVXPXQLTRFL-VQHVLOKHSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- VKIBGGWUVCBSQV-UHFFFAOYSA-N 4-methoxy-2-[2-(5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]quinoline Chemical compound C1=CC=C2C(OC)=CC(CCC3=NN4C(C)=CC=CC4=N3)=NC2=C1 VKIBGGWUVCBSQV-UHFFFAOYSA-N 0.000 description 1
- MOCHHWZVRUMXSG-UHFFFAOYSA-N 4-methoxy-2-[2-(8-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]quinoline Chemical compound C1=CC=CC2=NC(CCC3=NN4C(C)=CC=C(C4=N3)OC)=CC(OC)=C21 MOCHHWZVRUMXSG-UHFFFAOYSA-N 0.000 description 1
- ZDQFPGSMFKHPOH-UHFFFAOYSA-N 4-methyl-2-[2-(5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]quinoline Chemical compound C1=CC=C2C(C)=CC(CCC3=NN4C(C)=CC=CC4=N3)=NC2=C1 ZDQFPGSMFKHPOH-UHFFFAOYSA-N 0.000 description 1
- ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 1
- ZYTWORDIRAGTMT-UHFFFAOYSA-N 5,7-dichloro-2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]quinoline Chemical compound ClC1=CC(Cl)=CC2=NC(CCC3=NN4C(C)=CN=C(C4=N3)C)=CC=C21 ZYTWORDIRAGTMT-UHFFFAOYSA-N 0.000 description 1
- ONQPPHKGJCWOEV-UHFFFAOYSA-N 6-(trifluoromethyl)quinoline-2-carbaldehyde Chemical compound N1=C(C=O)C=CC2=CC(C(F)(F)F)=CC=C21 ONQPPHKGJCWOEV-UHFFFAOYSA-N 0.000 description 1
- RGSINRRUALOOMG-AATRIKPKSA-N 6-[(e)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethenyl]-[1,3]dioxolo[4,5-g]quinoline Chemical compound C1=C2OCOC2=CC2=NC(/C=C/C=3N=C4C(C)=NC=C(N4N=3)C)=CC=C21 RGSINRRUALOOMG-AATRIKPKSA-N 0.000 description 1
- MFPNSYFMTTWUKP-UHFFFAOYSA-N 6-chloro-2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-8-fluoroquinoline Chemical compound ClC=1C=C2C=CC(=NC2=C(C1)F)CCC1=NN2C(C(=NC=C2C)C)=N1 MFPNSYFMTTWUKP-UHFFFAOYSA-N 0.000 description 1
- VHJYDBZUHADEJZ-UHFFFAOYSA-N 6-chloro-2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]quinoline Chemical compound ClC=1C=C2C=CC(=NC2=CC1)CCC1=NN2C(C(=NC=C2C)C)=N1 VHJYDBZUHADEJZ-UHFFFAOYSA-N 0.000 description 1
- UWQBRNLTAQDTSL-UHFFFAOYSA-N 6-fluoro-2-[2-(8-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]quinoline Chemical compound C1=C(F)C=CC2=NC(CCC3=NN4C(C)=CC=C(C4=N3)OC)=CC=C21 UWQBRNLTAQDTSL-UHFFFAOYSA-N 0.000 description 1
- HAZXHJTUIBGDIX-UHFFFAOYSA-N 7-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-[1,4]dioxino[2,3-g]quinolin-2-one Chemical compound CC1=CN=C(C=2N1N=C(N=2)CCC1=NC=2C=C3C(=CC=2C=C1)OC(CO3)=O)C HAZXHJTUIBGDIX-UHFFFAOYSA-N 0.000 description 1
- FATJBQNFQIWTPW-UHFFFAOYSA-N 7-chloro-2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]quinoline Chemical compound ClC1=CC=C2C=CC(=NC2=C1)CCC1=NN2C(C(=NC=C2C)C)=N1 FATJBQNFQIWTPW-UHFFFAOYSA-N 0.000 description 1
- ZSQKRTOPDCDODI-UHFFFAOYSA-N 7-chloro-2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]quinoline-6-carbonitrile Chemical compound C1=C(C#N)C(Cl)=CC2=NC(CCC=3N=C4C(C)=NC=C(N4N=3)C)=CC=C21 ZSQKRTOPDCDODI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
- CIEPFSOSKLIFON-UHFFFAOYSA-N 8-chloro-2-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)ethyl]-6-methylquinoline Chemical compound ClC=1C=C(C=C2C=CC(=NC12)CCC1=NN2C(C(=NC=C2C)C)=N1)C CIEPFSOSKLIFON-UHFFFAOYSA-N 0.000 description 1
