SK2012003A3 - Phenoxybenzylamine derivatives as selective re-uptake inhibitors - Google Patents

Phenoxybenzylamine derivatives as selective re-uptake inhibitors Download PDF

Info

Publication number: SK2012003A3
Authority: SK; Slovakia
Prior art keywords: methyl; formula; compound; group; mhz
Prior art date: 2000-08-31

Application number

SK201-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Mavis Diane Adam

Mark David Andrews

Mark Leonard Elliott

Geoffrey Edward Gymer

David Hepworth

Harry Ralph Howard Jr

Donald Stuart Middleton

Alan Stobie

Original Assignee

Pfizer

Priority date (The priority date 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 date listed.)

2000-08-31

Filing date

2001-08-22

Publication date

2004-06-08

2000-08-31 Priority claimed from GB0021593A external-priority patent/GB0021593D0/en

2001-03-21 Priority claimed from GB0107116A external-priority patent/GB0107116D0/en

2001-08-22 Application filed by Pfizer filed Critical Pfizer

2004-06-08 Publication of SK2012003A3 publication Critical patent/SK2012003A3/sk

Links

239000003112 inhibitor Substances 0.000 title description 9
YXMXAXHPRPWBJB-UHFFFAOYSA-N n-phenoxy-1-phenylmethanamine Chemical class C=1C=CC=CC=1CNOC1=CC=CC=C1 YXMXAXHPRPWBJB-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 278
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 146
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 38
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 34
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 33
239000001257 hydrogen Substances 0.000 claims abstract description 29
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 24
229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 16
239000011593 sulfur Chemical group 0.000 claims abstract description 16
229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
125000005842 heteroatom Chemical group 0.000 claims abstract description 14
239000001301 oxygen Substances 0.000 claims abstract description 14
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 11
229910052731 fluorine Inorganic materials 0.000 claims abstract description 9
125000004429 atom Chemical group 0.000 claims abstract description 8
229910052736 halogen Inorganic materials 0.000 claims abstract description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 8
229910052794 bromium Inorganic materials 0.000 claims abstract description 7
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 6
239000011737 fluorine Substances 0.000 claims abstract description 6
125000005843 halogen group Chemical group 0.000 claims abstract description 6
125000001960 7 membered carbocyclic group Chemical group 0.000 claims abstract description 3
125000002393 azetidinyl group Chemical group 0.000 claims abstract description 3
125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 3
125000001188 haloalkyl group Chemical group 0.000 claims abstract description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 5
238000002360 preparation method Methods 0.000 claims description 110
-1 NH 2 Chemical group 0.000 claims description 77
238000006243 chemical reaction Methods 0.000 claims description 77
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 63
239000002904 solvent Substances 0.000 claims description 55
150000003839 salts Chemical class 0.000 claims description 53
238000000034 method Methods 0.000 claims description 37
239000012453 solvate Substances 0.000 claims description 27
238000011282 treatment Methods 0.000 claims description 24
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 22
150000001412 amines Chemical class 0.000 claims description 20
239000003814 drug Substances 0.000 claims description 17
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 16
239000000460 chlorine Chemical group 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
229920006395 saturated elastomer Polymers 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
239000003638 chemical reducing agent Substances 0.000 claims description 14
239000003795 chemical substances by application Substances 0.000 claims description 14
239000012442 inert solvent Substances 0.000 claims description 14
230000002411 adverse Effects 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 13
206010036596 premature ejaculation Diseases 0.000 claims description 13
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 12
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 12
229910052801 chlorine Inorganic materials 0.000 claims description 10
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 10
125000002883 imidazolyl group Chemical group 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 9
125000001425 triazolyl group Chemical group 0.000 claims description 9
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 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
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
201000001880 Sexual dysfunction Diseases 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
150000004678 hydrides Chemical class 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 6
208000028173 post-traumatic stress disease Diseases 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
231100000872 sexual dysfunction Toxicity 0.000 claims description 6
208000011117 substance-related disease Diseases 0.000 claims description 6
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
230000033228 biological regulation Effects 0.000 claims description 5
238000002955 isolation Methods 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 5
101710164184 Synaptic vesicular amine transporter Proteins 0.000 claims description 4
102100034333 Synaptic vesicular amine transporter Human genes 0.000 claims description 4
OMHSYKYTYRKAQR-UHFFFAOYSA-N [3-[(dimethylamino)methyl]-4-(3-fluoro-4-methylsulfanylphenoxy)phenyl]methanol Chemical compound C1=C(F)C(SC)=CC=C1OC1=CC=C(CO)C=C1CN(C)C OMHSYKYTYRKAQR-UHFFFAOYSA-N 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
238000011065 in-situ storage Methods 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 claims description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
230000002140 halogenating effect Effects 0.000 claims description 3
230000000802 nitrating effect Effects 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 claims description 2
