JP2008517032A - 新規なジアザ二環式アリール誘導体及びその医薬用途 - Google Patents
新規なジアザ二環式アリール誘導体及びその医薬用途 Download PDFInfo
- Publication number
- JP2008517032A JP2008517032A JP2007537263A JP2007537263A JP2008517032A JP 2008517032 A JP2008517032 A JP 2008517032A JP 2007537263 A JP2007537263 A JP 2007537263A JP 2007537263 A JP2007537263 A JP 2007537263A JP 2008517032 A JP2008517032 A JP 2008517032A
- Authority
- JP
- Japan
- Prior art keywords
- bicyclo
- octane
- methyl
- diaza
- phenyl
- 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.)
- Abandoned
Links
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 92
- 201000010099 disease Diseases 0.000 claims abstract description 49
- 208000035475 disorder Diseases 0.000 claims abstract description 41
- 208000002193 Pain Diseases 0.000 claims abstract description 15
- 230000036407 pain Effects 0.000 claims abstract description 15
- 239000000126 substance Substances 0.000 claims abstract description 12
- 102000005962 receptors Human genes 0.000 claims abstract description 11
- 108020003175 receptors Proteins 0.000 claims abstract description 11
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 10
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims abstract description 8
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 7
- 230000016160 smooth muscle contraction Effects 0.000 claims abstract description 7
- -1 selenophenyl Chemical group 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 15
- 125000002837 carbocyclic group Chemical group 0.000 claims description 15
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000001544 thienyl group Chemical group 0.000 claims description 15
- 125000004952 trihaloalkoxy group Chemical group 0.000 claims description 15
- 125000004385 trihaloalkyl group Chemical group 0.000 claims description 15
- 125000002541 furyl group Chemical group 0.000 claims description 14
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 14
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 14
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- 125000002971 oxazolyl group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 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
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 8
- 230000006735 deficit Effects 0.000 claims description 8
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 7
- 208000010877 cognitive disease Diseases 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 208000011580 syndromic disease Diseases 0.000 claims description 7
- 125000004306 triazinyl group Chemical group 0.000 claims description 7
- 125000001425 triazolyl group Chemical group 0.000 claims description 7
- 208000032841 Bulimia Diseases 0.000 claims description 6
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 6
- 208000028698 Cognitive impairment Diseases 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 6
- 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 6
- 208000019901 Anxiety disease Diseases 0.000 claims description 5
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 5
- 208000012661 Dyskinesia Diseases 0.000 claims description 5
- 230000036506 anxiety Effects 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 208000013403 hyperactivity Diseases 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 4
- 206010010904 Convulsion Diseases 0.000 claims description 4
- 206010039966 Senile dementia Diseases 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
- 230000004064 dysfunction Effects 0.000 claims description 4
- 206010015037 epilepsy Diseases 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 229960002715 nicotine Drugs 0.000 claims description 4
- YISXSTWECOJSAD-UHFFFAOYSA-N 2-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-5-phenyl-1,3-thiazole Chemical compound CN1C(C2)CCC1CC2C(S1)=NC=C1C1=CC=CC=C1 YISXSTWECOJSAD-UHFFFAOYSA-N 0.000 claims description 3
- WUSCINBBOHUBKL-UHFFFAOYSA-N 3-(5-thiophen-2-ylpyridin-2-yl)-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1C(N=C1)=CC=C1C1=CC=CS1 WUSCINBBOHUBKL-UHFFFAOYSA-N 0.000 claims description 3
- KEELKQCQWRDADH-UHFFFAOYSA-N 3-(5-thiophen-3-ylpyridin-2-yl)-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1C(N=C1)=CC=C1C=1C=CSC=1 KEELKQCQWRDADH-UHFFFAOYSA-N 0.000 claims description 3
- UQERIPBUTVPFMW-UHFFFAOYSA-N 3-(6-thiophen-2-ylpyridazin-3-yl)-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1C(N=N1)=CC=C1C1=CC=CS1 UQERIPBUTVPFMW-UHFFFAOYSA-N 0.000 claims description 3
- CEKSCQNRQATKLX-UHFFFAOYSA-N 3-(6-thiophen-3-ylpyridazin-3-yl)-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1C(N=N1)=CC=C1C=1C=CSC=1 CEKSCQNRQATKLX-UHFFFAOYSA-N 0.000 claims description 3
- RDWJMJFGEMAGPU-UHFFFAOYSA-N 3-[5-(2-chlorophenyl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=CC=C1Cl RDWJMJFGEMAGPU-UHFFFAOYSA-N 0.000 claims description 3
- OMOCGMRKVIWDNX-UHFFFAOYSA-N 3-[5-(2-fluorophenyl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=CC=C1F OMOCGMRKVIWDNX-UHFFFAOYSA-N 0.000 claims description 3
- IOJGWDHQADVSJB-UHFFFAOYSA-N 3-[5-(3-chlorophenyl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=CC(Cl)=C1 IOJGWDHQADVSJB-UHFFFAOYSA-N 0.000 claims description 3
- JFXVXKKGOUZCJR-UHFFFAOYSA-N 3-[5-(3-fluorophenyl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=CC(F)=C1 JFXVXKKGOUZCJR-UHFFFAOYSA-N 0.000 claims description 3
- FEFZIEXFOPAJTI-UHFFFAOYSA-N 3-[5-(4-chlorophenyl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=C(Cl)C=C1 FEFZIEXFOPAJTI-UHFFFAOYSA-N 0.000 claims description 3
- QTDHWMGAPMFAIO-UHFFFAOYSA-N 3-[5-(4-fluorophenyl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=C(F)C=C1 QTDHWMGAPMFAIO-UHFFFAOYSA-N 0.000 claims description 3
- GVBAMWCXJXPLCH-UHFFFAOYSA-N 3-[5-(furan-2-yl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=CO1 GVBAMWCXJXPLCH-UHFFFAOYSA-N 0.000 claims description 3
- DVYUXPSMWXNCQQ-UHFFFAOYSA-N 3-[5-(furan-3-yl)pyridin-2-yl]-8-methyl-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C=1C=COC=1 DVYUXPSMWXNCQQ-UHFFFAOYSA-N 0.000 claims description 3
- KMZPCIDWXCUCPD-UHFFFAOYSA-N 3-[6-(2-fluorophenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1F KMZPCIDWXCUCPD-UHFFFAOYSA-N 0.000 claims description 3
- TXFIHWUHZJMBHM-UHFFFAOYSA-N 3-[6-(2-methoxyphenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound COC1=CC=CC=C1C1=CC=C(N2CC3CCC(N3C)C2)N=N1 TXFIHWUHZJMBHM-UHFFFAOYSA-N 0.000 claims description 3
- IGBGHVHQEYSYQF-UHFFFAOYSA-N 3-[6-(3-chlorophenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC(Cl)=C1 IGBGHVHQEYSYQF-UHFFFAOYSA-N 0.000 claims description 3
- LOVITCACDLOTGT-UHFFFAOYSA-N 3-[6-(3-fluorophenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC(F)=C1 LOVITCACDLOTGT-UHFFFAOYSA-N 0.000 claims description 3
- IXCRJFKVIOQAAL-UHFFFAOYSA-N 3-[6-(3-methoxyphenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound COC1=CC=CC(C=2N=NC(=CC=2)N2CC3CCC(N3C)C2)=C1 IXCRJFKVIOQAAL-UHFFFAOYSA-N 0.000 claims description 3
- QTZOEHDPWANFNI-UHFFFAOYSA-N 3-[6-(4-chlorophenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=C(Cl)C=C1 QTZOEHDPWANFNI-UHFFFAOYSA-N 0.000 claims description 3
- MLCOLEAZHHTYBV-UHFFFAOYSA-N 3-[6-(4-fluorophenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=C(F)C=C1 MLCOLEAZHHTYBV-UHFFFAOYSA-N 0.000 claims description 3
- HMTDTAICRFCKHH-UHFFFAOYSA-N 3-[6-(4-methoxyphenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound C1=CC(OC)=CC=C1C1=CC=C(N2CC3CCC(N3C)C2)N=N1 HMTDTAICRFCKHH-UHFFFAOYSA-N 0.000 claims description 3
- JCZLHZSIUDMYNL-UHFFFAOYSA-N 3-[6-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]aniline Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC(N)=C1 JCZLHZSIUDMYNL-UHFFFAOYSA-N 0.000 claims description 3
- PWEZFKQNLWIPGJ-UHFFFAOYSA-N 3-[6-(furan-2-yl)pyridazin-3-yl]-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1C(N=N1)=CC=C1C1=CC=CO1 PWEZFKQNLWIPGJ-UHFFFAOYSA-N 0.000 claims description 3
- SUQCPEYDOLKQAL-UHFFFAOYSA-N 3-[6-(furan-2-yl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CO1 SUQCPEYDOLKQAL-UHFFFAOYSA-N 0.000 claims description 3
- FHKSYHPBPDFISF-UHFFFAOYSA-N 3-[6-(furan-3-yl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C=1C=COC=1 FHKSYHPBPDFISF-UHFFFAOYSA-N 0.000 claims description 3
- XUHXGBGWYUYLLC-UHFFFAOYSA-N 8-methyl-3-(2-phenylpyrimidin-4-yl)-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=1)=CC=NC=1C1=CC=CC=C1 XUHXGBGWYUYLLC-UHFFFAOYSA-N 0.000 claims description 3
- JDWFMJUWVMBXAI-UHFFFAOYSA-N 8-methyl-3-(5-phenylpyrazin-2-yl)-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CN=C1C1=CC=CC=C1 JDWFMJUWVMBXAI-UHFFFAOYSA-N 0.000 claims description 3
- JRKBDTXDEZLYJQ-UHFFFAOYSA-N 8-methyl-3-(5-phenylpyridin-2-yl)-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=C1)=CC=C1C1=CC=CC=C1 JRKBDTXDEZLYJQ-UHFFFAOYSA-N 0.000 claims description 3
