CA2504213A1 - New beta-agonists, processes for preparing them and their use as pharmaceutical compositions - Google Patents
New beta-agonists, processes for preparing them and their use as pharmaceutical compositions Download PDFInfo
- Publication number
- CA2504213A1 CA2504213A1 CA002504213A CA2504213A CA2504213A1 CA 2504213 A1 CA2504213 A1 CA 2504213A1 CA 002504213 A CA002504213 A CA 002504213A CA 2504213 A CA2504213 A CA 2504213A CA 2504213 A1 CA2504213 A1 CA 2504213A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- hydrogen
- denotes
- group selected
- aryl
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 15
- 229940125388 beta agonist Drugs 0.000 title abstract description 4
- 230000008569 process Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 68
- 239000001257 hydrogen Substances 0.000 claims description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims description 108
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 78
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 239000013543 active substance Substances 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- -1 substituted Chemical class 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 8
- 208000008589 Obesity Diseases 0.000 claims description 8
- 235000020824 obesity Nutrition 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 230000000638 stimulation Effects 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 239000012320 chlorinating reagent Substances 0.000 claims description 4
- 230000006806 disease prevention Effects 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- 101710204865 Tyrosine-protein phosphatase 1 Proteins 0.000 claims description 3
- 230000001800 adrenalinergic effect Effects 0.000 claims description 3
- 230000003178 anti-diabetic effect Effects 0.000 claims description 3
- 239000003524 antilipemic agent Substances 0.000 claims description 3
- 230000001906 cholesterol absorption Effects 0.000 claims description 3
- 230000002074 deregulated effect Effects 0.000 claims description 3
- 230000009229 glucose formation Effects 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 10
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 8
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 3
- KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical compound C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 1
- 125000006732 (C1-C15) alkyl group Chemical group 0.000 claims 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 29
- 239000000243 solution Substances 0.000 description 29
- 125000001424 substituent group Chemical group 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- 229910021529 ammonia Inorganic materials 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 20
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000008346 aqueous phase Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 239000012071 phase Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 229910052731 fluorine Inorganic materials 0.000 description 12
- 239000011737 fluorine Substances 0.000 description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 11
- 239000000556 agonist Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 229910052801 chlorine Inorganic materials 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- GOTDZEOIBMTRDU-UHFFFAOYSA-N 4-chloro-2-methylbutan-2-amine;hydrochloride Chemical compound Cl.CC(C)(N)CCCl GOTDZEOIBMTRDU-UHFFFAOYSA-N 0.000 description 7
- 229920002261 Corn starch Polymers 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000008120 corn starch Substances 0.000 description 7
- 239000008101 lactose Substances 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- UZRPHHXMFGRKDI-MHZLTWQESA-N (1r)-2-[[2-methyl-4-(4-phenylimidazol-1-yl)butan-2-yl]amino]-1-(3-nitro-4-phenylmethoxyphenyl)ethanol Chemical compound C([C@H](O)C=1C=C(C(OCC=2C=CC=CC=2)=CC=1)[N+]([O-])=O)NC(C)(C)CCN(C=1)C=NC=1C1=CC=CC=C1 UZRPHHXMFGRKDI-MHZLTWQESA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 6
