MXPA05008528A - Derivados de bifenilo que tienen actividad antagonista del receptor muscarinico y agonista del receptor adrenergico beta 2. - Google Patents
Derivados de bifenilo que tienen actividad antagonista del receptor muscarinico y agonista del receptor adrenergico beta 2.Info
- Publication number
- MXPA05008528A MXPA05008528A MXPA05008528A MXPA05008528A MXPA05008528A MX PA05008528 A MXPA05008528 A MX PA05008528A MX PA05008528 A MXPA05008528 A MX PA05008528A MX PA05008528 A MXPA05008528 A MX PA05008528A MX PA05008528 A MXPA05008528 A MX PA05008528A
- Authority
- MX
- Mexico
- Prior art keywords
- hydroxy
- piperidin
- ylene
- biphenyl
- oxo
- Prior art date
Links
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 100
- 239000012453 solvate Substances 0.000 claims abstract description 52
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 claims abstract description 36
- 230000000694 effects Effects 0.000 claims abstract description 28
- 208000019693 Lung disease Diseases 0.000 claims abstract description 21
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims abstract description 20
- 239000003149 muscarinic antagonist Substances 0.000 claims abstract description 16
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 12
- 208000006673 asthma Diseases 0.000 claims abstract description 10
- 102100039705 Beta-2 adrenergic receptor Human genes 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 406
- -1 oxiran-2,3-diyl Chemical group 0.000 claims description 199
- QMOVGVNKXUTCQU-UHFFFAOYSA-N (2-phenylphenyl)carbamic acid Chemical compound OC(=O)NC1=CC=CC=C1C1=CC=CC=C1 QMOVGVNKXUTCQU-UHFFFAOYSA-N 0.000 claims description 185
- 125000000217 alkyl group Chemical group 0.000 claims description 180
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 173
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 153
- 150000002148 esters Chemical class 0.000 claims description 146
- 239000000203 mixture Substances 0.000 claims description 144
- 239000001257 hydrogen Substances 0.000 claims description 138
- 229910052739 hydrogen Inorganic materials 0.000 claims description 138
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 136
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 95
- 238000000034 method Methods 0.000 claims description 94
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 87
- 238000006243 chemical reaction Methods 0.000 claims description 82
- 125000001424 substituent group Chemical group 0.000 claims description 71
- 239000007787 solid Substances 0.000 claims description 61
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 59
- 125000005843 halogen group Chemical group 0.000 claims description 57
- 125000002947 alkylene group Chemical group 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 53
- 239000002253 acid Substances 0.000 claims description 52
- 239000008194 pharmaceutical composition Substances 0.000 claims description 51
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 43
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 42
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 35
- 125000005549 heteroarylene group Chemical group 0.000 claims description 33
- 230000008569 process Effects 0.000 claims description 33
- 125000000732 arylene group Chemical group 0.000 claims description 31
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 31
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 125000003386 piperidinyl group Chemical group 0.000 claims description 29
- 125000004429 atom Chemical group 0.000 claims description 27
- 125000004450 alkenylene group Chemical group 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 150000004702 methyl esters Chemical class 0.000 claims description 20
- 239000003638 chemical reducing agent Substances 0.000 claims description 19
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 125000004419 alkynylene group Chemical group 0.000 claims description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims description 17
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims description 17
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
- 150000001721 carbon Chemical group 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 101150061972 zur gene Proteins 0.000 claims description 10
- 239000005977 Ethylene Substances 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- 230000007883 bronchodilation Effects 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 102000005962 receptors Human genes 0.000 claims description 8
- 108020003175 receptors Proteins 0.000 claims description 8
- 239000002294 steroidal antiinflammatory agent Substances 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 239000004202 carbamide Substances 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 102000007202 Muscarinic M3 Receptor Human genes 0.000 claims description 3
- 108010008405 Muscarinic M3 Receptor Proteins 0.000 claims description 3
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 229940015043 glyoxal Drugs 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 claims description 2
- 230000001800 adrenalinergic effect Effects 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
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 8
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 6
- 125000004494 ethyl ester group Chemical group 0.000 claims 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 5
- 229910052731 fluorine Inorganic materials 0.000 claims 5
- 239000011737 fluorine Substances 0.000 claims 5
- FJNCXZZQNBKEJT-UHFFFAOYSA-N 8beta-hydroxymarrubiin Natural products O1C(=O)C2(C)CCCC3(C)C2C1CC(C)(O)C3(O)CCC=1C=COC=1 FJNCXZZQNBKEJT-UHFFFAOYSA-N 0.000 claims 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims 4
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 2
- LKKLDKBWCWESPV-UHFFFAOYSA-N (2-phenylphenyl) hydrogen carbonate Chemical compound OC(=O)OC1=CC=CC=C1C1=CC=CC=C1 LKKLDKBWCWESPV-UHFFFAOYSA-N 0.000 claims 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 101100173726 Arabidopsis thaliana OR23 gene Proteins 0.000 claims 1
- CQNWWUOKWSRXNS-UHFFFAOYSA-N [2-(2-fluorophenyl)phenyl]carbamic acid Chemical compound OC(=O)NC1=CC=CC=C1C1=CC=CC=C1F CQNWWUOKWSRXNS-UHFFFAOYSA-N 0.000 claims 1
- IWWSZAVOVKSHDF-UHFFFAOYSA-N [2-(3,5-dichlorophenyl)-4,6-difluorophenyl]carbamic acid Chemical compound OC(=O)NC1=C(F)C=C(F)C=C1C1=CC(Cl)=CC(Cl)=C1 IWWSZAVOVKSHDF-UHFFFAOYSA-N 0.000 claims 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 1
- 229940080818 propionamide Drugs 0.000 claims 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
- 239000000018 receptor agonist Substances 0.000 claims 1
- 229940044601 receptor agonist Drugs 0.000 claims 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims 1
- 239000000048 adrenergic agonist Substances 0.000 abstract description 24
- 229940126157 adrenergic receptor agonist Drugs 0.000 abstract description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 249
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 168
- 238000002360 preparation method Methods 0.000 description 147
- 239000000243 solution Substances 0.000 description 133
- 239000011541 reaction mixture Substances 0.000 description 126
- 239000000047 product Substances 0.000 description 108
- 230000002829 reductive effect Effects 0.000 description 102
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 98
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 98
- 239000002904 solvent Substances 0.000 description 88
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 81
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 67
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 54
- 229910001868 water Inorganic materials 0.000 description 52
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 49
- 235000019341 magnesium sulphate Nutrition 0.000 description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 46
- 229920006395 saturated elastomer Polymers 0.000 description 38
- 235000017557 sodium bicarbonate Nutrition 0.000 description 37
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 31
- 239000012074 organic phase Substances 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000010410 layer Substances 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 235000019441 ethanol Nutrition 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 239000012267 brine Substances 0.000 description 22
- 238000009472 formulation Methods 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 21
- 239000002585 base Substances 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000013543 active substance Substances 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 18
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- 229910052763 palladium Inorganic materials 0.000 description 17
- 239000000725 suspension Substances 0.000 description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 239000002245 particle Substances 0.000 description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 14
- 229910052794 bromium Inorganic materials 0.000 description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- 239000003054 catalyst Chemical group 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000012043 crude product Substances 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
- 229910052751 metal Inorganic materials 0.000 description 10
- 239000002184 metal Substances 0.000 description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000002953 preparative HPLC Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 9
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- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical group C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
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- 230000002441 reversible effect Effects 0.000 description 1
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- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 1
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- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
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- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
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- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- QJXDSDLNUKLDBP-UHFFFAOYSA-M sodium;n-formylmethanimidate Chemical compound [Na+].O=C[N-]C=O QJXDSDLNUKLDBP-UHFFFAOYSA-M 0.000 description 1
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- 238000001694 spray drying Methods 0.000 description 1
