CA2196193A1 - Aryloxy and arylthiopropanolamine derivatives useful as beta 3-adrenoreceptor agonists and antagonists of the beta 1 and beta 2-adrenoreceptors and pharmaceutical composition thereof - Google Patents
Aryloxy and arylthiopropanolamine derivatives useful as beta 3-adrenoreceptor agonists and antagonists of the beta 1 and beta 2-adrenoreceptors and pharmaceutical composition thereofInfo
- Publication number
- CA2196193A1 CA2196193A1 CA002196193A CA2196193A CA2196193A1 CA 2196193 A1 CA2196193 A1 CA 2196193A1 CA 002196193 A CA002196193 A CA 002196193A CA 2196193 A CA2196193 A CA 2196193A CA 2196193 A1 CA2196193 A1 CA 2196193A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- acid
- compound
- procedure
- hydroxy
- 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
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 4
- 239000000556 agonist Substances 0.000 title description 8
- 239000005557 antagonist Substances 0.000 title description 3
- 102100040794 Beta-1 adrenergic receptor Human genes 0.000 title 1
- 101710181961 Beta-1 adrenergic receptor Proteins 0.000 title 1
- 102100039705 Beta-2 adrenergic receptor Human genes 0.000 title 1
- 101710152983 Beta-2 adrenergic receptor Proteins 0.000 title 1
- 125000004104 aryloxy group Chemical group 0.000 title 1
- 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 title 1
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 406
- 150000001875 compounds Chemical class 0.000 claims abstract description 374
- 150000002148 esters Chemical class 0.000 claims abstract description 101
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
- 239000001257 hydrogen Substances 0.000 claims abstract description 49
- -1 hydroxy, hydroxymethyl Chemical group 0.000 claims abstract description 46
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 42
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 35
- 239000012453 solvate Substances 0.000 claims abstract description 35
- 150000001408 amides Chemical class 0.000 claims abstract description 29
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical class 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 7
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims abstract description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 6
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims abstract description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 3
- 125000005324 aryloxy alkyloxy group Chemical group 0.000 claims abstract description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims description 322
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 116
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 72
- 239000000203 mixture Substances 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 244000144972 livestock Species 0.000 claims description 8
- 230000003247 decreasing effect Effects 0.000 claims description 7
- 231100000252 nontoxic Toxicity 0.000 claims description 7
- 230000003000 nontoxic effect Effects 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 4
- 230000004083 survival effect Effects 0.000 claims description 4
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 230000004584 weight gain Effects 0.000 claims description 3
- 235000019786 weight gain Nutrition 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 2
- 125000006515 benzyloxy alkyl group Chemical group 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 201000001421 hyperglycemia Diseases 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 230000036269 ulceration Effects 0.000 claims description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims 2
- GNOKWJFBPJGLEE-UHFFFAOYSA-N 2-[4-[2-[[2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]propyl]phenoxy]acetic acid Chemical compound C=1C=C(O)C=CC=1OCC(O)CNC(C)CC1=CC=C(OCC(O)=O)C=C1 GNOKWJFBPJGLEE-UHFFFAOYSA-N 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 230000035879 hyperinsulinaemia Effects 0.000 claims 1
- 125000004344 phenylpropyl group Chemical group 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 abstract description 100
- 125000006308 propyl amino group Chemical group 0.000 abstract description 13
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 252
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 64