- XKNLNSKAVFAJNQ-MHZLTWQESA-N (1r)-1-(3-amino-4-phenylmethoxyphenyl)-2-[[2-methyl-4-(4-phenylimidazol-1-yl)butan-2-yl]amino]ethanol Chemical compound C([C@H](O)C=1C=C(N)C(OCC=2C=CC=CC=2)=CC=1)NC(C)(C)CCN(C=1)C=NC=1C1=CC=CC=C1 XKNLNSKAVFAJNQ-MHZLTWQESA-N 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- RTIQXBOLSAYMGO-XIFFEERXSA-N n-[5-[(1r)-1-hydroxy-2-[[2-methyl-4-(4-phenylimidazol-1-yl)butan-2-yl]amino]ethyl]-2-phenylmethoxyphenyl]benzenesulfonamide Chemical compound C([C@H](O)C=1C=C(NS(=O)(=O)C=2C=CC=CC=2)C(OCC=2C=CC=CC=2)=CC=1)NC(C)(C)CCN(C=1)C=NC=1C1=CC=CC=C1 RTIQXBOLSAYMGO-XIFFEERXSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 235000012222 talc Nutrition 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- RGKMPFSMHTUFHJ-UHFFFAOYSA-N 2-chlorobenzenecarboximidoyl chloride Chemical compound ClC(=N)C1=CC=CC=C1Cl RGKMPFSMHTUFHJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 210000001789 adipocyte Anatomy 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 230000004130 lipolysis Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 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 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 239000001828 Gelatine Substances 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000007107 Stomach Ulcer Diseases 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- JYDDSVHULCTAOH-UHFFFAOYSA-N n-(4-chloro-2-methylbutan-2-yl)-1-(2,6-dichlorophenyl)methanimine Chemical compound ClCCC(C)(C)N=CC1=C(Cl)C=CC=C1Cl JYDDSVHULCTAOH-UHFFFAOYSA-N 0.000 description 3
- UISRMBBNFYPGMI-MHZLTWQESA-N n-[2-hydroxy-5-[(1r)-1-hydroxy-2-[[2-methyl-4-(4-phenylimidazol-1-yl)butan-2-yl]amino]ethyl]phenyl]benzenesulfonamide Chemical compound C([C@H](O)C=1C=C(NS(=O)(=O)C=2C=CC=CC=2)C(O)=CC=1)NC(C)(C)CCN(C=1)C=NC=1C1=CC=CC=C1 UISRMBBNFYPGMI-MHZLTWQESA-N 0.000 description 3
- HFUHXHXVHDPARF-UHFFFAOYSA-N n-[5-[1-hydroxy-2-[[2-methyl-4-(4-phenylimidazol-1-yl)butan-2-yl]amino]ethyl]-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(NS(C)(=O)=O)=CC=1C(O)CNC(C)(C)CCN(C=1)C=NC=1C1=CC=CC=C1 HFUHXHXVHDPARF-UHFFFAOYSA-N 0.000 description 3
- YYWWQVYOPYNAIW-UHFFFAOYSA-N n-[5-[1-hydroxy-2-[[4-(4-iodoimidazol-1-yl)-2-methylbutan-2-yl]amino]ethyl]-2-phenylmethoxyphenyl]benzenesulfonamide Chemical compound C=1C=C(OCC=2C=CC=CC=2)C(NS(=O)(=O)C=2C=CC=CC=2)=CC=1C(O)CNC(C)(C)CCN1C=NC(I)=C1 YYWWQVYOPYNAIW-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 3
- MOGUBMMGIJLRHQ-HNNXBMFYSA-N (2r)-2-(3-nitro-4-phenylmethoxyphenyl)oxirane Chemical compound [O-][N+](=O)C1=CC([C@H]2OC2)=CC=C1OCC1=CC=CC=C1 MOGUBMMGIJLRHQ-HNNXBMFYSA-N 0.000 description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
- DMIYKWPEFRFTPY-UHFFFAOYSA-N 2,6-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(Cl)=C1C=O DMIYKWPEFRFTPY-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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DE10251170A DE10251170A1 (de) | 2002-10-31 | 2002-10-31 | Neue Beta-Agonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
DE10251170.5 | 2002-10-31 | ||
PCT/EP2003/012049 WO2004039784A1 (de) | 2002-10-31 | 2003-10-30 | Neue phenylethanolaminderivate und deren verwendung als beta-3-agonisten |
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CA2504213A1 true CA2504213A1 (en) | 2004-05-13 |
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CA002504213A Abandoned CA2504213A1 (en) | 2002-10-31 | 2003-10-30 | New beta-agonists, processes for preparing them and their use as pharmaceutical compositions |
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EP (1) | EP1558583A1 (enrdf_load_stackoverflow) |
JP (1) | JP2006508090A (enrdf_load_stackoverflow) |
AU (1) | AU2003278157A1 (enrdf_load_stackoverflow) |
CA (1) | CA2504213A1 (enrdf_load_stackoverflow) |
DE (1) | DE10251170A1 (enrdf_load_stackoverflow) |
WO (1) | WO2004039784A1 (enrdf_load_stackoverflow) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7405232B2 (en) | 2004-02-14 | 2008-07-29 | Boehringer Ingelheim International Gmbh | Long acting beta-2 agonists and their use as medicaments |
US7754756B2 (en) | 2005-10-28 | 2010-07-13 | Boehringer Ingelheim International Gmbh | Indol-containing beta-agonists, methods for the preparation thereof and their use as pharmaceutical compositions |
US7977334B2 (en) | 2004-04-30 | 2011-07-12 | Boehringer Ingelheim International Gmbh | Beta-agonists, methods for the preparation thereof and their use as pharmaceutical compositions |
WO2024200736A1 (en) * | 2023-03-29 | 2024-10-03 | Atrogi Ab | Heterocycloalkyl beta-hydroxy alkyl amines for use in the treatment of hyperglycaemia and disorders characterised by hyperglycaemia |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4916317B2 (ja) * | 2004-02-14 | 2012-04-11 | 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 | 新規持続作用性β−2−アゴニスト及び薬剤としてのその使用 |
CA2580170A1 (en) * | 2004-10-18 | 2006-04-27 | Boehringer Ingelheim International Gmbh | Use of a beta-3 agonist for treating complaints of the prostate and the lower urogenital tract |
DE102005052101A1 (de) * | 2005-10-28 | 2007-05-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Beta-Agonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
DE102005052103A1 (de) * | 2005-10-28 | 2007-05-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Beta-Agonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
DE102005052102A1 (de) * | 2005-10-28 | 2007-05-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Beta-Agonisten, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
US20090221589A1 (en) * | 2005-12-19 | 2009-09-03 | Thomas Trieselmann | Use of aminoalcohol derivatives for the treatment of overactive bladder |
GB0705400D0 (en) * | 2007-03-21 | 2007-05-02 | Univ Aberdeen | Therapeutic compounds andm their use |
WO2008132162A1 (en) * | 2007-04-26 | 2008-11-06 | Boehringer Ingelheim International Gmbh | 3- (sulphonylamino) -phenyl-2 -hydroxy-ethylamino derivatives useful as beta-agonists, processes for preparing them and their use as medicaments |
GB0817208D0 (en) | 2008-09-19 | 2008-10-29 | Pimco 2664 Ltd | Therapeutic apsap compounds and their use |
GB0817207D0 (en) | 2008-09-19 | 2008-10-29 | Pimco 2664 Ltd | therapeutic apsac compounds and their use |
GB201311361D0 (en) | 2013-06-26 | 2013-08-14 | Pimco 2664 Ltd | Compounds and their therapeutic use |
LT3262028T (lt) | 2014-12-17 | 2022-01-10 | Pimco 2664 Limited | N-(4-hidroksi-4-metil-cikloheksil)-4-fenil-benzensulfonamido ir n-(-4-hidroksi-4-metil-cikloheksil)-4-(2-piridil)-benzensulfonamido junginiai ir jų terapinis panaudojimas |
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US2943090A (en) * | 1957-09-23 | 1960-06-28 | American Cyanamid Co | Substituted piperazines and method of preparing the same |
US3092636A (en) * | 1959-10-21 | 1963-06-04 | Upjohn Co | Alpha-[2-(1-alkyleneimino) ethylamino]-alkanophenones and the corresponding alcohols |
GB1200886A (en) * | 1966-09-23 | 1970-08-05 | Allen & Hanburys Ltd | Phenylaminoethanol derivatives |
DE2115926C3 (de) * | 1971-04-01 | 1978-05-03 | C.H. Boehringer Sohn, 6507 Ingelheim | 1 -(4-Hydroxy-3-dimethylaminosuIfamidophenyI)-2-aminoäthanderivate, Verfahren zu ihrer Herstellung und diese enthaltende Mittel |
DE2833140A1 (de) * | 1978-07-28 | 1980-02-07 | Boehringer Sohn Ingelheim | Neue n-substituierte heterocyclen |
JPS6183147A (ja) * | 1984-09-28 | 1986-04-26 | Nippon Chemiphar Co Ltd | 新規なアミノアルコール誘導体およびその製造法並びにそれを有効成分とするグルタミン酸遮断剤 |
JPH08165276A (ja) * | 1994-12-14 | 1996-06-25 | Dainippon Pharmaceut Co Ltd | 2−アルキルアミノ−1−フェニルエタノール誘導体 |
GB9525177D0 (en) * | 1995-12-08 | 1996-02-07 | Glaxo Group Ltd | Chemical compounds |
DE69717978T2 (de) * | 1996-04-05 | 2003-10-02 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.), Paris | Alpha-1 adrenergischer rezeptor antagonisten |
US6362371B1 (en) * | 1998-06-08 | 2002-03-26 | Advanced Medicine, Inc. | β2- adrenergic receptor agonists |
UA73965C2 (en) * | 1999-12-08 | 2005-10-17 | Theravance Inc | b2 ADRENERGIC RECEPTOR ANTAGONISTS |
-
2002
- 2002-10-31 DE DE10251170A patent/DE10251170A1/de not_active Withdrawn
-
2003
- 2003-10-30 WO PCT/EP2003/012049 patent/WO2004039784A1/de active Application Filing
- 2003-10-30 JP JP2004547613A patent/JP2006508090A/ja active Pending
- 2003-10-30 CA CA002504213A patent/CA2504213A1/en not_active Abandoned
- 2003-10-30 EP EP03769472A patent/EP1558583A1/de not_active Withdrawn
- 2003-10-30 AU AU2003278157A patent/AU2003278157A1/en not_active Abandoned
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7405232B2 (en) | 2004-02-14 | 2008-07-29 | Boehringer Ingelheim International Gmbh | Long acting beta-2 agonists and their use as medicaments |
US7977334B2 (en) | 2004-04-30 | 2011-07-12 | Boehringer Ingelheim International Gmbh | Beta-agonists, methods for the preparation thereof and their use as pharmaceutical compositions |
US7754756B2 (en) | 2005-10-28 | 2010-07-13 | Boehringer Ingelheim International Gmbh | Indol-containing beta-agonists, methods for the preparation thereof and their use as pharmaceutical compositions |
WO2024200736A1 (en) * | 2023-03-29 | 2024-10-03 | Atrogi Ab | Heterocycloalkyl beta-hydroxy alkyl amines for use in the treatment of hyperglycaemia and disorders characterised by hyperglycaemia |
Also Published As
Publication number | Publication date |
---|---|
WO2004039784A1 (de) | 2004-05-13 |
AU2003278157A1 (en) | 2004-05-25 |
EP1558583A1 (de) | 2005-08-03 |
JP2006508090A (ja) | 2006-03-09 |
DE10251170A1 (de) | 2004-05-13 |
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