- JCNZDLOAPDELQF-UHFFFAOYSA-N 8-fluoro-2-[2-(8-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)ethyl]quinoline Chemical compound C1=CC=C(F)C2=NC(CCC3=NN4C(C)=CC=C(C4=N3)OC)=CC=C21 JCNZDLOAPDELQF-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 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
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- WCUKDXLCDIBDFB-UHFFFAOYSA-N C(C)C=1C=2N(C(=CC1)C)N=C(N2)C=CC2=NC1=CC=C(C=C1C=C2)F.COC=2C=1N(C(=CC2)C)N=C(N1)C=CC1=NC2=CC=CC=C2C=C1 Chemical compound C(C)C=1C=2N(C(=CC1)C)N=C(N2)C=CC2=NC1=CC=C(C=C1C=C2)F.COC=2C=1N(C(=CC2)C)N=C(N1)C=CC1=NC2=CC=CC=C2C=C1 WCUKDXLCDIBDFB-UHFFFAOYSA-N 0.000 description 1
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 description 1
- HABJLNZCSQRPSQ-UHFFFAOYSA-N CC1=CC=C(C=2N1N=C(N2)C=CC2=NC1=CC=CC=C1C=C2)C.FC=2C=C1C=CC(=NC1=CC2)C=CC2=NN1C(C(=CC=C1C)OC)=N2 Chemical compound CC1=CC=C(C=2N1N=C(N2)C=CC2=NC1=CC=CC=C1C=C2)C.FC=2C=C1C=CC(=NC1=CC2)C=CC2=NN1C(C(=CC=C1C)OC)=N2 HABJLNZCSQRPSQ-UHFFFAOYSA-N 0.000 description 1
- SIZYNUBMMIKLHS-WVLIHFOGSA-N CC1=CN=C(C=2N1N=C(N2)/C=C/C2=NC1=CC=C(C=C1C=C2)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC=CC=C2C(=C1)F)C Chemical compound CC1=CN=C(C=2N1N=C(N2)/C=C/C2=NC1=CC=C(C=C1C=C2)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC=CC=C2C(=C1)F)C SIZYNUBMMIKLHS-WVLIHFOGSA-N 0.000 description 1
- KKDLWTPZCYDEDO-UHFFFAOYSA-N CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=C(C=C(C(=C1C=C2)F)F)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC(=CC(=C2C=C1)F)F)C Chemical compound CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=C(C=C(C(=C1C=C2)F)F)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC(=CC(=C2C=C1)F)F)C KKDLWTPZCYDEDO-UHFFFAOYSA-N 0.000 description 1
- ISAYRVSUFVVAQX-UHFFFAOYSA-N CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC(=C(C=C1C=C2)F)C)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=C(C=C(C=C2C=C1)F)C)C Chemical compound CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC(=C(C=C1C=C2)F)C)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=C(C=C(C=C2C=C1)F)C)C ISAYRVSUFVVAQX-UHFFFAOYSA-N 0.000 description 1
- MDGIOEJCIROQCG-UHFFFAOYSA-N CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC(=CC=C1C(=C2)O)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC(=CC=C2C(=C1)OC)F)C Chemical compound CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC(=CC=C1C(=C2)O)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC(=CC=C2C(=C1)OC)F)C MDGIOEJCIROQCG-UHFFFAOYSA-N 0.000 description 1
- XPTMBYYEZAOHEX-UHFFFAOYSA-N CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC(=CC=C1C=C2)F)C.FC=2C=CC=C1C=CC(=NC21)C=CC2=NN1C(C(=CC=C1C)OC)=N2 Chemical compound CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC(=CC=C1C=C2)F)C.FC=2C=CC=C1C=CC(=NC21)C=CC2=NN1C(C(=CC=C1C)OC)=N2 XPTMBYYEZAOHEX-UHFFFAOYSA-N 0.000 description 1
