DE60309740T2 - 1,4-dizabicyclo(3,2,2)nonane derivative, verfahren zu ihrer herstellung und therapeutical verwendung - Google Patents
1,4-dizabicyclo(3,2,2)nonane derivative, verfahren zu ihrer herstellung und therapeutical verwendung Download PDFInfo
- Publication number
- DE60309740T2 DE60309740T2 DE60309740T DE60309740T DE60309740T2 DE 60309740 T2 DE60309740 T2 DE 60309740T2 DE 60309740 T DE60309740 T DE 60309740T DE 60309740 T DE60309740 T DE 60309740T DE 60309740 T2 DE60309740 T2 DE 60309740T2
- Authority
- DE
- Germany
- Prior art keywords
- diazabicyclo
- nonane
- pyridazin
- disorder
- condition
- 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.)
- Expired - Lifetime
Links
- 238000002360 preparation method Methods 0.000 title claims description 5
- 230000001225 therapeutic effect Effects 0.000 title claims description 5
- 238000000034 method Methods 0.000 title description 22
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical class CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 title description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 65
- 201000010099 disease Diseases 0.000 claims abstract description 34
- 208000035475 disorder Diseases 0.000 claims abstract description 31
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 239000000126 substance Substances 0.000 claims abstract description 11
- 208000002193 Pain Diseases 0.000 claims abstract description 8
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 8
- 102000005962 receptors Human genes 0.000 claims abstract description 8
- 108020003175 receptors Proteins 0.000 claims abstract description 8
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims abstract description 7
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 28
- 150000005347 biaryls Chemical class 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 6
- -1 indol-6-yl group Chemical group 0.000 claims description 6
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 5
- 230000008602 contraction Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 210000002460 smooth muscle Anatomy 0.000 claims description 5
- 208000032841 Bulimia Diseases 0.000 claims description 4
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 4
- 206010012735 Diarrhoea Diseases 0.000 claims description 4
- 208000026097 Factitious disease Diseases 0.000 claims description 4
- 206010020651 Hyperkinesia Diseases 0.000 claims description 4
- 208000000269 Hyperkinesis Diseases 0.000 claims description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 4
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 4
- 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 claims description 4
- 206010009887 colitis Diseases 0.000 claims description 4
- 230000006735 deficit Effects 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 3
- 206010039966 Senile dementia Diseases 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 3
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 3
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 229960002715 nicotine Drugs 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- SPENYPHOPYNNMM-UHFFFAOYSA-N 2-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3,4-oxadiazole Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=NN=CO1 SPENYPHOPYNNMM-UHFFFAOYSA-N 0.000 claims description 2
- NWBQHUOIZCLTEN-UHFFFAOYSA-N 2-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3,4-thiadiazole Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=NN=CS1 NWBQHUOIZCLTEN-UHFFFAOYSA-N 0.000 claims description 2
- GQDZMLYERQCVCI-UHFFFAOYSA-N 2-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3-oxazole Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=NC=CO1 GQDZMLYERQCVCI-UHFFFAOYSA-N 0.000 claims description 2
- LWDIJZHGOFRRBY-UHFFFAOYSA-N 2-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3-thiazole Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=NC=CS1 LWDIJZHGOFRRBY-UHFFFAOYSA-N 0.000 claims description 2
- XGQNMFLIMAXOIY-UHFFFAOYSA-N 4-(6-pyridin-3-ylpyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=CN=C1 XGQNMFLIMAXOIY-UHFFFAOYSA-N 0.000 claims description 2