208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
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 description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
IMPIIVKYTNMBCD-UHFFFAOYSA-N 2-phenoxybenzaldehyde Chemical compound O=CC1=CC=CC=C1OC1=CC=CC=C1 IMPIIVKYTNMBCD-UHFFFAOYSA-N 0.000 claims 1
229940125890 compound Ia Drugs 0.000 claims 1
OKRFWLHFFMDJDB-UHFFFAOYSA-N n-[4-(2,3-dihydro-1,4-benzoxathiin-7-yloxy)-3-[(dimethylamino)methyl]phenyl]methanesulfonamide Chemical compound CN(C)CC1=CC(NS(C)(=O)=O)=CC=C1OC1=CC=C(SCCO2)C2=C1 OKRFWLHFFMDJDB-UHFFFAOYSA-N 0.000 claims 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims 1
230000002028 premature Effects 0.000 claims 1
230000001105 regulatory effect Effects 0.000 claims 1
229910052740 iodine Inorganic materials 0.000 abstract description 7
230000000694 effects Effects 0.000 abstract description 5
125000002373 5 membered heterocyclic group Chemical group 0.000 abstract description 3
125000004070 6 membered heterocyclic group Chemical group 0.000 abstract description 3
229940124834 selective serotonin reuptake inhibitor Drugs 0.000 abstract description 3
239000012896 selective serotonin reuptake inhibitor Substances 0.000 abstract description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
230000000407 monoamine reuptake Effects 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 165
239000000243 solution Substances 0.000 description 96
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 91
239000000203 mixture Substances 0.000 description 82
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 73
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 64
239000002243 precursor Substances 0.000 description 62
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
150000003840 hydrochlorides Chemical class 0.000 description 50
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
235000019439 ethyl acetate Nutrition 0.000 description 44
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
239000010410 layer Substances 0.000 description 38
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
239000012044 organic layer Substances 0.000 description 37
239000000047 product Substances 0.000 description 36
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000007787 solid Substances 0.000 description 26
239000011541 reaction mixture Substances 0.000 description 25
238000000746 purification Methods 0.000 description 23
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 22
239000003921 oil Substances 0.000 description 21
235000019198 oils Nutrition 0.000 description 21
229910004298 SiO 2 Inorganic materials 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
238000003756 stirring Methods 0.000 description 19
238000004440 column chromatography Methods 0.000 description 18
239000012267 brine Substances 0.000 description 17
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 14
239000000725 suspension Substances 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
238000001816 cooling Methods 0.000 description 13
150000002431 hydrogen Chemical class 0.000 description 13
239000008279 sol Substances 0.000 description 13
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
238000012360 testing method Methods 0.000 description 12
239000000284 extract Substances 0.000 description 11
241000282414 Homo sapiens Species 0.000 description 10
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
239000006260 foam Substances 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
125000003373 pyrazinyl group Chemical group 0.000 description 9
229920002472 Starch Polymers 0.000 description 8
208000035475 disorder Diseases 0.000 description 8
229940079593 drug Drugs 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
230000000697 serotonin reuptake Effects 0.000 description 8
229940032147 starch Drugs 0.000 description 8
239000008107 starch Substances 0.000 description 8
235000019698 starch Nutrition 0.000 description 8
239000000126 substance Substances 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
239000002253 acid Substances 0.000 description 7
125000002837 carbocyclic group Chemical group 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
239000002552 dosage form Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
239000000843 powder Substances 0.000 description 7
239000000651 prodrug Substances 0.000 description 7
229940002612 prodrug Drugs 0.000 description 7
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 7
239000007858 starting material Substances 0.000 description 7
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
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WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-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
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
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230000015572 biosynthetic process Effects 0.000 description 6
229960003638 dopamine Drugs 0.000 description 6
238000009472 formulation Methods 0.000 description 6
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230000002401 inhibitory effect Effects 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
125000003226 pyrazolyl group Chemical group 0.000 description 6
229940076279 serotonin Drugs 0.000 description 6
125000001424 substituent group Chemical group 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
239000012359 Methanesulfonyl chloride Substances 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
125000004093 cyano group Chemical group *C#N 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
239000000463 material Substances 0.000 description 5
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
229960002748 norepinephrine Drugs 0.000 description 5
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
229920001223 polyethylene glycol Polymers 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
150000003141 primary amines Chemical class 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 5
230000009467 reduction Effects 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000012321 sodium triacetoxyborohydride Substances 0.000 description 5
239000000758 substrate Substances 0.000 description 5
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Classifications

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- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07—ORGANIC CHEMISTRY
- 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
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- C07—ORGANIC CHEMISTRY
- 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
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/20—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- 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
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
- C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
- C07D327/06—Six-membered rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/72—Benzo[c]thiophenes; Hydrogenated benzo[c]thiophenes
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

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Chemical & Material Sciences (AREA)
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SK201-2003A 2000-08-31 2001-08-22 Phenoxybenzylamine derivatives as selective re-uptake inhibitors SK2012003A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB0021593A GB0021593D0 (en)	2000-08-31	2000-08-31	Diphenyl ether compounds useful in therapy
GB0107116A GB0107116D0 (en)	2001-03-21	2001-03-21	Novel compounds
PCT/IB2001/001521 WO2002018333A1 (en)	2000-08-31	2001-08-22	Phenoxybenzylamine derivatives as selective serotonin re-uptake inhibitors

Publications (1)

Publication Number	Publication Date
SK2012003A3 true SK2012003A3 (en)	2004-06-08

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Application Number	Title	Priority Date	Filing Date
SK201-2003A SK2012003A3 (en)	2000-08-31	2001-08-22	Phenoxybenzylamine derivatives as selective re-uptake inhibitors

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EP (1)	EP1313701A1 (es)
JP (1)	JP2004507523A (es)
KR (1)	KR20030029889A (es)
CN (1)	CN1449380A (es)
AP (1)	AP2001002265A0 (es)
AR (1)	AR031867A1 (es)
AU (1)	AU2001278650A1 (es)
BG (1)	BG107544A (es)
BR (1)	BR0113610A (es)
CA (1)	CA2420969A1 (es)
CZ (1)	CZ2003467A3 (es)
DO (1)	DOP2001000242A (es)
DZ (1)	DZ3414A1 (es)
EA (1)	EA200300206A1 (es)
EE (1)	EE200300084A (es)
HN (1)	HN2001000191A (es)
HR (1)	HRP20030141A2 (es)
HU (1)	HUP0303385A2 (es)
IL (1)	IL154343A0 (es)
IS (1)	IS6704A (es)
MA (1)	MA26945A1 (es)
MX (1)	MXPA03001848A (es)
NO (1)	NO20030842L (es)
NZ (1)	NZ523951A (es)
OA (1)	OA12372A (es)
PA (1)	PA8526701A1 (es)
PE (1)	PE20020346A1 (es)
PL (1)	PL360743A1 (es)
SK (1)	SK2012003A3 (es)
TN (1)	TNSN01131A1 (es)
UY (1)	UY26924A1 (es)
WO (1)	WO2002018333A1 (es)

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CA2570047C (en)	2004-07-08	2010-09-28	Warner-Lambert Company Llc	4-cycloalkoxy benzonitriles as androgen modulators
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CA2580024A1 (en) *	2004-09-10	2006-03-16	Pfizer Products Inc.	Therapeutic diphenyl ether ligands
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WO2007047397A2 (en)	2005-10-13	2007-04-26	Smithkline Beecham Corporation	Phenol ethers as modulators of the opioid receptors
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JP2009544579A (ja)	2006-06-29	2009-12-17	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	置換ベンジルアミン化合物
EP2046747A1 (en) *	2006-06-29	2009-04-15	Janssen Pharmaceutica N.V.	Substituted aminomethyl benzamide compounds
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KR101043200B1 (ko) *	2010-11-08	2011-06-21	성시민	호흡용 공기탱크의 공기 충전장치
DE112011104795T5 (de)	2011-01-27	2013-10-31	Hewlett-Packard Development Company, L.P.	Computer-Vorrichtung zur Verbindung an eine tragbare Vorrichtung
KR20210135521A (ko)	2019-03-06	2021-11-15	다이이찌 산쿄 가부시키가이샤	피롤로피라졸 유도체

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2001
- 2001-08-22 OA OA1200300056A patent/OA12372A/en unknown
- 2001-08-22 CN CN01814846A patent/CN1449380A/zh active Pending
- 2001-08-22 EA EA200300206A patent/EA200300206A1/ru unknown
- 2001-08-22 DZ DZ013414A patent/DZ3414A1/fr active
- 2001-08-22 CA CA002420969A patent/CA2420969A1/en not_active Abandoned
- 2001-08-22 IL IL15434301A patent/IL154343A0/xx unknown
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- 2001-08-22 PL PL36074301A patent/PL360743A1/xx not_active Application Discontinuation
- 2001-08-22 EE EEP200300084A patent/EE200300084A/xx unknown
- 2001-08-22 SK SK201-2003A patent/SK2012003A3/sk unknown
- 2001-08-22 KR KR10-2003-7003011A patent/KR20030029889A/ko not_active Ceased
- 2001-08-22 NZ NZ523951A patent/NZ523951A/en unknown
- 2001-08-22 CZ CZ2003467A patent/CZ2003467A3/cs unknown
- 2001-08-22 EP EP01956734A patent/EP1313701A1/en not_active Withdrawn
- 2001-08-22 WO PCT/IB2001/001521 patent/WO2002018333A1/en not_active Ceased
- 2001-08-22 BR BR0113610-0A patent/BR0113610A/pt not_active IP Right Cessation
- 2001-08-22 MX MXPA03001848A patent/MXPA03001848A/es active IP Right Grant
- 2001-08-22 JP JP2002523451A patent/JP2004507523A/ja active Pending
- 2001-08-22 HU HU0303385A patent/HUP0303385A2/hu unknown
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- 2001-08-22 AU AU2001278650A patent/AU2001278650A1/en not_active Abandoned
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- 2001-08-28 PE PE2001000862A patent/PE20020346A1/es not_active Application Discontinuation
- 2001-08-29 DO DO2001000242A patent/DOP2001000242A/es unknown
- 2001-08-29 AR ARP010104114A patent/AR031867A1/es unknown
- 2001-08-30 TN TNTNSN01131A patent/TNSN01131A1/fr unknown
- 2001-08-31 UY UY26924A patent/UY26924A1/es not_active Application Discontinuation
2003
- 2003-01-30 IS IS6704A patent/IS6704A/is unknown
- 2003-02-07 BG BG107544A patent/BG107544A/bg unknown
- 2003-02-21 MA MA27049A patent/MA26945A1/fr unknown
- 2003-02-24 NO NO20030842A patent/NO20030842L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
DOP2001000242A (es)	2002-05-15
NZ523951A (en)	2004-09-24
AU2001278650A1 (en)	2002-03-13
PL360743A1 (en)	2004-09-20
DZ3414A1 (fr)	2002-03-07
CA2420969A1 (en)	2002-03-07
TNSN01131A1 (fr)	2005-11-10
EP1313701A1 (en)	2003-05-28
AR031867A1 (es)	2003-10-08
HUP0303385A2 (hu)	2004-03-01
PE20020346A1 (es)	2002-05-08
WO2002018333A1 (en)	2002-03-07
EE200300084A (et)	2005-02-15
MXPA03001848A (es)	2003-06-04
EA200300206A1 (ru)	2003-06-26
IL154343A0 (en)	2003-09-17
IS6704A (is)	2003-01-30
AP2001002265A0 (en)	2001-09-30
MA26945A1 (fr)	2004-12-20
NO20030842D0 (no)	2003-02-24
KR20030029889A (ko)	2003-04-16
CN1449380A (zh)	2003-10-15
PA8526701A1 (es)	2003-07-28
HRP20030141A2 (en)	2003-04-30
HN2001000191A (es)	2002-03-11
BR0113610A (pt)	2003-06-24
NO20030842L (no)	2003-04-28
JP2004507523A (ja)	2004-03-11
OA12372A (en)	2006-04-17
UY26924A1 (es)	2002-03-22
BG107544A (bg)	2003-10-31
CZ2003467A3 (cs)	2004-04-14

Legal Events

Date	Code	Title	Description
2011-11-04	FB9A	Suspension of patent application procedure

Publication	Publication Date	Title
CZ2003467A3 (cs)	2004-04-14	Fenoxybenzylaminové deriváty jako selektivní inhibitory reuptake serotoninu
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US6610747B2 (en)	2003-08-26	Phenoxybenzylamine derivatives as SSRIs
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WO2005073183A1 (ja)	2005-08-11	アリールスルフィド誘導体
US6800652B2 (en)	2004-10-05	Diaryl compounds
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