UA75067C2 - Diphenyl ethers, pharmaceutical composition containing them, use thereof, a method for treatment (variants), a method for obtaining thereof and method for producing intermediary compounds - Google Patents
Diphenyl ethers, pharmaceutical composition containing them, use thereof, a method for treatment (variants), a method for obtaining thereof and method for producing intermediary compounds Download PDFInfo
- Publication number
- UA75067C2 UA75067C2 UA2002097628A UA2002097628A UA75067C2 UA 75067 C2 UA75067 C2 UA 75067C2 UA 2002097628 A UA2002097628 A UA 2002097628A UA 2002097628 A UA2002097628 A UA 2002097628A UA 75067 C2 UA75067 C2 UA 75067C2
- Authority
- UA
- Ukraine
- Prior art keywords
- phenoxy
- methyl
- methylsulfanyl
- pharmaceutically acceptable
- mixture
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 216
- 238000000034 method Methods 0.000 title claims description 67
- 238000011282 treatment Methods 0.000 title claims description 45
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical class C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 75
- 239000012453 solvate Substances 0.000 claims abstract description 34
- 206010036596 premature ejaculation Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 208000035475 disorder Diseases 0.000 claims abstract description 9
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims abstract description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims abstract description 7
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 7
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 7
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims abstract description 6
- 208000028173 post-traumatic stress disease Diseases 0.000 claims abstract description 6
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 97
- 238000006243 chemical reaction Methods 0.000 claims description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- -1 methylthio, ethylthio Chemical group 0.000 claims description 61
- 239000002904 solvent Substances 0.000 claims description 59
- 239000001257 hydrogen Substances 0.000 claims description 56
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
- 150000001412 amines Chemical class 0.000 claims description 45
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 32
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 30
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 239000012442 inert solvent Substances 0.000 claims description 25
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 23
- 239000003638 chemical reducing agent Substances 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 230000015572 biosynthetic process Effects 0.000 claims description 19
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 15
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 15
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 9
- 125000001425 triazolyl group Chemical group 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 7
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 7
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 7
- 230000003993 interaction Effects 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 230000033228 biological regulation Effects 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 230000002140 halogenating effect Effects 0.000 claims description 3
- 230000000802 nitrating effect Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000008177 pharmaceutical agent Substances 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 201000006152 substance dependence Diseases 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
- 125000004429 atom Chemical group 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 claims 1
- 235000010469 Glycine max Nutrition 0.000 claims 1
- 244000068988 Glycine max Species 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 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 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 230000000697 serotonin reuptake Effects 0.000 abstract description 9
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 230000000407 monoamine reuptake Effects 0.000 abstract description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 201000009032 substance abuse Diseases 0.000 abstract 1
- 231100000736 substance abuse Toxicity 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 237
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
- 239000000203 mixture Substances 0.000 description 182
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 144
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 144
- 238000002360 preparation method Methods 0.000 description 108
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 94
- 239000000243 solution Substances 0.000 description 92
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
- 239000003921 oil Substances 0.000 description 67
- 235000019198 oils Nutrition 0.000 description 67
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 64
- 235000019439 ethyl acetate Nutrition 0.000 description 63
- 238000003818 flash chromatography Methods 0.000 description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- 239000011541 reaction mixture Substances 0.000 description 61
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 44
- 239000007787 solid Substances 0.000 description 44
- 239000012044 organic layer Substances 0.000 description 43
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 40
- 239000010410 layer Substances 0.000 description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- 238000001816 cooling Methods 0.000 description 31
- 238000003756 stirring Methods 0.000 description 30
- 239000000284 extract Substances 0.000 description 29
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 28
- 150000001408 amides Chemical class 0.000 description 28
- 238000000746 purification Methods 0.000 description 28
- 239000007864 aqueous solution Substances 0.000 description 26
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical group [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 description 26
- 239000000725 suspension Substances 0.000 description 26
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 25
- 239000002585 base Substances 0.000 description 25
- 239000012266 salt solution Substances 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 22
- 239000000047 product Substances 0.000 description 22
- 238000010992 reflux Methods 0.000 description 21
- 229940124530 sulfonamide Drugs 0.000 description 21
- 150000003456 sulfonamides Chemical class 0.000 description 21
- 150000001299 aldehydes Chemical class 0.000 description 20
- 229910021529 ammonia Inorganic materials 0.000 description 19
- 239000012458 free base Substances 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 19
- 150000002825 nitriles Chemical class 0.000 description 19
- 239000003054 catalyst Substances 0.000 description 18
- 239000012299 nitrogen atmosphere Substances 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 150000002148 esters Chemical class 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000012230 colorless oil Substances 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 230000009467 reduction Effects 0.000 description 14
- 238000006722 reduction reaction Methods 0.000 description 14
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 13
- 238000009835 boiling Methods 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 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 description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 150000004678 hydrides Chemical class 0.000 description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 10
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 10
- 229910002091 carbon monoxide Inorganic materials 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 10
- 241000282414 Homo sapiens Species 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 239000010502 orange oil Substances 0.000 description 9
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- 235000019502 Orange oil Nutrition 0.000 description 8
- 150000001499 aryl bromides Chemical class 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 229960001866 silicon dioxide Drugs 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 229920000858 Cyclodextrin Polymers 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 7
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 7
- 229960003638 dopamine Drugs 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 150000003335 secondary amines Chemical class 0.000 description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 150000001916 cyano esters Chemical class 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
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Classifications
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- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/44—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by —CHO groups
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/58—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
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- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
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- G06F11/16—Error detection or correction of the data by redundancy in hardware
- G06F11/20—Error detection or correction of the data by redundancy in hardware using active fault-masking, e.g. by switching out faulty elements or by switching in spare elements
- G06F11/2097—Error detection or correction of the data by redundancy in hardware using active fault-masking, e.g. by switching out faulty elements or by switching in spare elements maintaining the standby controller/processing unit updated
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- H04L—TRANSMISSION OF DIGITAL INFORMATION, e.g. TELEGRAPHIC COMMUNICATION
- H04L12/00—Data switching networks
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- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- G06F11/07—Responding to the occurrence of a fault, e.g. fault tolerance
- G06F11/16—Error detection or correction of the data by redundancy in hardware
- G06F11/20—Error detection or correction of the data by redundancy in hardware using active fault-masking, e.g. by switching out faulty elements or by switching in spare elements
- G06F11/202—Error detection or correction of the data by redundancy in hardware using active fault-masking, e.g. by switching out faulty elements or by switching in spare elements where processing functionality is redundant
- G06F11/2038—Error detection or correction of the data by redundancy in hardware using active fault-masking, e.g. by switching out faulty elements or by switching in spare elements where processing functionality is redundant with a single idle spare processing component
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0007884.0A GB0007884D0 (en) | 2000-03-31 | 2000-03-31 | Diphenyl ether compounds useful in therapy |
PCT/IB2001/000428 WO2001072687A1 (en) | 2000-03-31 | 2001-03-19 | Diphenyl ether compounds useful in therapy |
Publications (1)
Publication Number | Publication Date |
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UA75067C2 true UA75067C2 (en) | 2006-03-15 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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UA2002097628A UA75067C2 (en) | 2000-03-31 | 2001-03-19 | Diphenyl ethers, pharmaceutical composition containing them, use thereof, a method for treatment (variants), a method for obtaining thereof and method for producing intermediary compounds |
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Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
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US6410736B1 (en) | 1999-11-29 | 2002-06-25 | Pfizer Inc. | Biaryl ether derivatives useful as monoamine reuptake inhibitors |
EE200300084A (et) * | 2000-08-31 | 2005-02-15 | Pfizer Inc. | Fenoksübensüülamiini derivaadid kui selektiivsed serotoniini tagasihaarde inhibiitorid |
US6610747B2 (en) | 2000-08-31 | 2003-08-26 | Pfizer Inc. | Phenoxybenzylamine derivatives as SSRIs |
US6436938B1 (en) * | 2001-01-22 | 2002-08-20 | Pfizer Inc. | Combination treatment for depression |
US20020107244A1 (en) * | 2001-02-02 | 2002-08-08 | Howard Harry R. | Combination treatment for depression |
US20020183306A1 (en) * | 2001-05-30 | 2002-12-05 | Pfizer Inc. | Combination treatment for sleep disorders including sleep apnea |
GB0202282D0 (en) | 2002-01-31 | 2002-03-20 | Pfizer Ltd | Treatment of male sexual dysfunction |
GB0219154D0 (en) * | 2002-08-16 | 2002-09-25 | Pfizer Ltd | Diaryl compounds |
US6800652B2 (en) | 2002-08-16 | 2004-10-05 | Pfizer Inc. | Diaryl compounds |
CA2451267A1 (en) * | 2002-12-13 | 2004-06-13 | Warner-Lambert Company Llc | Pharmaceutical uses for alpha2delta ligands |
GB0318706D0 (en) * | 2003-08-08 | 2003-09-10 | Pfizer Ltd | Selective serotonin reuptake inhibitors in the treatment of disease |
KR20060070566A (ko) * | 2003-09-22 | 2006-06-23 | 화이자 인코포레이티드 | 디페닐 에테르 화합물의 신규 제조방법 |
CA2656083A1 (en) * | 2006-06-29 | 2008-01-03 | Janssen Pharmaceutica N.V. | Substituted aminomethyl benzamide compounds |
WO2008002817A1 (en) * | 2006-06-29 | 2008-01-03 | Janssen Pharmaceutica N.V. | Butyl and butynyl benzyl amine compounds |
CA2656089A1 (en) | 2006-06-29 | 2008-01-03 | Janssen Pharmaceutica N.V. | Substituted benzyl amine compounds |
US20130017163A1 (en) * | 2011-07-14 | 2013-01-17 | Latham Keith R | Halogenated phenols for diagnostics, antioxidant protection and drug delivery |
US10220100B2 (en) | 2011-07-14 | 2019-03-05 | Keith R. Latham | Halogenated phenols for diagnostics, antioxidant protection and drug delivery |
EP2919788A4 (en) | 2012-11-14 | 2016-05-25 | Univ Johns Hopkins | METHODS AND COMPOSITIONS FOR THE TREATMENT OF SCHIZOPHRENIA |
MX2016016488A (es) * | 2014-08-27 | 2017-03-30 | Hoffmann La Roche | Derivados de azetidina sustituidos como ligandos de receptores asociados a aminas en trazas (taar). |
CN118290322A (zh) * | 2018-08-24 | 2024-07-05 | 赛尼欧普罗有限责任公司 | 用于治疗病态状况的芳香型分子 |
JP7413346B2 (ja) | 2019-03-06 | 2024-01-15 | 第一三共株式会社 | ピロロピラゾール誘導体 |
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ATE111885T1 (de) * | 1987-09-09 | 1994-10-15 | Zeneca Ltd | Schimmelbekämpfungsmittel. |
US4940731A (en) * | 1989-08-30 | 1990-07-10 | Pfizer Inc. | Method of treating premature ejaculation using sertraline |
ZA923283B (en) * | 1991-05-29 | 1993-01-27 | Akzo Nv | Phenoxyphenyl derivatives |
YU56301A (sh) * | 1999-02-23 | 2004-05-12 | Pfizer Products Inc. | Inhibitori resorpcije monoamina za tretiranje poremećaja cns |
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2002
- 2002-07-05 IS IS6457A patent/IS6457A/is unknown
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