JP4918486B2 - 苦痛、うつ病及び（又は）不安障害の治療に使用するための飽和及び不飽和３−ピリジル−ベンゾシクロアルキルメチル−アミン類 - Google Patents
苦痛、うつ病及び（又は）不安障害の治療に使用するための飽和及び不飽和３−ピリジル−ベンゾシクロアルキルメチル−アミン類 Download PDFInfo
- Publication number
- JP4918486B2 JP4918486B2 JP2007517174A JP2007517174A JP4918486B2 JP 4918486 B2 JP4918486 B2 JP 4918486B2 JP 2007517174 A JP2007517174 A JP 2007517174A JP 2007517174 A JP2007517174 A JP 2007517174A JP 4918486 B2 JP4918486 B2 JP 4918486B2
- Authority
- JP
- Japan
- Prior art keywords
- pyridin
- corresponding hydrochloride
- dimethylaminomethyl
- amine
- ylmethyl
- 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 - Fee Related
Links
- 208000002193 Pain Diseases 0.000 title claims abstract description 32
- 229920006395 saturated elastomer Polymers 0.000 title claims abstract description 21
- 208000019901 Anxiety disease Diseases 0.000 title claims abstract description 15
- 230000036407 pain Effects 0.000 title claims abstract description 15
- 238000011282 treatment Methods 0.000 title claims description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 85
- 238000000034 method Methods 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 96
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 230000008569 process Effects 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- QRKAPEZZSALFQR-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-methoxy-1-pyridin-3-yl-3,4-dihydro-2h-naphthalen-1-ol Chemical compound COC1=CC=CC2=C1CCC(CN(C)C)C2(O)C1=CC=CN=C1 QRKAPEZZSALFQR-UHFFFAOYSA-N 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- AYIMCOMVIZKFTL-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-2,3-dihydroinden-1-ol Chemical compound CN(C)CC1CC2=CC=CC=C2C1(O)C1=CC=CN=C1 AYIMCOMVIZKFTL-UHFFFAOYSA-N 0.000 claims description 7
- 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 6
- 239000002253 acid Substances 0.000 claims description 6
- 206010013663 drug dependence Diseases 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 208000017520 skin disease Diseases 0.000 claims description 6
- 208000011117 substance-related disease Diseases 0.000 claims description 6
- CJZGNRDVLLHEER-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-3h-inden-5-ol Chemical compound C12=CC=C(O)C=C2CC(CN(C)C)=C1C1=CC=CN=C1 CJZGNRDVLLHEER-UHFFFAOYSA-N 0.000 claims description 5
- YEENLRKTQJLHGC-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-fluoro-1-pyridin-3-yl-2,3-dihydroinden-1-ol Chemical compound CN(C)CC1CC2=CC(F)=CC=C2C1(O)C1=CC=CN=C1 YEENLRKTQJLHGC-UHFFFAOYSA-N 0.000 claims description 5
- AZFNLAWLWJOLDL-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-5-pyridin-3-yl-6,7,8,9-tetrahydrobenzo[7]annulen-5-ol Chemical compound CN(C)CC1CCCC2=CC=CC=C2C1(O)C1=CC=CN=C1 AZFNLAWLWJOLDL-UHFFFAOYSA-N 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000032841 Bulimia Diseases 0.000 claims description 5
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 5
- 208000030814 Eating disease Diseases 0.000 claims description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
- 208000001640 Fibromyalgia Diseases 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 5
- 208000003251 Pruritus Diseases 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 5
- 208000016620 Tourette disease Diseases 0.000 claims description 5
- 206010046543 Urinary incontinence Diseases 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 5
- 208000010877 cognitive disease Diseases 0.000 claims description 5
- 235000014632 disordered eating Nutrition 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- CYHKDODPXAVVJY-UHFFFAOYSA-N 1-(5-methoxy-1-pyridin-3-yl-3,4-dihydronaphthalen-2-yl)-n,n-dimethylmethanamine Chemical compound CN(C)CC=1CCC=2C(OC)=CC=CC=2C=1C1=CC=CN=C1 CYHKDODPXAVVJY-UHFFFAOYSA-N 0.000 claims description 4
- JKUVGEXRZZWOFY-UHFFFAOYSA-N 1-(6-fluoro-3-pyridin-3-yl-1h-inden-2-yl)-n,n-dimethylmethanamine Chemical compound C12=CC=C(F)C=C2CC(CN(C)C)=C1C1=CC=CN=C1 JKUVGEXRZZWOFY-UHFFFAOYSA-N 0.000 claims description 4
- GQPGBYGEQXBPQQ-UHFFFAOYSA-N 1-(6-methoxy-3-pyridin-3-yl-1h-inden-2-yl)-n,n-dimethylmethanamine Chemical compound CN(C)CC=1CC2=CC(OC)=CC=C2C=1C1=CC=CN=C1 GQPGBYGEQXBPQQ-UHFFFAOYSA-N 0.000 claims description 4
- JRQUDCPZCIGPEF-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-6-methoxy-1-pyridin-3-yl-2,3-dihydroinden-1-ol Chemical compound C12=CC(OC)=CC=C2CC(CN(C)C)C1(O)C1=CC=CN=C1 JRQUDCPZCIGPEF-UHFFFAOYSA-N 0.000 claims description 4
- GDMQXYMWMGHHKE-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-4-pyridin-3-yl-2,3-dihydrochromen-4-ol Chemical compound CN(C)CC1COC2=CC=CC=C2C1(O)C1=CC=CN=C1 GDMQXYMWMGHHKE-UHFFFAOYSA-N 0.000 claims description 4
- AHCCCKGSLZERRE-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-5-pyridin-3-yl-3,4-dihydro-2h-1-benzoxepin-5-ol Chemical compound CN(C)CC1CCOC2=CC=CC=C2C1(O)C1=CC=CN=C1 AHCCCKGSLZERRE-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- YGCWTLJXPQFPEQ-UHFFFAOYSA-N n,n-dimethyl-1-(3-pyridin-3-yl-1h-inden-2-yl)methanamine Chemical compound C12=CC=CC=C2CC(CN(C)C)=C1C1=CC=CN=C1 YGCWTLJXPQFPEQ-UHFFFAOYSA-N 0.000 claims description 4
- LAHZKUNEQKCMJZ-UHFFFAOYSA-N n,n-dimethyl-1-(5-pyridin-3-yl-8,9-dihydro-7h-benzo[7]annulen-6-yl)methanamine Chemical compound C12=CC=CC=C2CCCC(CN(C)C)=C1C1=CC=CN=C1 LAHZKUNEQKCMJZ-UHFFFAOYSA-N 0.000 claims description 4
- VQEYEIUTACZWBP-UHFFFAOYSA-N n,n-dimethyl-1-[3-pyridin-3-yl-6-(trifluoromethoxy)-1h-inden-2-yl]methanamine Chemical compound C12=CC=C(OC(F)(F)F)C=C2CC(CN(C)C)=C1C1=CC=CN=C1 VQEYEIUTACZWBP-UHFFFAOYSA-N 0.000 claims description 4
- PRPULZAHTDWDFW-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-5-(trifluoromethoxy)-2,3-dihydroinden-1-ol Chemical compound CN(C)CC1CC2=CC(OC(F)(F)F)=CC=C2C1(O)C1=CC=CN=C1 PRPULZAHTDWDFW-UHFFFAOYSA-N 0.000 claims description 3
- HSQDHZQNMRYXIH-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-methoxy-1-pyridin-3-yl-2,3-dihydroinden-1-ol Chemical compound C=1C(OC)=CC=C2C=1CC(CN(C)C)C2(O)C1=CC=CN=C1 HSQDHZQNMRYXIH-UHFFFAOYSA-N 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 3
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 208000013403 hyperactivity Diseases 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229920002866 paraformaldehyde Polymers 0.000 claims description 3
- AEVWRTLZSNHCLK-UHFFFAOYSA-N thiepin-4-ol Chemical compound OC1=CC=CSC=C1 AEVWRTLZSNHCLK-UHFFFAOYSA-N 0.000 claims description 3
- VSNLINZDYNIUSB-UHFFFAOYSA-N 1-(5-methoxy-3-pyridin-3-yl-1h-inden-2-yl)-n,n-dimethylmethanamine Chemical compound C12=CC(OC)=CC=C2CC(CN(C)C)=C1C1=CC=CN=C1 VSNLINZDYNIUSB-UHFFFAOYSA-N 0.000 claims description 2
- PWFIDZRWWJSWEM-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-3,4-dihydro-2h-naphthalen-1-ol Chemical compound CN(C)CC1CCC2=CC=CC=C2C1(O)C1=CC=CN=C1 PWFIDZRWWJSWEM-UHFFFAOYSA-N 0.000 claims description 2
- INBQRBCPBDIRFT-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-5-(trifluoromethyl)-2,3-dihydroinden-1-ol Chemical compound CN(C)CC1CC2=CC(C(F)(F)F)=CC=C2C1(O)C1=CC=CN=C1 INBQRBCPBDIRFT-UHFFFAOYSA-N 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 150000002366 halogen compounds Chemical class 0.000 claims description 2
- ZIKZSXHMGBOHMR-UHFFFAOYSA-N n,n-dimethyl-1-(1-pyridin-3-yl-1,2,3,4-tetrahydronaphthalen-2-yl)methanamine Chemical compound CN(C)CC1CCC2=CC=CC=C2C1C1=CC=CN=C1 ZIKZSXHMGBOHMR-UHFFFAOYSA-N 0.000 claims description 2
- AAMBJVCFOBUEQZ-UHFFFAOYSA-N n,n-dimethyl-1-(1-pyridin-3-yl-2,3-dihydro-1h-inden-2-yl)methanamine Chemical compound CN(C)CC1CC2=CC=CC=C2C1C1=CC=CN=C1 AAMBJVCFOBUEQZ-UHFFFAOYSA-N 0.000 claims description 2
- QVNAEAOVUDUJDB-UHFFFAOYSA-N n,n-dimethyl-1-(1-pyridin-3-yl-3,4-dihydronaphthalen-2-yl)methanamine Chemical compound C12=CC=CC=C2CCC(CN(C)C)=C1C1=CC=CN=C1 QVNAEAOVUDUJDB-UHFFFAOYSA-N 0.000 claims description 2
- MVFSHUNZGXRRAO-UHFFFAOYSA-N n,n-dimethyl-1-(4-pyridin-3-yl-2h-chromen-3-yl)methanamine Chemical compound C12=CC=CC=C2OCC(CN(C)C)=C1C1=CC=CN=C1 MVFSHUNZGXRRAO-UHFFFAOYSA-N 0.000 claims description 2
- CRILCMHJXQMVLZ-UHFFFAOYSA-N n,n-dimethyl-1-(5-pyridin-3-yl-2,3-dihydro-1-benzoxepin-4-yl)methanamine Chemical compound C12=CC=CC=C2OCCC(CN(C)C)=C1C1=CC=CN=C1 CRILCMHJXQMVLZ-UHFFFAOYSA-N 0.000 claims description 2
- CPRVRYUDZUPTAT-UHFFFAOYSA-N n,n-dimethyl-1-[3-pyridin-3-yl-6-(trifluoromethyl)-1h-inden-2-yl]methanamine Chemical compound C12=CC=C(C(F)(F)F)C=C2CC(CN(C)C)=C1C1=CC=CN=C1 CPRVRYUDZUPTAT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002902 organometallic compounds Chemical class 0.000 claims description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims 1
- KMKLUVYHNKQOSE-UHFFFAOYSA-N [Ce+2] Chemical compound [Ce+2] KMKLUVYHNKQOSE-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 208000002271 trichotillomania Diseases 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 102
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 53
- 239000000243 solution Substances 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000003756 stirring Methods 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 238000001816 cooling Methods 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 239000012141 concentrate Substances 0.000 description 14
- 235000008504 concentrate Nutrition 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 208000000094 Chronic Pain Diseases 0.000 description 12
- -1 heptenyl Chemical group 0.000 description 12
- 239000012043 crude product Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 208000020925 Bipolar disease Diseases 0.000 description 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 206010026749 Mania Diseases 0.000 description 7
- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 101001122476 Homo sapiens Mu-type opioid receptor Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 102100028647 Mu-type opioid receptor Human genes 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000003542 behavioural effect Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 5
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 5
- 125000005865 C2-C10alkynyl group Chemical group 0.000 description 5
- 208000020401 Depressive disease Diseases 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 125000002877 alkyl aryl group Chemical group 0.000 description 5
- 230000000407 monoamine reuptake Effects 0.000 description 5
- WUXBJDUDXDSMIL-UHFFFAOYSA-N n,n-dimethyl-1-(1-oxo-5-pyridin-3-yl-2,3-dihydro-1$l^{4}-benzothiepin-4-yl)methanamine Chemical compound C12=CC=CC=C2S(=O)CCC(CN(C)C)=C1C1=CC=CN=C1 WUXBJDUDXDSMIL-UHFFFAOYSA-N 0.000 description 5
- 230000003040 nociceptive effect Effects 0.000 description 5
- 229960002748 norepinephrine Drugs 0.000 description 5
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- WSZXXKMDHROGHF-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-methoxy-1-pyridin-3-yl-2,3-dihydroinden-1-ol;hydrochloride Chemical compound Cl.C=1C(OC)=CC=C2C=1CC(CN(C)C)C2(O)C1=CC=CN=C1 WSZXXKMDHROGHF-UHFFFAOYSA-N 0.000 description 4
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 4
- 206010021030 Hypomania Diseases 0.000 description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
- 208000005298 acute pain Diseases 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- VGIVLIHKENZQHQ-UHFFFAOYSA-N n,n,n',n'-tetramethylmethanediamine Chemical compound CN(C)CN(C)C VGIVLIHKENZQHQ-UHFFFAOYSA-N 0.000 description 4
- FBPFRVCEQMLXSS-UHFFFAOYSA-N n,n-dimethyl-1-(3-pyridin-3-yl-1h-inden-2-yl)methanamine;hydrochloride Chemical compound Cl.C12=CC=CC=C2CC(CN(C)C)=C1C1=CC=CN=C1 FBPFRVCEQMLXSS-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000011541 reaction mixture Substances 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
- TXIAGRUGTPQZPY-UHFFFAOYSA-N 1-(6-fluoro-3-pyridin-3-yl-1h-inden-2-yl)-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.C12=CC=C(F)C=C2CC(CN(C)C)=C1C1=CC=CN=C1 TXIAGRUGTPQZPY-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- RJJAPTUXYIJMRX-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-5-(trifluoromethoxy)-2,3-dihydroinden-1-ol;hydrochloride Chemical compound Cl.CN(C)CC1CC2=CC(OC(F)(F)F)=CC=C2C1(O)C1=CC=CN=C1 RJJAPTUXYIJMRX-UHFFFAOYSA-N 0.000 description 3
- VHMJVWWIOOIBDW-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-methoxy-1-pyridin-3-yl-3,4-dihydro-2h-naphthalen-1-ol;hydrochloride Chemical compound Cl.COC1=CC=CC2=C1CCC(CN(C)C)C2(O)C1=CC=CN=C1 VHMJVWWIOOIBDW-UHFFFAOYSA-N 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- KEAOSKLDFWJIGP-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-5-pyridin-3-yl-7,8-dihydronaphthalen-1-ol Chemical compound C12=CC=CC(O)=C2CCC(CN(C)C)=C1C1=CC=CN=C1 KEAOSKLDFWJIGP-UHFFFAOYSA-N 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- 206010012218 Delirium Diseases 0.000 description 3
- 208000011688 Generalised anxiety disease Diseases 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 206010065390 Inflammatory pain Diseases 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-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
- 206010034912 Phobia Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 206010041250 Social phobia Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 3
- 208000028683 bipolar I disease Diseases 0.000 description 3
- 208000025307 bipolar depression Diseases 0.000 description 3
- 239000003054 catalyst Substances 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
- 238000004440 column chromatography Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 208000029364 generalized anxiety disease Diseases 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 206010027175 memory impairment Diseases 0.000 description 3
- MGMPQPACTGGECP-UHFFFAOYSA-N n,n-dimethyl-1-(5-pyridin-3-yl-8,9-dihydro-7h-benzo[7]annulen-6-yl)methanamine;hydrochloride Chemical compound Cl.C12=CC=CC=C2CCCC(CN(C)C)=C1C1=CC=CN=C1 MGMPQPACTGGECP-UHFFFAOYSA-N 0.000 description 3
- HHTCNUIQRNVYOI-UHFFFAOYSA-N n,n-dimethyl-1-[3-pyridin-3-yl-6-(trifluoromethoxy)-1h-inden-2-yl]methanamine;hydrochloride Chemical compound Cl.C12=CC=C(OC(F)(F)F)C=C2CC(CN(C)C)=C1C1=CC=CN=C1 HHTCNUIQRNVYOI-UHFFFAOYSA-N 0.000 description 3
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 3
- 208000019906 panic disease Diseases 0.000 description 3
- 208000022821 personality disease Diseases 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- JTJFTHMLDCQKKT-UHFFFAOYSA-N 1-(5-methoxy-1-pyridin-3-yl-3,4-dihydronaphthalen-2-yl)-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC=1CCC=2C(OC)=CC=CC=2C=1C1=CC=CN=C1 JTJFTHMLDCQKKT-UHFFFAOYSA-N 0.000 description 2
- WKAXJSVKAGQLSQ-UHFFFAOYSA-N 1-(6-methoxy-3-pyridin-3-yl-1h-inden-2-yl)-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC=1CC2=CC(OC)=CC=C2C=1C1=CC=CN=C1 WKAXJSVKAGQLSQ-UHFFFAOYSA-N 0.000 description 2
- VELHUGWCSGRWTQ-UHFFFAOYSA-N 2-(dimethylamino)-2-methyl-1-pyridin-3-yl-5-(trifluoromethoxy)-3h-inden-1-ol Chemical compound CN(C)C1(C)CC2=CC(OC(F)(F)F)=CC=C2C1(O)C1=CC=CN=C1 VELHUGWCSGRWTQ-UHFFFAOYSA-N 0.000 description 2
- YZXXYWYUUBCYTK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-2,3-dihydroinden-1-ol;hydrochloride Chemical compound Cl.CN(C)CC1CC2=CC=CC=C2C1(O)C1=CC=CN=C1 YZXXYWYUUBCYTK-UHFFFAOYSA-N 0.000 description 2
- ZBOOYBIVSNLAQR-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-3h-inden-5-ol;hydrochloride Chemical compound Cl.C12=CC=C(O)C=C2CC(CN(C)C)=C1C1=CC=CN=C1 ZBOOYBIVSNLAQR-UHFFFAOYSA-N 0.000 description 2
- RTWTVJFXVOXZAI-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-5-(trifluoromethyl)-2,3-dihydroinden-1-ol;hydrochloride Chemical compound Cl.CN(C)CC1CC2=CC(C(F)(F)F)=CC=C2C1(O)C1=CC=CN=C1 RTWTVJFXVOXZAI-UHFFFAOYSA-N 0.000 description 2
- VCZXLAZXPIQNOK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-fluoro-1-pyridin-3-yl-2,3-dihydroinden-1-ol;hydrochloride Chemical compound Cl.CN(C)CC1CC2=CC(F)=CC=C2C1(O)C1=CC=CN=C1 VCZXLAZXPIQNOK-UHFFFAOYSA-N 0.000 description 2
- SMRWZKSCFZBTGV-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-fluoro-2,3-dihydroinden-1-one;hydrochloride Chemical compound Cl.FC1=CC=C2C(=O)C(CN(C)C)CC2=C1 SMRWZKSCFZBTGV-UHFFFAOYSA-N 0.000 description 2
- HCYZQCDUOXFBGY-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-4-pyridin-3-yl-2,3-dihydrothiochromen-4-ol Chemical compound CN(C)CC1CSC2=CC=CC=C2C1(O)C1=CC=CN=C1 HCYZQCDUOXFBGY-UHFFFAOYSA-N 0.000 description 2
- AHSXMYSALCGWSP-UHFFFAOYSA-N 5-(trifluoromethyl)-2,3-dihydroinden-1-one Chemical group FC(F)(F)C1=CC=C2C(=O)CCC2=C1 AHSXMYSALCGWSP-UHFFFAOYSA-N 0.000 description 2
- OABRYVZJJUKADZ-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-5-pyridin-3-yl-6,7,8,9-tetrahydrobenzo[7]annulen-5-ol;hydrochloride Chemical compound Cl.CN(C)CC1CCCC2=CC=CC=C2C1(O)C1=CC=CN=C1 OABRYVZJJUKADZ-UHFFFAOYSA-N 0.000 description 2
- ICKWGXXFMPNALZ-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-5-pyridin-3-yl-7,8-dihydronaphthalen-1-ol;hydrochloride Chemical compound Cl.C12=CC=CC(O)=C2CCC(CN(C)C)=C1C1=CC=CN=C1 ICKWGXXFMPNALZ-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 206010010305 Confusional state Diseases 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000019022 Mood disease Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 2