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- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- NBNBICNWNFQDDD-UHFFFAOYSA-N sulfuryl dibromide Chemical compound BrS(Br)(=O)=O NBNBICNWNFQDDD-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- TZRQZPMQUXEZMC-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCBr TZRQZPMQUXEZMC-UHFFFAOYSA-N 0.000 description 1
- DPLOGSUBQDREOU-UHFFFAOYSA-N tert-butyl n-(5-aminopentyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCCN DPLOGSUBQDREOU-UHFFFAOYSA-N 0.000 description 1
- XCAQIUOFDMREBA-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=O)OC(C)(C)C XCAQIUOFDMREBA-UHFFFAOYSA-N 0.000 description 1
- FMTUFNCQKOLKON-UHFFFAOYSA-N tert-butyl n-[(4-amino-3-chlorophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(N)C(Cl)=C1 FMTUFNCQKOLKON-UHFFFAOYSA-N 0.000 description 1
- UXWQXBSQQHAGMG-UHFFFAOYSA-N tert-butyl n-[(4-aminophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(N)C=C1 UXWQXBSQQHAGMG-UHFFFAOYSA-N 0.000 description 1
- HFYJFKDJYCFNIC-UHFFFAOYSA-N tert-butyl n-[[3-chloro-4-(prop-2-enoylamino)phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(NC(=O)C=C)C(Cl)=C1 HFYJFKDJYCFNIC-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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- 229940110309 tiotropium Drugs 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
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- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
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- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
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- QDWJJTJNXAKQKD-UHFFFAOYSA-N trihexyphenidyl hydrochloride Chemical compound Cl.C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 QDWJJTJNXAKQKD-UHFFFAOYSA-N 0.000 description 1
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- 229960002147 tripelennamine citrate Drugs 0.000 description 1
- 229960000732 tripelennamine hydrochloride Drugs 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- 229960004791 tropicamide Drugs 0.000 description 1
- 239000002750 tryptase inhibitor Substances 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/452—Piperidinium derivatives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 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
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
- G01N33/9406—Neurotransmitters
- G01N33/9433—(Nor)adrenaline
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| US44784303P | 2003-02-14 | 2003-02-14 | |
| US46703503P | 2003-05-01 | 2003-05-01 | |
| PCT/US2004/004449 WO2004074246A2 (en) | 2003-02-14 | 2004-02-13 | Biphenyl derivatives having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
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| MXPA05008528A true MXPA05008528A (es) | 2005-10-20 |
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Families Citing this family (165)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6693202B1 (en) * | 1999-02-16 | 2004-02-17 | Theravance, Inc. | Muscarinic receptor antagonists |
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| PE20050130A1 (es) * | 2002-08-09 | 2005-03-29 | Novartis Ag | Compuestos organicos |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| PE20040950A1 (es) * | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
| US7317102B2 (en) | 2003-04-01 | 2008-01-08 | Theravance, Inc. | Diarylmethyl and related compounds |
| EP1626970B1 (en) * | 2003-05-28 | 2009-07-08 | Theravance, Inc. | Azabicycloalkane compounds as muscarinic receptor antagonists |
| KR101099409B1 (ko) * | 2003-06-06 | 2011-12-27 | 아렉시스 악티에볼라그 | 피부 상태 또는 암 치료를 위한 scce 저해제로서의융합된 헤테로사이클 화합물의 용도 |
| US20050026948A1 (en) * | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a betamimetic |
| ES2329586T3 (es) * | 2003-11-21 | 2009-11-27 | Theravance, Inc. | Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. |
| TW200531692A (en) * | 2004-01-12 | 2005-10-01 | Theravance Inc | Aryl aniline derivatives as β2 adrenergic receptor agonists |
| US7320990B2 (en) * | 2004-02-13 | 2008-01-22 | Theravance, Inc. | Crystalline form of a biphenyl compound |
| US7524962B2 (en) * | 2004-03-11 | 2009-04-28 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| EP1723108A1 (en) * | 2004-03-11 | 2006-11-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2005087736A1 (en) * | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TW200538095A (en) * | 2004-03-11 | 2005-12-01 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| JP2007528410A (ja) * | 2004-03-11 | 2007-10-11 | セラヴァンス, インコーポレーテッド | ムスカリンレセプターアンタゴニストとしての有用なビフェニル化合物 |
| WO2005087735A1 (en) * | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| EP1723109A1 (en) * | 2004-03-11 | 2006-11-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TWI341836B (en) * | 2004-03-11 | 2011-05-11 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| AU2005247105B2 (en) * | 2004-05-31 | 2010-11-11 | Laboratorios Almirall, S.A. | Combinations comprising antimuscarinic agents and corticosteroids |
| ES2257152B1 (es) * | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos. |
| TWI374883B (en) | 2004-08-16 | 2012-10-21 | Theravance Inc | Crystalline form of a biphenyl compound |
