HUP0300922A2 - Új vegyületek, eljárás az előállításukra, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk - Google Patents
Új vegyületek, eljárás az előállításukra, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk Download PDFInfo
- Publication number
- HUP0300922A2 HUP0300922A2 HU0300922A HUP0300922A HUP0300922A2 HU P0300922 A2 HUP0300922 A2 HU P0300922A2 HU 0300922 A HU0300922 A HU 0300922A HU P0300922 A HUP0300922 A HU P0300922A HU P0300922 A2 HUP0300922 A2 HU P0300922A2
- Authority
- HU
- Hungary
- Prior art keywords
- hydroxypropoxy
- acetamide
- phenyl
- pyrrolidinyl
- piperidyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 245
- 238000000034 method Methods 0.000 title claims description 51
- 238000002360 preparation method Methods 0.000 title claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 51
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 239000012453 solvate Substances 0.000 claims abstract description 30
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 26
- 239000001301 oxygen Substances 0.000 claims abstract description 26
- 229910052717 sulfur Chemical group 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 22
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract 2
- -1 nitro, carboxy Chemical group 0.000 claims description 99
- 239000000203 mixture Substances 0.000 claims description 97
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 77
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 68
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 52
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 49
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 48
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 45
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 229920006395 saturated elastomer Polymers 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 9
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 229910052744 lithium Inorganic materials 0.000 claims description 9
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 9
- 239000011593 sulfur Chemical group 0.000 claims description 9
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 8
- 239000004202 carbamide Substances 0.000 claims description 8
- NPSKGQWYPOEEPS-UHFFFAOYSA-N n-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 NPSKGQWYPOEEPS-UHFFFAOYSA-N 0.000 claims description 8
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 claims description 7
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 7
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- DIOVKBRFROAMJA-UHFFFAOYSA-N methyl 3-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 DIOVKBRFROAMJA-UHFFFAOYSA-N 0.000 claims description 6
- MFDCXLFWYSMGDK-UHFFFAOYSA-N n-[5-chloro-2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC(Cl)=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 MFDCXLFWYSMGDK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- WSGAYMDZRMHRIW-WNPSOCMYSA-N (2s,4s)-1-[3-(2-acetamidophenoxy)-2-hydroxypropyl]-4-(4-chlorophenoxy)pyrrolidine-2-carboxylic acid Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1[C@H](C(O)=O)C[C@H](OC=2C=CC(Cl)=CC=2)C1 WSGAYMDZRMHRIW-WNPSOCMYSA-N 0.000 claims description 4
- IHYMOMJDLVRLGK-UHFFFAOYSA-N 1-[7-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]indol-1-yl]ethanone Chemical compound C=12N(C(=O)C)C=CC2=CC=CC=1OCC(O)CN(C1)CCC1OC1=CC=C(F)C=C1 IHYMOMJDLVRLGK-UHFFFAOYSA-N 0.000 claims description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 4
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- JFRFEFKQNZHIHM-UHFFFAOYSA-N n-[2-[3-[3-(4-chloroanilino)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CC(NC=2C=CC(Cl)=CC=2)CC1 JFRFEFKQNZHIHM-UHFFFAOYSA-N 0.000 claims description 4
- RTJSEBBDMFDCMK-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxy-2-methylpropoxy]phenyl]acetamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=CC=C1OCC(C)(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 RTJSEBBDMFDCMK-UHFFFAOYSA-N 0.000 claims description 4
- GWTPBGQICZEEFZ-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 GWTPBGQICZEEFZ-UHFFFAOYSA-N 0.000 claims description 4
- OYSQIIUDNHUIFD-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 OYSQIIUDNHUIFD-UHFFFAOYSA-N 0.000 claims description 4
- LVEHZKKZVZQIQX-UHFFFAOYSA-N n-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxy-2-methylpropoxy]-4-fluorophenyl]acetamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=C(F)C=C1OCC(C)(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 LVEHZKKZVZQIQX-UHFFFAOYSA-N 0.000 claims description 4
- IWIUJTLMFKBYLJ-UHFFFAOYSA-N n-[5-chloro-2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC(Cl)=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 IWIUJTLMFKBYLJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- QLLXNJVUUSJAKY-UHFFFAOYSA-N 1-(2,6-dimethoxyphenoxy)-3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]propan-2-ol Chemical compound COC1=CC=CC(OC)=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 QLLXNJVUUSJAKY-UHFFFAOYSA-N 0.000 claims description 3
- XQFRFKZWYYBUNY-UHFFFAOYSA-N 1-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-3-(1h-indol-7-yloxy)propan-2-ol Chemical compound N1C2=CC=C(Cl)C=C2C(C2)=C1CCN2CC(O)COC1=CC=CC2=C1NC=C2 XQFRFKZWYYBUNY-UHFFFAOYSA-N 0.000 claims description 3
- VPHFPBPFTWHPDA-UHFFFAOYSA-N 1-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-6-methoxyphenyl]ethanone Chemical compound COC1=CC=CC(OCC(O)CN2CC(CC2)OC=2C=C(Cl)C(Cl)=CC=2)=C1C(C)=O VPHFPBPFTWHPDA-UHFFFAOYSA-N 0.000 claims description 3
- FARBNVQQUGMTBJ-UHFFFAOYSA-N 1-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 FARBNVQQUGMTBJ-UHFFFAOYSA-N 0.000 claims description 3
- SKZRGXXYDAUHQV-UHFFFAOYSA-N 1-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 SKZRGXXYDAUHQV-UHFFFAOYSA-N 0.000 claims description 3
- QHFFUNPIGPVCDI-UHFFFAOYSA-N 1-[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 QHFFUNPIGPVCDI-UHFFFAOYSA-N 0.000 claims description 3
- TXUJOWGKGLIRIX-UHFFFAOYSA-N 1-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-6-methoxyphenyl]ethanone Chemical compound COC1=CC=CC(OCC(O)CN2CC(CC2)OC=2C=CC(Cl)=CC=2)=C1C(C)=O TXUJOWGKGLIRIX-UHFFFAOYSA-N 0.000 claims description 3
- IWDYEFIKVGBLLT-UHFFFAOYSA-N 1-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]-1-ethylurea;hydrochloride Chemical compound Cl.CCN(C(N)=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 IWDYEFIKVGBLLT-UHFFFAOYSA-N 0.000 claims description 3
- RDOMSIRDJMZQFG-UHFFFAOYSA-N 1-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 RDOMSIRDJMZQFG-UHFFFAOYSA-N 0.000 claims description 3
- SXGHXBQJMAXRGT-UHFFFAOYSA-N 1-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 SXGHXBQJMAXRGT-UHFFFAOYSA-N 0.000 claims description 3
- XHGDGEDAPFJBII-UHFFFAOYSA-N 1-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 XHGDGEDAPFJBII-UHFFFAOYSA-N 0.000 claims description 3
- CLRMKSASWXDYCE-UHFFFAOYSA-N 1-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 CLRMKSASWXDYCE-UHFFFAOYSA-N 0.000 claims description 3
- QHRFWGPGUXDOIE-UHFFFAOYSA-N 1-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-6-methoxyphenyl]ethanone Chemical compound COC1=CC=CC(OCC(O)CN2CCC(CC2)OC=2C=CC(Cl)=CC=2)=C1C(C)=O QHRFWGPGUXDOIE-UHFFFAOYSA-N 0.000 claims description 3
- KIBYECUCMQMOEK-UHFFFAOYSA-N 1-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-3-(1h-indol-7-yloxy)propan-2-ol Chemical compound C=1C=CC=2C=CNC=2C=1OCC(O)CN(C1)CCC1OC1=CC=C(F)C(F)=C1 KIBYECUCMQMOEK-UHFFFAOYSA-N 0.000 claims description 3
- BHQCLOGTSTZCTH-UHFFFAOYSA-N 1-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-3-(1h-indol-7-yloxy)propan-2-ol Chemical compound C=1C=CC=2C=CNC=2C=1OCC(O)CN(C1)CCC1OC1=CC=C(F)C=C1 BHQCLOGTSTZCTH-UHFFFAOYSA-N 0.000 claims description 3
- BFWIUIIIURTQDH-UHFFFAOYSA-N 1-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-3-(2-methoxyphenoxy)propan-2-ol Chemical compound COC1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 BFWIUIIIURTQDH-UHFFFAOYSA-N 0.000 claims description 3
- VBTPAYQPEMGVLO-UHFFFAOYSA-N 1-[7-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]indol-1-yl]ethanone Chemical compound N1C2=CC=C(Cl)C=C2C(C2)=C1CCN2CC(O)COC1=C2N(C(=O)C)C=CC2=CC=C1 VBTPAYQPEMGVLO-UHFFFAOYSA-N 0.000 claims description 3
- UGWTUVHOFVFPOT-UHFFFAOYSA-N 1-[7-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]indol-1-yl]ethanone Chemical compound C=12N(C(=O)C)C=CC2=CC=CC=1OCC(O)CN(C1)CCC1OC1=CC=C(F)C(F)=C1 UGWTUVHOFVFPOT-UHFFFAOYSA-N 0.000 claims description 3
- YMMQRIMRPSDHAG-UHFFFAOYSA-N 1-[7-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]indol-1-yl]ethanone Chemical compound C=12N(C(=O)C)C=CC2=CC=CC=1OCC(O)CN(CC1)CCC1OC1=CC=C(Cl)C(Cl)=C1 YMMQRIMRPSDHAG-UHFFFAOYSA-N 0.000 claims description 3
- FOMMNTFZWFKBNX-UHFFFAOYSA-N 1-[7-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]indol-1-yl]ethanone Chemical compound C=12N(C(=O)C)C=CC2=CC=CC=1OCC(O)CN(CC1)CCC1OC1=CC=C(Cl)C=C1 FOMMNTFZWFKBNX-UHFFFAOYSA-N 0.000 claims description 3
- YZQFHSSAYSQXAV-UHFFFAOYSA-N 2-[3-[4-(3,4-difluorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(F)C(F)=CC=2)CC1 YZQFHSSAYSQXAV-UHFFFAOYSA-N 0.000 claims description 3
- NRMGSPWZPSIZJU-UHFFFAOYSA-N 4-[1-[2-hydroxy-3-(2-propanoylphenoxy)propyl]pyrrolidin-3-yl]oxybenzonitrile Chemical compound CCC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(=CC=2)C#N)CC1 NRMGSPWZPSIZJU-UHFFFAOYSA-N 0.000 claims description 3
- 102000009410 Chemokine receptor Human genes 0.000 claims description 3
- 108050000299 Chemokine receptor Proteins 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- INXZHUAEBUHVSI-XHSROADOSA-N Cl.C([C@@H](C[C@H]1C(=O)OC)OCC=2C=CC(Cl)=CC=2)N1CC(O)COC1=CC=CC=C1NC(C)=O Chemical compound Cl.C([C@@H](C[C@H]1C(=O)OC)OCC=2C=CC(Cl)=CC=2)N1CC(O)COC1=CC=CC=C1NC(C)=O INXZHUAEBUHVSI-XHSROADOSA-N 0.000 claims description 3
- OYSQIIUDNHUIFD-PKOBYXMFSA-N N-[2-[(2S)-3-[(3R)-3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound C(C)(=O)NC1=C(C=CC=C1)OC[C@H](CN1C[C@@H](CC1)OC1=CC=C(C=C1)Cl)O OYSQIIUDNHUIFD-PKOBYXMFSA-N 0.000 claims description 3
- TZWAHAICMKJIAK-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)NC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 TZWAHAICMKJIAK-UHFFFAOYSA-N 0.000 claims description 3
- ITTHNWIVJRLOLO-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)NC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 ITTHNWIVJRLOLO-UHFFFAOYSA-N 0.000 claims description 3
- LPBKOUDEQGSXLH-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 LPBKOUDEQGSXLH-UHFFFAOYSA-N 0.000 claims description 3
- GHEVXOJVKXRIOT-UHFFFAOYSA-N methyl 2-[[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 GHEVXOJVKXRIOT-UHFFFAOYSA-N 0.000 claims description 3
- PKOSZUPRPIRFIF-UHFFFAOYSA-N methyl 3-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 PKOSZUPRPIRFIF-UHFFFAOYSA-N 0.000 claims description 3
- MRVWUOPLHITFDN-UHFFFAOYSA-N methyl 3-[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 MRVWUOPLHITFDN-UHFFFAOYSA-N 0.000 claims description 3
- NIDMBYPVESCCIN-UHFFFAOYSA-N methyl 4-acetamido-3-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoate Chemical compound COC(=O)C1=CC=C(NC(C)=O)C(OCC(O)CN2CC(CC2)OC=2C=C(Cl)C(Cl)=CC=2)=C1 NIDMBYPVESCCIN-UHFFFAOYSA-N 0.000 claims description 3
- LTEBHGJIUUPQCP-UHFFFAOYSA-N methyl 4-acetamido-3-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoate Chemical compound COC(=O)C1=CC=C(NC(C)=O)C(OCC(O)CN2CC(CC2)OC=2C=CC(Cl)=CC=2)=C1 LTEBHGJIUUPQCP-UHFFFAOYSA-N 0.000 claims description 3
- YMGPPKWCKCGFSZ-HRFCLUMMSA-N n-[2-[(2s)-3-[(2s,4s)-4-(4-chlorophenoxy)-2-methylpyrrolidin-1-yl]-2-hydroxypropoxy]-4-fluorophenyl]acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](O)CN1C[C@H](C[C@@H]1C)OC=1C=CC(Cl)=CC=1)OC1=CC(F)=CC=C1NC(C)=O YMGPPKWCKCGFSZ-HRFCLUMMSA-N 0.000 claims description 3
- ZDHUCNWQOIIMMU-HKUYNNGSSA-N n-[2-[(2s)-3-[(3s)-3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4-hydroxyphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(O)C=C1OC[C@@H](O)CN1C[C@@H](OC=2C=CC(Cl)=CC=2)CC1 ZDHUCNWQOIIMMU-HKUYNNGSSA-N 0.000 claims description 3
- NZRCPNJOFMGJPO-UHFFFAOYSA-N n-[2-[2-hydroxy-3-[3-(4-methoxyphenoxy)pyrrolidin-1-yl]propoxy]phenyl]acetamide Chemical compound C1=CC(OC)=CC=C1OC1CN(CC(O)COC=2C(=CC=CC=2)NC(C)=O)CC1 NZRCPNJOFMGJPO-UHFFFAOYSA-N 0.000 claims description 3
- OLUIFDUXSFCMFP-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CC(C2=CC(Cl)=CC=C2N2)=C2CC1 OLUIFDUXSFCMFP-UHFFFAOYSA-N 0.000 claims description 3
- NQXKGNVOZPLZFD-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC(O)CN1CC(C2=CC(Cl)=CC=C2N2)=C2CC1 NQXKGNVOZPLZFD-UHFFFAOYSA-N 0.000 claims description 3
- HJXTUHFNJFGPKW-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CN1CC(C2=CC(Cl)=CC=C2N2)=C2CC1 HJXTUHFNJFGPKW-UHFFFAOYSA-N 0.000 claims description 3
- SGWYUMVCYDJSDQ-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CC(C2=CC(Cl)=CC=C2N2)=C2CC1 SGWYUMVCYDJSDQ-UHFFFAOYSA-N 0.000 claims description 3
- SOMAAHQRBOTAQC-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-phenylphenyl]acetamide Chemical compound C=1C=C(OCC(O)CN2CC=3C4=CC(Cl)=CC=C4NC=3CC2)C(NC(=O)C)=CC=1C1=CC=CC=C1 SOMAAHQRBOTAQC-UHFFFAOYSA-N 0.000 claims description 3
- QNSCIKGEWXTILN-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CC(C2=CC(Cl)=CC=C2N2)=C2CC1 QNSCIKGEWXTILN-UHFFFAOYSA-N 0.000 claims description 3
- JQSHSKZXGCZOMY-UHFFFAOYSA-N n-[2-[3-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC(O)CN1CC(C2=CC(F)=CC=C2N2)=C2CC1 JQSHSKZXGCZOMY-UHFFFAOYSA-N 0.000 claims description 3
- QPDTUPDMJYQGEV-UHFFFAOYSA-N n-[2-[3-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CC(C2=CC(F)=CC=C2N2)=C2CC1 QPDTUPDMJYQGEV-UHFFFAOYSA-N 0.000 claims description 3
- SMBABFGRRDRQJL-UHFFFAOYSA-N n-[2-[3-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-phenylphenyl]acetamide Chemical compound C=1C=C(OCC(O)CN2CC=3C4=CC(F)=CC=C4NC=3CC2)C(NC(=O)C)=CC=1C1=CC=CC=C1 SMBABFGRRDRQJL-UHFFFAOYSA-N 0.000 claims description 3
- OOKLHYPTMVSBRZ-UHFFFAOYSA-N n-[2-[3-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CC(C2=CC(F)=CC=C2N2)=C2CC1 OOKLHYPTMVSBRZ-UHFFFAOYSA-N 0.000 claims description 3
- ULETZENVLCQKMB-UHFFFAOYSA-N n-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 ULETZENVLCQKMB-UHFFFAOYSA-N 0.000 claims description 3
- RMBKJNBIXIYPQU-UHFFFAOYSA-N n-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 RMBKJNBIXIYPQU-UHFFFAOYSA-N 0.000 claims description 3
- NOMLLELOQYXVIH-UHFFFAOYSA-N n-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-phenylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C=2C=CC=CC=2)=CC=C1OCC(O)CN(C1)CCC1OC1=CC=C(Cl)C(Cl)=C1 NOMLLELOQYXVIH-UHFFFAOYSA-N 0.000 claims description 3
- HGNIDALZAVHSJF-UHFFFAOYSA-N n-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 HGNIDALZAVHSJF-UHFFFAOYSA-N 0.000 claims description 3
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- JJVFMGXCCCAZHA-UHFFFAOYSA-N n-[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 JJVFMGXCCCAZHA-UHFFFAOYSA-N 0.000 claims description 3
- STLZSLMTIYPXRK-UHFFFAOYSA-N n-[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 STLZSLMTIYPXRK-UHFFFAOYSA-N 0.000 claims description 3
- AHQSAUUVFOOHEF-UHFFFAOYSA-N n-[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 AHQSAUUVFOOHEF-UHFFFAOYSA-N 0.000 claims description 3
- RHZAIGHQGUAMFQ-UHFFFAOYSA-N n-[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-phenylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C=2C=CC=CC=2)=CC=C1OCC(O)CN(C1)CCC1OC1=CC=C(F)C(F)=C1 RHZAIGHQGUAMFQ-UHFFFAOYSA-N 0.000 claims description 3
- GUQYXMSYSJSFHQ-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4,5-difluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=C(F)C=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 GUQYXMSYSJSFHQ-UHFFFAOYSA-N 0.000 claims description 3
- ZCGQELYDYMAKCP-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 ZCGQELYDYMAKCP-UHFFFAOYSA-N 0.000 claims description 3
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- ZGYCCYGURVETKP-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 ZGYCCYGURVETKP-UHFFFAOYSA-N 0.000 claims description 3