- DKNVASBUXQCCPF-UHFFFAOYSA-N CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC=C(C=C1C=C2)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC=C(C=C2C=C1)F)C Chemical compound CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC=C(C=C1C=C2)F)C.CC2=CN=C(C=1N2N=C(N1)C=CC1=NC2=CC=C(C=C2C=C1)F)C DKNVASBUXQCCPF-UHFFFAOYSA-N 0.000 description 1
- OHFQWNSMDMFQLD-UHFFFAOYSA-N CC1=CN=C(C=2N1N=C(N2)C=CC2=NC=1C=C3C(=CC1C=C2)OCO3)C.CC3=CN=C(C=2N3N=C(N2)C=CC2=NC3=C(C=C(C=C3C=C2)F)F)C Chemical compound CC1=CN=C(C=2N1N=C(N2)C=CC2=NC=1C=C3C(=CC1C=C2)OCO3)C.CC3=CN=C(C=2N3N=C(N2)C=CC2=NC3=C(C=C(C=C3C=C2)F)F)C OHFQWNSMDMFQLD-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- LXPYFISOHVFMLM-UHFFFAOYSA-N ClC1=C2C=CC(=NC2=CC(=C1)Cl)C=CC1=NN2C(C(=NC=C2C)C)=N1.ClC=1C=C(C=C2C=CC(=NC12)C=CC1=NN2C(C(=NC=C2C)C)=N1)C Chemical compound ClC1=C2C=CC(=NC2=CC(=C1)Cl)C=CC1=NN2C(C(=NC=C2C)C)=N1.ClC=1C=C(C=C2C=CC(=NC12)C=CC1=NN2C(C(=NC=C2C)C)=N1)C LXPYFISOHVFMLM-UHFFFAOYSA-N 0.000 description 1
- PLZCZPUVPHFKNL-UHFFFAOYSA-N ClC1=CC=C2C=CC(=NC2=C1)C=CC1=NN2C(C(=NC=C2C)C)=N1.CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC=CC(=C1C=C2)F)C Chemical compound ClC1=CC=C2C=CC(=NC2=C1)C=CC1=NN2C(C(=NC=C2C)C)=N1.CC1=CN=C(C=2N1N=C(N2)C=CC2=NC1=CC=CC(=C1C=C2)F)C PLZCZPUVPHFKNL-UHFFFAOYSA-N 0.000 description 1
- 206010010219 Compulsions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 208000024254 Delusional disease Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- KLPWJLBORRMFGK-UHFFFAOYSA-N Molindone Chemical compound O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 KLPWJLBORRMFGK-UHFFFAOYSA-N 0.000 description 1
- 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class 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
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000011963 Substance-induced psychotic disease Diseases 0.000 description 1
- 231100000393 Substance-induced psychotic disorder 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
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DWAVARUDIVSTBG-UHFFFAOYSA-N [1,3]dioxolo[4,5-g]quinoline Chemical compound C1=CN=C2C=C(OCO3)C3=CC2=C1 DWAVARUDIVSTBG-UHFFFAOYSA-N 0.000 description 1
- DUGZEIOARNXYLR-UHFFFAOYSA-N [1,4]dioxino[2,3-g]quinoline Chemical compound O1C=COC=2C1=CC=1C=CC=NC=1C=2 DUGZEIOARNXYLR-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 238000011292 agonist therapy Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 150000008316 benzisoxazoles 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
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical class CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 230000011496 cAMP-mediated signaling Effects 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 230000002903 catalepsic effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000001159 caudate nucleus Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 125000000259 cinnolinyl group Chemical class N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream 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
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000000380 hallucinogen Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 102000054918 human PDE10A Human genes 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- XJGVXQDUIWGIRW-UHFFFAOYSA-N loxapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2OC2=CC=C(Cl)C=C12 XJGVXQDUIWGIRW-UHFFFAOYSA-N 0.000 description 1
- 229960000423 loxapine Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 240000004308 marijuana Species 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229960004938 molindone Drugs 0.000 description 1
- 125000002757 morpholinyl group Chemical group 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
- 125000001298 n-hexoxy 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
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 208000002851 paranoid schizophrenia Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002990 phenothiazines Chemical class 0.000 description 1
- 150000004841 phenylimidazoles Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 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 1
- 229960003634 pimozide Drugs 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001300 stimulation of adenylate cyclase Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 150000005075 thioxanthenes Chemical class 0.000 description 1
- 208000016686 tic disease Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
- WFPIAZLQTJBIFN-DVZOWYKESA-N zuclopenthixol Chemical compound C1CN(CCO)CCN1CC\C=C\1C2=CC(Cl)=CC=C2SC2=CC=CC=C2/1 WFPIAZLQTJBIFN-DVZOWYKESA-N 0.000 description 1
- 229960004141 zuclopenthixol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4741—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161578320P | 2011-12-21 | 2011-12-21 | |
| DKPA201100990 | 2011-12-21 | ||
| DKPA201100990 | 2011-12-21 | ||
| PCT/EP2012/076590 WO2013092974A1 (en) | 2011-12-21 | 2012-12-21 | Quinoline derivatives as pde10a enzyme inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2012356885A1 AU2012356885A1 (en) | 2014-07-10 |
| AU2012356885B2 true AU2012356885B2 (en) | 2016-09-08 |
Family
ID=48667762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012356885A Ceased AU2012356885B2 (en) | 2011-12-21 | 2012-12-21 | Quinoline derivatives as PDE10A enzyme inhibitors |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US9216986B1 (OSRAM) |
| EP (1) | EP2794606A1 (OSRAM) |
| JP (1) | JP6073918B2 (OSRAM) |
| KR (1) | KR20140105574A (OSRAM) |
| CN (1) | CN104114554A (OSRAM) |
| AP (1) | AP2014007697A0 (OSRAM) |
| AR (1) | AR089361A1 (OSRAM) |
| AU (1) | AU2012356885B2 (OSRAM) |
| BR (1) | BR112014015192A8 (OSRAM) |
| CA (1) | CA2859702A1 (OSRAM) |
| CL (1) | CL2014001643A1 (OSRAM) |
| CO (1) | CO6990727A2 (OSRAM) |
| CR (1) | CR20140289A (OSRAM) |
| DO (1) | DOP2014000141A (OSRAM) |
| EA (1) | EA028824B1 (OSRAM) |
| EC (1) | ECSP14010000A (OSRAM) |
| GE (1) | GEP201706657B (OSRAM) |
| HK (1) | HK1202861A1 (OSRAM) |
| IL (1) | IL233226A (OSRAM) |
| MA (1) | MA35860B1 (OSRAM) |
| MD (1) | MD20140070A2 (OSRAM) |
| MX (1) | MX348792B (OSRAM) |
| MY (1) | MY165216A (OSRAM) |
| PE (1) | PE20141945A1 (OSRAM) |
| PH (1) | PH12014501434B1 (OSRAM) |
| RU (1) | RU2624440C2 (OSRAM) |
| SG (1) | SG11201403339YA (OSRAM) |
| TN (1) | TN2014000268A1 (OSRAM) |
| TW (1) | TWI570124B (OSRAM) |
| UA (1) | UA111871C2 (OSRAM) |
| WO (1) | WO2013092974A1 (OSRAM) |
| ZA (1) | ZA201404533B (OSRAM) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI570124B (zh) | 2011-12-21 | 2017-02-11 | H 朗德貝克公司 | 作為pde10a酵素抑制劑的喹啉衍生物 |
| CN108690053A (zh) * | 2012-11-29 | 2018-10-23 | 桑诺维恩药品公司 | 杂芳基化合物和其使用方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011150156A2 (en) * | 2010-05-26 | 2011-12-01 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030032579A1 (en) | 2001-04-20 | 2003-02-13 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| US20070105840A1 (en) | 2003-06-30 | 2007-05-10 | Altana Pharma Ag | Pyrrolo-dihydroisoquinoline derivatives as pde10 inhibitors |
| TW200510407A (en) | 2003-06-30 | 2005-03-16 | Altana Pharma Ag | Novel pyrrolodihydroisoquinolines as PDE 10 inhibitors |
| US20070032404A1 (en) | 2003-07-31 | 2007-02-08 | Bayer Pharmaceuticals Corporation | Methods for treating diabetes and related disorders using pde10a inhibitors |
| CA2556413A1 (en) | 2004-02-18 | 2005-09-09 | Pfizer Products Inc. | Tetrahydroisoquinolinyl derivatives of quinazoline and isoquinoline |
| WO2005120514A1 (en) | 2004-06-07 | 2005-12-22 | Pfizer Products Inc. | Phosphodiesterase 10 inhibition as treatment for obesity-related and metabolic syndrome-related conditions |
| US20060019975A1 (en) | 2004-07-23 | 2006-01-26 | Pfizer Inc | Novel piperidyl derivatives of quinazoline and isoquinoline |
| AU2005282721A1 (en) | 2004-09-03 | 2006-03-16 | Memory Pharmaceuticals Corporation | 4-substituted 4, 6-dialkoxy-cinnoline derivatives as phospodiesterase 10 inhibitors for the treatment of psychiatric or neurological syndroms |
| KR101612971B1 (ko) | 2008-05-14 | 2016-04-15 | 아스테라스 세이야쿠 가부시키가이샤 | 아미드 화합물 |
| TWI501965B (zh) * | 2008-06-20 | 2015-10-01 | Lundbeck & Co As H | 作為pde10a酵素抑制劑之新穎苯基咪唑衍生物 |
| UA102693C2 (ru) | 2008-06-20 | 2013-08-12 | Х. Луннбек А/С | Производные фенилимидазола как ингибиторы фермента pde10a |
| TWI485151B (zh) | 2009-12-17 | 2015-05-21 | Lundbeck & Co As H | 作為pde10a酵素抑制劑之雜芳香族苯基咪唑衍生物 |
| TWI481607B (zh) | 2009-12-17 | 2015-04-21 | Lundbeck & Co As H | 作為pde10a酵素抑制劑的2-芳基咪唑衍生物 |
| JP2011201873A (ja) * | 2010-03-03 | 2011-10-13 | Mitsubishi Tanabe Pharma Corp | 三置換ピリミジン化合物及びそのpde10阻害薬としての使用 |
| TWI570124B (zh) | 2011-12-21 | 2017-02-11 | H 朗德貝克公司 | 作為pde10a酵素抑制劑的喹啉衍生物 |
-
2012
- 2012-12-20 TW TW101148618A patent/TWI570124B/zh not_active IP Right Cessation
- 2012-12-20 AR ARP120104861A patent/AR089361A1/es unknown
- 2012-12-21 SG SG11201403339YA patent/SG11201403339YA/en unknown
- 2012-12-21 CA CA2859702A patent/CA2859702A1/en not_active Abandoned
- 2012-12-21 HK HK15103345.9A patent/HK1202861A1/xx unknown
- 2012-12-21 KR KR1020147019800A patent/KR20140105574A/ko not_active Ceased
- 2012-12-21 GE GEAP201213526A patent/GEP201706657B/en unknown
- 2012-12-21 CN CN201280069658.7A patent/CN104114554A/zh active Pending
- 2012-12-21 BR BR112014015192A patent/BR112014015192A8/pt active Search and Examination
- 2012-12-21 MY MYPI2014001793A patent/MY165216A/en unknown
- 2012-12-21 EP EP12815695.7A patent/EP2794606A1/en not_active Withdrawn
- 2012-12-21 UA UAA201407913A patent/UA111871C2/uk unknown
- 2012-12-21 US US14/305,736 patent/US9216986B1/en not_active Expired - Fee Related
- 2012-12-21 PE PE2014000989A patent/PE20141945A1/es not_active Application Discontinuation
- 2012-12-21 AU AU2012356885A patent/AU2012356885B2/en not_active Ceased
- 2012-12-21 AP AP2014007697A patent/AP2014007697A0/xx unknown
- 2012-12-21 RU RU2014127984A patent/RU2624440C2/ru not_active IP Right Cessation
- 2012-12-21 MX MX2014007409A patent/MX348792B/es active IP Right Grant
- 2012-12-21 WO PCT/EP2012/076590 patent/WO2013092974A1/en not_active Ceased
- 2012-12-21 EA EA201491152A patent/EA028824B1/ru not_active IP Right Cessation
- 2012-12-21 JP JP2014548059A patent/JP6073918B2/ja not_active Expired - Fee Related
- 2012-12-21 MD MDA20140070A patent/MD20140070A2/ro not_active Application Discontinuation
-
2014
- 2014-06-16 TN TNP2014000268A patent/TN2014000268A1/en unknown
- 2014-06-17 CR CR20140289A patent/CR20140289A/es unknown
- 2014-06-17 DO DO2014000141A patent/DOP2014000141A/es unknown
- 2014-06-18 IL IL233226A patent/IL233226A/en not_active IP Right Cessation
- 2014-06-19 CL CL2014001643A patent/CL2014001643A1/es unknown
- 2014-06-20 CO CO14134658A patent/CO6990727A2/es unknown
- 2014-06-20 ZA ZA2014/04533A patent/ZA201404533B/en unknown
- 2014-06-20 PH PH12014501434A patent/PH12014501434B1/en unknown
- 2014-07-11 MA MA37201A patent/MA35860B1/fr unknown
- 2014-07-18 EC ECIEPI201410000A patent/ECSP14010000A/es unknown
-
2015
- 2015-11-13 US US14/940,272 patent/US9801878B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011150156A2 (en) * | 2010-05-26 | 2011-12-01 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2513105B1 (en) | 2-arylimidazole derivatives as pde10a enzyme inhibitors | |
| KR101916487B1 (ko) | Pde10a 효소 저해제로서 이미다졸 유도체 | |
| US9801878B2 (en) | Quinoline derivatives as PDE10A enzyme inhibitors | |
| US9062060B2 (en) | Substituted imidazo[2,1-A]isoindoles as PDE10 inhibitors | |
| NZ626279B2 (en) | Quinoline derivatives as pde10a enzyme inhibitors | |
| OA16934A (en) | Quinoline derivatives as PDE10A enzyme inhibitors. | |
| WO2013127817A1 (en) | Imidazole derivatives as pde10a enzyme inhibitors | |
| WO2013107856A1 (en) | Imidazole derivatives as pde10a enzyme inhibitors | |
| WO2013045607A1 (en) | Quinazoline linked heteroaromatic tricycle derivatives as pde10a enzyme inhibitors | |
| HK1189593B (en) | Imidazole derivatives as pde10a enzyme inhibitors | |
| MX2013005592A (es) | Derivados de imidazol como inhibidores de la enzima pde10a. | |
| OA16430A (en) | Imidazole derivatives as PDE10A ensyme inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE PRIORITY DETAILS TO READ PA 2011 00990 21 DEC 2011 DK |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |