ZA200302635B - A method for treating allergies using substituted pyrazoles. - Google Patents

Info

Publication number

ZA200302635B

ZA200302635B ZA200302635A ZA200302635A ZA200302635B ZA 200302635 B ZA200302635 B ZA 200302635B ZA 200302635 A ZA200302635 A ZA 200302635A ZA 200302635 A ZA200302635 A ZA 200302635A ZA 200302635 B ZA200302635 B ZA 200302635B

Authority

ZA

South Africa

Prior art keywords

phenyl

tetrahydro

pyrazolo

piperidin

pyridin

Prior art date

2000-09-06

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims description 38
• 206010020751 Hypersensitivity Diseases 0.000 title description 13
• 230000007815 allergy Effects 0.000 title description 12
• 150000003217 pyrazoles Chemical class 0.000 title description 5
• -1 cyano, amino, hydroxy Chemical group 0.000 claims description 250
• 239000000203 mixture Substances 0.000 claims description 188
• 229910052739 hydrogen Inorganic materials 0.000 claims description 129
• 125000000217 alkyl group Chemical group 0.000 claims description 128
• 239000001257 hydrogen Substances 0.000 claims description 104
• 150000001875 compounds Chemical class 0.000 claims description 96
• 125000000623 heterocyclic group Chemical group 0.000 claims description 96
• 229920006395 saturated elastomer Polymers 0.000 claims description 84
• 150000002431 hydrogen Chemical class 0.000 claims description 73
• 125000003342 alkenyl group Chemical group 0.000 claims description 61
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 60
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
• 125000002252 acyl group Chemical group 0.000 claims description 50
• 125000003118 aryl group Chemical group 0.000 claims description 47
• 125000003545 alkoxy group Chemical group 0.000 claims description 46
• 229910052736 halogen Inorganic materials 0.000 claims description 45
• 150000002367 halogens Chemical class 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 41
• 125000001424 substituent group Chemical group 0.000 claims description 40
• 229910052757 nitrogen Inorganic materials 0.000 claims description 38
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 37
• 125000002947 alkylene group Chemical group 0.000 claims description 35
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
• 229910052760 oxygen Inorganic materials 0.000 claims description 33
• 150000001408 amides Chemical class 0.000 claims description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 27
• 229910052717 sulfur Inorganic materials 0.000 claims description 26
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 23
• 150000002148 esters Chemical class 0.000 claims description 23
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
• 206010027654 Allergic conditions Diseases 0.000 claims description 20
• 125000003435 aroyl group Chemical group 0.000 claims description 20
• 239000000126 substance Substances 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 17
• 125000005843 halogen group Chemical group 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 14
• 125000002950 monocyclic group Chemical group 0.000 claims description 11
• 125000002837 carbocyclic group Chemical group 0.000 claims description 10
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 7
• 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 7
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 7
• 125000002757 morpholinyl group Chemical group 0.000 claims description 7
• 125000001624 naphthyl group Chemical group 0.000 claims description 7
• 125000004193 piperazinyl group Chemical group 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
• 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 125000001188 haloalkyl group Chemical group 0.000 claims description 6
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 125000004970 halomethyl group Chemical group 0.000 claims description 5
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 3
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• VBIFOHHKLKGTEY-UHFFFAOYSA-N 1-[1-[2-hydroxy-3-[4-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]piperidin-1-yl]propyl]-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]ethanone Chemical compound C1N(C(=O)C)CCC(N(N=2)CC(O)CN3CCC(CC3)C=3SC4=CC=C(C=C4N=3)C(F)(F)F)=C1C=2C1=CC=C(C(F)(F)F)C=C1 VBIFOHHKLKGTEY-UHFFFAOYSA-N 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• NVAHQQYCEWEDKM-UHFFFAOYSA-N 5-chloro-1-methyl-3-[1-[3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]benzimidazol-2-one Chemical compound O=C1N(C)C2=CC=C(Cl)C=C2N1C(CC1)CCN1CCCN(C=1CCN(CC=11)S(C)(=O)=O)N=C1C1=CC=C(C(F)(F)F)C=C1 NVAHQQYCEWEDKM-UHFFFAOYSA-N 0.000 claims description 2
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 2
• 125000004995 haloalkylthio group Chemical group 0.000 claims description 2
• QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 claims description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
• GOLVHZSOSHXYKB-UHFFFAOYSA-N 5-chloro-1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-3h-indol-2-one Chemical compound C1N(S(=O)(=O)C)CCC(N(N=2)CC(O)CN3CCC(CC3)N3C4=CC=C(Cl)C=C4CC3=O)=C1C=2C1=CC=C(C(F)(F)F)C=C1 GOLVHZSOSHXYKB-UHFFFAOYSA-N 0.000 claims 1
• PPNRZJCYXTWNEF-UHFFFAOYSA-N 6-chloro-1-[1-[2-hydroxy-3-[5-methylsulfonyl-3-[4-(trifluoromethyl)phenyl]-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-1-yl]propyl]piperidin-4-yl]-3,4-dihydroquinazolin-2-one Chemical compound C1N(S(=O)(=O)C)CCC(N(N=2)CC(O)CN3CCC(CC3)N3C4=CC=C(Cl)C=C4CNC3=O)=C1C=2C1=CC=C(C(F)(F)F)C=C1 PPNRZJCYXTWNEF-UHFFFAOYSA-N 0.000 claims 1
• 125000004043 oxo group Chemical group O=* 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 315
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 276
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 258
• 239000000377 silicon dioxide Substances 0.000 description 135
• 235000019439 ethyl acetate Nutrition 0.000 description 128
• 239000000243 solution Substances 0.000 description 122
• 238000005481 NMR spectroscopy Methods 0.000 description 101
• 238000003756 stirring Methods 0.000 description 91
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• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 74
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 70
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
• 238000004809 thin layer chromatography Methods 0.000 description 70
• 239000002904 solvent Substances 0.000 description 63
• 230000002829 reductive effect Effects 0.000 description 59
• 239000010410 layer Substances 0.000 description 58
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
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• 238000004440 column chromatography Methods 0.000 description 39
• 239000012267 brine Substances 0.000 description 36
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
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• 108090000613 Cathepsin S Proteins 0.000 description 33
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