- JZJGLRRCNWYFCK-UHFFFAOYSA-N n-[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 JZJGLRRCNWYFCK-UHFFFAOYSA-N 0.000 claims description 3
- FREBHOAWPILZSJ-UHFFFAOYSA-N n-[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 FREBHOAWPILZSJ-UHFFFAOYSA-N 0.000 claims description 3
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- ACFXKJABHQBAHQ-UHFFFAOYSA-N n-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 ACFXKJABHQBAHQ-UHFFFAOYSA-N 0.000 claims description 3
- RKLNTIFIFKQCPZ-UHFFFAOYSA-N n-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 RKLNTIFIFKQCPZ-UHFFFAOYSA-N 0.000 claims description 3
- KBLGAWULZUADJW-UHFFFAOYSA-N n-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-(trifluoromethyl)phenyl]acetamide Chemical compound CC(=O)NC1=CC(C(F)(F)F)=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 KBLGAWULZUADJW-UHFFFAOYSA-N 0.000 claims description 3
- WIABMSYVVDYHPQ-UHFFFAOYSA-N n-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 WIABMSYVVDYHPQ-UHFFFAOYSA-N 0.000 claims description 3
- HJNQNRLZXHRIFJ-UHFFFAOYSA-N n-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-phenylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C=2C=CC=CC=2)=CC=C1OCC(O)CN(CC1)CCC1OC1=CC=C(Cl)C(Cl)=C1 HJNQNRLZXHRIFJ-UHFFFAOYSA-N 0.000 claims description 3
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- LVMXDNGUMOQOAX-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 LVMXDNGUMOQOAX-UHFFFAOYSA-N 0.000 claims description 3
- KHBUVDGWAHKZBC-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-4-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 KHBUVDGWAHKZBC-UHFFFAOYSA-N 0.000 claims description 3
- SXANOEDUEPQSBI-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 SXANOEDUEPQSBI-UHFFFAOYSA-N 0.000 claims description 3
- PUIKOTNZTNASDA-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 PUIKOTNZTNASDA-UHFFFAOYSA-N 0.000 claims description 3
- ZJOOWPMRQFSVEC-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-phenylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C=2C=CC=CC=2)=CC=C1OCC(O)CN(CC1)CCC1OC1=CC=C(Cl)C=C1 ZJOOWPMRQFSVEC-UHFFFAOYSA-N 0.000 claims description 3
- IKKKQDKSODKSOV-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 IKKKQDKSODKSOV-UHFFFAOYSA-N 0.000 claims description 3
- YMDMKCVIIFUUCT-UHFFFAOYSA-N n-[2-[3-[4-[(3,4-dichlorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC1CN(CC(O)COC=2C(=CC=CC=2)NC(C)=O)C(C)CN1CC1=CC=C(Cl)C(Cl)=C1 YMDMKCVIIFUUCT-UHFFFAOYSA-N 0.000 claims description 3
- TUYPYVZHQFDABG-UHFFFAOYSA-N n-[2-[3-[4-[(3,4-dichlorophenyl)methyl]piperazin-1-yl]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 TUYPYVZHQFDABG-UHFFFAOYSA-N 0.000 claims description 3
- VPUFLPWGYJOTAP-UHFFFAOYSA-N n-[3-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]naphthalen-2-yl]acetamide Chemical compound CC(=O)NC1=CC2=CC=CC=C2C=C1OCC(O)CN(C1)CCC1OC1=CC=C(Cl)C=C1 VPUFLPWGYJOTAP-UHFFFAOYSA-N 0.000 claims description 3
- MZDRHDBZCFEEPZ-UHFFFAOYSA-N n-[3-acetyl-2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CN1CC(C2=CC(Cl)=CC=C2N2)=C2CC1 MZDRHDBZCFEEPZ-UHFFFAOYSA-N 0.000 claims description 3
- QFSWFKDEDIARGH-UHFFFAOYSA-N n-[3-acetyl-2-[3-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CN1CC(C2=CC(F)=CC=C2N2)=C2CC1 QFSWFKDEDIARGH-UHFFFAOYSA-N 0.000 claims description 3
- SZHXVARCWXKSAS-UHFFFAOYSA-N n-[3-acetyl-2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 SZHXVARCWXKSAS-UHFFFAOYSA-N 0.000 claims description 3
- VWHUXRFAAKDQJN-UHFFFAOYSA-N n-[3-acetyl-2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 VWHUXRFAAKDQJN-UHFFFAOYSA-N 0.000 claims description 3
- XHRTZTLTIGTBSV-UHFFFAOYSA-N n-[3-acetyl-2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 XHRTZTLTIGTBSV-UHFFFAOYSA-N 0.000 claims description 3
- PRAGNWZBRUWZHW-UHFFFAOYSA-N n-[4-chloro-2-[3-[4-(3,4-dichloroanilino)piperidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(Cl)C=C1OCC(O)CN1CCC(NC=2C=C(Cl)C(Cl)=CC=2)CC1 PRAGNWZBRUWZHW-UHFFFAOYSA-N 0.000 claims description 3
- AYCHQFXGPRWJJB-UHFFFAOYSA-N n-[4-chloro-2-[3-[4-(4-chloroanilino)piperidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(Cl)C=C1OCC(O)CN1CCC(NC=2C=CC(Cl)=CC=2)CC1 AYCHQFXGPRWJJB-UHFFFAOYSA-N 0.000 claims description 3
- OMCXZJNJUZNUPA-UHFFFAOYSA-N n-[4-cyano-2-[3-[4-(3,4-dichloroanilino)piperidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C#N)C=C1OCC(O)CN1CCC(NC=2C=C(Cl)C(Cl)=CC=2)CC1 OMCXZJNJUZNUPA-UHFFFAOYSA-N 0.000 claims description 3
- QIPWQVBJZHYYOL-UHFFFAOYSA-N n-[4-fluoro-2-[3-(8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CC(C2=CC(F)=CC=C2N2)=C2CC1 QIPWQVBJZHYYOL-UHFFFAOYSA-N 0.000 claims description 3
- ABBYBQMCWKEBOY-UHFFFAOYSA-N n-[4-fluoro-2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 ABBYBQMCWKEBOY-UHFFFAOYSA-N 0.000 claims description 3
- UMIZPQNBEFKPEL-UZVYXBEXSA-N n-[5-chloro-2-[(1s,2r,3s)-3-[(3s)-3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxycyclopentyl]oxyphenyl]acetamide Chemical compound CC(=O)NC1=CC(Cl)=CC=C1O[C@@H]1[C@H](O)[C@@H](N2C[C@H](CC2)OC=2C=CC(Cl)=CC=2)CC1 UMIZPQNBEFKPEL-UZVYXBEXSA-N 0.000 claims description 3
- XVWKFDLTGXGYKL-PKOBYXMFSA-N n-[5-chloro-2-[(2s)-3-[(3r)-3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC(Cl)=CC=C1OC[C@@H](O)CN1C[C@H](OC=2C=CC(Cl)=CC=2)CC1 XVWKFDLTGXGYKL-PKOBYXMFSA-N 0.000 claims description 3
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- LIYLZRRAZDJBHQ-UHFFFAOYSA-N 2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 LIYLZRRAZDJBHQ-UHFFFAOYSA-N 0.000 claims description 2
- AAQPRMBFQMBKCJ-UHFFFAOYSA-N 2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 AAQPRMBFQMBKCJ-UHFFFAOYSA-N 0.000 claims description 2
- QYJXEAZIMHMEEY-UHFFFAOYSA-N 2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 QYJXEAZIMHMEEY-UHFFFAOYSA-N 0.000 claims description 2
- VGEAKGVEESETKL-UHFFFAOYSA-N 2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 VGEAKGVEESETKL-UHFFFAOYSA-N 0.000 claims description 2
- JWWRFTZGEXUHEH-UHFFFAOYSA-N 2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 JWWRFTZGEXUHEH-UHFFFAOYSA-N 0.000 claims description 2
- QKHNYMKYBXIVNC-UHFFFAOYSA-N 2-[3-[4-(4-fluorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(F)=CC=2)CC1 QKHNYMKYBXIVNC-UHFFFAOYSA-N 0.000 claims description 2
- DAVBMXTZRNJTOM-UHFFFAOYSA-N [5-chloro-2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-ium-1-yl]-2-hydroxypropoxy]phenyl]urea;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.NC(=O)NC1=CC(Cl)=CC=C1OCC(O)C[NH+]1CC(OC=2C=CC(Cl)=CC=2)CC1 DAVBMXTZRNJTOM-UHFFFAOYSA-N 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- KCCQNRMPLZQBNY-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 KCCQNRMPLZQBNY-UHFFFAOYSA-N 0.000 claims description 2
- MXJURQMLRCSLNO-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 MXJURQMLRCSLNO-UHFFFAOYSA-N 0.000 claims description 2
- DVEZRDFJNCHBBZ-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(4-cyanophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(=CC=2)C#N)CC1 DVEZRDFJNCHBBZ-UHFFFAOYSA-N 0.000 claims description 2
- SJHKDUFERPKWDB-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)NC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 SJHKDUFERPKWDB-UHFFFAOYSA-N 0.000 claims description 2
- BRHWKZMRINCYQP-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 BRHWKZMRINCYQP-UHFFFAOYSA-N 0.000 claims description 2
- GNGCKTIWOSSTJN-UHFFFAOYSA-N methyl 2-[[2-[3-[4-(3,4-difluorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(F)C(F)=CC=2)CC1 GNGCKTIWOSSTJN-UHFFFAOYSA-N 0.000 claims description 2
- XGBORGQAOKFWQS-UHFFFAOYSA-N methyl 2-[[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)NC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 XGBORGQAOKFWQS-UHFFFAOYSA-N 0.000 claims description 2
- XILVPBNPAZQANO-UHFFFAOYSA-N methyl 2-[[2-[3-[4-(4-fluorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(F)=CC=2)CC1 XILVPBNPAZQANO-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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| CN102227431A (zh) | 2008-09-29 | 2011-10-26 | 雅培制药有限公司 | 吲哚和二氢吲哚衍生物及其应用方法 |
| US9073925B2 (en) | 2009-07-01 | 2015-07-07 | Albany Molecular Research, Inc. | Azinone-substituted azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine MCH-1 antagonists, methods of making, and use thereof |
| WO2011003012A1 (en) * | 2009-07-01 | 2011-01-06 | Albany Molecular Research, Inc. | Azinone-substituted azapolycycle mch-1 antagonists, methods of making, and use thereof |
| US8629158B2 (en) | 2009-07-01 | 2014-01-14 | Albany Molecular Research, Inc. | Azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine MCH-1 antagonists, methods of making, and use thereof |
| US8637501B2 (en) | 2009-07-01 | 2014-01-28 | Albany Molecular Research, Inc. | Azinone-substituted azepino[b]indole and pyrido-pyrrolo-azepine MCH-1 antagonists, methods of making, and use thereof |
| GB0913345D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | New combination 802 |
| WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
| WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
| WO2012088038A2 (en) | 2010-12-21 | 2012-06-28 | Albany Molecular Research, Inc. | Piperazinone-substituted tetrahydro-carboline mch-1 antagonists, methods of making, and uses thereof |
| US8993765B2 (en) | 2010-12-21 | 2015-03-31 | Albany Molecular Research, Inc. | Tetrahydro-azacarboline MCH-1 antagonists, methods of making, and uses thereof |
| GB201021992D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | Compound |
| GB201021979D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | New compound |
| WO2012163848A1 (en) | 2011-05-27 | 2012-12-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of crohn's disease |
| GB201209587D0 (en) | 2012-05-30 | 2012-07-11 | Takeda Pharmaceutical | Therapeutic compounds |
| CN104710419B (zh) * | 2015-03-18 | 2017-05-24 | 中国药科大学 | 四氢吡啶[4,3‑b]骈吲哚类化合物、其制备方法及医药用途 |
| US11186564B2 (en) * | 2016-08-04 | 2021-11-30 | Sunovion Pharmaceuticals Inc. | Dual NAV1.2/5HT2a inhibitors for treating CNS disorders |
| EP4115885A1 (en) | 2021-07-05 | 2023-01-11 | Charité - Universitätsmedizin Berlin | A pharmaceutical composition comprising bay 86-5277 and salts thereof for use in the treatment of viral infections and hyperinflammation |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1220440B (de) | 1962-02-14 | 1966-07-07 | Sanol Arznei Schwarz Gmbh | Verfahren zur Herstellung von Derivaten des 1-(o-Bromphenoxy)-2-hydroxy-3-amino-propans und deren Saeureadditionssalzen |
| US3577432A (en) * | 1968-12-23 | 1971-05-04 | Robins Co Inc A H | 1-substituted-3-phenoxypyrrolidines |
| US4029801A (en) | 1970-09-03 | 1977-06-14 | John Wyeth & Brother Limited | Pharmaceutical compositions and methods of treating hypertension |
| JPS5511670B1 (https=) | 1971-07-13 | 1980-03-26 | ||
| US3755584A (en) * | 1972-04-03 | 1973-08-28 | Abbott Lab | Tranquilizers |
| FR2190430A1 (en) | 1972-06-29 | 1974-02-01 | Ferlux | N-aminomethylhydroxamic acids - with antiinflammatory activity pre-pared by Mannich reaction |
| US3775584A (en) * | 1972-11-30 | 1973-11-27 | D Moerke | Welding gun |
| US3894030A (en) | 1973-01-04 | 1975-07-08 | Janssen Pharmaceutica Nv | 1-{8 1-(2-Hydroxy-3-aryloxypropyl)-4-piperidyl{9 -2-benzimidazolinones and related compounds |
| US3818017A (en) | 1973-01-04 | 1974-06-18 | Janssen Pharmaceutica Nv | 1-{8 1-(2-hydroxy-3-aryloxypropyl)-4-piperidyl{9 -2-benzimidazolinones and related compounds |
| US4166119A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing spiro[dihydrobenzofuran]piperidines and pyrrolidines |
| US4264613A (en) | 1979-08-01 | 1981-04-28 | Science Union Et Cie, Societe Francaise De Recherche Medicale | Piperidylbenzimidazolinone compounds |
| FR2469411A1 (fr) | 1979-11-15 | 1981-05-22 | Science Union & Cie | Nouveaux derives de la piperidylbenzimidazolinone, leurs procedes de preparation et les compositions pharmaceutiques les renfermant |
| EP0095454A3 (de) | 1982-05-13 | 1985-04-03 | Gerot-Pharmazeutika Gesellschaft m.b.H. | Neue kernsubstituierte Pyrogallol-Derivate |
| JPS59222484A (ja) | 1983-06-02 | 1984-12-14 | Kowa Co | テトラヒドロナフチルカルボン酸フエニルエステル誘導体 |
| US5614533A (en) | 1987-03-13 | 1997-03-25 | Bio-Mega/Boehringer Ingelheim Research, Inc. | Substituted pipecolinic acid derivatives as HIV protease inhibitors |
| DE3723568C2 (de) | 1987-07-16 | 1994-01-27 | Siemens Ag | Differenzstromschutzschalter |
| DE3723648A1 (de) | 1987-07-17 | 1989-01-26 | Sandoz Ag | Indol-derivate, ihre herstellung und sie enthaltende arzneimittel |
| ES2027897A6 (es) | 1991-01-24 | 1992-06-16 | Espanola Prod Quimicos | Procedimiento de preparacion de nuevos derivados de la difenilmetilpiperacina. |
| IL105716A0 (en) | 1992-06-08 | 1993-09-22 | Richter Gedeon Vegyeszet | Aminopropanol derivatives,their preparation and pharmaceutical compositions containing them |
| IL106600A (en) | 1992-08-07 | 1997-09-30 | Sankyo Co | Peptides, pharmaceutical compositions containing the same and processes for the preparation thereof |
| US5627196A (en) * | 1995-01-17 | 1997-05-06 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| US5741789A (en) * | 1995-01-17 | 1998-04-21 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| US5614523A (en) | 1995-01-17 | 1997-03-25 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| US5576321A (en) * | 1995-01-17 | 1996-11-19 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| US5789402A (en) * | 1995-01-17 | 1998-08-04 | Eli Lilly Company | Compounds having effects on serotonin-related systems |
| ZA9610738B (en) * | 1995-12-22 | 1997-06-24 | Warner Lambert Co | Subtype selective nmda receptor ligands and the use thereof |
| DE19703131A1 (de) | 1997-01-29 | 1998-07-30 | Bayer Ag | Verwendung von Chinoxalin in Dreier-Kombination mit Protease-Inhibitoren und Reverse Transkriptaseinhibitoren als Arzneimittel zur Behandlung von AIDS und/oder HIV-Infektionen |
| IL125658A0 (en) | 1997-08-18 | 1999-04-11 | Hoffmann La Roche | Ccr-3 receptor antagonists |
| IL135488A0 (en) | 1997-11-18 | 2001-05-20 | Teijin Ltd | Cyclic amine derivatives |
| DE19755268A1 (de) | 1997-12-12 | 1999-06-17 | Merck Patent Gmbh | Benzamidinderivate |
| FR2780057B1 (fr) | 1998-06-18 | 2002-09-13 | Sanofi Sa | Phenoxypropanolamines, procede pour leur preparation et compositions pharmaceutiques les contenant |
| AU2482100A (en) | 1998-12-18 | 2000-07-03 | Du Pont Pharmaceuticals Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| AU2057200A (en) | 1998-12-18 | 2000-07-03 | Du Pont Pharmaceuticals Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| WO2000053600A1 (en) | 1999-03-11 | 2000-09-14 | Banyu Pharmaceutical Co., Ltd. | Novel piperidine derivatives |
| US6518286B1 (en) | 1999-03-26 | 2003-02-11 | Astrazeneca Ab | Compounds |
| DE19922316A1 (de) | 1999-05-14 | 2000-11-16 | Goedecke Ag | Verfahren zur Herstellung von (R)-N-[(Benzo[b]furan-2-yl)-alkoxycarbonyl]-tryptophanalkylestern |
| CA2373607A1 (en) | 1999-05-14 | 2000-11-23 | Bristol-Myers Squibb Pharma Research Labs, Inc. | Cyclic amine derivatives and their uses |
| SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| JP4782342B2 (ja) | 1999-12-17 | 2011-09-28 | サノフィ−アベンティス | フェノキシプロパノールアミン類、それらの製造方法およびそれらを含む医薬組成物 |
| FR2802533B1 (fr) | 1999-12-17 | 2002-02-15 | Sanofi Synthelabo | Phenoxypropanolamines, leur preparation et leur application en therapeutique |
| CO5300399A1 (es) | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | Heterocicliocs que contienen nitrogeno, proceso para su preparacion y composiciones farmaceuticas que los contienen |
| GB0011838D0 (en) | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
| AR028947A1 (es) * | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
| AR028948A1 (es) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
| US7005439B2 (en) | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
| SE0100903D0 (sv) | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
| SE0101038D0 (sv) | 2001-03-23 | 2001-03-23 | Astrazeneca Ab | Novel compounds |
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