UA76443C2 - Phenetanolamine derivatives for the treatment of respiratory diseases, a method for producing thereof (variants), intermediary compounds, pharmaceutical composition, combination and a method for prophylaxis or treatment of state to which selective agonist of ?2- adrenoreceptor is prescribed - Google Patents

Info

Publication number

UA76443C2

UA76443C2 UA2003087450A UA2003087450A UA76443C2 UA 76443 C2 UA76443 C2 UA 76443C2 UA 2003087450 A UA2003087450 A UA 2003087450A UA 2003087450 A UA2003087450 A UA 2003087450A UA 76443 C2 UA76443 C2 UA 76443C2

Authority

UA

Ukraine

Prior art keywords

hydroxy

compound

oxy

formula

phenyl

Prior art date

2001-02-14

Links

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• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 300
• 238000000034 method Methods 0.000 title claims abstract description 224
• 238000011282 treatment Methods 0.000 title claims abstract description 24
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 6
• 239000000556 agonist Substances 0.000 title claims description 14
• 208000023504 respiratory system disease Diseases 0.000 title abstract description 3
• 238000011321 prophylaxis Methods 0.000 title abstract 2
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 222
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 194
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 164
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 153
• 239000000203 mixture Substances 0.000 claims description 143
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 136
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 126
• 150000003839 salts Chemical class 0.000 claims description 106
• -1 because C(OME8H Chemical group 0.000 claims description 78
• 239000012453 solvate Substances 0.000 claims description 78
• 229910052757 nitrogen Inorganic materials 0.000 claims description 36
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 35
• 125000006239 protecting group Chemical group 0.000 claims description 32
• 239000003112 inhibitor Substances 0.000 claims description 30
• 239000002253 acid Substances 0.000 claims description 24
• 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 description 23
• 238000006243 chemical reaction Methods 0.000 claims description 20
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• 125000000217 alkyl group Chemical group 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 230000002265 prevention Effects 0.000 claims description 12
• 229940124530 sulfonamide Drugs 0.000 claims description 12
• 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 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 10
• 150000001412 amines Chemical class 0.000 claims description 8
• 239000003246 corticosteroid Substances 0.000 claims description 8
• 239000004615 ingredient Substances 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• 230000001225 therapeutic effect Effects 0.000 claims description 8
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 7
• 239000000812 cholinergic antagonist Substances 0.000 claims description 7
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 238000010511 deprotection reaction Methods 0.000 claims description 5
• AFDXODALSZRGIH-QPJJXVBHSA-N (E)-3-(4-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1 AFDXODALSZRGIH-QPJJXVBHSA-N 0.000 claims description 4
• KWGPBDBAAXYWOJ-SOFGYWHQSA-N (e)-3-naphthalen-2-ylprop-2-enoic acid Chemical compound C1=CC=CC2=CC(/C=C/C(=O)O)=CC=C21 KWGPBDBAAXYWOJ-SOFGYWHQSA-N 0.000 claims description 4
• NNJMFJSKMRYHSR-UHFFFAOYSA-M 4-phenylbenzoate Chemical compound C1=CC(C(=O)[O-])=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-M 0.000 claims description 4
• 108060003345 Adrenergic Receptor Proteins 0.000 claims description 4
• 102000017910 Adrenergic receptor Human genes 0.000 claims description 4
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
• 125000004450 alkenylene group Chemical group 0.000 claims description 4
• 125000004432 carbon atom Chemical group C* 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 4
• DCYGAPKNVCQNOE-UHFFFAOYSA-N 2,2,2-triphenylacetic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)O)C1=CC=CC=C1 DCYGAPKNVCQNOE-UHFFFAOYSA-N 0.000 claims description 3
• RURHILYUWQEGOS-UHFFFAOYSA-N 3-(4-methylphenyl)prop-2-enoic acid Chemical compound CC1=CC=C(C=CC(O)=O)C=C1 RURHILYUWQEGOS-UHFFFAOYSA-N 0.000 claims description 3
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
• 241000124008 Mammalia Species 0.000 claims description 3
• 125000003118 aryl group Chemical group 0.000 claims description 3
• 229940114081 cinnamate Drugs 0.000 claims description 3
• 229910052802 copper Inorganic materials 0.000 claims description 3
• 239000010949 copper Substances 0.000 claims description 3
• 125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 3
• POTBKLVBOJZRNG-UHFFFAOYSA-N 1-hydroxy-2h-naphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)(O)CC=CC2=C1 POTBKLVBOJZRNG-UHFFFAOYSA-N 0.000 claims description 2
• 125000005274 4-hydroxybenzoic acid group Chemical group 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 2
• NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical class C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 claims 1
• 230000002152 alkylating effect Effects 0.000 claims 1
• 238000013160 medical therapy Methods 0.000 claims 1
• UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 abstract description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 122
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 106
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 97
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
• 239000000243 solution Substances 0.000 description 71
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 62
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 44
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• 235000019439 ethyl acetate Nutrition 0.000 description 37
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 27
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 26
• 239000000047 product Substances 0.000 description 25
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
• 239000002904 solvent Substances 0.000 description 22
• 229950005741 rolipram Drugs 0.000 description 21
• 239000010410 layer Substances 0.000 description 20
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• 239000003054 catalyst Substances 0.000 description 19
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
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• 230000015572 biosynthetic process Effects 0.000 description 18
• 230000002829 reductive effect Effects 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
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• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 14
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• 239000004480 active ingredient Substances 0.000 description 13
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 13
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• 238000003756 stirring Methods 0.000 description 11
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
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