- DKHBMBRMHHQCDB-UHFFFAOYSA-N 4-(6-selenophen-2-ylpyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=C[se]1 DKHBMBRMHHQCDB-UHFFFAOYSA-N 0.000 claims description 2
- DOFUKSVDRJDFPT-UHFFFAOYSA-N 4-(6-selenophen-3-ylpyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=C[se]C=1 DOFUKSVDRJDFPT-UHFFFAOYSA-N 0.000 claims description 2
- JZWLASCGBSGJJP-UHFFFAOYSA-N 4-(6-thiophen-2-ylpyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=CS1 JZWLASCGBSGJJP-UHFFFAOYSA-N 0.000 claims description 2
- GDHIPSSNCMRUGD-UHFFFAOYSA-N 4-(6-thiophen-3-ylpyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=CSC=1 GDHIPSSNCMRUGD-UHFFFAOYSA-N 0.000 claims description 2
- UUMMBUCFQAZHOZ-UHFFFAOYSA-N 4-[6-(1h-indol-2-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CC2CCN1CCN2C1=CC=C(C=2NC3=CC=CC=C3C=2)N=N1 UUMMBUCFQAZHOZ-UHFFFAOYSA-N 0.000 claims description 2
- AAJWPKMRKNHGJB-UHFFFAOYSA-N 4-[6-(1h-indol-3-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CC2CCN1CCN2C1=CC=C(C=2C3=CC=CC=C3NC=2)N=N1 AAJWPKMRKNHGJB-UHFFFAOYSA-N 0.000 claims description 2
- VSQKKGSKQLKGLK-UHFFFAOYSA-N 4-[6-(1h-indol-5-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CC2CCN1CCN2C1=CC=C(C=2C=C3C=CNC3=CC=2)N=N1 VSQKKGSKQLKGLK-UHFFFAOYSA-N 0.000 claims description 2
- GQLYDXLVVUJUNQ-UHFFFAOYSA-N 4-[6-(1h-indol-6-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CC2CCN1CCN2C1=CC=C(C=2C=C3NC=CC3=CC=2)N=N1 GQLYDXLVVUJUNQ-UHFFFAOYSA-N 0.000 claims description 2
- PUSFZEHEZVTHLC-UHFFFAOYSA-N 4-[6-(furan-2-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=CO1 PUSFZEHEZVTHLC-UHFFFAOYSA-N 0.000 claims description 2
- IPMBYUWDOKOAHU-UHFFFAOYSA-N 4-[6-(furan-3-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=COC=1 IPMBYUWDOKOAHU-UHFFFAOYSA-N 0.000 claims description 2
- VCXNGLKVCYWXLQ-UHFFFAOYSA-N 5-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3-thiazole Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CN=CS1 VCXNGLKVCYWXLQ-UHFFFAOYSA-N 0.000 claims description 2
- 208000030507 AIDS Diseases 0.000 claims description 2
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
- 206010002660 Anoxia Diseases 0.000 claims description 2
- 241000976983 Anoxia Species 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
- 206010003805 Autism Diseases 0.000 claims description 2
- 208000020706 Autistic disease Diseases 0.000 claims description 2
- 208000020925 Bipolar disease Diseases 0.000 claims description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 2
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 208000030814 Eating disease Diseases 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 2
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 206010020850 Hyperthyroidism Diseases 0.000 claims description 2
- 206010021143 Hypoxia Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 206010026749 Mania Diseases 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 206010028403 Mutism Diseases 0.000 claims description 2
- 241000208125 Nicotiana Species 0.000 claims description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 208000004983 Phantom Limb Diseases 0.000 claims description 2
- 206010056238 Phantom pain Diseases 0.000 claims description 2
- 208000008348 Post-Concussion Syndrome Diseases 0.000 claims description 2
- 208000004550 Postoperative Pain Diseases 0.000 claims description 2
- 208000006399 Premature Obstetric Labor Diseases 0.000 claims description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 2
- 206010052276 Pseudodementia Diseases 0.000 claims description 2
- 206010041250 Social phobia Diseases 0.000 claims description 2
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 2
- 206010000496 acne Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 230000007953 anoxia Effects 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 2
- 229940049706 benzodiazepine Drugs 0.000 claims description 2