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 62
- 239000002904 solvent Substances 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- 238000006243 chemical reaction Methods 0.000 description 53
- 239000012043 crude product Substances 0.000 description 53
- 239000003921 oil Substances 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
- 125000004494 ethyl ester group Chemical group 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
- 239000007787 solid Substances 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 35
- 229910002027 silica gel Inorganic materials 0.000 description 35
- 229960001866 silicon dioxide Drugs 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
- 229910052786 argon Inorganic materials 0.000 description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- 239000012071 phase Substances 0.000 description 25
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 229910003002 lithium salt Inorganic materials 0.000 description 18
- 159000000002 lithium salts Chemical class 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 239000012267 brine Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 14
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical group O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 235000011054 acetic acid Nutrition 0.000 description 13
- 238000004108 freeze drying Methods 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 8
- 102000015779 HDL Lipoproteins Human genes 0.000 description 8
- 108010010234 HDL Lipoproteins Proteins 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 229930040373 Paraformaldehyde Natural products 0.000 description 8
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
- 229960004132 diethyl ether Drugs 0.000 description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 8
- 229920002866 paraformaldehyde Polymers 0.000 description 8
- 239000000010 aprotic solvent Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- YJSXLGKPMXKZJR-UHFFFAOYSA-N ethoxy-oxo-phenylphosphanium Chemical compound CCO[P+](=O)C1=CC=CC=C1 YJSXLGKPMXKZJR-UHFFFAOYSA-N 0.000 description 6
- 238000007327 hydrogenolysis reaction Methods 0.000 description 6
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 6
- 150000004702 methyl esters Chemical class 0.000 description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- KWBIXTIBYFUAGV-UHFFFAOYSA-N ethylcarbamic acid Chemical compound CCNC(O)=O KWBIXTIBYFUAGV-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N hydrogen bromide Substances Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- 208000007882 Gastritis Diseases 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001024304 Mino Species 0.000 description 4
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- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
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- 235000012000 cholesterol Nutrition 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 229910052770 Uranium Inorganic materials 0.000 description 3
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 102000030621 adenylate cyclase Human genes 0.000 description 3
- 108060000200 adenylate cyclase Proteins 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 150000003973 alkyl amines Chemical class 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 150000002466 imines Chemical class 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 3
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
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Classifications
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
- C07C217/30—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring
- C07C217/32—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
- C07C217/34—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having the oxygen atom of at least one of the etherified hydroxy groups further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/303—Cycloaliphatic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3223—Esters of cycloaliphatic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9415304A GB9415304D0 (en) | 1994-07-29 | 1994-07-29 | Novel compounds |
| GB9415304.6 | 1994-07-29 | ||
| GB9423179A GB9423179D0 (en) | 1994-11-17 | 1994-11-17 | Novel compounds |
| GB9423179.2 | 1994-11-17 | ||
| GB9510485.7 | 1995-05-24 | ||
| GBGB9510485.7A GB9510485D0 (en) | 1995-05-24 | 1995-05-24 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2196193A1 true CA2196193A1 (en) | 1996-02-15 |
Family
ID=27267307
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002196193A Abandoned CA2196193A1 (en) | 1994-07-29 | 1995-07-27 | Aryloxy and arylthiopropanolamine derivatives useful as beta 3-adrenoreceptor agonists and antagonists of the beta 1 and beta 2-adrenoreceptors and pharmaceutical composition thereof |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0772585A1 (cs) |
| JP (1) | JPH10503507A (cs) |
| CN (1) | CN1159797A (cs) |
| AU (1) | AU3254695A (cs) |
| BR (1) | BR9508991A (cs) |
| CA (1) | CA2196193A1 (cs) |
| CZ (1) | CZ25597A3 (cs) |
| HU (1) | HUT76800A (cs) |
| MX (1) | MX9700765A (cs) |
| NO (1) | NO970372L (cs) |
| PL (1) | PL318381A1 (cs) |
| WO (1) | WO1996004233A1 (cs) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9605495D0 (en) * | 1996-03-15 | 1996-05-15 | Smithkline Beecham Plc | Novel compounds |
| US5914339A (en) * | 1996-05-14 | 1999-06-22 | American Home Products Corporation | Substituted 1,3-benzodioxoles |
| EP0827746B1 (en) | 1996-09-05 | 2002-04-03 | Eli Lilly And Company | Carbazole analogues as selective beta3 adrenergic agonists |
| WO1998022480A1 (en) * | 1996-11-18 | 1998-05-28 | Smithkline Beecham Plc | Phosphorus containing aryloxy or arylthio propanolamine derivatives |
| GB9703492D0 (en) * | 1997-02-20 | 1997-04-09 | Smithkline Beecham Plc | Novel compounds |
| CO5011072A1 (es) | 1997-12-05 | 2001-02-28 | Lilly Co Eli | Etanolaminas pirazinil substituidas como agfonistas de los receptores |
| DE69928185T2 (de) * | 1998-01-30 | 2006-07-20 | Boulder Scientific Co., Mead | Synthese von n-silylierten verbindungen |
| US6495546B1 (en) | 1998-04-06 | 2002-12-17 | Fujisawa Pharmaceutical Co., Ltd. | Propanolamine derivatives |
| AUPP549998A0 (en) * | 1998-08-26 | 1998-09-17 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
| US7098248B2 (en) | 2001-07-09 | 2006-08-29 | Research Development Foundation | Beta-adrenergic blockade reversal of catabolism after severe burn |
| DE102008064003A1 (de) * | 2008-12-19 | 2010-06-24 | Clariant International Limited | Verfahren zur Herstellung von mono-funktionalisierten Dialkylphosphinsäuren, -estern und -salzen und ihre Verwendung |
| CN107266341B (zh) * | 2017-06-23 | 2020-01-07 | 华东师范大学 | 芳氧基取代丙-2-醇胺的衍生物作为β3肾上腺素能受体拮抗剂、制备方法和用途 |
| CN112442167A (zh) * | 2019-08-28 | 2021-03-05 | 广东广山新材料股份有限公司 | 一种反应型阻燃剂及其制备方法和应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1262729A (en) * | 1983-10-19 | 1989-11-07 | Leo Alig | Phenoxypropanolamines |
| EP0300290B1 (de) * | 1987-07-21 | 1991-12-18 | F. Hoffmann-La Roche Ag | Phenoxypropanolamine |
| GB8801306D0 (en) * | 1988-01-21 | 1988-02-17 | Ici Plc | Chemical compounds |
| GB9215844D0 (en) * | 1992-07-25 | 1992-09-09 | Smithkline Beecham Plc | Novel compounds |
-
1995
- 1995-07-27 CA CA002196193A patent/CA2196193A1/en not_active Abandoned
- 1995-07-27 HU HU9700262A patent/HUT76800A/hu unknown
- 1995-07-27 EP EP95929029A patent/EP0772585A1/en not_active Withdrawn
- 1995-07-27 CN CN95195371A patent/CN1159797A/zh active Pending
- 1995-07-27 MX MX9700765A patent/MX9700765A/es unknown
- 1995-07-27 BR BR9508991A patent/BR9508991A/pt not_active Application Discontinuation
- 1995-07-27 CZ CZ97255A patent/CZ25597A3/cs unknown
- 1995-07-27 WO PCT/EP1995/003037 patent/WO1996004233A1/en not_active Application Discontinuation
- 1995-07-27 AU AU32546/95A patent/AU3254695A/en not_active Abandoned
- 1995-07-27 JP JP8506193A patent/JPH10503507A/ja active Pending
- 1995-07-27 PL PL95318381A patent/PL318381A1/xx unknown
-
1997
- 1997-01-28 NO NO970372A patent/NO970372L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL318381A1 (en) | 1997-06-09 |
| CZ25597A3 (cs) | 1998-02-18 |
| AU3254695A (en) | 1996-03-04 |
| NO970372L (no) | 1997-03-18 |
| EP0772585A1 (en) | 1997-05-14 |
| HUT76800A (en) | 1997-11-28 |
| NO970372D0 (no) | 1997-01-28 |
| WO1996004233A1 (en) | 1996-02-15 |
| JPH10503507A (ja) | 1998-03-31 |
| MX9700765A (es) | 1997-05-31 |
| BR9508991A (pt) | 1997-10-21 |
| CN1159797A (zh) | 1997-09-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |