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
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 Download PDFInfo
- 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
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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
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- 230000001225 therapeutic effect Effects 0.000 claims description 8
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- 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
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- 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
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- 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
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- 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
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- 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
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/23—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atoms of the sulfonamide groups bound to acyclic carbon atoms
- C07C311/27—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atoms of the sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/52—Y being a hetero atom
- C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
- C07C311/57—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
- C07C311/58—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to hydrogen atoms or to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- 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
Applications Claiming Priority (3)
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PCT/EP2002/001387 WO2002066422A1 (en) | 2001-02-14 | 2002-02-11 | Phenethanolamine derivatives for treatment of respiratory diseases |
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