- 208000028683 bipolar I disease Diseases 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 229960003920 cocaine Drugs 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 229960002069 diamorphine Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 235000014632 disordered eating Nutrition 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 206010013932 dyslexia Diseases 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 2
- 230000029849 luteinization Effects 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 229960005181 morphine Drugs 0.000 claims description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 2
- 201000003631 narcolepsy Diseases 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 229940005483 opioid analgesics Drugs 0.000 claims description 2
- 208000019906 panic disease Diseases 0.000 claims description 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
- 208000028591 pheochromocytoma Diseases 0.000 claims description 2
- 206010036596 premature ejaculation Diseases 0.000 claims description 2
- 201000004700 rosacea Diseases 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 230000020341 sensory perception of pain Effects 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 208000005057 thyrotoxicosis Diseases 0.000 claims description 2
- 208000002271 trichotillomania Diseases 0.000 claims description 2
- YZICOXNXTNFTLQ-UHFFFAOYSA-N 5-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3-oxazole Chemical compound C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CN=CO1 YZICOXNXTNFTLQ-UHFFFAOYSA-N 0.000 claims 1
- 208000007101 Muscle Cramp Diseases 0.000 claims 1
- 208000005392 Spasm Diseases 0.000 claims 1
- 102000034337 acetylcholine receptors Human genes 0.000 claims 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- 210000000750 endocrine system Anatomy 0.000 claims 1
- 230000001856 erectile effect Effects 0.000 claims 1
- 230000000306 recurrent effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 39
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 abstract description 15
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 abstract description 15
- 230000001713 cholinergic effect Effects 0.000 abstract description 9
- 210000001428 peripheral nervous system Anatomy 0.000 abstract description 7
- 108010078791 Carrier Proteins Proteins 0.000 abstract description 5
- 208000017701 Endocrine disease Diseases 0.000 abstract description 5
- 206010061218 Inflammation Diseases 0.000 abstract description 4
- 230000004054 inflammatory process Effects 0.000 abstract description 4
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 208000030172 endocrine system disease Diseases 0.000 abstract description 3
- 239000003446 ligand Substances 0.000 abstract description 3
- 125000005841 biaryl group Chemical class 0.000 abstract 1
- 230000016160 smooth muscle contraction Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 9
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 7
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000001530 fumaric acid Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
- 108060003345 Adrenergic Receptor Proteins 0.000 description 4
- 102000017910 Adrenergic receptor Human genes 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 102000009660 Cholinergic Receptors Human genes 0.000 description 4
- 102000015554 Dopamine receptor Human genes 0.000 description 4
- 108050004812 Dopamine receptor Proteins 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 229960003638 dopamine Drugs 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 229960002748 norepinephrine Drugs 0.000 description 4
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VCIKVHACZDLJCT-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-3-one Chemical compound N1C(=O)CN2CCC1CC2 VCIKVHACZDLJCT-UHFFFAOYSA-N 0.000 description 3
- XJKNACDCUAFDHD-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonane Chemical compound C1CC2CCN1CCN2 XJKNACDCUAFDHD-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 3
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000000035 biogenic effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 2
- AQBWMWFCHAHVQQ-WLHGVMLRSA-N (E)-but-2-enedioic acid 2-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3-thiazole Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=NC=CS1 AQBWMWFCHAHVQQ-WLHGVMLRSA-N 0.000 description 2
- KDIOUVTYAHYWKB-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-(5-thiophen-2-yl-1H-pyrrol-2-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N1)=CC=C1C1=CC=CS1 KDIOUVTYAHYWKB-WLHGVMLRSA-N 0.000 description 2
- ZOCHBGBQVNNKGC-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-[6-(furan-2-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=CO1 ZOCHBGBQVNNKGC-WLHGVMLRSA-N 0.000 description 2
- ZIUHIBKNHCHGLR-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-[6-(furan-3-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=COC=1 ZIUHIBKNHCHGLR-WLHGVMLRSA-N 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- VQAFMTSSCUETHA-UHFFFAOYSA-N 3,6-dibromopyridazine Chemical compound BrC1=CC=C(Br)N=N1 VQAFMTSSCUETHA-UHFFFAOYSA-N 0.000 description 2
- HPVOPUHYDQGKGI-UHFFFAOYSA-N 3-bromo-6-thiophen-3-ylpyridazine Chemical compound N1=NC(Br)=CC=C1C1=CSC=C1 HPVOPUHYDQGKGI-UHFFFAOYSA-N 0.000 description 2
- AMXXPSGBFKIRRX-UHFFFAOYSA-N 3-chloro-6-thiophen-3-ylpyridazine;hydrochloride Chemical compound Cl.N1=NC(Cl)=CC=C1C1=CSC=C1 AMXXPSGBFKIRRX-UHFFFAOYSA-N 0.000 description 2
- HDTMGTDXVWAWEJ-UHFFFAOYSA-N 4-(6-bromopyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound N1=NC(Br)=CC=C1N1C(CC2)CCN2CC1 HDTMGTDXVWAWEJ-UHFFFAOYSA-N 0.000 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- QMWFFGJTLGBVJJ-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=CS1 QMWFFGJTLGBVJJ-WLHGVMLRSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- KPWKPGFLZGMMFX-VHSXEESVSA-N (-)-camphanic acid Chemical compound C1C[C@]2(C(O)=O)OC(=O)[C@@]1(C)C2(C)C KPWKPGFLZGMMFX-VHSXEESVSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- KPWKPGFLZGMMFX-ZJUUUORDSA-N (1s,4r)-1,7,7-trimethyl-2-oxo-3-oxabicyclo[2.2.1]heptane-4-carboxylic acid Chemical compound C1C[C@@]2(C(O)=O)OC(=O)[C@]1(C)C2(C)C KPWKPGFLZGMMFX-ZJUUUORDSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- HNNRSIKEKXWEFN-WLHGVMLRSA-N (E)-but-2-enedioic acid 2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-5-thiophen-2-yl-1,3-oxazole Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(O1)=NC=C1C1=CC=CS1 HNNRSIKEKXWEFN-WLHGVMLRSA-N 0.000 description 1
- LQDOHYIEHFMQNL-WLHGVMLRSA-N (E)-but-2-enedioic acid 2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-5-thiophen-2-yl-1,3-thiazole Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(S1)=NC=C1C1=CC=CS1 LQDOHYIEHFMQNL-WLHGVMLRSA-N 0.000 description 1
- AFTPOMYUZZPTNJ-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-(1-methyl-5-thiophen-2-ylimidazol-2-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C=1N=C(N2C3CCN(CC3)CC2)N(C)C=1C1=CC=CS1 AFTPOMYUZZPTNJ-WLHGVMLRSA-N 0.000 description 1
- JXYFIGXTLTYPIE-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-(1-methyl-5-thiophen-2-ylpyrrol-2-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.CN1C(N2C3CCN(CC3)CC2)=CC=C1C1=CC=CS1 JXYFIGXTLTYPIE-WLHGVMLRSA-N 0.000 description 1
- WHLVKQVJEBMSNT-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-(2-thiophen-2-yl-1H-imidazol-5-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N1)=CN=C1C1=CC=CS1 WHLVKQVJEBMSNT-WLHGVMLRSA-N 0.000 description 1
- GAHYMRVUHGGLKQ-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-(6-pyridin-3-ylpyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=CN=C1 GAHYMRVUHGGLKQ-WLHGVMLRSA-N 0.000 description 1
- UGMPPTJSHBSGMJ-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-[6-(1H-indol-3-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C1CC2CCN1CCN2C1=CC=C(C=2C3=CC=CC=C3NC=2)N=N1 UGMPPTJSHBSGMJ-WLHGVMLRSA-N 0.000 description 1
- WKUQSUFDYCAHLB-WLHGVMLRSA-N (E)-but-2-enedioic acid 4-[6-(1H-indol-5-yl)pyridazin-3-yl]-1,4-diazabicyclo[3.2.2]nonane Chemical compound OC(=O)\C=C\C(O)=O.C1CC2CCN1CCN2C1=CC=C(C=2C=C3C=CNC3=CC=2)N=N1 WKUQSUFDYCAHLB-WLHGVMLRSA-N 0.000 description 1
- KYCVDQFATMZVLF-WLHGVMLRSA-N (E)-but-2-enedioic acid 5-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3-oxazole Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CN=CO1 KYCVDQFATMZVLF-WLHGVMLRSA-N 0.000 description 1
- ILRBYMXXVMTZRF-WLHGVMLRSA-N (E)-but-2-enedioic acid 5-[6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)pyridazin-3-yl]-1,3-thiazole Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CN=CS1 ILRBYMXXVMTZRF-WLHGVMLRSA-N 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- 229930182840 (S)-nicotine Natural products 0.000 description 1
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 1
- AYCVROPXDAWLQR-UHFFFAOYSA-N 1,3-diazabicyclo[3.2.2]nonan-4-one Chemical compound O=C1NCN2CCC1CC2 AYCVROPXDAWLQR-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- RFDPHKHXPMDJJD-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-one;hydron;chloride Chemical compound Cl.C1CC2C(=O)CN1CC2 RFDPHKHXPMDJJD-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- ABEBCTCOPRULFS-UHFFFAOYSA-N 3-amino-3-phenylpropanoic acid;hydrochloride Chemical compound Cl.OC(=O)CC(N)C1=CC=CC=C1 ABEBCTCOPRULFS-UHFFFAOYSA-N 0.000 description 1
- VJCQFNXBDNGZPZ-WLHGVMLRSA-N 4-(6-bromopyridazin-3-yl)-1,4-diazabicyclo[3.2.2]nonane (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.N1=NC(Br)=CC=C1N1C(CC2)CCN2CC1 VJCQFNXBDNGZPZ-WLHGVMLRSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 101710195183 Alpha-bungarotoxin Proteins 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000272079 Bungarus multicinctus Species 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- DPXUKJSWRTXLMS-UHFFFAOYSA-N Cc1c[o]c(S2C(C)=NC=C2)c1 Chemical compound Cc1c[o]c(S2C(C)=NC=C2)c1 DPXUKJSWRTXLMS-UHFFFAOYSA-N 0.000 description 1
- KZYFUNLHKMWHCG-UHFFFAOYSA-N Cc1c[s]cc1-[O]1c(C)cnc1 Chemical compound Cc1c[s]cc1-[O]1c(C)cnc1 KZYFUNLHKMWHCG-UHFFFAOYSA-N 0.000 description 1
- FQFVNKBPMHJSEG-UHFFFAOYSA-N Cc1c[s]cc1S1C(C)=CN=C1 Chemical compound Cc1c[s]cc1S1C(C)=CN=C1 FQFVNKBPMHJSEG-UHFFFAOYSA-N 0.000 description 1
- ZMSIFDIKIXVLDF-UHFFFAOYSA-N Cc1nnc[o]1 Chemical compound Cc1nnc[o]1 ZMSIFDIKIXVLDF-UHFFFAOYSA-N 0.000 description 1
- RQSCFNPNNLWQBJ-UHFFFAOYSA-N Cc1nnc[s]1 Chemical compound Cc1nnc[s]1 RQSCFNPNNLWQBJ-UHFFFAOYSA-N 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
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000272060 Elapidae Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- XAFKGYLHFAZYPQ-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CC2CCN1CCN2C1=CC=C(C=2C=C3NC=CC3=CC=2)N=N1 Chemical compound OC(=O)\C=C\C(O)=O.C1CC2CCN1CCN2C1=CC=C(C=2C=C3NC=CC3=CC=2)N=N1 XAFKGYLHFAZYPQ-WLHGVMLRSA-N 0.000 description 1
- CMMRRSYVGOGOQR-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CC2CCN1CCN2C1=CC=C(C=2NC3=CC=CC=C3C=2)N=N1 Chemical compound OC(=O)\C=C\C(O)=O.C1CC2CCN1CCN2C1=CC=C(C=2NC3=CC=CC=C3C=2)N=N1 CMMRRSYVGOGOQR-WLHGVMLRSA-N 0.000 description 1
- YRKACRPVFCINBD-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(=NO1)C=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(=NO1)C=C1C1=CC=CS1 YRKACRPVFCINBD-WLHGVMLRSA-N 0.000 description 1
- BLELUQHHPVUIAF-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(=NS1)C=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(=NS1)C=C1C1=CC=CS1 BLELUQHHPVUIAF-WLHGVMLRSA-N 0.000 description 1
- YAUQQBUMBMSJBO-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N1)=NC=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N1)=NC=C1C1=CC=CS1 YAUQQBUMBMSJBO-WLHGVMLRSA-N 0.000 description 1
- GWRAEDMXTFMHIW-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=C[se]1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=CC=C[se]1 GWRAEDMXTFMHIW-WLHGVMLRSA-N 0.000 description 1
- MSSGLSIOAMHWAC-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=NC=CO1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C1=NC=CO1 MSSGLSIOAMHWAC-WLHGVMLRSA-N 0.000 description 1
- SEGQJUIRGHLIQH-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=CSC=1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=CSC=1 SEGQJUIRGHLIQH-WLHGVMLRSA-N 0.000 description 1
- DESPETYWHQIPLA-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=C[se]C=1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(N=N1)=CC=C1C=1C=C[se]C=1 DESPETYWHQIPLA-WLHGVMLRSA-N 0.000 description 1
- RCASOWAGQIQTSW-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(O1)=CC=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(O1)=CC=C1C1=CC=CS1 RCASOWAGQIQTSW-WLHGVMLRSA-N 0.000 description 1
- JCPIQCGBVMMSBA-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(O1)=CN=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(O1)=CN=C1C1=CC=CS1 JCPIQCGBVMMSBA-WLHGVMLRSA-N 0.000 description 1
- IXWGANHKPKVNHW-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(ON=1)=CC=1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(ON=1)=CC=1C1=CC=CS1 IXWGANHKPKVNHW-WLHGVMLRSA-N 0.000 description 1
- WWQSPYIYUGVGEI-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(S1)=CC=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(S1)=CC=C1C1=CC=CS1 WWQSPYIYUGVGEI-WLHGVMLRSA-N 0.000 description 1
- BOODYJUMSSGFDQ-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(S1)=CN=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(S1)=CN=C1C1=CC=CS1 BOODYJUMSSGFDQ-WLHGVMLRSA-N 0.000 description 1
- CQPUKFHJABHIGH-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(SN=1)=CC=1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(CC2)CCC1N2C(SN=1)=CC=1C1=CC=CS1 CQPUKFHJABHIGH-WLHGVMLRSA-N 0.000 description 1
- CYDZIFWTMHBPDZ-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CN1C(N2C3CCN(CC3)CC2)=CN=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.CN1C(N2C3CCN(CC3)CC2)=CN=C1C1=CC=CS1 CYDZIFWTMHBPDZ-WLHGVMLRSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- QEUKJXIMRVFORY-UHFFFAOYSA-M [Cl-].[Zn+]C1=NC=CS1 Chemical compound [Cl-].[Zn+]C1=NC=CS1 QEUKJXIMRVFORY-UHFFFAOYSA-M 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- OJKBCQOJVMAHDX-UHFFFAOYSA-N diethyl(pyridin-3-yl)borane Chemical compound CCB(CC)C1=CC=CN=C1 OJKBCQOJVMAHDX-UHFFFAOYSA-N 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- XARAKXAOSOBLBZ-UHFFFAOYSA-N furan-2-yl(trimethyl)stannane Chemical compound C[Sn](C)(C)C1=CC=CO1 XARAKXAOSOBLBZ-UHFFFAOYSA-N 0.000 description 1
- LAZWQQYSPSFJQN-UHFFFAOYSA-N furan-3-yl(trimethyl)stannane Chemical compound C[Sn](C)(C)C=1C=COC=1 LAZWQQYSPSFJQN-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 206010021654 increased appetite Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- XLTANAWLDBYGFU-UHFFFAOYSA-N methyllycaconitine hydrochloride Natural products C1CC(OC)C2(C3C4OC)C5CC(C(C6)OC)C(OC)C5C6(O)C4(O)C2N(CC)CC31COC(=O)C1=CC=CC=C1N1C(=O)CC(C)C1=O XLTANAWLDBYGFU-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- FUIJZJKRMCMLKO-UHFFFAOYSA-N trimethyl(selenophen-2-yl)stannane Chemical compound C[Sn](C)(C)C1=CC=C[se]1 FUIJZJKRMCMLKO-UHFFFAOYSA-N 0.000 description 1
- NPIWLHQDDTZHMK-UHFFFAOYSA-N trimethyl(selenophen-3-yl)stannane Chemical compound C[Sn](C)(C)C=1C=C[se]C=1 NPIWLHQDDTZHMK-UHFFFAOYSA-N 0.000 description 1
- ZGWZWRHJHVTXEL-UHFFFAOYSA-N trimethyl(thiophen-2-yl)stannane Chemical compound C[Sn](C)(C)C1=CC=CS1 ZGWZWRHJHVTXEL-UHFFFAOYSA-N 0.000 description 1
- 208000037820 vascular cognitive impairment Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- LYTCVQQGCSNFJU-LKGYBJPKSA-N α-bungarotoxin Chemical compound C(/[C@H]1O[C@H]2C[C@H]3O[C@@H](CC(=C)C=O)C[C@H](O)[C@]3(C)O[C@@H]2C[C@@H]1O[C@@H]1C2)=C/C[C@]1(C)O[C@H]1[C@@]2(C)O[C@]2(C)CC[C@@H]3O[C@@H]4C[C@]5(C)O[C@@H]6C(C)=CC(=O)O[C@H]6C[C@H]5O[C@H]4C[C@@H](C)[C@H]3O[C@H]2C1 LYTCVQQGCSNFJU-LKGYBJPKSA-N 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
- C07D471/08—Bridged 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D487/08—Bridged systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Pulmonology (AREA)
- Gynecology & Obstetrics (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pregnancy & Childbirth (AREA)
- Dermatology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK200201737 | 2002-11-11 | ||
| DKPA200201737 | 2002-11-11 | ||
| PCT/DK2003/000769 WO2004043960A1 (en) | 2002-11-11 | 2003-11-10 | 1,4-diazabicyclo (3,2,2)nonane derivatives, preparation and therapeutical use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60309740D1 DE60309740D1 (de) | 2006-12-28 |
| DE60309740T2 true DE60309740T2 (de) | 2007-03-29 |
Family
ID=32309262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60309740T Expired - Lifetime DE60309740T2 (de) | 2002-11-11 | 2003-11-10 | 1,4-dizabicyclo(3,2,2)nonane derivative, verfahren zu ihrer herstellung und therapeutical verwendung |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1562945B1 (OSRAM) |
| JP (1) | JP2006508109A (OSRAM) |
| AT (1) | ATE345342T1 (OSRAM) |
| AU (1) | AU2003280309A1 (OSRAM) |
| DE (1) | DE60309740T2 (OSRAM) |
| DK (1) | DK1562945T3 (OSRAM) |
| WO (1) | WO2004043960A1 (OSRAM) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
| US7094572B2 (en) | 2003-03-14 | 2006-08-22 | Bristol-Myers Squibb | Polynucleotide encoding a novel human G-protein coupled receptor variant of HM74, HGPRBMY74 |
| SE0303076D0 (sv) * | 2003-11-19 | 2003-11-19 | Astrazeneca Ab | 5-substituted imidazoles |
| SE0303075D0 (sv) * | 2003-11-19 | 2003-11-19 | Astrazeneca Ab | 4-substituted imidazoles |
| GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| MX2007003331A (es) * | 2004-11-30 | 2007-06-05 | Neurosearch As | Nuevos derivados de arilo diazabiciclico. |
| US7662812B2 (en) | 2005-02-16 | 2010-02-16 | Neurosearch A/S | Diazabicyclic aryl derivatives and their use as chinolinergic ligands at nicotinic acetylcholine receptors |
| ATE481407T1 (de) | 2005-02-16 | 2010-10-15 | Neurosearch As | Neue diazabicyclische arylderivate und medizinische verwendung dafür |
| EP1963323B1 (en) | 2005-12-06 | 2010-07-14 | Neurosearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| GB0525672D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| GB0525673D0 (en) * | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| US7855208B2 (en) | 2006-02-14 | 2010-12-21 | Neurosearch A/S | 3, 9-diazabicyclo(3.3.1)non-3-yl-aryl methanone derivatives as nicotinic acetylcholine receptor agonists |
| ATE518862T1 (de) * | 2006-05-30 | 2011-08-15 | Neurosearch As | Neue 1,4-diaza-bicycloä3.2.2ünonyl-oxadiazolyl- derivate und deren medizinische verwendung |
| AU2007267178A1 (en) | 2006-05-30 | 2007-12-06 | Neurosearch A/S | Novel 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidinyl derivatives and their medical use |
| US8778987B2 (en) | 2007-03-13 | 2014-07-15 | Symrise Ag | Use of 4-hydroxychalcone derivatives for masking an unpleasant taste |
| EP1977655B1 (de) | 2007-03-29 | 2011-05-18 | Symrise AG | Aromakompositionen von Alkamiden mit Hesperetin und/oder 4-Hydroxydihydrochalkonen und deren Salzen zur Verstärkung süßer sensorischer Eindrücke |
| EP2209783B8 (en) | 2007-11-14 | 2016-06-01 | Saniona A/S | Novel 1,4-diaza-bicyclo[3.2.2]nonyl pyrimidine derivatives and their medical use |
| US20110257161A1 (en) * | 2008-12-04 | 2011-10-20 | Neurosearch A/S | Novel diaza-bicyclononyl-phenyl derivatives and their medical use |
| CN103221411B (zh) | 2010-05-17 | 2016-05-11 | 富瑞姆制药公司 | (R)-7-氯-N-(奎宁环-3-基)苯并[b]噻吩-2-甲酰胺盐酸盐单水合物的晶型 |
| EP2559346B1 (en) | 2011-08-15 | 2014-03-26 | Symrise AG | Oleanene-type triterpene glycosides as masking agents |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
| US8729263B2 (en) * | 2012-08-13 | 2014-05-20 | Novartis Ag | 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions |
| MX383686B (es) | 2013-07-31 | 2025-03-14 | Novartis Ag | Derivados de piridazina 1,4-disustituida, y su uso para el tratamiento de afecciones relacionadas con la deficiencia de smn. |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2786770B1 (fr) * | 1998-12-04 | 2001-01-19 | Synthelabo | Derives de 1,4-diazabicyclo[3.2.2.]nonane, leur preparation et leur application en therapeutique |
| FR2809730B1 (fr) * | 2000-05-31 | 2002-07-19 | Sanofi Synthelabo | Derives de 1,4-diazabicyclo[3.2.2] nonanebenzoxazole, -benzothiazole et -benzimidazole, leur preparation et leur application therapeutique |
| FR2809732B1 (fr) * | 2000-05-31 | 2002-07-19 | Sanofi Synthelabo | DERIVES DE 4(-2-PHENYLTHIAZOL-5-yl)-1,4-DIAZABICYCLO-[3.2.2] NONANE, LEUR PREPARATION ET LEUR APPLICATION ENTHERAPEUTIQUE |
| FR2809731B1 (fr) * | 2000-05-31 | 2002-07-19 | Sanofi Synthelabo | Derives de 1,4-diazabicyclo-[3.2.2] nonane-pheylisoxazole, leur preparation et leur application en therapeutique |
| US20020086871A1 (en) * | 2000-12-29 | 2002-07-04 | O'neill Brian Thomas | Pharmaceutical composition for the treatment of CNS and other disorders |
| FR2832713B1 (fr) * | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(1,3,4-thiadiazol-2-yl)-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
| FR2832714B1 (fr) * | 2001-11-23 | 2004-07-16 | Sanofi Synthelabo | Derives de 4-(oxazolopyridin-2-yl)-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
| FR2832712B1 (fr) * | 2001-11-23 | 2004-02-13 | Sanofi Synthelabo | Derives de 4-(oxadiazol-3-yl)-1,4-diazabicyclo[3.2.2]nonane, leur preparation et leur application en therapeutique |
| DE10162442A1 (de) * | 2001-12-19 | 2003-07-03 | Bayer Ag | Monocyclische N-Aryl-amide |
-
2003
- 2003-11-10 AT AT03770918T patent/ATE345342T1/de active
- 2003-11-10 DK DK03770918T patent/DK1562945T3/da active
- 2003-11-10 EP EP03770918A patent/EP1562945B1/en not_active Expired - Lifetime
- 2003-11-10 AU AU2003280309A patent/AU2003280309A1/en not_active Abandoned
- 2003-11-10 JP JP2004550659A patent/JP2006508109A/ja not_active Ceased
- 2003-11-10 WO PCT/DK2003/000769 patent/WO2004043960A1/en not_active Ceased
- 2003-11-10 DE DE60309740T patent/DE60309740T2/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ATE345342T1 (de) | 2006-12-15 |
| WO2004043960A1 (en) | 2004-05-27 |
| DE60309740D1 (de) | 2006-12-28 |
| AU2003280309A1 (en) | 2004-06-03 |
| JP2006508109A (ja) | 2006-03-09 |
| EP1562945B1 (en) | 2006-11-15 |
| EP1562945A1 (en) | 2005-08-17 |
| DK1562945T3 (da) | 2007-03-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60309740T2 (de) | 1,4-dizabicyclo(3,2,2)nonane derivative, verfahren zu ihrer herstellung und therapeutical verwendung | |
| DE60311853T2 (de) | Neue 1,4-diazabicycloalkanderivate, deren herstellung und verwendung | |
| DE60318860T2 (de) | Chinucledin - derivate und deren verwendung | |
| DE60132710T2 (de) | 3-substituierte chinuclidine und ihre verwendung als nikotinische agonisten | |
| DE60310548T2 (de) | Diazabicyclische biarylderivate | |
| DE69823994T2 (de) | 8-azabicyclo(3,2,1)oct-2-en- und octanderivate als liganden der nicotinergen ach rezeptoren | |
| DE69705608T2 (de) | Tropanderivate, deren herstellung und verwendung | |
| DE60008866T2 (de) | Heteroaryl diazabicycloalkene, deren herstellung und verwendung | |
| JP2656699B2 (ja) | 置換ベンジルアミノキヌクリジン | |
| DE69516524T2 (de) | Therapeutisch verwendbare spiro-azabicyclische verbindungen | |
| DE60203007T2 (de) | Heteroaryl-diazabicycloalkanderivaten als cns-modulatoren | |
| EP1487834B1 (de) | Aza-bicyclische n-biarylamide mit affinität zum alpha7 nikotinischen acetylcholin-rezeptor | |
| DE60215172T2 (de) | Neue verbindungen, deren herstellung und verwendung | |
| DE60108639T2 (de) | Aryl- und heteroaryldiazabicycloalkane, deren zubereitung und verwendung | |
| DE69623799T2 (de) | Kondensierte tropanderivate als neurotransmitter-reuptake-inhibitoren | |
| DE69811070T2 (de) | 9-azabicyclo(3.3.1)non-2-ene und nonanderivate als liganden der nicotinergen rezeptoren | |
| DE69637097T2 (de) | 8-Azabicyclo(3.2.1)Oct-2-en-Derivate, deren Herstellung und Anwendung | |
| EP0984970B1 (en) | Spiro-quinuclidine derivatives, their preparation and use | |
| JP3223192B2 (ja) | アザビシクロおよびアザシクロオキシムおよびアミンコリン作働剤 | |
| DE69914935T2 (de) | 8-azabicyclo[3.2.1]okt-2-en- und -oktanderivate | |
| DE60003911T2 (de) | Heteroaryl-diazacycloalkane, ihre herstellung und verwendung | |
| DE69817214T2 (de) | Azaring-ether-derivate und ihre verwendung als nicotinic-ach-rezeptormodulatoren | |
| DE60307102T2 (de) | 3-substituierte chinuclidine und ihre verwendung | |
| DE69900220T2 (de) | Diaza-spiro[3,5]nonan-Derivate | |
| DE69817557T2 (de) | Piperidine derivate als inhibitoren der neurotransmitter-wiederaufbaunahme |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |