ES2270861T3 - Derivados de 2-aminoalquilbifenilo. - Google Patents
Derivados de 2-aminoalquilbifenilo. Download PDFInfo
- Publication number
- ES2270861T3 ES2270861T3 ES00951440T ES00951440T ES2270861T3 ES 2270861 T3 ES2270861 T3 ES 2270861T3 ES 00951440 T ES00951440 T ES 00951440T ES 00951440 T ES00951440 T ES 00951440T ES 2270861 T3 ES2270861 T3 ES 2270861T3
- Authority
- ES
- Spain
- Prior art keywords
- corresponding hydrochloride
- dimethylamine
- group
- ylmethyl
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000002253 acid Substances 0.000 claims abstract description 61
- -1 acetamidyl group Chemical group 0.000 claims abstract description 45
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 125000003118 aryl group Chemical group 0.000 claims abstract description 40
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims abstract description 12
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 12
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 11
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 150000002367 halogens Chemical class 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 330
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 197
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 120
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 101
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 92
- 239000000203 mixture Substances 0.000 claims description 89
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 89
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 54
- 229910052757 nitrogen Inorganic materials 0.000 claims description 45
- 238000002360 preparation method Methods 0.000 claims description 44
- 239000003814 drug Substances 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 23
- 150000002941 palladium compounds Chemical class 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 12
- 208000002193 Pain Diseases 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 230000036407 pain Effects 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 8
- 239000011777 magnesium Substances 0.000 claims description 8
- 229910052749 magnesium Inorganic materials 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 7
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 206010011224 Cough Diseases 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 6
- 206010013654 Drug abuse Diseases 0.000 claims description 6
- 208000007882 Gastritis Diseases 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 206010046543 Urinary incontinence Diseases 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 150000002430 hydrocarbons Chemical class 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 208000020016 psychiatric disease Diseases 0.000 claims description 6
- 208000011117 substance-related disease Diseases 0.000 claims description 6
- 208000007848 Alcoholism Diseases 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 5
- 206010001584 alcohol abuse Diseases 0.000 claims description 5
- 208000025746 alcohol use disease Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 claims description 5
- UKSZBOKPHAQOMP-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1.C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 UKSZBOKPHAQOMP-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 208000018569 Respiratory Tract disease Diseases 0.000 claims description 3
- 230000000172 allergic effect Effects 0.000 claims description 3
- 208000010668 atopic eczema Diseases 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 3
- 230000007704 transition Effects 0.000 claims description 3
- DBACJLCLFSETSR-UHFFFAOYSA-N 5-chloro-2-[2-[(dimethylamino)methyl]phenyl]benzonitrile Chemical compound CN(C)CC1=CC=CC=C1C1=CC=C(Cl)C=C1C#N DBACJLCLFSETSR-UHFFFAOYSA-N 0.000 claims description 2
- 239000011260 aqueous acid Substances 0.000 claims description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 2
- 150000002739 metals Chemical class 0.000 claims description 2
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims description 2
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- 150000002940 palladium Chemical class 0.000 claims description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- 230000002650 habitual effect Effects 0.000 claims 3
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 claims 2
- JTJQMICKNVMEDF-UHFFFAOYSA-N 1-[2-(1,3-benzodioxol-5-yl)phenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC=C1C1=CC=C(OCO2)C2=C1 JTJQMICKNVMEDF-UHFFFAOYSA-N 0.000 claims 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 claims 1
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 230000002526 effect on cardiovascular system Effects 0.000 claims 1
- 239000012280 lithium aluminium hydride Substances 0.000 claims 1
- 150000007513 acids Chemical class 0.000 abstract description 3
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 abstract 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 118
- 239000000243 solution Substances 0.000 description 90
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 86
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 76
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 73
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 71
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 47
- 238000010992 reflux Methods 0.000 description 44
- 239000012074 organic phase Substances 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 38
- 238000002844 melting Methods 0.000 description 38
- 230000008018 melting Effects 0.000 description 38
- 238000010828 elution Methods 0.000 description 34
- 229910000029 sodium carbonate Inorganic materials 0.000 description 34
- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- 239000012071 phase Substances 0.000 description 27
- OIYCEQKBCIYXQG-UHFFFAOYSA-N C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[N] Chemical compound C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.[N] OIYCEQKBCIYXQG-UHFFFAOYSA-N 0.000 description 24
- 230000002378 acidificating effect Effects 0.000 description 24
- ZPZPSZZVDFMNQS-UHFFFAOYSA-N 1-(2-bromophenyl)-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC=C1Br ZPZPSZZVDFMNQS-UHFFFAOYSA-N 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 18
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000012545 processing Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 229940091250 magnesium supplement Drugs 0.000 description 7
- CEQDOZNXFWUMTG-UHFFFAOYSA-N 2-(2-bromophenyl)-n,n-dimethylethanamine Chemical compound CN(C)CCC1=CC=CC=C1Br CEQDOZNXFWUMTG-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
- LGRYHSLXNXZNJT-UHFFFAOYSA-N butan-2-one chloro(trimethyl)silane Chemical compound CCC(=O)C.C[Si](C)(C)Cl LGRYHSLXNXZNJT-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- PFPFBJNHLYMTGR-UHFFFAOYSA-N 2-[2-(3-methoxyphenyl)phenyl]-n,n-dimethylethanamine Chemical compound COC1=CC=CC(C=2C(=CC=CC=2)CCN(C)C)=C1 PFPFBJNHLYMTGR-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 5
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- RNPNPSHONPWTCI-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)-N,N-dimethylmethanamine Chemical compound CN(C)Cc1c(C)cccc1C RNPNPSHONPWTCI-UHFFFAOYSA-N 0.000 description 4
- SSIDIGWIEQDEDG-UHFFFAOYSA-N 1-[2-(3-methoxyphenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C(=CC=CC=2)CN(C)C)=C1 SSIDIGWIEQDEDG-UHFFFAOYSA-N 0.000 description 4
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 235000011089 carbon dioxide Nutrition 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- SUOYYQRYHPEYLQ-UHFFFAOYSA-N 1-[2-(4-chloro-3-methoxyphenyl)phenyl]-n,n-dimethylmethanamine Chemical compound C1=C(Cl)C(OC)=CC(C=2C(=CC=CC=2)CN(C)C)=C1 SUOYYQRYHPEYLQ-UHFFFAOYSA-N 0.000 description 3
- ITRNQMJXZUWZQL-UHFFFAOYSA-N 2-(2-bromophenyl)ethanamine Chemical compound NCCC1=CC=CC=C1Br ITRNQMJXZUWZQL-UHFFFAOYSA-N 0.000 description 3
- ATBFEBMKNZQVRM-UHFFFAOYSA-N 2-[2-(3-methoxyphenyl)phenyl]-n,n-dimethylethanamine;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C(=CC=CC=2)CCN(C)C)=C1 ATBFEBMKNZQVRM-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 238000010908 decantation Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- PSRAHCYZRYXJAE-UHFFFAOYSA-N n,n-dimethyl-2-[2-(3-propan-2-yloxyphenyl)phenyl]ethanamine;hydrochloride Chemical compound Cl.CC(C)OC1=CC=CC(C=2C(=CC=CC=2)CCN(C)C)=C1 PSRAHCYZRYXJAE-UHFFFAOYSA-N 0.000 description 3
- MRRVGKUDNXCCTR-UHFFFAOYSA-N n-[4-[2-[(dimethylamino)methyl]phenyl]-2-(trifluoromethoxy)phenyl]acetamide;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=CC=C(NC(C)=O)C(OC(F)(F)F)=C1 MRRVGKUDNXCCTR-UHFFFAOYSA-N 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- LOTJKAVABSBRAJ-UHFFFAOYSA-N 1-[2-(1,3-benzodioxol-5-yl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=CC=C(OCO2)C2=C1 LOTJKAVABSBRAJ-UHFFFAOYSA-N 0.000 description 2
- PDXBFKSMNSEDCE-UHFFFAOYSA-N 1-[2-(1h-indol-5-yl)phenyl]-n,n-dimethylmethanamine Chemical compound CN(C)CC1=CC=CC=C1C1=CC=C(NC=C2)C2=C1 PDXBFKSMNSEDCE-UHFFFAOYSA-N 0.000 description 2
- NNTSLBLAWBQHFT-UHFFFAOYSA-N 1-[2-(2,3-difluorophenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=CC=CC(F)=C1F NNTSLBLAWBQHFT-UHFFFAOYSA-N 0.000 description 2
- JGTYWHKITUBWHM-UHFFFAOYSA-N 1-[2-(2,4-dichlorophenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=CC=C(Cl)C=C1Cl JGTYWHKITUBWHM-UHFFFAOYSA-N 0.000 description 2
- YEERDUIEZIAHCJ-UHFFFAOYSA-N 1-[2-(2,5-difluorophenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=CC(F)=CC=C1F YEERDUIEZIAHCJ-UHFFFAOYSA-N 0.000 description 2
- PSADEDQTWJIDSQ-UHFFFAOYSA-N 1-[2-(2,5-dimethoxyphenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.COC1=CC=C(OC)C(C=2C(=CC=CC=2)CN(C)C)=C1 PSADEDQTWJIDSQ-UHFFFAOYSA-N 0.000 description 2
- SPCRKWSUFQTLCR-UHFFFAOYSA-N 1-[2-(2-fluorophenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=CC=CC=C1F SPCRKWSUFQTLCR-UHFFFAOYSA-N 0.000 description 2
- GHLKMHYJCAGBIQ-UHFFFAOYSA-N 1-[2-(2-methoxyphenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C1=CC=CC=C1CN(C)C GHLKMHYJCAGBIQ-UHFFFAOYSA-N 0.000 description 2
- SITODMCTLAGQAT-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenyl)phenyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC1=CC=CC=C1C1=CC=C(Cl)C(Cl)=C1 SITODMCTLAGQAT-UHFFFAOYSA-N 0.000 description 2
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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Applications Claiming Priority (2)
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| DE19937537A DE19937537A1 (de) | 1999-08-09 | 1999-08-09 | Substituierte 2-Dialkylaminoalkylbiphenyl-Derivate |
| DE19937537 | 1999-08-09 |
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| ES2270861T3 true ES2270861T3 (es) | 2007-04-16 |
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| ES00951440T Expired - Lifetime ES2270861T3 (es) | 1999-08-09 | 2000-07-25 | Derivados de 2-aminoalquilbifenilo. |
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| US6946559B2 (en) | 2000-02-02 | 2005-09-20 | Banyu Pharmaceutical Co., Ltd. | Method of converting functional group through halogen-metal exchange reaction |
| US7506197B2 (en) * | 2005-02-07 | 2009-03-17 | International Business Machines Corporation | Multi-directional fault detection system |
| CN100364966C (zh) * | 2005-04-14 | 2008-01-30 | 上海雅本化学有限公司 | 1-[2-氨基-1-(对甲氧苯基)乙基]环己醇甲酸盐的合成方法 |
| TW200823204A (en) * | 2006-10-17 | 2008-06-01 | Arena Pharm Inc | Biphenyl sulfonyl and phenyl-heteroaryl sulfonyl modulators of the histamine H3-receptor useful for the treatment of disorders related thereto |
| EP1997493A1 (en) * | 2007-05-28 | 2008-12-03 | Laboratorios del Dr. Esteve S.A. | Combination of a 5-HT7 receptor ligand and an opioid receptor ligand |
| UA98839C2 (en) * | 2008-02-01 | 2012-06-25 | Панмира Фармасьютикалз, Ллк. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
| EP2257524B1 (en) * | 2008-02-01 | 2016-01-06 | Brickell Biotech, Inc. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
| JP2011512359A (ja) * | 2008-02-14 | 2011-04-21 | アミラ ファーマシューティカルズ,インク. | プロスタグランジンd2受容体のアンタゴニストとしての環式ジアリールエーテル化合物 |
| US8497381B2 (en) * | 2008-02-25 | 2013-07-30 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
| JP2011518130A (ja) * | 2008-04-02 | 2011-06-23 | アミラ ファーマシューティカルズ,インク. | プロスタグランジンd2受容体のアミノアルキルフェニルアンタゴニスト |
| WO2010003120A2 (en) * | 2008-07-03 | 2010-01-07 | Amira Pharmaceuticals, Inc. | Antagonists of prostaglandin d2 receptors |
| GB2463788B (en) * | 2008-09-29 | 2010-12-15 | Amira Pharmaceuticals Inc | Heteroaryl antagonists of prostaglandin D2 receptors |
| WO2010039977A2 (en) * | 2008-10-01 | 2010-04-08 | Amira Pharmaceuticals, Inc. | Heteroaryl antagonists of prostaglandin d2 receptors |
| WO2010042652A2 (en) | 2008-10-08 | 2010-04-15 | Amira Pharmaceuticals, Inc. | Heteroalkyl biphenyl antagonists of prostaglandin d2 receptors |
| US8383654B2 (en) | 2008-11-17 | 2013-02-26 | Panmira Pharmaceuticals, Llc | Heterocyclic antagonists of prostaglandin D2 receptors |
| US20100173313A1 (en) * | 2009-01-08 | 2010-07-08 | Amira Pharmaceuticals, Inc. | Biomarkers of inflammation |
| EP2461809A4 (en) | 2009-07-31 | 2013-06-19 | Panmira Pharmaceuticals Llc | OPHTHALMIC PHARMACEUTICAL COMPOSITIONS OF DP2 RECEPTOR ANTAGONSITES |
| CA2768587A1 (en) | 2009-08-05 | 2011-02-10 | Panmira Pharmaceuticals, Llc | Dp2 antagonist and uses thereof |
| CA2782085A1 (en) | 2010-01-06 | 2011-07-14 | Panmira Pharmaceuticals, Llc | Dp2 antagonist and uses thereof |
| DE102010055322A1 (de) | 2010-12-21 | 2012-06-21 | Christian-Albrechts-Universität Zu Kiel | Antibakteriell und antimykotisch wirkende Substanzen |
| US20120309796A1 (en) | 2011-06-06 | 2012-12-06 | Fariborz Firooznia | Benzocycloheptene acetic acids |
| CN103864624A (zh) * | 2014-03-05 | 2014-06-18 | 湖北大学 | 一种简单碱催化的n-烷基化高效制备仲胺的方法 |
| CN115636775B (zh) * | 2021-07-20 | 2024-02-06 | 晶美晟光电材料(南京)有限公司 | 一种含硫的联苯类液晶化合物的制备方法 |
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| US3443943A (en) * | 1967-07-24 | 1969-05-13 | Polaroid Corp | Photographic products and processes employing ring - closing 2 - equivalent silver halide developing agents |
| US4315926A (en) | 1979-12-26 | 1982-02-16 | Ciba-Geigy Corporation | Dibenz[c,e]azepines |
| US4473709A (en) * | 1980-07-14 | 1984-09-25 | Fmc Corporation | Pyrethroid intermediates and process |
| US5283241A (en) * | 1992-08-28 | 1994-02-01 | Merck & Co., Inc. | Benzo-fused lactams promote release of growth hormone |
| ATE296797T1 (de) * | 1996-11-22 | 2005-06-15 | Elan Pharm Inc | N-(aryl/heteroaryl/alkylacetyl) amino saüre amide,pharmazeutische zusammensetzungen damit, und methodenzur inhibierung beta-amyloid peptid freisetzung oder synthese |
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- 2000-07-25 IL IL14805800A patent/IL148058A0/xx active IP Right Grant
- 2000-07-25 SK SK203-2002A patent/SK287353B6/sk not_active IP Right Cessation
- 2000-08-01 PE PE2000000759A patent/PE20010384A1/es not_active Application Discontinuation
- 2000-08-03 CO CO00058414A patent/CO5200790A1/es not_active Application Discontinuation
- 2000-08-04 AR ARP000104054A patent/AR025052A1/es active IP Right Grant
-
2002
- 2002-02-06 IL IL148058A patent/IL148058A/en not_active IP Right Cessation
- 2002-02-07 NO NO20020610A patent/NO327670B1/no not_active IP Right Cessation
- 2002-02-11 US US10/071,229 patent/US6710080B2/en not_active Expired - Fee Related
- 2002-03-07 ZA ZA200201917A patent/ZA200201917B/en unknown
-
2006
- 2006-09-27 CY CY20061101399T patent/CY1105387T1/el unknown
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