- ZLDUJUWZLYQFHQ-UHFFFAOYSA-N 8-methyl-3-(5-phenylpyrimidin-2-yl)-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=NC=C1C1=CC=CC=C1 ZLDUJUWZLYQFHQ-UHFFFAOYSA-N 0.000 claims description 3
- DWQHUVLKWBYGRE-UHFFFAOYSA-N 8-methyl-3-(5-thiophen-2-ylpyridin-2-yl)-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C1=CC=CS1 DWQHUVLKWBYGRE-UHFFFAOYSA-N 0.000 claims description 3
- NYQZOEBFIHJXQX-UHFFFAOYSA-N 8-methyl-3-(5-thiophen-3-ylpyridin-2-yl)-8-azabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CC2C(N=C1)=CC=C1C=1C=CSC=1 NYQZOEBFIHJXQX-UHFFFAOYSA-N 0.000 claims description 3
- DOAQPGBYYNURQR-UHFFFAOYSA-N 8-methyl-3-(6-pyridin-3-ylpyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CN=C1 DOAQPGBYYNURQR-UHFFFAOYSA-N 0.000 claims description 3
- HCDLATBHMBZZNA-UHFFFAOYSA-N 8-methyl-3-(6-thiophen-2-ylpyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CS1 HCDLATBHMBZZNA-UHFFFAOYSA-N 0.000 claims description 3
- XZXNRTFDNADLMF-UHFFFAOYSA-N 8-methyl-3-(6-thiophen-3-ylpyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C=1C=CSC=1 XZXNRTFDNADLMF-UHFFFAOYSA-N 0.000 claims description 3
- 208000030507 AIDS Diseases 0.000 claims description 3
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 3
- 201000004384 Alopecia Diseases 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 3
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 3
- 206010003805 Autism Diseases 0.000 claims description 3
- 208000020706 Autistic disease Diseases 0.000 claims description 3
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 3
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 208000030814 Eating disease Diseases 0.000 claims description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 208000026097 Factitious disease Diseases 0.000 claims description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 3
- 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 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 206010020850 Hyperthyroidism Diseases 0.000 claims description 3
- 206010021143 Hypoxia Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 3
- 206010026749 Mania Diseases 0.000 claims description 3
- 208000019695 Migraine disease Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 241000208125 Nicotiana Species 0.000 claims description 3
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000004983 Phantom Limb Diseases 0.000 claims description 3
- 208000008348 Post-Concussion Syndrome Diseases 0.000 claims description 3
- 208000004550 Postoperative Pain Diseases 0.000 claims description 3
- 208000005107 Premature Birth Diseases 0.000 claims description 3
- 206010036590 Premature baby Diseases 0.000 claims description 3
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 3
- 206010052276 Pseudodementia Diseases 0.000 claims description 3
- 206010000496 acne Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 230000006793 arrhythmia Effects 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 229940049706 benzodiazepine Drugs 0.000 claims description 3
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
- 208000028683 bipolar I disease Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 229960003920 cocaine Drugs 0.000 claims description 3
- 230000036461 convulsion Effects 0.000 claims description 3
- 230000003111 delayed effect Effects 0.000 claims description 3
- 229960002069 diamorphine Drugs 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 235000014632 disordered eating Nutrition 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 206010013932 dyslexia Diseases 0.000 claims description 3
- 208000024963 hair loss Diseases 0.000 claims description 3
- 230000003676 hair loss Effects 0.000 claims description 3
- 230000007954 hypoxia Effects 0.000 claims description 3
- 201000001881 impotence Diseases 0.000 claims description 3
- 201000009863 inflammatory diarrhea Diseases 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 3
- 230000000938 luteal effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 206010027175 memory impairment Diseases 0.000 claims description 3
- 206010027599 migraine Diseases 0.000 claims description 3
- 229960005181 morphine Drugs 0.000 claims description 3
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 3
- 201000003631 narcolepsy Diseases 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 229940005483 opioid analgesics Drugs 0.000 claims description 3
- 208000019906 panic disease Diseases 0.000 claims description 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 208000028591 pheochromocytoma Diseases 0.000 claims description 3
- 206010036596 premature ejaculation Diseases 0.000 claims description 3
- 201000004700 rosacea Diseases 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- 208000020685 sleep-wake disease Diseases 0.000 claims description 3
- 230000001052 transient effect Effects 0.000 claims description 3
- QRCGAJXDQNYPMX-UHFFFAOYSA-N 2-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-5-phenyl-1,3,4-thiadiazole Chemical compound CN1C(C2)CCC1CN2C(S1)=NN=C1C1=CC=CC=C1 QRCGAJXDQNYPMX-UHFFFAOYSA-N 0.000 claims description 2
- LHCADAWQIOZWDH-UHFFFAOYSA-N 2-[6-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]aniline Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1N LHCADAWQIOZWDH-UHFFFAOYSA-N 0.000 claims description 2
- XBOLMJAIWSSQIB-UHFFFAOYSA-N 3-[6-(2-chlorophenyl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1Cl XBOLMJAIWSSQIB-UHFFFAOYSA-N 0.000 claims description 2
- KBAJSWABYPAQTG-UHFFFAOYSA-N 3-[6-(6-methoxynaphthalen-2-yl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound C1C(N2C)CCC2CN1C(N=N1)=CC=C1C1=CC2=CC=C(OC)C=C2C=C1 KBAJSWABYPAQTG-UHFFFAOYSA-N 0.000 claims description 2
- MGXGJGTTXATIJI-UHFFFAOYSA-N 3-[6-(furan-3-yl)pyridazin-3-yl]-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1C(N=N1)=CC=C1C=1C=COC=1 MGXGJGTTXATIJI-UHFFFAOYSA-N 0.000 claims description 2
- BEYZUTVKKFZHCP-UHFFFAOYSA-N 8-methyl-3-(6-phenylpyridin-2-yl)-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=1)=CC=CC=1C1=CC=CC=C1 BEYZUTVKKFZHCP-UHFFFAOYSA-N 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 206010065390 Inflammatory pain Diseases 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 208000010886 Peripheral nerve injury Diseases 0.000 claims description 2
- 206010056238 Phantom pain Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 230000002920 convulsive effect Effects 0.000 claims description 2
- 210000000750 endocrine system Anatomy 0.000 claims description 2
- IDKMYYJLMVVTIE-UHFFFAOYSA-N n-[2-[6-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenyl]acetamide Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1NC(C)=O IDKMYYJLMVVTIE-UHFFFAOYSA-N 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- 230000000306 recurrent effect Effects 0.000 claims description 2
- 230000020341 sensory perception of pain Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 102000034337 acetylcholine receptors Human genes 0.000 claims 2
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims 1
- 206010036790 Productive cough Diseases 0.000 claims 1
- 208000000323 Tourette Syndrome Diseases 0.000 claims 1
- 208000016620 Tourette disease Diseases 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims 1
- 230000001568 sexual effect Effects 0.000 claims 1
- 208000024794 sputum Diseases 0.000 claims 1
- 210000003802 sputum Anatomy 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 70
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 abstract description 17
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 abstract description 17
- 230000001713 cholinergic effect Effects 0.000 abstract description 9
- 210000001428 peripheral nervous system Anatomy 0.000 abstract description 7
- 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
- 108010078791 Carrier Proteins Proteins 0.000 abstract description 3
- 208000030172 endocrine system disease Diseases 0.000 abstract description 3
- 239000003446 ligand Substances 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000012458 free base Substances 0.000 description 18
- 238000002844 melting Methods 0.000 description 16
- 230000008018 melting Effects 0.000 description 16
- 125000005843 halogen group Chemical group 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 102000009660 Cholinergic Receptors Human genes 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 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
- OFNWMZRPXFBZPX-UHFFFAOYSA-N 8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1N2C OFNWMZRPXFBZPX-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 4
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 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
- 210000001519 tissue Anatomy 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000001530 fumaric acid Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- HWSITRIWQWMMMC-WLHGVMLRSA-N (E)-but-2-enedioic acid 3-[6-(6-methoxynaphthalen-2-yl)pyridazin-3-yl]-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound OC(=O)\C=C\C(O)=O.C1C(N2C)CCC2CN1C(N=N1)=CC=C1C1=CC2=CC=C(OC)C=C2C=C1 HWSITRIWQWMMMC-WLHGVMLRSA-N 0.000 description 2
- CEUROJCMQWJATQ-WLHGVMLRSA-N (E)-but-2-enedioic acid N-[2-[6-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenyl]acetamide Chemical compound OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1NC(C)=O CEUROJCMQWJATQ-WLHGVMLRSA-N 0.000 description 2
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 description 2
- KHQDKIXTZAIIFA-UHFFFAOYSA-N 2-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]benzenethiol Chemical compound SC1=CC=CC=C1CC1=NN=C(C=2C=CC=CC=2)O1 KHQDKIXTZAIIFA-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
- 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 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- PBWPJLZOJXFPNA-UHFFFAOYSA-N 3-(6-bromopyridazin-3-yl)-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C1=CC=C(Br)N=N1 PBWPJLZOJXFPNA-UHFFFAOYSA-N 0.000 description 2
- RQYVDNGHABJKNV-UHFFFAOYSA-N 3-(6-phenylpyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CN1C(N=N1)=CC=C1C1=CC=CC=C1 RQYVDNGHABJKNV-UHFFFAOYSA-N 0.000 description 2
- GQIXVQRBAFSAQT-UHFFFAOYSA-N 3-benzyl-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2CC1=CC=CC=C1 GQIXVQRBAFSAQT-UHFFFAOYSA-N 0.000 description 2
- LAEFEQWBXJQNGP-UHFFFAOYSA-N 3-benzyl-8-methyl-3,8-diazabicyclo[3.2.1]octane-2,4-dione Chemical compound CN1C(C2=O)CCC1C(=O)N2CC1=CC=CC=C1 LAEFEQWBXJQNGP-UHFFFAOYSA-N 0.000 description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 2
- 108060003345 Adrenergic Receptor Proteins 0.000 description 2
- 102000017910 Adrenergic receptor Human genes 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
- 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
- 102000015554 Dopamine receptor Human genes 0.000 description 2
- 108050004812 Dopamine receptor Proteins 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
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- MYRDXCCAWOYUEL-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(N=1)=CC=CC=1C1=CC=CC=C1 Chemical compound OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(N=1)=CC=CC=1C1=CC=CC=C1 MYRDXCCAWOYUEL-WLHGVMLRSA-N 0.000 description 2
- PLWGADMSTKBBLK-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1Cl Chemical compound OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1Cl PLWGADMSTKBBLK-WLHGVMLRSA-N 0.000 description 2
- PIWDHEMNLKDXCG-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1N Chemical compound OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1N PIWDHEMNLKDXCG-WLHGVMLRSA-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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- BEWYHVAWEKZDPP-UHFFFAOYSA-N bornane Chemical compound C1CC2(C)CCC1C2(C)C BEWYHVAWEKZDPP-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 2
- FZWJIDROOOWMRA-UHFFFAOYSA-N n-[3-[6-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]phenyl]acetamide Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC(NC(C)=O)=C1 FZWJIDROOOWMRA-UHFFFAOYSA-N 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 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
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 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
- IILMTDADGAOEDP-UHFFFAOYSA-N 3-(5-bromopyridin-2-yl)-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C1=CC=C(Br)C=N1 IILMTDADGAOEDP-UHFFFAOYSA-N 0.000 description 1
- PBCFPEKWIMJHHD-UHFFFAOYSA-N 3-(6-bromopyridin-2-yl)-8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C1=CC=CC(Br)=N1 PBCFPEKWIMJHHD-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
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- ANBJJAROENDFHC-UHFFFAOYSA-N 5-phenyl-1,3,4-thiadiazol-2-amine;sulfuric acid Chemical compound OS(O)(=O)=O.S1C(N)=NN=C1C1=CC=CC=C1 ANBJJAROENDFHC-UHFFFAOYSA-N 0.000 description 1
- FOHWXVBZGSVUGO-UHFFFAOYSA-N 5-phenyl-3h-1,3,4-oxadiazole-2-thione Chemical compound O1C(S)=NN=C1C1=CC=CC=C1 FOHWXVBZGSVUGO-UHFFFAOYSA-N 0.000 description 1
- SFHYNDMGZXWXBU-LIMNOBDPSA-N 6-amino-2-[[(e)-(3-formylphenyl)methylideneamino]carbamoylamino]-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1NC(=O)N\N=C\C1=CC=CC(C=O)=C1 SFHYNDMGZXWXBU-LIMNOBDPSA-N 0.000 description 1
- 125000006164 6-membered heteroaryl group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- XMWHYEQWVQHSHG-UHFFFAOYSA-N 8-methyl-3-(6-phenylpyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octane Chemical compound CN1C(C2)CCC1CN2C(N=N1)=CC=C1C1=CC=CC=C1 XMWHYEQWVQHSHG-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000173529 Aconitum napellus Species 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
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-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
- 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
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- XETQTCAMTVHYPO-UHFFFAOYSA-N Isocamphan von ungewisser Konfiguration Natural products C1CC2C(C)(C)C(C)C1C2 XETQTCAMTVHYPO-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
- 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
- BXYRLMDMMDILNK-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(S1)=NN=C1C1=CC=CC=C1 Chemical compound OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C(S1)=NN=C1C1=CC=CC=C1 BXYRLMDMMDILNK-WLHGVMLRSA-N 0.000 description 1
- GNSWXVHRYWXXRE-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C1=CC=CC(Br)=N1 Chemical compound OC(=O)\C=C\C(O)=O.CN1C(C2)CCC1CN2C1=CC=CC(Br)=N1 GNSWXVHRYWXXRE-WLHGVMLRSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 206010034912 Phobia 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
- 208000034189 Sclerosis Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940023019 aconite Drugs 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 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
- 125000003943 azolyl group Chemical group 0.000 description 1
- 125000003828 azulenyl group Chemical group 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
- 125000005605 benzo group Chemical group 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 1
- 125000004540 benzothiazol-5-yl group Chemical group S1C=NC2=C1C=CC(=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004534 benzothien-2-yl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004535 benzothien-5-yl group Chemical group S1C=CC2=C1C=CC(=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 229930006742 bornane Natural products 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 208000015114 central nervous system disease Diseases 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
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 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
- CXYVVNXQWYWPIL-DTORHVGOSA-N diethyl (2s,5r)-1-methylpyrrolidine-2,5-dicarboxylate Chemical compound CCOC(=O)[C@H]1CC[C@@H](C(=O)OCC)N1C CXYVVNXQWYWPIL-DTORHVGOSA-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
- 239000003480 eluent Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229940044170 formate Drugs 0.000 description 1
- 238000001640 fractional crystallisation Methods 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
- 238000010438 heat treatment Methods 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 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
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 description 1
- 125000004500 isothiazol-4-yl group Chemical group S1N=CC(=C1)* 0.000 description 1
- 125000004501 isothiazol-5-yl group Chemical group S1N=CC=C1* 0.000 description 1
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 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
- 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
- 238000012544 monitoring process Methods 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
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000005036 nerve Anatomy 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
- 230000009871 nonspecific binding Effects 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
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 1
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 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
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 208000019899 phobic disease Diseases 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
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate 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
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000003252 repetitive effect Effects 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
- 229940076279 serotonin Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 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
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration 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
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-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
- 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
- COHOGNZHAUOXPA-UHFFFAOYSA-N trimethyl(phenyl)stannane Chemical compound C[Sn](C)(C)C1=CC=CC=C1 COHOGNZHAUOXPA-UHFFFAOYSA-N 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 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
- 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
- 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
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- 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
- A61P15/10—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
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/20—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
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Reproductive Health (AREA)
- Psychology (AREA)
- Pulmonology (AREA)
- Child & Adolescent Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Anesthesiology (AREA)
- Gynecology & Obstetrics (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200401603 | 2004-10-20 | ||
| US62032704P | 2004-10-21 | 2004-10-21 | |
| PCT/EP2005/055333 WO2006045716A1 (en) | 2004-10-20 | 2005-10-18 | Novel diazabicyclic aryl derivatives and their medical use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008517032A true JP2008517032A (ja) | 2008-05-22 |
| JP2008517032A5 JP2008517032A5 (enExample) | 2008-12-11 |
Family
ID=38731691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007537263A Abandoned JP2008517032A (ja) | 2004-10-20 | 2005-10-18 | 新規なジアザ二環式アリール誘導体及びその医薬用途 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20080153806A1 (enExample) |
| EP (1) | EP1805183B1 (enExample) |
| JP (1) | JP2008517032A (enExample) |
| CN (1) | CN101035792B (enExample) |
| AT (1) | ATE493415T1 (enExample) |
| AU (1) | AU2005298693A1 (enExample) |
| CA (1) | CA2584838A1 (enExample) |
| DE (1) | DE602005025667D1 (enExample) |
| MX (1) | MX2007004269A (enExample) |
| NZ (1) | NZ553622A (enExample) |
| WO (1) | WO2006045716A1 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014515754A (ja) * | 2011-04-20 | 2014-07-03 | サントル ナスィオナル ド ラ ルシェルシュ スィアンティフィク（セ．エン．エル．エス．） | １，４−二置換１，２，３−トリアゾール、その調製方法、ならびにその診断的および治療的使用 |
| JPWO2022014680A1 (enExample) * | 2020-07-17 | 2022-01-20 | ||
| JP2023103981A (ja) * | 2022-01-14 | 2023-07-27 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 置換ピペリジン化合物を含有する医薬 |
| RU2840772C1 (ru) * | 2020-07-17 | 2025-05-28 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Замещенные пиперидиновые соединения и их применение |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2005295441B2 (en) | 2004-10-18 | 2009-04-23 | Amgen, Inc. | Thiadiazole compounds and methods of use |
| ATE495178T1 (de) | 2005-02-16 | 2011-01-15 | Neurosearch As | Diazabicyclische arylderivate und ihre verwendung als chinolinergische liganden an nikotin- acetylcholin-rezeptoren |
| EP1963323B1 (en) | 2005-12-06 | 2010-07-14 | Neurosearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| US7700596B2 (en) | 2006-02-10 | 2010-04-20 | Neurosearch A/S | 3,9-diazabicyclo[3.3.1]nonane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| EP1987031A1 (en) | 2006-02-10 | 2008-11-05 | NeuroSearch A/S | 3-heteroaryl- 3,9-diazabicyclo[3.3.1]nonane derivatives as nicotinic acetylcholine receptor agonists |
| AU2007213670A1 (en) | 2006-02-10 | 2007-08-16 | Neurosearch A/S | 3,9-diazabicyclo[3.3.1]nonane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| JP2009526777A (ja) | 2006-02-14 | 2009-07-23 | ノイロサーチ アクティーゼルスカブ | ニコチン性アセチルコリン受容体作用薬としての３，９−ジアザビシクロ（３．３．１）ノナ−３−イル−アリールメタノン誘導体 |
| JP2009537599A (ja) | 2006-05-23 | 2009-10-29 | ノイロサーチ アクティーゼルスカブ | 新規８，１０−ジアザ−ビシクロ［４．３．１］デカン誘導体及びそれらの医学的使用 |
| US8314119B2 (en) * | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| US7897619B2 (en) | 2007-07-17 | 2011-03-01 | Amgen Inc. | Heterocyclic modulators of PKB |
| AU2008276512A1 (en) | 2007-07-17 | 2009-01-22 | Amgen Inc. | Thiadiazole modulators of PKB |
| 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 |
| FR2937641A1 (fr) * | 2008-10-28 | 2010-04-30 | Sanofi Aventis | Derives d'urees de tropane, leur preparation et leur application en therapeutique |
| CN106074548A (zh) | 2010-09-23 | 2016-11-09 | 艾伯维巴哈马有限公司 | 氮杂金刚烷衍生物的一水合物 |
| TW201311698A (zh) * | 2011-08-22 | 2013-03-16 | Targacept Inc | 作為神經元菸鹼乙醯膽鹼受體配位體之１，４－二氮雜雙環［３．２．２］壬烷 |
| 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 |
| US11530207B2 (en) | 2018-04-10 | 2022-12-20 | Skyhawk Therapeutics, Inc. | Compounds for the treatment of cancer |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7265115B2 (en) * | 1999-01-29 | 2007-09-04 | Abbott Laboratories | Diazabicyclic CNS active agents |
| CA2365258A1 (en) * | 1999-05-04 | 2000-11-09 | Neurosearch A/S | Heteroaryl diazabicycloalkanes, their preparation and use |
| US20050065178A1 (en) * | 2003-09-19 | 2005-03-24 | Anwer Basha | Substituted diazabicycloakane derivatives |
| US7399765B2 (en) * | 2003-09-19 | 2008-07-15 | Abbott Laboratories | Substituted diazabicycloalkane derivatives |
-
2005
- 2005-10-18 MX MX2007004269A patent/MX2007004269A/es active IP Right Grant
- 2005-10-18 DE DE602005025667T patent/DE602005025667D1/de not_active Expired - Lifetime
- 2005-10-18 AT AT05801524T patent/ATE493415T1/de not_active IP Right Cessation
- 2005-10-18 CN CN2005800337300A patent/CN101035792B/zh not_active Expired - Fee Related
- 2005-10-18 WO PCT/EP2005/055333 patent/WO2006045716A1/en not_active Ceased
- 2005-10-18 US US11/665,387 patent/US20080153806A1/en not_active Abandoned
- 2005-10-18 JP JP2007537263A patent/JP2008517032A/ja not_active Abandoned
- 2005-10-18 CA CA002584838A patent/CA2584838A1/en not_active Abandoned
- 2005-10-18 NZ NZ553622A patent/NZ553622A/en unknown
- 2005-10-18 AU AU2005298693A patent/AU2005298693A1/en not_active Abandoned
- 2005-10-18 EP EP05801524A patent/EP1805183B1/en not_active Expired - Lifetime
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014515754A (ja) * | 2011-04-20 | 2014-07-03 | サントル ナスィオナル ド ラ ルシェルシュ スィアンティフィク（セ．エン．エル．エス．） | １，４−二置換１，２，３−トリアゾール、その調製方法、ならびにその診断的および治療的使用 |
| JPWO2022014680A1 (enExample) * | 2020-07-17 | 2022-01-20 | ||
| WO2022014680A1 (ja) * | 2020-07-17 | 2022-01-20 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 置換ピペリジン化合物及びその用途 |
| US11479552B2 (en) | 2020-07-17 | 2022-10-25 | Eisai R&D Management Co., Ltd. | Substituted piperidine compounds and their use |
| JP7190612B2 (ja) | 2020-07-17 | 2022-12-15 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 置換ピペリジン化合物及びその用途 |
| RU2840772C1 (ru) * | 2020-07-17 | 2025-05-28 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Замещенные пиперидиновые соединения и их применение |
| TWI888599B (zh) * | 2020-07-17 | 2025-07-01 | 日商衛材R&D企管股份有限公司 | 取代哌啶化合物及其用途 |
| JP2023103981A (ja) * | 2022-01-14 | 2023-07-27 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 置換ピペリジン化合物を含有する医薬 |
| JP7591592B2 (ja) | 2022-01-14 | 2024-11-28 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 置換ピペリジン化合物を含有する医薬 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005298693A1 (en) | 2006-05-04 |
| MX2007004269A (es) | 2007-06-15 |
| ATE493415T1 (de) | 2011-01-15 |
| US20080153806A1 (en) | 2008-06-26 |
| EP1805183B1 (en) | 2010-12-29 |
| CN101035792A (zh) | 2007-09-12 |
| EP1805183A1 (en) | 2007-07-11 |
| DE602005025667D1 (de) | 2011-02-10 |
| CN101035792B (zh) | 2010-09-15 |
| CA2584838A1 (en) | 2006-05-04 |
| NZ553622A (en) | 2010-08-27 |
| WO2006045716A1 (en) | 2006-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003250322B2 (en) | Novel quinuclidine derivatives and their use | |
| JP2008517032A (ja) | 新規なジアザ二環式アリール誘導体及びその医薬用途 | |
| JP2006508109A (ja) | １，４−ジアザビシクロ（３，２，２）ノナン誘導体、その製造方法及びその使用 | |
| US7750011B2 (en) | Diazabicyclic aryl derivatives and their medical 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 | |
| JP2006519208A (ja) | 新規ジアザビシクロアリール誘導体 | |
| US7652010B2 (en) | Azabicyclic aryl derivatives and their medical use | |
| JP2009518357A (ja) | 新規なジアザ二環式アリール誘導体及びそれらの医学的使用 | |
| JP2007520525A (ja) | 二量体のアザ環式化合物及びその使用 | |
| US7223753B2 (en) | Diazabicyclic biaryl derivatives | |
| US7612074B2 (en) | Diazabicyclic aryl derivatives as cholinergy ligands | |
| NZ553277A (en) | Novel azabicyclic aryl derivatives and their medical use | |
| HK1080860B (en) | Novel quinuclidine derivatives and their use | |
| HK1106513B (en) | Novel azabicyclic aryl derivatives and their medical use | |
| MXPA06008748A (es) | Derivados arildiazabiciclos como moduladores del receptor colinérgico |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081020 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081020 |
|
| A762 | Written abandonment of application |
Free format text: JAPANESE INTERMEDIATE CODE: A762 Effective date: 20110217 |