| WO2006023457A1 (en) * | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
| JP2008510015A (ja) * | 2004-08-16 | 2008-04-03 | セラヴァンス, インコーポレーテッド | β2アドレナリン作用性レセプターアゴニスト活性およびムスカリン性レセプターアンタゴニスト活性を有する化合物 |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
| JP2008518939A (ja) * | 2004-10-29 | 2008-06-05 | グラクソ グループ リミテッド | ムスカリン性アセチルコリン受容体アンタゴニスト |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| GB0426164D0 (en) * | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| JP2008533028A (ja) * | 2005-03-10 | 2008-08-21 | セラヴァンス, インコーポレーテッド | ムスカリン性受容体アンタゴニストとして有用なビフェニル化合物 |
| WO2006099031A1 (en) * | 2005-03-10 | 2006-09-21 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7642355B2 (en) | 2005-03-10 | 2010-01-05 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7659403B2 (en) * | 2005-03-10 | 2010-02-09 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TW200714587A (en) * | 2005-03-10 | 2007-04-16 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| ES2265276B1 (es) | 2005-05-20 | 2008-02-01 | Laboratorios Almirall S.A. | Derivados de 4-(2-amino-1-hidroxietil)fenol como agonistas del receptor beta2 adrenergico. |
| JP2008546695A (ja) * | 2005-06-13 | 2008-12-25 | セラヴァンス, インコーポレーテッド | ムスカリン受容体アンタゴニストとして有用なビフェニル化合物 |
| US8429052B2 (en) * | 2005-07-19 | 2013-04-23 | Lincoln National Life Insurance Company | Method and system for providing employer-sponsored retirement plan |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| EP1924553A1 (en) | 2005-08-08 | 2008-05-28 | Argenta Discovery Limited | Bicyclo[2.2.]hept-7-ylamine derivatives and their uses |
| TW200738658A (en) | 2005-08-09 | 2007-10-16 | Astrazeneca Ab | Novel compounds |
| CA2625664C (en) | 2005-10-21 | 2016-01-05 | Novartis Ag | Human antibodies against il13 and therapeutic uses |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| GB0602778D0 (en) * | 2006-02-10 | 2006-03-22 | Glaxo Group Ltd | Novel compound |
| US7973055B2 (en) * | 2006-03-09 | 2011-07-05 | Theravance, Inc. | Crystalline forms of a biphenyl compound |
| TW200745067A (en) | 2006-03-14 | 2007-12-16 | Astrazeneca Ab | Novel compounds |
| WO2007107828A2 (en) | 2006-03-20 | 2007-09-27 | Pfizer Limited | Amine derivatives |
| PE20080361A1 (es) | 2006-04-21 | 2008-06-03 | Novartis Ag | Compuestos derivados de purina como activadores del receptor de adenosina a2a |
| TW200811104A (en) | 2006-04-25 | 2008-03-01 | Theravance Inc | Crystalline forms of a dimethylphenyl compound |
| TW200811105A (en) * | 2006-04-25 | 2008-03-01 | Theravance Inc | Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
| ES2296516B1 (es) * | 2006-04-27 | 2009-04-01 | Laboratorios Almirall S.A. | Derivados de 4-(2-amino-1-hidroxietil)fenol como agonistas del receptor beta2 adrenergico. |
| PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| EA030606B1 (ru) | 2006-05-04 | 2018-08-31 | Бёрингер Ингельхайм Интернациональ Гмбх | Способы приготовления лекарственного средства, содержащего полиморфы |
| GB0613154D0 (en) * | 2006-06-30 | 2006-08-09 | Novartis Ag | Organic Compounds |
| AU2007303909A1 (en) * | 2006-10-04 | 2008-04-10 | Pfizer Limited | Sulfonamide derivatives as adrenergic agonists and muscarinic antagonists |
| ES2302447B1 (es) * | 2006-10-20 | 2009-06-12 | Laboratorios Almirall S.A. | Derivados de 4-(2-amino-1-hidroxietil)fenol como agonistas del receptor beta2 adrenergico. |
| TW200833670A (en) | 2006-12-20 | 2008-08-16 | Astrazeneca Ab | Novel compounds 569 |
| EP2279777A2 (en) | 2007-01-10 | 2011-02-02 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
| US8148427B2 (en) * | 2007-01-31 | 2012-04-03 | Toray Industries, Inc. | Benzylamine derivative or pharmaceutically acceptable acid addition salt thereof, and use thereof for medical purposes |
| GB0702458D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | Salts 668 |
| ES2306595B1 (es) | 2007-02-09 | 2009-09-11 | Laboratorios Almirall S.A. | Sal de napadisilato de 5-(2-((6-(2,2-difluoro-2-feniletoxi)hexil)amino)-1-hidroxietil)-8-hidroxiquinolin-2(1h)-ona como agonista del receptor adrenergico beta2. |
| US7974728B2 (en) * | 2007-05-04 | 2011-07-05 | Taiwan Semiconductor Manufacturing Company, Ltd. | System for extraction of key process parameters from fault detection classification to enable wafer prediction |
| AU2008248598B2 (en) | 2007-05-07 | 2011-11-17 | Novartis Ag | Organic compounds |
| ES2320961B1 (es) * | 2007-11-28 | 2010-03-17 | Laboratorios Almirall, S.A. | Derivados de 4-(2-amino-1-hidroxietil)fenol como agonistas del receptor adrenergico beta2. |
| CN101939054B (zh) | 2007-12-10 | 2014-10-29 | 诺华股份有限公司 | 有机化合物 |
| JP5584138B2 (ja) | 2008-01-11 | 2014-09-03 | ノバルティス アーゲー | キナーゼ阻害剤としてのピリミジン類 |
| CA2713322C (en) * | 2008-02-06 | 2017-01-17 | Astrazeneca Ab | Diazaspiro [5.5] undecane derivatives and their use in the treatment of pulmonary disorders |
| EP2096105A1 (en) * | 2008-02-28 | 2009-09-02 | Laboratorios Almirall, S.A. | Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the b2 adrenergic receptor |
| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| PE20140960A1 (es) | 2008-04-03 | 2014-08-15 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| ES2535736T3 (es) | 2008-06-10 | 2015-05-14 | Novartis Ag | Derivados de pirazina como bloqueadores de los canales de sodio epitelial |
| WO2009154557A1 (en) | 2008-06-18 | 2009-12-23 | Astrazeneca Ab | Benzoxazinone derivatives acting as beta2-adrenoreceptor agonist for the treatment of respiratory disorders |
| US8263623B2 (en) * | 2008-07-11 | 2012-09-11 | Pfizer Inc. | Triazol derivatives useful for the treatment of diseases |
| WO2010007561A1 (en) * | 2008-07-15 | 2010-01-21 | Pfizer Limited | Novel compounds active as muscarinic receptor antagonists |
| KR20110017452A (ko) * | 2008-07-15 | 2011-02-21 | 화이자 리미티드 | 무스칼린 수용체 길항제로서 활성인 신규한 화합물 |
| KR20200118243A (ko) | 2008-08-06 | 2020-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| UY32297A (es) | 2008-12-22 | 2010-05-31 | Almirall Sa | Sal mesilato de 5-(2-{[6-(2,2-difluoro-2-fenilitoxi) hexil]amino}-1-hidroxietil)-8-hidroxiquinolin-2( 1h)-ona como agonista del receptor b(beta)2 acrenérgico |
| CN102256976A (zh) | 2008-12-23 | 2011-11-23 | 贝林格尔.英格海姆国际有限公司 | 有机化合物的盐形式 |
| TW201036957A (en) | 2009-02-20 | 2010-10-16 | Astrazeneca Ab | Novel salt 628 |
| EP2228368A1 (en) | 2009-03-12 | 2010-09-15 | Almirall, S.A. | Process for manufacturing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one |
| AU2010225747A1 (en) | 2009-03-17 | 2011-11-10 | Daiichi Sankyo Company,Limited | Amide derivative |
| US8519138B2 (en) * | 2009-04-14 | 2013-08-27 | Glaxo Group Limited | Process for the preparation of a biphenyl-2-yl carbamic acid ester |
| CN102405218B (zh) | 2009-04-23 | 2014-06-04 | 施万制药 | 具蕈毒碱受体拮抗剂和β2 肾上腺素受体激动剂活性的二酰胺化合物 |
| AU2015234331B2 (en) * | 2009-04-23 | 2017-08-03 | Theravance Biopharma R&D Ip, Llc | Diamide compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| JP5379224B2 (ja) * | 2009-04-30 | 2013-12-25 | 帝人ファーマ株式会社 | 四級アンモニウム塩化合物 |
| MX2012004792A (es) | 2009-10-22 | 2013-02-01 | Vertex Pharma | Composiciones para el tratamiento de fibrosis quistica y otras enfermedades cronicas. |
| WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
| EA034869B1 (ru) | 2009-11-27 | 2020-03-31 | Бёрингер Ингельхайм Интернациональ Гмбх | Лечение генотипированных пациентов с диабетом ингибиторами дпп-4, такими как линаглиптин |
| WO2011081937A1 (en) | 2009-12-15 | 2011-07-07 | Gilead Sciences, Inc. | Corticosteroid-beta-agonist-muscarinic antagonist compounds for use in therapy |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| KR101819609B1 (ko) | 2010-05-05 | 2018-01-17 | 베링거 인겔하임 인터내셔날 게엠베하 | 체중 감소 치료에 후속하는 dpp-4 억제제에 의한 순차적 병용 요법 |
| ITRM20110083U1 (it) | 2010-05-13 | 2011-11-14 | De La Cruz Jose Antonio Freire | Piastra per la costruzione di carrelli per aeroplani |
| EP2386555A1 (en) | 2010-05-13 | 2011-11-16 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and m3 muscarinic antagonist activities |
| RS54201B1 (sr) * | 2010-07-13 | 2015-12-31 | Theravance Biopharma R&D Ip, Llc | Postupak za pripremu bifenil-2-ilkarbaminske kiseline |
| ES2622519T3 (es) | 2010-07-14 | 2017-07-06 | Novartis Ag | Componentes heterocíclicos agonistas del receptor IP |
| WO2012032546A2 (en) * | 2010-09-08 | 2012-03-15 | Cadila Healthcare Limited | Process for the preparation of salmeterol and its intermediates |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| AR083115A1 (es) * | 2010-09-30 | 2013-01-30 | Theravance Inc | Sales oxalato cristalinas de un compuesto diamida |
| GB201016912D0 (en) | 2010-10-07 | 2010-11-24 | Astrazeneca Ab | Novel combination |
| AR083878A1 (es) | 2010-11-15 | 2013-03-27 | Boehringer Ingelheim Int | Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento |
| JP6060242B2 (ja) * | 2010-11-30 | 2017-01-11 | 株式会社日立国際電気 | 基板処理装置、半導体装置の製造方法及びバッフル構造 |
| CA2828219A1 (en) | 2011-02-25 | 2012-08-30 | Irm Llc | Pyrazolo [1,5-a] pyridines as trk inhibitors |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
| RU2606121C2 (ru) * | 2011-06-10 | 2017-01-10 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Соединения, обладающие антагонистической активностью в отношении мускариновых рецепторов и агонистической активностью в отношении бета2-адренорецепторов |
| RS54365B1 (sr) | 2011-06-10 | 2016-04-28 | Chiesi Farmaceutici S.P.A. | Jedinjenja koja imaju aktivnost antagonista muskarinskih receptora i agonist beta2 adrenergičnog receptora |
| MX366629B (es) | 2011-07-15 | 2019-07-17 | Boehringer Ingelheim Int | Quinazolinas sustituidas, su preparación y su uso en composiciones farmacéuticas. |
| US8883819B2 (en) | 2011-09-01 | 2014-11-11 | Irm Llc | Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| EP2755652B1 (en) | 2011-09-16 | 2021-06-02 | Novartis AG | N-substituted heterocyclyl carboxamides |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| ES2558457T3 (es) | 2011-09-16 | 2016-02-04 | Novartis Ag | Compuestos heterocíclicos para el tratamiento de fibrosis quística |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| EP2578570A1 (en) | 2011-10-07 | 2013-04-10 | Almirall, S.A. | Novel process for preparing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(r)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one via novel intermediates of synthesis. |
| EP2592078A1 (en) | 2011-11-11 | 2013-05-15 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activities |
| EP2802583A1 (en) | 2012-01-13 | 2014-11-19 | Novartis AG | Fused piperidines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
| EP2802585A1 (en) | 2012-01-13 | 2014-11-19 | Novartis AG | Fused piperidines as ip receptor agonists for the treatment of pah and related disorders |
| AR089698A1 (es) | 2012-01-13 | 2014-09-10 | Novartis Ag | Compuestos heterociclicos antagonistas del receptor ip |
| WO2013105058A1 (en) | 2012-01-13 | 2013-07-18 | Novartis Ag | 7,8- dihydropyrido [3, 4 - b] pyrazines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
| EP2802584B1 (en) | 2012-01-13 | 2015-11-18 | Novartis AG | Salts of an ip receptor agonist |
| EP2802582A1 (en) | 2012-01-13 | 2014-11-19 | Novartis AG | Fused dihydropyrido [2,3 -b]pyrazines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| EP2641900A1 (en) | 2012-03-20 | 2013-09-25 | Almirall, S.A. | Novel polymorphic Crystal forms of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1h)-one, heminapadisylate as agonist of the ß2 adrenergic receptor. |
| EP2849755A1 (en) | 2012-05-14 | 2015-03-25 | Boehringer Ingelheim International GmbH | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
| JP6218811B2 (ja) | 2012-05-14 | 2017-10-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Sirs及び/又は敗血症の治療に用いるdpp−4阻害薬としてのキサンチン誘導体 |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| WO2014044288A1 (en) * | 2012-09-21 | 2014-03-27 | Crystal Pharma Sa | Methods for the preparation of indacaterol and pharmaceutically acceptable salts thereof |
| CN104854105B (zh) | 2012-12-06 | 2017-05-17 | 奇斯药制品公司 | 具有毒蕈碱受体拮抗剂和β2肾上腺素能受体激动剂活性的化合物 |
| HRP20180915T1 (hr) | 2012-12-06 | 2018-07-27 | Chiesi Farmaceutici S.P.A. | Spojevi koji imaju aktivnost kao antagonist muskarinskog receptora i kao agonist beta2 adrenergijskog receptora |
| JP6307091B2 (ja) | 2012-12-18 | 2018-04-04 | アルミラル・ソシエダッド・アノニマAlmirall, S.A. | β2アドレナリンアゴニスト活性およびM3ムスカリンアンタゴニスト活性を有する新規のシクロヘキシルおよびキヌクリジニルカルバメート誘導体 |
| US9604981B2 (en) | 2013-02-13 | 2017-03-28 | Novartis Ag | IP receptor agonist heterocyclic compounds |
| TWI643853B (zh) | 2013-02-27 | 2018-12-11 | 阿爾米雷爾有限公司 | 同時具有β2腎上腺素受體促效劑和M3毒蕈鹼受體拮抗劑活性之2-氨基-1-羥乙基-8-羥基喹啉-2(1H)-酮衍生物之鹽類 |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| CZ306252B6 (cs) | 2013-03-15 | 2016-10-26 | Zentiva, K.S. | Způsob přípravy 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-(1H)-chinolin-2-onu (indacaterolu) |
| CU24355B1 (es) | 2013-07-18 | 2018-08-06 | Novartis Ag | Derivados de 2((( oxadiazol/triazol/tetrazol/isoxazol) metil) fenil)-1-(heterociclil)-ona como inhibidores activos de autotaxina |
| WO2015008229A1 (en) | 2013-07-18 | 2015-01-22 | Novartis Ag | Autotaxin inhibitors |
| TW201517906A (zh) | 2013-07-25 | 2015-05-16 | Almirall Sa | 含有maba化合物和皮質類固醇之組合 |
| TWI641373B (zh) | 2013-07-25 | 2018-11-21 | 阿爾米雷爾有限公司 | 具有蕈毒鹼受體拮抗劑和β2腎上腺素受體促效劑二者之活性的2-胺基-1-羥乙基-8-羥基喹啉-2(1H)-酮衍生物之鹽 |
| WO2015128453A1 (en) | 2014-02-28 | 2015-09-03 | Boehringer Ingelheim International Gmbh | Medical use of a dpp-4 inhibitor |
| WO2015162461A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| KR20160145780A (ko) | 2014-04-24 | 2016-12-20 | 노파르티스 아게 | 포스파티딜이노시톨 3-키나제 억제제로서의 아미노 피리딘 유도체 |
| BR112016024533A8 (pt) | 2014-04-24 | 2021-03-30 | Novartis Ag | derivados de amino pirazina como inibidores de fosfatidilinositol 3-cinase ou sal, seu uso, e composição e combinação farmacêuticas |
| TW201617343A (zh) | 2014-09-26 | 2016-05-16 | 阿爾米雷爾有限公司 | 具有β2腎上腺素促效劑及M3蕈毒拮抗劑活性之新穎雙環衍生物 |
| TWI703138B (zh) | 2015-02-12 | 2020-09-01 | 義大利商吉斯藥品公司 | 具有蕈毒鹼受體拮抗劑及β2腎上腺素受體促效劑活性之化合物 |
| AR104828A1 (es) | 2015-06-01 | 2017-08-16 | Chiesi Farm Spa | COMPUESTOS CON ACTIVIDAD ANTAGONISTA DE LOS RECEPTORES MUSCARÍNICOS Y ACTIVIDAD AGONISTA DEL RECEPTOR b2 ADRENÉRGICO |
| WO2017001907A1 (en) * | 2015-06-29 | 2017-01-05 | Teva Pharmaceuticals International Gmbh | Biocatalytic processes for the preparation of vilanterol |
| WO2017093208A1 (en) | 2015-12-03 | 2017-06-08 | Chiesi Farmaceutici S.P.A. | Compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| KR20180100106A (ko) * | 2016-01-22 | 2018-09-07 | 스촨 하이스코 파마수티컬 씨오., 엘티디 | 질소함유 헤테로 고리 아미드 유도체 및 그 제조방법과 약학적 용도 |
| US10155000B2 (en) | 2016-06-10 | 2018-12-18 | Boehringer Ingelheim International Gmbh | Medical use of pharmaceutical combination or composition |
| WO2018011090A1 (en) | 2016-07-13 | 2018-01-18 | Chiesi Farmaceutici S.P.A. | Hydroxyquinolinone compounds having muscarinic receptor antagonist and beta2 adrenergic receptor agonist activity |
| CN106706868B (zh) * | 2016-11-15 | 2018-12-04 | 河南省农业科学院 | 人工表达HSP27蛋白在检测β2-肾上腺素受体激动剂类药物残留方面的应用 |
| ES2836113T3 (es) | 2016-12-14 | 2021-06-24 | Beijing Showby Pharmaceutical Co Ltd | Clase de compuestos bifuncionales con estructura de sal de amonio cuaternario |
| CN106632257B (zh) * | 2016-12-15 | 2019-02-12 | 上海市奉贤区中心医院 | Gsk961081及其中间体的合成方法 |
| WO2019157144A1 (en) | 2018-02-07 | 2019-08-15 | Duke University | System and method for homogenous gpcr phosphorylation and identification of beta-2 adrenergic receptor positive allosteric modulators |
| US11484531B2 (en) | 2018-08-30 | 2022-11-01 | Theravance Biopharma R&D Ip, Llc | Methods for treating chronic obstructive pulmonary disease |
| KR20220019015A (ko) | 2019-06-10 | 2022-02-15 | 노파르티스 아게 | Cf, copd, 및 기관지확장증 치료를 위한 피리딘 및 피라진 유도체 |
| AU2020338971B2 (en) | 2019-08-28 | 2023-11-23 | Novartis Ag | Substituted 1,3-phenyl heteroaryl derivatives and their use in the treatment of disease |
| WO2022175982A1 (en) * | 2021-02-19 | 2022-08-25 | Gbr Laboratories Private Limited | A process for preparing batefenterol and intermediates thereof |
| CN114409890A (zh) * | 2022-02-28 | 2022-04-29 | 中国科学院长春应用化学研究所 | 一种氨基功能化的聚乙二醇衍生物及其制备方法 |
| CN118420569B (zh) * | 2024-04-24 | 2025-02-11 | 渭南瑞联制药有限责任公司 | 一种(s)-氧杂环丁烷-2-甲胺的合成方法 |
Family Cites Families (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4022776A (en) * | 1974-01-31 | 1977-05-10 | Otsuka Pharmaceutical Company Limited | 5-[1-Hydroxy-2-(substituted-amino)]ethyl-8-hydroxycarbostyril derivatives |
| BR8007911A (pt) | 1979-12-06 | 1981-06-16 | Glaxo Group Ltd | Inalador aperfeicoado |
| ATE23272T1 (de) | 1981-07-08 | 1986-11-15 | Draco Ab | Pulverinhalator. |
| DE3134590A1 (de) | 1981-09-01 | 1983-03-10 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue benzo-heterocyclen |
| US4460581A (en) * | 1982-10-12 | 1984-07-17 | Boehringer Ingelheim Kg | (1-Hydroxy-2-amino-alkyl)-substituted benzoxazinones and benzoxazolinones |
| ZW6584A1 (en) | 1983-04-18 | 1985-04-17 | Glaxo Group Ltd | Phenethanolamine derivatives |
| FI88112C (fi) | 1985-07-30 | 1993-04-13 | Glaxo Group Ltd | Anordning foer administrering av laekemedel till patienter |
| US4894219A (en) * | 1988-03-29 | 1990-01-16 | University Of Florida | Beta-agonist carbostyril derivatives, assay method and pharmacological composition |
| US5225183A (en) | 1988-12-06 | 1993-07-06 | Riker Laboratories, Inc. | Medicinal aerosol formulations |
| DK443489D0 (da) | 1989-09-08 | 1989-09-08 | Ferrosan As | Substituerede urinstofforbindelser, deres fremstilling og anvendelse |
| SK280967B6 (sk) | 1990-03-02 | 2000-10-09 | Glaxo Group Limited | Inhalačný prístroj |
| US6006745A (en) | 1990-12-21 | 1999-12-28 | Minnesota Mining And Manufacturing Company | Device for delivering an aerosol |
| US5874063A (en) | 1991-04-11 | 1999-02-23 | Astra Aktiebolag | Pharmaceutical formulation |
| AU2178392A (en) | 1991-06-12 | 1993-01-12 | Minnesota Mining And Manufacturing Company | Albuterol sulfate suspension aerosol formulations |
| US5337740A (en) | 1991-08-01 | 1994-08-16 | New England Pharmaceuticals, Inc. | Inhalation devices |
| ES2216800T3 (es) | 1991-12-18 | 2004-11-01 | Minnesota Mining And Manufacturing Company | Formulaciones de aerosol en suspension. |
| TW297025B (enExample) * | 1992-02-14 | 1997-02-01 | Squibb & Sons Inc | |
| DK0640081T3 (da) | 1992-03-31 | 2000-06-19 | Glaxo Group Ltd | Substituerede phenylcarbarmater og phenylurinstoffer, deres fremstilling og deres anvendelse som 5-HT4-antagonister |
| US5239993A (en) | 1992-08-26 | 1993-08-31 | Glaxo Inc. | Dosage inhalator providing optimized compound inhalation trajectory |
| US5497763A (en) | 1993-05-21 | 1996-03-12 | Aradigm Corporation | Disposable package for intrapulmonary delivery of aerosolized formulations |
| CA2123728A1 (en) * | 1993-05-21 | 1994-11-22 | Noriyoshi Sueda | Urea derivatives and their use as acat inhibitors |
| AU7545894A (en) | 1993-09-02 | 1995-03-22 | Yamanouchi Pharmaceutical Co., Ltd. | Carbamate derivative and medicine containing the same |
| US5415162A (en) | 1994-01-18 | 1995-05-16 | Glaxo Inc. | Multi-dose dry powder inhalation device |
| CA2182568A1 (en) | 1994-02-10 | 1995-08-17 | Makoto Takeuchi | Novel carbamate derivative and medicinal composition containing the same |
| US5495054A (en) | 1994-05-31 | 1996-02-27 | Sepracor, Inc. | Tetrahydroindeno[1,2-D][1,3,2]oxazaboroles and their use as enantioselective catalysts |
| US5983956A (en) | 1994-10-03 | 1999-11-16 | Astra Aktiebolag | Formulation for inhalation |
| SE9501384D0 (sv) | 1995-04-13 | 1995-04-13 | Astra Ab | Process for the preparation of respirable particles |
| AU718263B2 (en) | 1995-04-14 | 2000-04-13 | Smithkline Beecham Corporation | Metered dose inhaler for salmeterol |
| DE19536902A1 (de) | 1995-10-04 | 1997-04-10 | Boehringer Ingelheim Int | Vorrichtung zur Hochdruckerzeugung in einem Fluid in Miniaturausführung |
| EP0863141B1 (en) | 1995-10-13 | 2001-09-12 | Banyu Pharmaceutical Co., Ltd. | Substituted heteroaromatic derivatives |
| PE92198A1 (es) | 1996-08-01 | 1999-01-09 | Banyu Pharma Co Ltd | Derivados de 1,4-piperidina disustituida que contienen fluor |
| US6040344A (en) | 1996-11-11 | 2000-03-21 | Sepracor Inc. | Formoterol process |
| AU9281298A (en) | 1997-10-01 | 1999-04-23 | Kyowa Hakko Kogyo Co. Ltd. | Benzodioxole derivatives |
| WO1999031086A1 (en) | 1997-12-12 | 1999-06-24 | Smithkline Beecham Plc | Quinolinepiperazine and quinolinepiperidine derivatives, their preparation and their use as combined 5-ht1a, 5-ht1b and 5-ht1d receptor antagonists |
| US6255303B1 (en) | 1998-03-14 | 2001-07-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Phthalazinone PDE III/IV inhibitors |
| EA200000956A1 (ru) | 1998-04-18 | 2001-04-23 | Глаксо Груп Лимитед | Фармацевтический аэрозольный препарат |
| GB9808802D0 (en) | 1998-04-24 | 1998-06-24 | Glaxo Group Ltd | Pharmaceutical formulations |
| GB9812088D0 (en) * | 1998-06-05 | 1998-08-05 | Celltech Therapeutics Ltd | Chemical compounds |
| US6713651B1 (en) * | 1999-06-07 | 2004-03-30 | Theravance, Inc. | β2-adrenergic receptor agonists |
| JP2002517464A (ja) | 1998-06-08 | 2002-06-18 | アドバンスド メディスン インコーポレーテッド | ムスカリン性レセプターアンタゴニスト |
| US6541669B1 (en) * | 1998-06-08 | 2003-04-01 | Theravance, Inc. | β2-adrenergic receptor agonists |
| SE9804000D0 (sv) | 1998-11-23 | 1998-11-23 | Astra Ab | New composition of matter |
| AU2056800A (en) * | 1998-12-18 | 2000-07-03 | Du Pont Pharmaceuticals Company | Heterocyclic piperidines as modulators of chemokine receptor activity |
| US6693202B1 (en) * | 1999-02-16 | 2004-02-17 | Theravance, Inc. | Muscarinic receptor antagonists |
| DE19921693A1 (de) | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika |
| GB9913083D0 (en) | 1999-06-04 | 1999-08-04 | Novartis Ag | Organic compounds |
| EP1169019B1 (en) | 1999-04-14 | 2003-02-26 | Glaxo Group Limited | Pharmaceutical aerosol formulation |
| US6593497B1 (en) | 1999-06-02 | 2003-07-15 | Theravance, Inc. | β2-adrenergic receptor agonists |
| AU783095B2 (en) * | 1999-12-07 | 2005-09-22 | Theravance Biopharma R&D Ip, Llc | Carbamate derivatives having muscarinic receptor antagonist activity |
| UA73543C2 (uk) * | 1999-12-07 | 2005-08-15 | Тераванс, Інк. | Похідні сечовини, фармацевтична композиція та застосування похідного при приготуванні лікарського засобу для лікування захворювання, яке опосередковується мускариновим рецептором |
| UA73965C2 (en) * | 1999-12-08 | 2005-10-17 | Theravance Inc | b2 ADRENERGIC RECEPTOR ANTAGONISTS |
| NZ522882A (en) | 2000-06-05 | 2004-07-30 | Altana Pharma Bv | Pyridazinone compounds effective as beta-2-adrenoreceptor agonists as well as PDE4-inhibitors |
| JP4445704B2 (ja) | 2000-12-22 | 2010-04-07 | アルミラル・ソシエダッド・アノニマ | キヌクリジンカルバメート誘導体およびm3アンダゴニストとしてのそれらの使用 |
| GB0103630D0 (en) | 2001-02-14 | 2001-03-28 | Glaxo Group Ltd | Chemical compounds |
| WO2002070490A1 (en) | 2001-03-08 | 2002-09-12 | Glaxo Group Limited | Agonists of beta-adrenoceptors |
| EP1370521B1 (en) | 2001-03-22 | 2007-12-19 | Glaxo Group Limited | Formanilide derivatives as beta2-adrenoreceptor agonists |
| US20030018019A1 (en) * | 2001-06-23 | 2003-01-23 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics |
| PL211953B1 (pl) | 2001-09-14 | 2012-07-31 | Glaxo Group Ltd | Pochodna fenetanoloaminy, zawierający ją środek farmaceutyczny i zastosowanie pochodnej fenetanoloaminy |
| TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
| US6653323B2 (en) * | 2001-11-13 | 2003-11-25 | Theravance, Inc. | Aryl aniline β2 adrenergic receptor agonists |
| ES2248767T3 (es) | 2002-04-12 | 2006-03-16 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Medicamento que contiene beta-mimeticos y un nuevo anticolinergico. |
| JP2005527618A (ja) * | 2002-05-28 | 2005-09-15 | セラヴァンス インコーポレーテッド | アルコキシアリールβ2アドレナリン作動性レセプターアゴニスト |
| US6711451B2 (en) * | 2002-07-02 | 2004-03-23 | 3D Systems, Inc. | Power management in selective deposition modeling |
| GB0217225D0 (en) | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicinal compounds |
| TW200410951A (en) | 2002-08-06 | 2004-07-01 | Glaxo Group Ltd | M3 muscarinic acetylcholine receptor antagonists |
| PE20040950A1 (es) * | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
| US7317102B2 (en) | 2003-04-01 | 2008-01-08 | Theravance, Inc. | Diarylmethyl and related compounds |
| EP1626970B1 (en) * | 2003-05-28 | 2009-07-08 | Theravance, Inc. | Azabicycloalkane compounds as muscarinic receptor antagonists |
| TW200510298A (en) * | 2003-06-13 | 2005-03-16 | Theravance Inc | Substituted pyrrolidine and related compounds |
| EP1644356A1 (en) * | 2003-07-11 | 2006-04-12 | Theravance, Inc. | Substituted 4-amino-1-benzylpiperidine compounds |
| ES2329586T3 (es) | 2003-11-21 | 2009-11-27 | Theravance, Inc. | Compuestos que tienen actividad agonista del receptor beta2 adrenergico y antagonista del receptor muscarino. |
| US7320990B2 (en) * | 2004-02-13 | 2008-01-22 | Theravance, Inc. | Crystalline form of a biphenyl compound |
| JP2007528414A (ja) * | 2004-03-11 | 2007-10-11 | セラヴァンス, インコーポレーテッド | ムスカリンレセプターアンタゴニストとしての有用なジフェニルメチル化合物 |
| WO2005087736A1 (en) * | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| EP1723109A1 (en) * | 2004-03-11 | 2006-11-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| US7524962B2 (en) * | 2004-03-11 | 2009-04-28 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| WO2005087735A1 (en) * | 2004-03-11 | 2005-09-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TW200538095A (en) * | 2004-03-11 | 2005-12-01 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
| EP1723108A1 (en) * | 2004-03-11 | 2006-11-22 | Theravance, Inc. | Biphenyl compounds useful as muscarinic receptor antagonists |
| TWI374883B (en) * | 2004-08-16 | 2012-10-21 | Theravance Inc | Crystalline form of a biphenyl compound |
| WO2006023457A1 (en) * | 2004-08-16 | 2006-03-02 | Theravance, Inc. | COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY |
| JP2008510015A (ja) * | 2004-08-16 | 2008-04-03 | セラヴァンス, インコーポレーテッド | β2アドレナリン作用性レセプターアゴニスト活性およびムスカリン性レセプターアンタゴニスト活性を有する化合物 |
| TW200811104A (en) * | 2006-04-25 | 2008-03-01 | Theravance Inc | Crystalline forms of a dimethylphenyl compound |
| TW200811105A (en) * | 2006-04-25 | 2008-03-01 | Theravance Inc | Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity |
-
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