JP2011512331A5 - - Google Patents
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- JP2011512331A5 JP2011512331A5 JP2010545545A JP2010545545A JP2011512331A5 JP 2011512331 A5 JP2011512331 A5 JP 2011512331A5 JP 2010545545 A JP2010545545 A JP 2010545545A JP 2010545545 A JP2010545545 A JP 2010545545A JP 2011512331 A5 JP2011512331 A5 JP 2011512331A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- ring
- cycloalkyl
- independently selected
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 192
- 125000000217 alkyl group Chemical group 0.000 claims description 152
- -1 R 46 Chemical compound 0.000 claims description 101
- 125000001424 substituent group Chemical group 0.000 claims description 97
- 229910052736 halogen Inorganic materials 0.000 claims description 84
- 150000002367 halogens Chemical class 0.000 claims description 82
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 74
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 49
- 125000003545 alkoxy group Chemical group 0.000 claims description 47
- 229910052717 sulfur Inorganic materials 0.000 claims description 46
- 229910052760 oxygen Inorganic materials 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 125000001931 aliphatic group Chemical group 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000006413 ring segment Chemical group 0.000 claims description 12
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 5
- SVSARCCKBMZNMR-UHFFFAOYSA-N [1-[2-[methyl-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethyl]amino]ethyl]pyridin-4-ylidene]methyl-oxoazanium;dichloride Chemical compound [Cl-].[Cl-].C1=CC(=C[NH+]=O)C=CN1CCN(C)CCN1C=CC(=C[NH+]=O)C=C1 SVSARCCKBMZNMR-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims description 2
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical group C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims 11
- 239000003638 chemical reducing agent Substances 0.000 claims 3
- 239000002671 adjuvant Substances 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 102000009410 Chemokine receptor Human genes 0.000 claims 1
- 108050000299 Chemokine receptor Proteins 0.000 claims 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims 1
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003850 glucocorticoid receptor antagonist Substances 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 208000023504 respiratory system disease Diseases 0.000 claims 1
- 230000003637 steroidlike Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 273
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 228
- 239000000203 mixture Substances 0.000 description 160
- 239000000243 solution Substances 0.000 description 158
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 114
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 108
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 102
- 239000002904 solvent Substances 0.000 description 88
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 73
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 55
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 52
- 229910052938 sodium sulfate Inorganic materials 0.000 description 52
- 235000011152 sodium sulphate Nutrition 0.000 description 52
- 239000000047 product Substances 0.000 description 49
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 41
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 40
- 239000012267 brine Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 28
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 28
- 238000010898 silica gel chromatography Methods 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 27
- 239000007787 solid Substances 0.000 description 25
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 238000002953 preparative HPLC Methods 0.000 description 21
- 239000000377 silicon dioxide Substances 0.000 description 21
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 21
- 239000012043 crude product Substances 0.000 description 19
- 238000000746 purification Methods 0.000 description 19
- ZMEVAJOHVFUPMR-LURJTMIESA-N 7-[(1r)-2-amino-1-hydroxyethyl]-4-hydroxy-3h-1,3-benzothiazol-2-one Chemical compound NC[C@H](O)C1=CC=C(O)C2=C1SC(=O)N2 ZMEVAJOHVFUPMR-LURJTMIESA-N 0.000 description 17
- 239000008346 aqueous phase Substances 0.000 description 17
- 238000004587 chromatography analysis Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ANZZCQPQOLRQDD-AWEZNQCLSA-N 5-[(1r)-2-amino-1-[tert-butyl(dimethyl)silyl]oxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@H](CN)O[Si](C)(C)C(C)(C)C ANZZCQPQOLRQDD-AWEZNQCLSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical compound F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- LQXFYESLKHNKJL-UHFFFAOYSA-N (2-methyl-1,3-thiazol-4-yl)-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone Chemical compound S1C(C)=NC(C(=O)N2CC3(CCNCC3)OCC2)=C1 LQXFYESLKHNKJL-UHFFFAOYSA-N 0.000 description 2
- PFYPDUUXDADWKC-UHFFFAOYSA-N 2-propan-2-ylpyridine Chemical compound CC(C)C1=CC=CC=N1 PFYPDUUXDADWKC-UHFFFAOYSA-N 0.000 description 2
- DTIYLGZWTNZJRL-UHFFFAOYSA-N 3-[3-[4-(2-methyl-1,3-thiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl]propoxy]benzaldehyde Chemical compound S1C(C)=NC(C(=O)N2CC3(CCN(CCCOC=4C=C(C=O)C=CC=4)CC3)OCC2)=C1 DTIYLGZWTNZJRL-UHFFFAOYSA-N 0.000 description 2
- SMYDATNZBHACQA-HNNXBMFYSA-N 5-[(1R)-2-amino-1-[tert-butyl(dimethyl)silyl]oxyethyl]quinolin-8-ol Chemical compound NC[C@H](O[Si](C)(C)C(C)(C)C)C1=C2C=CC=NC2=C(C=C1)O SMYDATNZBHACQA-HNNXBMFYSA-N 0.000 description 2
- MNNCRGDOZWOPAQ-PMERELPUSA-N 5-[(1r)-2-[[2-[2-fluoro-3-[[4-(2-propan-2-yl-1,3-thiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl]methyl]phenyl]-2-methylpropyl]amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound S1C(C(C)C)=NC(C(=O)N2CC3(CCN(CC=4C(=C(C=CC=4)C(C)(C)CNC[C@H](O)C=4C=5C=CC(=O)NC=5C(O)=CC=4)F)CC3)OCC2)=C1 MNNCRGDOZWOPAQ-PMERELPUSA-N 0.000 description 2
- FLJKCSKQOOBGNP-UHFFFAOYSA-N 8-[tert-butyl(dimethyl)silyl]oxy-2,2-dimethyloctanal Chemical compound CC(C)(C)[Si](C)(C)OCCCCCCC(C)(C)C=O FLJKCSKQOOBGNP-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CWPZUIOSJDGBTA-UJXPALLWSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.FC1=C(CCNC[C@H](O)C2=CC=C(C=3NC(SC32)=O)O)C=CC=C1CN1CCC3(CN(CCO3)C(C3=NC(=CC=C3)C(C)C)=O)CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.FC1=C(CCNC[C@H](O)C2=CC=C(C=3NC(SC32)=O)O)C=CC=C1CN1CCC3(CN(CCO3)C(C3=NC(=CC=C3)C(C)C)=O)CC1 CWPZUIOSJDGBTA-UJXPALLWSA-N 0.000 description 2
- FJEOERBYSYBKIH-UHFFFAOYSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.N1C(C=CC2=CC=CC=C12)=O Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.N1C(C=CC2=CC=CC=C12)=O FJEOERBYSYBKIH-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- UENHHQDPJYVROE-UHFFFAOYSA-N [3-(2,2-diethoxyethoxy)phenyl]methanol Chemical compound CCOC(OCC)COC1=CC=CC(CO)=C1 UENHHQDPJYVROE-UHFFFAOYSA-N 0.000 description 2
- ZPGPVOOOWBGXCL-UHFFFAOYSA-N [9-[[3-(2-hydroxyethyl)phenyl]methyl]-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl]-(4-propan-2-yl-1,3-thiazol-2-yl)methanone Chemical compound CC(C)C1=CSC(C(=O)N2CC3(CCN(CC=4C=C(CCO)C=CC=4)CC3)OCC2)=N1 ZPGPVOOOWBGXCL-UHFFFAOYSA-N 0.000 description 2
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- INWTXLJINKPKJK-UHFFFAOYSA-N (2-cyclopentyl-1,3-thiazol-4-yl)-[9-[[3-fluoro-5-(2-hydroxyethyl)phenyl]methyl]-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl]methanone Chemical compound OCCC1=CC(F)=CC(CN2CCC3(CC2)OCCN(C3)C(=O)C=2N=C(SC=2)C2CCCC2)=C1 INWTXLJINKPKJK-UHFFFAOYSA-N 0.000 description 1
- ZDTQSTYYYAWYBW-UHFFFAOYSA-N (2-cyclopropyl-1,3-thiazol-4-yl)-[9-[[3-fluoro-5-(2-hydroxyethyl)phenyl]methyl]-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl]methanone Chemical compound OCCC1=CC(F)=CC(CN2CCC3(CC2)OCCN(C3)C(=O)C=2N=C(SC=2)C2CC2)=C1 ZDTQSTYYYAWYBW-UHFFFAOYSA-N 0.000 description 1
- BVLAWRSJVJWXFW-UHFFFAOYSA-N (2-methyl-1,3-thiazol-4-yl)-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(C)=NC(C(=O)N2CC3(CCNCC3)OCC2)=C1 BVLAWRSJVJWXFW-UHFFFAOYSA-N 0.000 description 1
- DDDUWUQZWGSAJF-UHFFFAOYSA-N (5-ethylthiophen-3-yl)-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(CC)=CC(C(=O)N2CC3(CCNCC3)OCC2)=C1 DDDUWUQZWGSAJF-UHFFFAOYSA-N 0.000 description 1
- HUBJAVXIPWDYDQ-UHFFFAOYSA-N (5-methylthiophen-2-yl)-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(C)=CC=C1C(=O)N1CC2(CCNCC2)OCC1 HUBJAVXIPWDYDQ-UHFFFAOYSA-N 0.000 description 1
- NJOLPFUMCIFDGC-UHFFFAOYSA-N (5-methylthiophen-2-yl)-(5-oxa-2,8-diazaspiro[3.5]nonan-8-yl)methanone;hydrochloride Chemical compound Cl.S1C(C)=CC=C1C(=O)N1CC2(CNC2)OCC1 NJOLPFUMCIFDGC-UHFFFAOYSA-N 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
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| JP2009521483A (ja) * | 2005-12-22 | 2009-06-04 | バーテックス ファーマシューティカルズ インコーポレイテッド | ムスカリン受容体のモジュレーター |
| TW200745084A (en) | 2006-03-08 | 2007-12-16 | Astrazeneca Ab | Novel compounds |
| TW200811105A (en) * | 2006-04-25 | 2008-03-01 | Theravance Inc | Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
| GB0613154D0 (en) * | 2006-06-30 | 2006-08-09 | Novartis Ag | Organic Compounds |
| US20100056508A1 (en) | 2006-12-20 | 2010-03-04 | Astrazeneca Ab | Amine derivatives and their use in beta-2-adrenoreceptor mediated diseases |
| WO2008096129A1 (en) | 2007-02-07 | 2008-08-14 | Argenta Discovery Ltd | Nitrogen containing hetrocyclic compounds useful as bifunctional modulators of m3 receptors and beta- 2 receptors |
| GB0702413D0 (en) | 2007-02-07 | 2007-03-21 | Argenta Discovery Ltd | New chemical compounds |
| KR101273200B1 (ko) | 2008-02-06 | 2013-06-17 | 펄마젠 쎄라퓨틱스 (시너지) 리미티드 | 화합물 |
| GB0913345D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | New combination 802 |
| GB0913342D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | Compounds - 801 |
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