- 206010038678 Respiratory depression Diseases 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- 206010040108 Serotonin syndrome Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 210000000548 hind-foot Anatomy 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 229940102223 injectable solution Drugs 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 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 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- FJJHDKFYUCZYRS-UHFFFAOYSA-N n,n-dimethyl-1-(1-pyridin-3-yl-2,3-dihydro-1h-inden-2-yl)methanamine;hydrochloride Chemical compound Cl.CN(C)CC1CC2=CC=CC=C2C1C1=CC=CN=C1 FJJHDKFYUCZYRS-UHFFFAOYSA-N 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- 229960004127 naloxone Drugs 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- 230000000966 norepinephrine reuptake Effects 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 229940127240 opiate Drugs 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 208000019899 phobic disease Diseases 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- ZNSIZMQNQCNRBW-UHFFFAOYSA-N sevelamer Chemical compound NCC=C.ClCC1CO1 ZNSIZMQNQCNRBW-UHFFFAOYSA-N 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- 208000020685 sleep-wake disease Diseases 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical group [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- 229960004688 venlafaxine Drugs 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- KSBWHDDGWSYETA-SNAWJCMRSA-N (E)-3-(trifluoromethyl)cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC(C(F)(F)F)=C1 KSBWHDDGWSYETA-SNAWJCMRSA-N 0.000 description 1
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
- 0 **(CN(*)*)C(*)(c1cccnc1)c1c(*I)c(*)c(*)c(*)c1* Chemical compound **(CN(*)*)C(*)(c1cccnc1)c1c(*I)c(*)c(*)c(*)c1* 0.000 description 1
- FKFBLEBNTNLODY-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-pyridin-3-yl-5-(trifluoromethoxy)-2,3-dihydroinden-1-ol 5-(trifluoromethoxy)-2,3-dihydroinden-1-one hydrochloride Chemical compound FC(OC=1C=C2CCC(C2=CC1)=O)(F)F.Cl.CN(C)CC1C(C2=CC=C(C=C2C1)OC(F)(F)F)(O)C=1C=NC=CC1 FKFBLEBNTNLODY-UHFFFAOYSA-N 0.000 description 1
- UEUVQLNDXGDBLK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-(trifluoromethoxy)-2,3-dihydroinden-1-one Chemical compound FC(F)(F)OC1=CC=C2C(=O)C(CN(C)C)CC2=C1 UEUVQLNDXGDBLK-UHFFFAOYSA-N 0.000 description 1
- LDCHJHHRNWNKAY-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-(trifluoromethoxy)-2,3-dihydroinden-1-one;hydrochloride Chemical compound Cl.FC(F)(F)OC1=CC=C2C(=O)C(CN(C)C)CC2=C1 LDCHJHHRNWNKAY-UHFFFAOYSA-N 0.000 description 1
- QHNYYAVQWSEQLN-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-fluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=C2C(=O)C(CN(C)C)CC2=C1 QHNYYAVQWSEQLN-UHFFFAOYSA-N 0.000 description 1
- AIGPTOVAWSXKTH-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2C(=O)C(CN(C)C)CC2=C1 AIGPTOVAWSXKTH-UHFFFAOYSA-N 0.000 description 1
- LTYHOOSIBPZOEQ-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1C(CN(C)C)CCC2=C1C=CC=C2OC LTYHOOSIBPZOEQ-UHFFFAOYSA-N 0.000 description 1
- YQLFBLALPPKCKU-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-5-methoxy-3,4-dihydro-2h-naphthalen-1-one;hydrochloride Chemical compound Cl.O=C1C(CN(C)C)CCC2=C1C=CC=C2OC YQLFBLALPPKCKU-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- TVSPPYGAFOVROT-UHFFFAOYSA-N 2-phenoxybutanoic acid Chemical compound CCC(C(O)=O)OC1=CC=CC=C1 TVSPPYGAFOVROT-UHFFFAOYSA-N 0.000 description 1
- OVDGMAPDTIRBTC-UHFFFAOYSA-N 2H-oxepin-5-one Chemical compound O=C1C=CCOC=C1 OVDGMAPDTIRBTC-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- KNTMEDNZPJADJU-UHFFFAOYSA-N 3,4-dihydro-2h-1-benzoxepin-5-one Chemical compound O=C1CCCOC2=CC=CC=C12 KNTMEDNZPJADJU-UHFFFAOYSA-N 0.000 description 1
- WGEVFUNNEITJFQ-UHFFFAOYSA-N 3-[3-(trifluoromethoxy)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=CC(OC(F)(F)F)=C1 WGEVFUNNEITJFQ-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 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
- UEGSXBYJSNTXTE-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-5-pyridin-3-yl-3,4-dihydro-2h-1-benzothiepin-5-ol;hydrochloride Chemical compound Cl.CN(C)CC1CCSC2=CC=CC=C2C1(O)C1=CC=CN=C1 UEGSXBYJSNTXTE-UHFFFAOYSA-N 0.000 description 1
- SLOOCJUIRYAQPQ-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-5-pyridin-3-yl-3,4-dihydro-2h-1-benzoxepin-5-ol;hydrochloride Chemical compound Cl.CN(C)CC1CCOC2=CC=CC=C2C1(O)C1=CC=CN=C1 SLOOCJUIRYAQPQ-UHFFFAOYSA-N 0.000 description 1
- HDBVHUFMISYAOD-UHFFFAOYSA-N 5-(trifluoromethoxy)-2,3-dihydro-1h-inden-1-ol Chemical compound FC(F)(F)OC1=CC=C2C(O)CCC2=C1 HDBVHUFMISYAOD-UHFFFAOYSA-N 0.000 description 1
- DJGOAKVCWWDUHQ-UHFFFAOYSA-N 5-(trifluoromethoxy)-2,3-dihydroinden-1-one Chemical compound FC(F)(F)OC1=CC=C2C(=O)CCC2=C1 DJGOAKVCWWDUHQ-UHFFFAOYSA-N 0.000 description 1
- WVPPBVAMKNQXJA-UHFFFAOYSA-N 5-fluoro-2,3-dihydroinden-1-one Chemical compound FC1=CC=C2C(=O)CCC2=C1 WVPPBVAMKNQXJA-UHFFFAOYSA-N 0.000 description 1
- BRCPWISABURVIH-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=C1C=CC=C2OC BRCPWISABURVIH-UHFFFAOYSA-N 0.000 description 1
- RHHGHWBHOQXKNZ-UHFFFAOYSA-N 7-(trifluoromethyl)-2,3-dihydroinden-1-one Chemical compound FC(F)(F)C1=CC=CC2=C1C(=O)CC2 RHHGHWBHOQXKNZ-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- JCTYWLASTKEQOR-UHFFFAOYSA-N C1(CCC2=CC=CC=C12)=O.Cl.CN(C)CC1C(C2=C(OCC1)C=CC=C2)(O)C=2C=NC=CC2 Chemical compound C1(CCC2=CC=CC=C12)=O.Cl.CN(C)CC1C(C2=C(OCC1)C=CC=C2)(O)C=2C=NC=CC2 JCTYWLASTKEQOR-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 230000005526 G1 to G0 transition Effects 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
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- 206010027940 Mood altered Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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
- 206010045171 Tumour pain Diseases 0.000 description 1
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003502 anti-nociceptive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl 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
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 230000003001 depressive effect Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229960002866 duloxetine Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- NGAZZOYFWWSOGK-UHFFFAOYSA-N heptan-3-one Chemical compound CCCCC(=O)CC NGAZZOYFWWSOGK-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008517 inhibition of serotonin uptake Effects 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 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
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 239000002623 mu opiate receptor antagonist Substances 0.000 description 1
- FRWCVGXMJMQFIM-UHFFFAOYSA-N n,n-dimethyl-1-(4-pyridin-3-yl-2h-thiochromen-3-yl)methanamine Chemical compound C12=CC=CC=C2SCC(CN(C)C)=C1C1=CC=CN=C1 FRWCVGXMJMQFIM-UHFFFAOYSA-N 0.000 description 1
- XWCLZRAFFXUXTB-UHFFFAOYSA-N n,n-dimethyl-1-(5-pyridin-3-yl-2,3-dihydro-1-benzothiepin-4-yl)methanamine;hydrochloride Chemical compound Cl.C12=CC=CC=C2SCCC(CN(C)C)=C1C1=CC=CN=C1 XWCLZRAFFXUXTB-UHFFFAOYSA-N 0.000 description 1
- RGPDIGOSVORSAK-STHHAXOLSA-N naloxone hydrochloride Chemical compound Cl.O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C RGPDIGOSVORSAK-STHHAXOLSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 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
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical class NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000003568 synaptosome Anatomy 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- AWIJRPNMLHPLNC-UHFFFAOYSA-N thiocarboxylic acid group Chemical group C(=S)O AWIJRPNMLHPLNC-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Nutrition Science (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004030099A DE102004030099A1 (de) | 2004-06-22 | 2004-06-22 | Gesättigte und ungesättigte 3-Pyridyl-benzocycloalkylmethyl-amine als Serotonin- und/oder Noradrenalin-Reuptake-Hemmer und/oder µ-Opioidrezeptor-Modulatoren |
| DE102004030099.2 | 2004-06-22 | ||
| PCT/EP2005/006624 WO2005123681A1 (de) | 2004-06-22 | 2005-06-20 | Gesättigte und ungesättigte 3-pyridyl-benzocycloalkylmethyl-amine zur behandlung von schmerzen, depressionen und angstzuständen |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008503523A JP2008503523A (ja) | 2008-02-07 |
| JP2008503523A5 JP2008503523A5 (OSRAM) | 2011-12-22 |
| JP4918486B2 true JP4918486B2 (ja) | 2012-04-18 |
Family
ID=35106829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007517174A Expired - Fee Related JP4918486B2 (ja) | 2004-06-22 | 2005-06-20 | 苦痛、うつ病及び（又は）不安障害の治療に使用するための飽和及び不飽和３−ピリジル−ベンゾシクロアルキルメチル−アミン類 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8278338B2 (OSRAM) |
| EP (1) | EP1758860B1 (OSRAM) |
| JP (1) | JP4918486B2 (OSRAM) |
| AT (1) | ATE441632T1 (OSRAM) |
| CA (1) | CA2568897C (OSRAM) |
| CY (1) | CY1109519T1 (OSRAM) |
| DE (2) | DE102004030099A1 (OSRAM) |
| DK (1) | DK1758860T3 (OSRAM) |
| ES (1) | ES2333976T3 (OSRAM) |
| PL (1) | PL1758860T3 (OSRAM) |
| PT (1) | PT1758860E (OSRAM) |
| SI (1) | SI1758860T1 (OSRAM) |
| WO (1) | WO2005123681A1 (OSRAM) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7435837B2 (en) | 2003-10-24 | 2008-10-14 | Wyeth | Dihydrobenzofuranyl alkanamine derivatives and methods for using same |
| CA2604915A1 (en) | 2005-04-22 | 2006-11-02 | Wyeth | New therapeutic combinations for the treatment or prevention of depression |
| WO2007081542A2 (en) * | 2006-01-06 | 2007-07-19 | Sepracor Inc. | Tetralone-based monoamine reuptake inhibitors |
| ES2397764T3 (es) | 2008-04-01 | 2013-03-11 | Abbott Gmbh & Co. Kg | Tetrahidroisoquinolinas, composiciones farmacéuticas que las contienen, y su uso en terapia |
| AR075442A1 (es) | 2009-02-16 | 2011-03-30 | Abbott Gmbh & Co Kg | Derivados de aminotetralina, composiciones farmaceuticas que las contienen y sus usos en terapia |
| US8877794B2 (en) | 2010-08-13 | 2014-11-04 | Abbott Laboratories | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9051280B2 (en) | 2010-08-13 | 2015-06-09 | AbbVie Deutschland GmbH & Co. KG | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9045459B2 (en) | 2010-08-13 | 2015-06-02 | AbbVie Deutschland GmbH & Co. KG | Phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8883839B2 (en) | 2010-08-13 | 2014-11-11 | Abbott Laboratories | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8846743B2 (en) | 2010-08-13 | 2014-09-30 | Abbott Laboratories | Aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9309200B2 (en) | 2011-05-12 | 2016-04-12 | AbbVie Deutschland GmbH & Co. KG | Benzazepine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US8853196B2 (en) | 2011-08-05 | 2014-10-07 | AbbVie Deutschland GmbH & Co. KG | Aminochromane, aminothiochromane and amino-1,2,3,4-tetrahydroquinoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
| CA2853254A1 (en) | 2011-11-18 | 2013-05-23 | Abbvie Inc. | N-substituted aminobenzocycloheptene, aminotetraline, aminoindane and phenalkylamine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9365512B2 (en) | 2012-02-13 | 2016-06-14 | AbbVie Deutschland GmbH & Co. KG | Isoindoline derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9650334B2 (en) | 2013-03-15 | 2017-05-16 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9656955B2 (en) | 2013-03-15 | 2017-05-23 | Abbvie Inc. | Pyrrolidine derivatives, pharmaceutical compositions containing them, and their use in therapy |
| US9643947B2 (en) | 2013-08-28 | 2017-05-09 | Northwestern University | 7-membered fused heterocycles and methods of their synthesis |
| CA2924699A1 (en) | 2013-10-17 | 2015-04-23 | AbbVie Deutschland GmbH & Co. KG | Aminotetraline and aminoindane derivatives, pharmaceutical compositions containing them, and their use in therapy |
| MX2016004936A (es) | 2013-10-17 | 2016-12-20 | Abbvie Deutschland | Derivados de aminocromano, aminotiocromano y amino-1,2,3,4-tetrahi droquinilina, composiciones farmaceuticas que los contienen, y su uso en terapia. |
| CN104844471B (zh) * | 2015-04-21 | 2017-05-03 | 苏州远智医药科技有限公司 | 一种作为dor受体拮抗剂的化合物 |
| CN109896991B (zh) * | 2017-12-08 | 2020-11-20 | 苏州远智医药科技有限公司 | 一种δ阿片受体拮抗剂及其用途和药物组合物 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3444176A (en) * | 1967-04-28 | 1969-05-13 | Mcneilab Inc | Certain 4-diloweralkylamino-lower alkyl - 5 - pyridyl (or phenyl)-2,3-dihydro - 1 - benzothiepins and derivatives thereof |
| US4845221A (en) * | 1988-04-15 | 1989-07-04 | American Home Products Corporation | Serotonergic substituted piperazinyl tetralins |
| AU648359B2 (en) * | 1990-11-22 | 1994-04-21 | Janssen Pharmaceutica N.V. | Isonicotinic acid derivatives |
| US5668141A (en) * | 1996-04-02 | 1997-09-16 | Abbott Laboratories | Trans-2,6-,3,6-and 4,6-diaza-5,6,6a,7,8,12b-hexahydrobenzo[c]phenanthrene compounds as dopamine agonists |
| DE19805370A1 (de) * | 1997-03-14 | 1998-09-17 | Gruenenthal Gmbh | Substituierte Aminoverbindungen und ihre Verwendung als analgetisch wirksame Substanzen |
| AU4037699A (en) * | 1998-05-08 | 1999-11-29 | Akzo Nobel N.V. | Novel aryl-hydro naphthalenal kanamines |
| TW555757B (en) * | 1998-07-31 | 2003-10-01 | Akzo Nobel Nv | Aminomethylcarboxylic acid derivatives |
| CO5271697A1 (es) * | 2000-01-12 | 2003-04-30 | Pfizer Prod Inc | Composiciones y procedimientos para el tratamiento de afecciones que responden a un aumento de testosterona |
| JP4612990B2 (ja) * | 2001-03-16 | 2011-01-12 | アボット・ラボラトリーズ | ヒスタミン−３受容体リガンドとしての新規アミンおよびそれらの治療的適用 |
| CA2452596C (en) * | 2001-07-05 | 2010-12-21 | Takeda Chemical Industries, Ltd. | Benzo-fused 5-membered heterocyclic compounds, their production and use |
| JP2004149429A (ja) * | 2002-10-29 | 2004-05-27 | Takeda Chem Ind Ltd | インドール化合物およびその用途 |
-
2004
- 2004-06-22 DE DE102004030099A patent/DE102004030099A1/de not_active Withdrawn
-
2005
- 2005-06-20 JP JP2007517174A patent/JP4918486B2/ja not_active Expired - Fee Related
- 2005-06-20 PL PL05766092T patent/PL1758860T3/pl unknown
- 2005-06-20 ES ES05766092T patent/ES2333976T3/es not_active Expired - Lifetime
- 2005-06-20 EP EP05766092A patent/EP1758860B1/de not_active Expired - Lifetime
- 2005-06-20 WO PCT/EP2005/006624 patent/WO2005123681A1/de not_active Ceased
- 2005-06-20 AT AT05766092T patent/ATE441632T1/de active
- 2005-06-20 DK DK05766092T patent/DK1758860T3/da active
- 2005-06-20 PT PT05766092T patent/PT1758860E/pt unknown
- 2005-06-20 SI SI200530854T patent/SI1758860T1/sl unknown
- 2005-06-20 CA CA2568897A patent/CA2568897C/en not_active Expired - Fee Related
- 2005-06-20 DE DE502005008058T patent/DE502005008058D1/de not_active Expired - Lifetime
-
2006
- 2006-12-22 US US11/643,792 patent/US8278338B2/en not_active Expired - Fee Related
-
2009
- 2009-11-30 CY CY20091101251T patent/CY1109519T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ATE441632T1 (de) | 2009-09-15 |
| DK1758860T3 (da) | 2010-01-11 |
| DE102004030099A1 (de) | 2006-01-12 |
| PL1758860T3 (pl) | 2010-02-26 |
| CA2568897A1 (en) | 2005-12-29 |
| JP2008503523A (ja) | 2008-02-07 |
| PT1758860E (pt) | 2009-12-07 |
| DE502005008058D1 (de) | 2009-10-15 |
| EP1758860A1 (de) | 2007-03-07 |
| CA2568897C (en) | 2012-08-07 |
| ES2333976T3 (es) | 2010-03-03 |
| US20070203192A1 (en) | 2007-08-30 |
| SI1758860T1 (sl) | 2010-01-29 |
| CY1109519T1 (el) | 2014-08-13 |
| US8278338B2 (en) | 2012-10-02 |
| WO2005123681A1 (de) | 2005-12-29 |
| EP1758860B1 (de) | 2009-09-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4918486B2 (ja) | 苦痛、うつ病及び（又は）不安障害の治療に使用するための飽和及び不飽和３−ピリジル−ベンゾシクロアルキルメチル−アミン類 | |
| AU692788B2 (en) | Piperazine compounds used in therapy | |
| TWI339121B (en) | 1-piperazine- and 1-homopiperazine-carboxylate derivatives, preparation and therapeutic application thereof | |
| EP2170805B1 (en) | Methods of synthesizing cinacalcet and salts thereof | |
| DE60112269T2 (de) | Phenylethylamine und ringkondensierte varianten als pro-drugs von katecholaminen sowie ihre verwendung | |
| NO340728B1 (no) | Kjemiske forbindelser, fremstilling av disse, farmasøytiske preparater omfattende disse samt slike forbindelser for anvendelse i behandling av sykdommer | |
| JPH05279357A (ja) | アザヘテロサイクリルメチル−クロマン類 | |
| HUP0103466A2 (hu) | Foszfo-diészteráz-4 gátló hatású helyettesített 1,8-naftiridin-4(1H)-on származékok és ezeket tartalmazó gyógyszerkészítmények | |
| EP0529462A1 (de) | Benzodioxanderivate | |
| JP2006515618A (ja) | 置換アルキルアミドピペリジン類 | |
| KR101204751B1 (ko) | 카복사미도 아편유사약물 화합물 | |
| MX2007015678A (es) | Antagonistas y agonistas de piperazina-piperidina del receptor 5-ht-1a. | |
| WO1998033763A1 (en) | Substituted hydroxy-anilino derivatives of cyclobutene-3,4-diones | |
| CN103772176B (zh) | Vibsane型二萜衍生物及其药物组合物和应用 | |
| JP2010535174A (ja) | Ｎ−ピペリジン−４−イルメチルアミド誘導体及びモノアミン神経伝達物質再取り込み阻害薬としてのその使用 | |
| JP2005532399A (ja) | Ｍｃｈ１アンタゴニストとしての二級アミノアニリンピペリジン類およびその使用 | |
| EP0929550A1 (fr) | DERIVES DE $i(N)-(BENZOTHIAZOL-2-YL)PIPERIDINE-1-ETHANAMINE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE | |
| JPH05255302A (ja) | 新規なクロマニルオキシアルキルアミン誘導体 | |
| KR20020072782A (ko) | 이소인돌로인돌론 화합물, 이들의 제조 방법, 및 이들을함유하는 약제 조성물 | |
| JPH037280A (ja) | 新規ベンゾチオピラニルアミン | |
| CN109810115B (zh) | 异黄酮类化合物及其制备方法与应用 | |
| JP2009517357A (ja) | イソキノリンおよびベンゾ［ｈ］イソキノリン誘導体、調製およびヒスタミンｈ３受容体のアンタゴニストとしてのこの治療上の使用 | |
| JP2006523182A (ja) | 抗うつ薬としての飽和及び不飽和ヘテロアリールシクロアルキルメチル−アミン類 | |
| GB2126230A (en) | Substituted 1-pyridyloxy-3- indolylakylamino-2-propanols, preparation, and use thereof | |
| CN106278994B (zh) | 螺环化合物及其制备方法和用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080617 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080617 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20100518 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20110518 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110607 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110906 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110913 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20111006 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20111014 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20111104 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120124 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120130 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150203 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |