DE60318860T2 - Chinucledin - derivate und deren verwendung - Google Patents
Chinucledin - derivate und deren verwendung Download PDFInfo
- Publication number
- DE60318860T2 DE60318860T2 DE60318860T DE60318860T DE60318860T2 DE 60318860 T2 DE60318860 T2 DE 60318860T2 DE 60318860 T DE60318860 T DE 60318860T DE 60318860 T DE60318860 T DE 60318860T DE 60318860 T2 DE60318860 T2 DE 60318860T2
- Authority
- DE
- Germany
- Prior art keywords
- aza
- yloxy
- bicyclo
- octane
- disorder
- 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 66
- 201000010099 disease Diseases 0.000 claims abstract description 34
- 208000035475 disorder Diseases 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 208000002193 Pain Diseases 0.000 claims abstract description 13
- 239000000126 substance Substances 0.000 claims abstract description 11
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 9
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 7
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 6
- 230000016160 smooth muscle contraction Effects 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- UANSQQFYKHHDJM-KRWDZBQOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(N[C@@H]3C4CCN(CC4)C3)=O)=CC=CC2=C1 UANSQQFYKHHDJM-KRWDZBQOSA-N 0.000 claims description 9
- 102000005962 receptors Human genes 0.000 claims description 8
- 108020003175 receptors Proteins 0.000 claims description 8
- UYDJFXWILYZAEM-UHFFFAOYSA-N 3-(6-bromopyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound N1=NC(Br)=CC=C1OC1C(CC2)CCN2C1 UYDJFXWILYZAEM-UHFFFAOYSA-N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000032841 Bulimia Diseases 0.000 claims description 4
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 4
- 108010009685 Cholinergic Receptors Proteins 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
- 206010015037 epilepsy Diseases 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
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 230000001225 therapeutic effect Effects 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
- 125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 claims description 3
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 3
- VSKHAHUONMJJFL-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-bromo-1,3-thiazole Chemical compound S1C(Br)=CN=C1OC1C(CC2)CCN2C1 VSKHAHUONMJJFL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 206010010904 Convulsion Diseases 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 208000028017 Psychotic disease Diseases 0.000 claims description 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 229960002715 nicotine Drugs 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 3
- BWNSGMZYAPFBRL-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-(2,4-difluorophenyl)-1,3-thiazole Chemical compound FC1=CC(F)=CC=C1C(S1)=CN=C1OC1C(CC2)CCN2C1 BWNSGMZYAPFBRL-UHFFFAOYSA-N 0.000 claims description 2
- BQVJZWBRVUEZKU-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-(furan-3-yl)-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=COC=1 BQVJZWBRVUEZKU-UHFFFAOYSA-N 0.000 claims description 2
- RMCHOLPMARHFKR-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-phenyl-1,3,4-thiadiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NN=C1C1=CC=CC=C1 RMCHOLPMARHFKR-UHFFFAOYSA-N 0.000 claims description 2
- KHJZSFUHZDEQIU-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-phenyl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CC=C1 KHJZSFUHZDEQIU-UHFFFAOYSA-N 0.000 claims description 2
- PTPLMYRMZXCHSZ-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-pyridin-3-yl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CN=C1 PTPLMYRMZXCHSZ-UHFFFAOYSA-N 0.000 claims description 2
- FPVAPJYIZHSJKF-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-2-yl-1,3,4-thiadiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NN=C1C1=CC=CS1 FPVAPJYIZHSJKF-UHFFFAOYSA-N 0.000 claims description 2
- WENRZTCKEUNEMA-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-2-yl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CS1 WENRZTCKEUNEMA-UHFFFAOYSA-N 0.000 claims description 2
- GCNWMXJESTZDJB-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-3-yl-1,3-thiazole Chemical compound C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=CSC=1 GCNWMXJESTZDJB-UHFFFAOYSA-N 0.000 claims description 2
- NMFVGYWXADHCBK-UHFFFAOYSA-N 3-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-phenyl-1,2,4-thiadiazole Chemical compound C1CN(C2)CCC1C2OC(N=1)=NSC=1C1=CC=CC=C1 NMFVGYWXADHCBK-UHFFFAOYSA-N 0.000 claims description 2
- MCAXDSHKPBDHIW-UHFFFAOYSA-N 3-(6-chloropyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound N1=NC(Cl)=CC=C1OC1C(CC2)CCN2C1 MCAXDSHKPBDHIW-UHFFFAOYSA-N 0.000 claims description 2
- FWJYJIHEZKZYMF-UHFFFAOYSA-N 3-(6-phenylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CC=C1 FWJYJIHEZKZYMF-UHFFFAOYSA-N 0.000 claims description 2
- HMJIRHSCISEZOV-UHFFFAOYSA-N 3-(6-pyridin-3-ylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CN=C1 HMJIRHSCISEZOV-UHFFFAOYSA-N 0.000 claims description 2
- BGMCIWWSQXKNSS-UHFFFAOYSA-N 3-(6-thiophen-2-ylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CS1 BGMCIWWSQXKNSS-UHFFFAOYSA-N 0.000 claims description 2
- WDLZVIQQVWKVEO-UHFFFAOYSA-N 3-(6-thiophen-3-ylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C=1C=CSC=1 WDLZVIQQVWKVEO-UHFFFAOYSA-N 0.000 claims description 2
- IIDQULJVLLYOIG-UHFFFAOYSA-N 3-[6-(furan-2-yl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CO1 IIDQULJVLLYOIG-UHFFFAOYSA-N 0.000 claims description 2
- PYLFURFAUASCCK-UHFFFAOYSA-N 3-[6-(furan-3-yl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1CN(C2)CCC1C2OC(N=N1)=CC=C1C=1C=COC=1 PYLFURFAUASCCK-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
- 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
- 208000032131 Diabetic Neuropathies 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
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 2
- 206010019233 Headaches 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
- 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
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 206010041250 Social phobia Diseases 0.000 claims description 2
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 2
- 208000016620 Tourette disease 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
- 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
- 229960002069 diamorphine Drugs 0.000 claims description 2
- 235000014632 disordered eating Nutrition 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
- 230000001537 neural effect Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 208000021722 neuropathic pain 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
- 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
- 208000007101 Muscle Cramp Diseases 0.000 claims 1
- 208000005392 Spasm Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 102000034337 acetylcholine receptors Human genes 0.000 claims 1
- 150000001557 benzodiazepines Chemical class 0.000 claims 1
- 230000006378 damage Effects 0.000 claims 1
- 210000000750 endocrine system Anatomy 0.000 claims 1
- 230000001856 erectile effect Effects 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 230000000306 recurrent effect Effects 0.000 claims 1
- 230000001052 transient effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 36
- 150000008584 quinuclidines Chemical class 0.000 abstract description 22
- 210000001428 peripheral nervous system Anatomy 0.000 abstract description 7
- 208000017701 Endocrine disease Diseases 0.000 abstract description 5
- 230000001713 cholinergic effect Effects 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
- 238000000034 method Methods 0.000 description 30
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 9
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000003551 muscarinic effect Effects 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
- -1 3-substituted quinuclidine Chemical class 0.000 description 4
- 108060003345 Adrenergic Receptor Proteins 0.000 description 4
- 102000017910 Adrenergic receptor Human genes 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 102000015554 Dopamine receptor Human genes 0.000 description 4
- 108050004812 Dopamine receptor Proteins 0.000 description 4
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 4
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 229960003638 dopamine Drugs 0.000 description 4
- 150000002367 halogens Chemical group 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
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 210000002460 smooth muscle Anatomy 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 102000009660 Cholinergic Receptors Human genes 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 230000000035 biogenic effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000001530 fumaric acid Substances 0.000 description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- KQVVHCZXIWWDKE-WLHGVMLRSA-N (E)-but-2-enedioic acid 3-(6-chloropyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound OC(=O)\C=C\C(O)=O.N1=NC(Cl)=CC=C1OC1C(CC2)CCN2C1 KQVVHCZXIWWDKE-WLHGVMLRSA-N 0.000 description 2
- YZVSCZHAMXTFNT-WLHGVMLRSA-N (E)-but-2-enedioic acid 3-(6-phenylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CC=C1 YZVSCZHAMXTFNT-WLHGVMLRSA-N 0.000 description 2
- VDAYOSQIRJFMQQ-WLHGVMLRSA-N (E)-but-2-enedioic acid 3-(6-thiophen-3-ylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C=1C=CSC=1 VDAYOSQIRJFMQQ-WLHGVMLRSA-N 0.000 description 2
- LRFYCQRVOUVFCX-WLHGVMLRSA-N (E)-but-2-enedioic acid 3-[6-(furan-2-yl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CO1 LRFYCQRVOUVFCX-WLHGVMLRSA-N 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
- YZYRHVNZLQBWNQ-WLHGVMLRSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-(2,4-difluorophenyl)-1,3-thiazole (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.FC1=CC(F)=CC=C1C(S1)=CN=C1OC1C(CC2)CCN2C1 YZYRHVNZLQBWNQ-WLHGVMLRSA-N 0.000 description 2
- XCBDLWVCLSVQKJ-WLHGVMLRSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-2-yl-1,3-thiazole;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CS1 XCBDLWVCLSVQKJ-WLHGVMLRSA-N 0.000 description 2
- KQKHVGYDJKESPX-WLHGVMLRSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-thiophen-3-yl-1,3,4-thiadiazole (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NN=C1C=1C=CSC=1 KQKHVGYDJKESPX-WLHGVMLRSA-N 0.000 description 2
- UYMMKRJRQOPBHI-WLHGVMLRSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)quinoline (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=CC=CC2=NC(OC3C4CCN(C3)CC4)=CC=C21 UYMMKRJRQOPBHI-WLHGVMLRSA-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
- NWXJCZHPCMOVFY-WLHGVMLRSA-N 3-(6-bromopyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.N1=NC(Br)=CC=C1OC1C(CC2)CCN2C1 NWXJCZHPCMOVFY-WLHGVMLRSA-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
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
- SLOIQLYBYINVIH-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=1)=NSC=1C1=CC=CC=C1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=1)=NSC=1C1=CC=CC=C1 SLOIQLYBYINVIH-WLHGVMLRSA-N 0.000 description 2
- MSCAVTCVXAGXQB-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CS1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CS1 MSCAVTCVXAGXQB-WLHGVMLRSA-N 0.000 description 2
- QCEYEEQQIIEXEE-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C=1C=COC=1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C=1C=COC=1 QCEYEEQQIIEXEE-WLHGVMLRSA-N 0.000 description 2
- YENLQNQFHMAKES-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CN=C1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CN=C1 YENLQNQFHMAKES-WLHGVMLRSA-N 0.000 description 2
- PZZZLZGHKGFXIP-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=COC=1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=COC=1 PZZZLZGHKGFXIP-WLHGVMLRSA-N 0.000 description 2
- MZPQPOOVQDJBMJ-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=CSC=1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C=1C=CSC=1 MZPQPOOVQDJBMJ-WLHGVMLRSA-N 0.000 description 2
- CSXAKOPEZRKZPA-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NN=C1C1=CC=CC=C1 Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NN=C1C1=CC=CC=C1 CSXAKOPEZRKZPA-WLHGVMLRSA-N 0.000 description 2
- XVXBXFCVRSCZOZ-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.S1C(Br)=CN=C1OC1C(CC2)CCN2C1 Chemical compound OC(=O)\C=C\C(O)=O.S1C(Br)=CN=C1OC1C(CC2)CCN2C1 XVXBXFCVRSCZOZ-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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical class C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 description 2
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical class C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical class [H]C([H])([H])* 0.000 description 2
- 239000003149 muscarinic antagonist Substances 0.000 description 2
- 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 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000004059 squalene synthase inhibitor Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- ZKRSYCGPZSXTHX-WLHGVMLRSA-N (E)-but-2-enedioic acid 3-(6-pyridin-3-ylpyridazin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(N=N1)=CC=C1C1=CC=CN=C1 ZKRSYCGPZSXTHX-WLHGVMLRSA-N 0.000 description 1
- 239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 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
- QYIMSPSDBYKPPY-RSKUXYSASA-N (S)-2,3-epoxysqualene Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C=C(/C)CC\C=C(/C)CC[C@@H]1OC1(C)C QYIMSPSDBYKPPY-RSKUXYSASA-N 0.000 description 1
- 229930182840 (S)-nicotine Natural products 0.000 description 1
- 0 *=CN1*2CC(*C3CC3)C1CC2 Chemical compound *=CN1*2CC(*C3CC3)C1CC2 0.000 description 1
- 150000004868 1,2,5-thiadiazoles Chemical class 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- XIBIQFJKUZZLLX-UHFFFAOYSA-N 2,5-dibromo-1,3-thiazole Chemical compound BrC1=CN=C(Br)S1 XIBIQFJKUZZLLX-UHFFFAOYSA-N 0.000 description 1
- GGVBVLIHTBOYDQ-WLHGVMLRSA-N 2-(1-azabicyclo[2.2.2]octan-3-yloxy)-5-phenyl-1,3-thiazole (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C2)CCC1C2OC(S1)=NC=C1C1=CC=CC=C1 GGVBVLIHTBOYDQ-WLHGVMLRSA-N 0.000 description 1
- ASSPGHHANNDMET-UHFFFAOYSA-N 2-chloro-5-phenyl-1,3,4-thiadiazole Chemical compound S1C(Cl)=NN=C1C1=CC=CC=C1 ASSPGHHANNDMET-UHFFFAOYSA-N 0.000 description 1
- DRDNOLRPUJJPCU-UHFFFAOYSA-N 2-chloro-5-thiophen-3-yl-1,3,4-thiadiazole Chemical compound S1C(Cl)=NN=C1C1=CSC=C1 DRDNOLRPUJJPCU-UHFFFAOYSA-N 0.000 description 1
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
- VQAFMTSSCUETHA-UHFFFAOYSA-N 3,6-dibromopyridazine Chemical compound BrC1=CC=C(Br)N=N1 VQAFMTSSCUETHA-UHFFFAOYSA-N 0.000 description 1
- GUSWJGOYDXFJSI-UHFFFAOYSA-N 3,6-dichloropyridazine Chemical compound ClC1=CC=C(Cl)N=N1 GUSWJGOYDXFJSI-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZGROIHXQCKYCPT-UHFFFAOYSA-N 3-chloro-5-phenyl-1,2,4-thiadiazole Chemical compound ClC1=NSC(C=2C=CC=CC=2)=N1 ZGROIHXQCKYCPT-UHFFFAOYSA-N 0.000 description 1
- BUBRFWDEAVIFMV-UHFFFAOYSA-N 3-chloro-6-phenylpyridazine Chemical compound N1=NC(Cl)=CC=C1C1=CC=CC=C1 BUBRFWDEAVIFMV-UHFFFAOYSA-N 0.000 description 1
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-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
- 101710195183 Alpha-bungarotoxin Proteins 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000272079 Bungarus multicinctus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-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
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-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
- 208000020358 Learning disease Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- QYIMSPSDBYKPPY-UHFFFAOYSA-N OS Natural products CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC1OC1(C)C QYIMSPSDBYKPPY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 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
- 150000007513 acids Chemical class 0.000 description 1
- 229940091181 aconitic acid Drugs 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
- 230000003281 allosteric effect Effects 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 208000015606 cardiovascular system disease Diseases 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
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000011161 development Methods 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
- 239000003085 diluting agent Substances 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
- 239000003937 drug carrier Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical class 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
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940058690 lanosterol Drugs 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 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
- 238000012544 monitoring process Methods 0.000 description 1
- 230000008764 nerve damage 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
- 229910017604 nitric acid Inorganic materials 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
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 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
- 210000000578 peripheral nerve Anatomy 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
- 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
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 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
- 239000000047 product Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940075993 receptor modulator Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- 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
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/22—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
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Gynecology & Obstetrics (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Psychology (AREA)
- Pregnancy & Childbirth (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200201208 | 2002-08-14 | ||
| DK200201208 | 2002-08-14 | ||
| DKPA200201472 | 2002-10-02 | ||
| DK200201472 | 2002-10-02 | ||
| PCT/DK2003/000538 WO2004016608A1 (en) | 2002-08-14 | 2003-08-13 | Novel quinuclidine derivatives and their use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60318860D1 DE60318860D1 (de) | 2008-03-13 |
| DE60318860T2 true DE60318860T2 (de) | 2008-05-21 |
Family
ID=31889349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60318860T Expired - Lifetime DE60318860T2 (de) | 2002-08-14 | 2003-08-13 | Chinucledin - derivate und deren verwendung |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20050245567A1 (enExample) |
| EP (2) | EP1905771A3 (enExample) |
| JP (1) | JP2005538187A (enExample) |
| KR (1) | KR20050055711A (enExample) |
| CN (1) | CN100513406C (enExample) |
| AT (1) | ATE384720T1 (enExample) |
| AU (1) | AU2003250322B2 (enExample) |
| BR (1) | BR0313153A (enExample) |
| CA (1) | CA2493245A1 (enExample) |
| DE (1) | DE60318860T2 (enExample) |
| IL (1) | IL166254A0 (enExample) |
| IS (1) | IS7742A (enExample) |
| MX (1) | MXPA05001702A (enExample) |
| NO (1) | NO20051264L (enExample) |
| NZ (1) | NZ538058A (enExample) |
| PL (1) | PL375533A1 (enExample) |
| RU (1) | RU2323217C2 (enExample) |
| WO (1) | WO2004016608A1 (enExample) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6262265A (ja) * | 1985-09-13 | 1987-03-18 | Hitachi Ltd | 復水器自動検査補修システム |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| GB0220581D0 (en) * | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
| EP1603585A2 (en) | 2003-03-14 | 2005-12-14 | Bristol-Myers Squibb Company | Polynucleotide encoding a novel human g-protein coupled receptor variant of hm74, hgprbmy74 |
| DE602004031124D1 (de) * | 2003-08-13 | 2011-03-03 | Neurosearch As | Neue chinuklidinderivative und deren pharmazeutische verwendung |
| US7160876B2 (en) | 2003-12-22 | 2007-01-09 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US7309699B2 (en) | 2003-12-22 | 2007-12-18 | Abbott Laboratories | 3-Quinuclidinyl amino-substituted biaryl derivatives |
| US7655657B2 (en) | 2003-12-22 | 2010-02-02 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US7241773B2 (en) | 2003-12-22 | 2007-07-10 | Abbott Laboratories | 3-quinuclidinyl heteroatom bridged biaryl derivatives |
| US20050137203A1 (en) * | 2003-12-22 | 2005-06-23 | Jianguo Ji | 3-quinuclidinyl amino-substituted biaryl derivatives |
| US20050245531A1 (en) * | 2003-12-22 | 2005-11-03 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US20050137398A1 (en) * | 2003-12-22 | 2005-06-23 | Jianguo Ji | 3-Quinuclidinyl heteroatom bridged biaryl derivatives |
| EP1824848A1 (en) * | 2004-12-10 | 2007-08-29 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
| US7365193B2 (en) | 2004-02-04 | 2008-04-29 | Abbott Laboratories | Amino-substituted tricyclic derivatives and methods of use |
| US20050171079A1 (en) * | 2004-02-04 | 2005-08-04 | Schrimpf Michael R. | Amino-substituted tricyclic derivatives and methods of use |
| SE0400970D0 (sv) * | 2004-04-14 | 2004-04-14 | Astrazeneca Ab | Nicotinic acetylcholine receptor ligands |
| PE20060437A1 (es) | 2004-06-18 | 2006-06-08 | Novartis Ag | COMPUESTOS AZA-BICICLONONANOS COMO LIGANDOS COLINERGICOS DE nAChR |
| GB0415746D0 (en) * | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| GB0424564D0 (en) | 2004-11-05 | 2004-12-08 | Novartis Ag | Organic compounds |
| CA2591817A1 (en) * | 2004-12-22 | 2006-06-29 | Memory Pharmaceuticals Corporation | Nicotinic alpha-7 receptor ligands and preparation and uses thereof |
| BRPI0617534A2 (pt) * | 2005-09-23 | 2011-07-26 | Memory Pharm Corp | Composto, composição farmacêutica, método para a ativação/estimulação seletiva de receptores nicotínicos de a-7 em um paciente, método para o tratamento de um paciente que sofre de uma doença psicótica, uma doença neurodegenerativa que envolve uma disfunção do sistema colinérgico, e/ou uma condição de degeneração da memória e/ou da cognição, método para o tratamento de um paciente que sofre de demência e/ou uma outra condição com perda da memória, método para o tratamento de um paciente que sofre de degeneração da memória devida à degeneração cognitiva suave devida ao envelhecimento, mal de alzheimer, esquizofrenia, mal de parkinson, mal de huntington, mal de pick, mal de creutzfeldt-jakob, depressão, envelhecimento, trauma na cabeça, acidente vascular cerebral, hipoxia do cns, senilidade cerebral, demência de multiinfarto, hiv e/ou doença cardiovascular, método para o tratamento e/ou a prevenção da demência em um paciente com mal de alzheimer, método para o tratamento de um paciente para a retirada do álcool ou para o tratamento de um paciente com terapia anti-intoxicação, método para o tratamento de um paciente para conferir neuroproteção contra os danos associados com acidentes vasculares cerebrais e isquemia e excitotoxicidade induzida por glutamato, método para o tratamento de um paciente que sofre de vício de nicotina, dor, tontura de fuso horário, obesidade e/ou diabetes, método de indução de um paciente a parar de fumar, método para o tratamento de um paciente que sofre de degeneração cognitiva suave (mci), demência vascular (vad), declínio cognitivo associado com a idade (aacd), amnésia associada com a cirurgia de coração aberto, apreensão cardíaca, anestesia geral, déficits da memória devido à exposição a agentes anestésicos(...) |
| GB0521508D0 (en) * | 2005-10-21 | 2005-11-30 | Novartis Ag | Organic compounds |
| GB0525672D0 (en) * | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| GB0525673D0 (en) * | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| FR2904002A1 (fr) * | 2006-07-19 | 2008-01-25 | Galderma Res & Dev S N C Snc | Modulateurs de la lanosterol synthetase dans le traitement de l'acne ou de l'hyperseborrhee |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use thereof |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| WO2011009890A2 (en) * | 2009-07-23 | 2011-01-27 | Novartis Ag | Use of azabicycloalkyl derivatives or pyrrolidine-2-one derivatives |
| JO3250B1 (ar) | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
| PT3029039T (pt) | 2010-05-17 | 2017-11-28 | Forum Pharmaceuticals Inc | Formulações farmacêuticas que compreendem formas cristalinas de cloridrato de (r)-7-cloro-n-(quinuclidin-3-il)benzo(b)tiofeno-2-carboxamida mono-hidratado |
| PE20131394A1 (es) | 2010-09-23 | 2014-01-11 | Abbvie Inc | Monohidrato de derivados de aza-adamantano |
| US20120220729A1 (en) * | 2011-02-28 | 2012-08-30 | Boehringer Ingelheim International Gmbh | Liquid phase separation of plasmid dna isoforms and topoisomers |
| EP2846796A4 (en) | 2012-05-08 | 2015-10-21 | Forum Pharmaceuticals Inc | METHODS OF MAINTAINING, PROCESSING OR ENHANCING COGNITIVE FUNCTION |
| WO2014111837A1 (en) * | 2013-01-15 | 2014-07-24 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
| US20150313884A1 (en) | 2013-01-15 | 2015-11-05 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
| BR112015016994A8 (pt) * | 2013-01-15 | 2018-01-23 | Novartis Ag | uso de agonistas do receptor alfa 7 nicotínico de acetilcolina |
| WO2016100184A1 (en) | 2014-12-16 | 2016-06-23 | Forum Pharmaceuticals, Inc. | Geminal substituted quinuclidine amide compounds as agonists of alpha-7 nicotinic acetylcholine receptors |
| WO2016201096A1 (en) | 2015-06-10 | 2016-12-15 | Forum Pharmaceuticals, Inc. | Aminobenzisoxazole compounds as agonists of a7-nicotinic acetylcholine receptors |
| WO2017027600A1 (en) | 2015-08-12 | 2017-02-16 | Forum Pharmaceuticals, Inc. | GEMINAL SUBSTITUTED AMINOBENZISOXAZOLE COMPOUNDS AS AGONISTS OF α7-NICOTINIC ACETYLCHOLINE RECEPTORS |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3534053A (en) * | 1967-05-24 | 1970-10-13 | American Home Prod | Quinuclidine derivatives |
| SU495310A1 (ru) * | 1974-03-05 | 1975-12-15 | Всесоюзный Научно-Исследовательский Химико-Фармацевтический Институт Им.С.Орджоникидзе | Хинуклидил-3-диарал(гетерил) карбинолы, про вл ющие антигистаминную, антисеротониновую и антиаллергическую активность и способ их получени |
| DE3718317A1 (de) * | 1986-12-10 | 1988-06-16 | Bayer Ag | Substituierte basische 2-aminotetraline |
| CA1307790C (en) * | 1987-08-04 | 1992-09-22 | Ian Anthony Cliffe | Ethers |
| US5405853A (en) * | 1987-09-10 | 1995-04-11 | Merck Sharpe & Dohme Ltd. | Thiadiazoles useful in the treatment of senile dementia |
| JP2752143B2 (ja) * | 1988-04-01 | 1998-05-18 | 三共株式会社 | カルバペネム誘導体 |
| EP0363085A3 (en) * | 1988-10-03 | 1991-03-27 | Beecham Group Plc | Novel compounds |
| IT1227729B (it) * | 1988-12-23 | 1991-05-06 | Savio Spa | Procedimento e dispositivo per la rimozione delle fibre deteriorate durante il riattacco del filo in un filatoio open-end |
| YU84791A (sh) * | 1990-05-19 | 1994-06-10 | Boehringer Ingelheim Kg. | Biciklicni 1-aza-cikloalkalni |
| EP0555478A4 (en) * | 1990-08-31 | 1993-11-18 | Nippon Shinyaku Company, Limited | Pyrimidine derivative and medicine |
| ZA92278B (en) * | 1991-02-01 | 1992-10-28 | Akzo Nv | 3-quinuclidine derivatives |
| GB9201749D0 (en) * | 1992-01-28 | 1992-03-11 | Smithkline Beecham Plc | Medicaments |
| US5948793A (en) * | 1992-10-09 | 1999-09-07 | Abbott Laboratories | 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling neurotransmitter release |
| WO1995030675A1 (en) * | 1994-05-06 | 1995-11-16 | Smithkline Beecham Plc | Biphenylcarboxamides useful as 5-ht1d antagonists |
| JPH0840999A (ja) * | 1994-08-04 | 1996-02-13 | Yamanouchi Pharmaceut Co Ltd | フルオロインダン誘導体 |
| US5998404A (en) * | 1994-10-24 | 1999-12-07 | Eli Lilly And Company | Heterocyclic compounds and their use |
| US5821371A (en) * | 1994-10-24 | 1998-10-13 | Eli Lilly And Comany | Heterocyclic compounds and their preparation and use |
| JPH08134067A (ja) * | 1994-11-11 | 1996-05-28 | Yamanouchi Pharmaceut Co Ltd | キヌクリジン誘導体 |
| US5512574A (en) * | 1994-12-21 | 1996-04-30 | American Home Products Corporation | Quinuclidine and azabicyclo 2.2.1! heptane pyrazinyl ethers as muscarinic agonists |
| US5852037A (en) * | 1995-11-13 | 1998-12-22 | Eli Lilly And Company | Method for treating anxiety |
| JP2000500452A (ja) * | 1995-11-13 | 2000-01-18 | イーライ・リリー・アンド・カンパニー | 不安の処置法 |
| US5763457A (en) * | 1995-11-13 | 1998-06-09 | Eli Lilly And Company | Method for treating anxiety |
| FR2754261B1 (fr) * | 1996-10-08 | 1998-10-30 | Synthelabo | Derives de quinuclidine, leur preparation et leur application en therapeutique |
| AU7871498A (en) * | 1996-12-20 | 1998-07-17 | Novo Nordisk A/S | A method of treating hypercholesterolemia and related disorders |
| HN1998000118A (es) * | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
| FR2772378B1 (fr) * | 1997-12-12 | 2000-02-04 | Synthelabo | Derives d'imidazole, leur preparation et leur application en therapeutique |
| WO1999042461A1 (en) * | 1998-02-23 | 1999-08-26 | Warner-Lambert Company | Substituted quinoxaline derivatives as interleukin-8 receptor antagonists |
| JP4616971B2 (ja) * | 2000-07-18 | 2011-01-19 | 田辺三菱製薬株式会社 | 1−アザビシクロアルカン化合物およびその医薬用途 |
| ATE385497T1 (de) * | 2000-12-01 | 2008-02-15 | Neurosearch As | 3-substituierte quinuclidin-derivate und deren verwendung als nikotinischen agonisten |
-
2003
- 2003-08-13 RU RU2005101748/04A patent/RU2323217C2/ru not_active IP Right Cessation
- 2003-08-13 WO PCT/DK2003/000538 patent/WO2004016608A1/en not_active Ceased
- 2003-08-13 NZ NZ538058A patent/NZ538058A/en not_active IP Right Cessation
- 2003-08-13 AU AU2003250322A patent/AU2003250322B2/en not_active Ceased
- 2003-08-13 US US10/522,150 patent/US20050245567A1/en not_active Abandoned
- 2003-08-13 PL PL03375533A patent/PL375533A1/xx not_active Application Discontinuation
- 2003-08-13 AT AT03787742T patent/ATE384720T1/de not_active IP Right Cessation
- 2003-08-13 EP EP08100204A patent/EP1905771A3/en not_active Withdrawn
- 2003-08-13 CN CNB038190788A patent/CN100513406C/zh not_active Expired - Fee Related
- 2003-08-13 EP EP03787742A patent/EP1532144B1/en not_active Expired - Lifetime
- 2003-08-13 CA CA002493245A patent/CA2493245A1/en not_active Abandoned
- 2003-08-13 DE DE60318860T patent/DE60318860T2/de not_active Expired - Lifetime
- 2003-08-13 MX MXPA05001702A patent/MXPA05001702A/es active IP Right Grant
- 2003-08-13 BR BR0313153-0A patent/BR0313153A/pt not_active IP Right Cessation
- 2003-08-13 JP JP2005502013A patent/JP2005538187A/ja active Pending
- 2003-08-13 KR KR1020057002514A patent/KR20050055711A/ko not_active Ceased
-
2005
- 2005-01-12 IL IL16625405A patent/IL166254A0/xx unknown
- 2005-03-11 NO NO20051264A patent/NO20051264L/no not_active Application Discontinuation
- 2005-03-14 IS IS7742A patent/IS7742A/is unknown
-
2008
- 2008-09-08 US US12/206,302 patent/US20090005390A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1532144B1 (en) | 2008-01-23 |
| RU2323217C2 (ru) | 2008-04-27 |
| MXPA05001702A (es) | 2005-04-19 |
| CN100513406C (zh) | 2009-07-15 |
| RU2005101748A (ru) | 2006-01-20 |
| IL166254A0 (en) | 2006-01-15 |
| US20050245567A1 (en) | 2005-11-03 |
| JP2005538187A (ja) | 2005-12-15 |
| EP1532144A1 (en) | 2005-05-25 |
| AU2003250322B2 (en) | 2010-01-21 |
| DE60318860D1 (de) | 2008-03-13 |
| BR0313153A (pt) | 2005-06-28 |
| US20090005390A1 (en) | 2009-01-01 |
| CN1675205A (zh) | 2005-09-28 |
| IS7742A (is) | 2005-03-14 |
| EP1905771A2 (en) | 2008-04-02 |
| AU2003250322A1 (en) | 2004-03-03 |
| PL375533A1 (en) | 2005-11-28 |
| CA2493245A1 (en) | 2004-02-26 |
| NZ538058A (en) | 2006-11-30 |
| HK1080860A1 (zh) | 2006-05-04 |
| KR20050055711A (ko) | 2005-06-13 |
| ATE384720T1 (de) | 2008-02-15 |
| NO20051264L (no) | 2005-05-18 |
| WO2004016608A1 (en) | 2004-02-26 |
| EP1905771A3 (en) | 2008-11-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60318860T2 (de) | Chinucledin - derivate und deren verwendung | |
| DE60311853T2 (de) | Neue 1,4-diazabicycloalkanderivate, deren herstellung und verwendung | |
| DE60309740T2 (de) | 1,4-dizabicyclo(3,2,2)nonane derivative, verfahren zu ihrer herstellung und therapeutical verwendung | |
| DE60132710T2 (de) | 3-substituierte chinuclidine und ihre verwendung als nikotinische agonisten | |
| DE69823994T2 (de) | 8-azabicyclo(3,2,1)oct-2-en- und octanderivate als liganden der nicotinergen ach rezeptoren | |
| DE60310548T2 (de) | Diazabicyclische biarylderivate | |
| DE69637097T2 (de) | 8-Azabicyclo(3.2.1)Oct-2-en-Derivate, deren Herstellung und Anwendung | |
| DE69623799T2 (de) | Kondensierte tropanderivate als neurotransmitter-reuptake-inhibitoren | |
| DE60108639T2 (de) | Aryl- und heteroaryldiazabicycloalkane, deren zubereitung und verwendung | |
| DE60203007T2 (de) | Heteroaryl-diazabicycloalkanderivaten als cns-modulatoren | |
| US7750011B2 (en) | Diazabicyclic aryl derivatives and their medical use | |
| CN101426790A (zh) | 新颖的1,4-二氮杂-双环[3.2.2]壬基二唑基衍生物和它们的医药用途 | |
| DE60215172T2 (de) | Neue verbindungen, deren herstellung und verwendung | |
| 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 | |
| US7667040B2 (en) | Azacyclic ethynyl derivatives | |
| DE69914935T2 (de) | 8-azabicyclo[3.2.1]okt-2-en- und -oktanderivate | |
| EP1713809B1 (en) | Dimeric azacyclic compounds and their use | |
| JP2008530172A (ja) | ジアザ二環系アリール誘導体及びそれらのニコチン様アセチルコリン受容体におけるコリン作動性リガンドとしての使用 | |
| DE60307102T2 (de) | 3-substituierte chinuclidine und ihre verwendung | |
| US7514450B2 (en) | Azabicyclic aryl derivatives | |
| AU2005293510A1 (en) | Novel azabicyclic aryl derivatives and their medical use | |
| US20040127491A1 (en) | Novel diazabicyclic biaryl derivatives | |
| US7612074B2 (en) | Diazabicyclic aryl derivatives as cholinergy ligands | |
| US7750022B2 (en) | Quinuclidine derivatives and their pharmaceutical use | |
| DE60202667T2 (de) | Neue 2,5-diazabicyclo [2.2.1] heptanderivate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8381 | Inventor (new situation) |
Inventor name: PETERS, DAN, 2750 BALLERUP, DK Inventor name: OLSEN, GUNNAR M., 2750 BALLERUP, DK Inventor name: NIELSEN, ELSEBET OSTERGAARD, 2750 BALLERUP, DK Inventor name: AHRING, PHILIP K., 2750 BALLERUP, DK Inventor name: JORGENSEN, TINO DYHRING, 2750 BALLERUP, DK |
|
| 8364 | No opposition during term of opposition |