ZA200407135B - 1,2-Dihydropyrazol-3-ones as cytokine mediators. - Google Patents
1,2-Dihydropyrazol-3-ones as cytokine mediators. Download PDFInfo
- Publication number
- ZA200407135B ZA200407135B ZA200407135A ZA200407135A ZA200407135B ZA 200407135 B ZA200407135 B ZA 200407135B ZA 200407135 A ZA200407135 A ZA 200407135A ZA 200407135 A ZA200407135 A ZA 200407135A ZA 200407135 B ZA200407135 B ZA 200407135B
- Authority
- ZA
- South Africa
- Prior art keywords
- fluorophenyl
- methyl
- pyrimidin
- substituted
- unsubstituted
- Prior art date
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- 102000004127 Cytokines Human genes 0.000 title claims description 21
- 108090000695 Cytokines Proteins 0.000 title claims description 21
- XBYRMPXUBGMOJC-UHFFFAOYSA-N 1,2-dihydropyrazol-3-one Chemical class OC=1C=CNN=1 XBYRMPXUBGMOJC-UHFFFAOYSA-N 0.000 title claims description 13
- -1 N-methylpiperidin-4-yl Chemical group 0.000 claims description 119
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 68
- 125000003118 aryl group Chemical group 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 52
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 26
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 13
- 230000002757 inflammatory effect Effects 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 150000001768 cations Chemical class 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 102000000589 Interleukin-1 Human genes 0.000 claims description 6
- 108010002352 Interleukin-1 Proteins 0.000 claims description 6
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- KEEBBIPAGWEDGB-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-methyl-5-(2-phenoxypyrimidin-4-yl)-1-piperidin-4-ylpyrazol-3-one Chemical compound C=1C=NC(OC=2C=CC=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(C)N1C1CCNCC1 KEEBBIPAGWEDGB-UHFFFAOYSA-N 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- 206010054094 Tumour necrosis Diseases 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 6
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 6
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 6
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 5
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 3
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims 2
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 2
- 102000004889 Interleukin-6 Human genes 0.000 claims 2
- 108090001005 Interleukin-6 Proteins 0.000 claims 2
- 102000004890 Interleukin-8 Human genes 0.000 claims 2
- 108090001007 Interleukin-8 Proteins 0.000 claims 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 2
- 229940100601 interleukin-6 Drugs 0.000 claims 2
- 229940096397 interleukin-8 Drugs 0.000 claims 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 claims 2
- NTGGMONDXPCRKJ-UHFFFAOYSA-N 1,2-diethyl-4-(4-fluorophenyl)-5-(2-phenoxypyrimidin-4-yl)pyrazol-3-one Chemical compound O=C1N(CC)N(CC)C(C=2N=C(OC=3C=CC=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 NTGGMONDXPCRKJ-UHFFFAOYSA-N 0.000 claims 1
- CKXHZVQLEHNKNW-UHFFFAOYSA-N 1,2-diethyl-5-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)pyrazol-3-one Chemical compound O=C1N(CC)N(CC)C(C=2N=C(OC=3C(=CC=CC=3)F)N=CC=2)=C1C1=CC=C(F)C=C1 CKXHZVQLEHNKNW-UHFFFAOYSA-N 0.000 claims 1
- SVFWOQLGCKIJMW-UHFFFAOYSA-N 1,2-diethyl-5-[2-(3-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)pyrazol-3-one Chemical compound O=C1N(CC)N(CC)C(C=2N=C(OC=3C=C(F)C=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 SVFWOQLGCKIJMW-UHFFFAOYSA-N 0.000 claims 1
- ARDMNBQQASYHDT-UHFFFAOYSA-N 1-[1-ethyl-3-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)piperidin-4-yl]-2-methylpyrazol-3-one Chemical compound C1N(CC)CCC(N2N(C(=O)C=C2)C)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=CC=C1F ARDMNBQQASYHDT-UHFFFAOYSA-N 0.000 claims 1
- DGOYFGDDCFWSPV-UHFFFAOYSA-N 1-[1-ethyl-3-[2-(3-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)piperidin-4-yl]-2-methylpyrazol-3-one Chemical compound C1N(CC)CCC(N2N(C(=O)C=C2)C)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=CC(F)=C1 DGOYFGDDCFWSPV-UHFFFAOYSA-N 0.000 claims 1
- LEJKVPQQDDIKBQ-UHFFFAOYSA-N 1-[1-ethyl-4-(4-fluorophenyl)-3-(2-phenoxypyrimidin-4-yl)piperidin-4-yl]-2-methylpyrazol-3-one Chemical compound C1N(CC)CCC(N2N(C(=O)C=C2)C)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=CC=C1 LEJKVPQQDDIKBQ-UHFFFAOYSA-N 0.000 claims 1
- WOTRNWQEFLBWQW-UHFFFAOYSA-N 1-[3-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1-methylpiperidin-4-yl]-2-methylpyrazol-3-one Chemical compound C1N(C)CCC(N2N(C(=O)C=C2)C)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=CC=C1F WOTRNWQEFLBWQW-UHFFFAOYSA-N 0.000 claims 1
- QPILUVCLFZLGAF-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)-1-methyl-3-(2-phenoxypyrimidin-4-yl)piperidin-4-yl]-2-methylpyrazol-3-one Chemical compound C1N(C)CCC(N2N(C(=O)C=C2)C)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=CC=C1 QPILUVCLFZLGAF-UHFFFAOYSA-N 0.000 claims 1
- BICJVQDUCPOQOI-UHFFFAOYSA-N 1-ethyl-5-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-2-piperidin-4-ylpyrazol-3-one Chemical compound O=C1N(C2CCNCC2)N(CC)C(C=2N=C(OC=3C(=CC=CC=3)F)N=CC=2)=C1C1=CC=C(F)C=C1 BICJVQDUCPOQOI-UHFFFAOYSA-N 0.000 claims 1
- UXLINVRJHSOQQZ-UHFFFAOYSA-N 1-ethyl-5-[2-(3-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-2-morpholin-4-ylpyrazol-3-one Chemical compound O=C1N(N2CCOCC2)N(CC)C(C=2N=C(OC=3C=C(F)C=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 UXLINVRJHSOQQZ-UHFFFAOYSA-N 0.000 claims 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 1
- JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 claims 1
- PWUMVFIJCBTSCC-UHFFFAOYSA-N 2-(2-methoxyethyl)-1-methylpyrazol-3-one Chemical compound CN1N(C(C=C1)=O)CCOC PWUMVFIJCBTSCC-UHFFFAOYSA-N 0.000 claims 1
- YSZAUYQMINHIAK-UHFFFAOYSA-N 2-[2-ethyl-4-(4-fluorophenyl)-5-(2-phenoxypyrimidin-4-yl)piperidin-4-yl]-1-methylpyrazol-3-one Chemical compound C1NC(CC)CC(N2C(C=CN2C)=O)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=CC=C1 YSZAUYQMINHIAK-UHFFFAOYSA-N 0.000 claims 1
- BAKNMXLKLPIGNC-UHFFFAOYSA-N 2-[2-ethyl-5-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)piperidin-4-yl]-1-methylpyrazol-3-one Chemical compound C1NC(CC)CC(N2C(C=CN2C)=O)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=CC=C1F BAKNMXLKLPIGNC-UHFFFAOYSA-N 0.000 claims 1
- UFGQKVZTIHSWCD-UHFFFAOYSA-N 2-[2-ethyl-5-[2-(4-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)piperidin-4-yl]-1-methylpyrazol-3-one Chemical compound C1NC(CC)CC(N2C(C=CN2C)=O)(C=2C=CC(F)=CC=2)C1C(N=1)=CC=NC=1OC1=CC=C(F)C=C1 UFGQKVZTIHSWCD-UHFFFAOYSA-N 0.000 claims 1
- ZKHXZVHQSPIPHR-UHFFFAOYSA-N 2-ethyl-4-(4-fluorophenyl)-1-morpholin-4-yl-5-(2-phenoxypyrimidin-4-yl)pyrazol-3-one Chemical compound C=1C=NC(OC=2C=CC=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(CC)N1N1CCOCC1 ZKHXZVHQSPIPHR-UHFFFAOYSA-N 0.000 claims 1
- MVRMQJHJLAJKSS-UHFFFAOYSA-N 2-ethyl-4-(4-fluorophenyl)-5-(2-phenoxypyrimidin-4-yl)-1-piperidin-4-ylpyrazol-3-one Chemical compound C=1C=NC(OC=2C=CC=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(CC)N1C1CCNCC1 MVRMQJHJLAJKSS-UHFFFAOYSA-N 0.000 claims 1
- BLFYLEGJPYAYPE-UHFFFAOYSA-N 2-ethyl-5-[2-(3-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1-morpholin-4-ylpyrazol-3-one Chemical compound C=1C=NC(OC=2C=C(F)C=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(CC)N1N1CCOCC1 BLFYLEGJPYAYPE-UHFFFAOYSA-N 0.000 claims 1
- GPNAVMVZNNNCSH-UHFFFAOYSA-N 2-morpholin-4-yl-1H-pyrazol-5-one Chemical compound N1(CCOCC1)N1NC(C=C1)=O GPNAVMVZNNNCSH-UHFFFAOYSA-N 0.000 claims 1
- NPAKFJPXCSLFLH-UHFFFAOYSA-N 4-(4-fluorophenyl)-1-methyl-2-morpholin-4-yl-5-(2-phenoxypyrimidin-4-yl)pyrazol-3-one Chemical compound O=C1N(N2CCOCC2)N(C)C(C=2N=C(OC=3C=CC=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 NPAKFJPXCSLFLH-UHFFFAOYSA-N 0.000 claims 1
- WXYZHFXLDSHICE-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-[2-[(2-fluorophenyl)methylamino]pyrimidin-4-yl]-2-methyl-1-piperidin-4-ylpyrazol-3-one Chemical compound C=1C=NC(NCC=2C(=CC=CC=2)F)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(C)N1C1CCNCC1 WXYZHFXLDSHICE-UHFFFAOYSA-N 0.000 claims 1
- YZFRYKYFHGNHAT-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-[2-[(3-fluorophenyl)methylamino]pyrimidin-4-yl]-2-methyl-1-morpholin-4-ylpyrazol-3-one Chemical compound C=1C=NC(NCC=2C=C(F)C=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(C)N1N1CCOCC1 YZFRYKYFHGNHAT-UHFFFAOYSA-N 0.000 claims 1
- AGSJYZLHVWDBSG-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-[2-[(3-fluorophenyl)methylamino]pyrimidin-4-yl]-2-methyl-1-piperidin-4-ylpyrazol-3-one Chemical compound C=1C=NC(NCC=2C=C(F)C=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(C)N1C1CCNCC1 AGSJYZLHVWDBSG-UHFFFAOYSA-N 0.000 claims 1
- WXULRZBGBVZBPA-UHFFFAOYSA-N 4-(4-fluorophenyl)-5-[2-[(4-fluorophenyl)methylamino]pyrimidin-4-yl]-2-methyl-1-morpholin-4-ylpyrazol-3-one Chemical compound C=1C=NC(NCC=2C=CC(F)=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(C)N1N1CCOCC1 WXULRZBGBVZBPA-UHFFFAOYSA-N 0.000 claims 1
- UYFYUGOQQJDVKH-HNNXBMFYSA-N 4-(4-fluorophenyl)-5-[2-[[(2s)-1-methoxypropan-2-yl]amino]pyrimidin-4-yl]-2-methyl-1-piperidin-4-ylpyrazol-3-one Chemical compound COC[C@H](C)NC1=NC=CC(C=2N(N(C)C(=O)C=2C=2C=CC(F)=CC=2)C2CCNCC2)=N1 UYFYUGOQQJDVKH-HNNXBMFYSA-N 0.000 claims 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
- XHHGGSDIGDNMJN-UHFFFAOYSA-N 5-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1-methyl-2-morpholin-4-ylpyrazol-3-one Chemical compound O=C1N(N2CCOCC2)N(C)C(C=2N=C(OC=3C(=CC=CC=3)F)N=CC=2)=C1C1=CC=C(F)C=C1 XHHGGSDIGDNMJN-UHFFFAOYSA-N 0.000 claims 1
- IOFVYWSYNJPJEK-UHFFFAOYSA-N 5-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1-methyl-2-piperidin-4-ylpyrazol-3-one Chemical compound O=C1N(C2CCNCC2)N(C)C(C=2N=C(OC=3C(=CC=CC=3)F)N=CC=2)=C1C1=CC=C(F)C=C1 IOFVYWSYNJPJEK-UHFFFAOYSA-N 0.000 claims 1
- GAPDQTHVUZEQRZ-UHFFFAOYSA-N 5-[2-(2-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-2-methyl-1-morpholin-4-ylpyrazol-3-one Chemical compound C=1C=NC(OC=2C(=CC=CC=2)F)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(C)N1N1CCOCC1 GAPDQTHVUZEQRZ-UHFFFAOYSA-N 0.000 claims 1
- QANCGKSEEIECSL-UHFFFAOYSA-N 5-[2-(3-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1,2-dimethylpyrazol-3-one Chemical compound O=C1N(C)N(C)C(C=2N=C(OC=3C=C(F)C=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 QANCGKSEEIECSL-UHFFFAOYSA-N 0.000 claims 1
- HYQGWURXXOINQJ-UHFFFAOYSA-N 5-[2-(3-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1-methyl-2-morpholin-4-ylpyrazol-3-one Chemical compound O=C1N(N2CCOCC2)N(C)C(C=2N=C(OC=3C=C(F)C=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 HYQGWURXXOINQJ-UHFFFAOYSA-N 0.000 claims 1
- SXWDFWUADXCIJP-UHFFFAOYSA-N 5-[2-(3-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1-methyl-2-piperidin-4-ylpyrazol-3-one Chemical compound O=C1N(C2CCNCC2)N(C)C(C=2N=C(OC=3C=C(F)C=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 SXWDFWUADXCIJP-UHFFFAOYSA-N 0.000 claims 1
- ZSULUULIZLVBCC-UHFFFAOYSA-N 5-[2-(4-fluorophenoxy)pyrimidin-4-yl]-4-(4-fluorophenyl)-1-methyl-2-morpholin-4-ylpyrazol-3-one Chemical compound O=C1N(N2CCOCC2)N(C)C(C=2N=C(OC=3C=CC(F)=CC=3)N=CC=2)=C1C1=CC=C(F)C=C1 ZSULUULIZLVBCC-UHFFFAOYSA-N 0.000 claims 1
- AFGSGDGGYZYDHK-UHFFFAOYSA-N 5-[2-(benzylamino)pyrimidin-4-yl]-4-(4-fluorophenyl)-2-methyl-1-piperidin-4-ylpyrazol-3-one Chemical compound C=1C=NC(NCC=2C=CC=CC=2)=NC=1C1=C(C=2C=CC(F)=CC=2)C(=O)N(C)N1C1CCNCC1 AFGSGDGGYZYDHK-UHFFFAOYSA-N 0.000 claims 1
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- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- FJESTSZQODSANC-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)-3-hydroxy-3-(2-methylsulfanylpyrimidin-4-yl)propanoate Chemical compound C=1C=C(F)C=CC=1C(C(=O)OC)C(O)C1=CC=NC(SC)=N1 FJESTSZQODSANC-UHFFFAOYSA-N 0.000 description 1
- AJPPKGMEHMXPMC-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)acetate Chemical compound COC(=O)CC1=CC=C(F)C=C1 AJPPKGMEHMXPMC-UHFFFAOYSA-N 0.000 description 1
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000003585 oxepinyl group Chemical group 0.000 description 1
- 125000005646 oximino group Chemical group 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- NJFIRKIBUWXWPI-UHFFFAOYSA-N tert-butyl 4-[[[2-(4-fluorophenyl)acetyl]-methylamino]-(2-methylsulfanylpyrimidine-4-carbonyl)amino]piperidine-1-carboxylate Chemical compound CSC1=NC=CC(C(=O)N(C2CCN(CC2)C(=O)OC(C)(C)C)N(C)C(=O)CC=2C=CC(F)=CC=2)=N1 NJFIRKIBUWXWPI-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US36570102P | 2002-03-19 | 2002-03-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200407135B true ZA200407135B (en) | 2005-09-21 |
Family
ID=28454704
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200407135A ZA200407135B (en) | 2002-03-19 | 2004-09-07 | 1,2-Dihydropyrazol-3-ones as cytokine mediators. |
Country Status (22)
Country | Link |
---|---|
US (1) | US6677337B2 (zh) |
EP (1) | EP1485167A1 (zh) |
JP (1) | JP2006502093A (zh) |
KR (1) | KR20040093158A (zh) |
CN (1) | CN1642600A (zh) |
AR (1) | AR039001A1 (zh) |
AU (1) | AU2003220216A1 (zh) |
BR (1) | BR0308579A (zh) |
CA (1) | CA2477091A1 (zh) |
CO (1) | CO5611175A2 (zh) |
IL (1) | IL163712A0 (zh) |
MA (1) | MA27784A1 (zh) |
MX (1) | MXPA04009088A (zh) |
MY (1) | MY134226A (zh) |
NO (1) | NO20044413L (zh) |
NZ (1) | NZ534869A (zh) |
PE (1) | PE20040160A1 (zh) |
PL (1) | PL372882A1 (zh) |
RU (1) | RU2004130843A (zh) |
TW (1) | TW200306182A (zh) |
WO (1) | WO2003080184A1 (zh) |
ZA (1) | ZA200407135B (zh) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7473695B2 (en) * | 2001-10-22 | 2009-01-06 | Mitsubishi Tanabe Pharma Corporation | 4-imidazolin-2-one compounds |
CA2497007A1 (en) * | 2002-09-09 | 2004-03-18 | Amgen Inc. | 1, 4, 5-substituted 1, 2-dihydro-pyrazol-3-one and 3-alkoxy-1h-pyrazole derivatives s tnf-alpha and interleukin lowering agents for the treatment of inflammations |
US7482356B2 (en) * | 2003-11-10 | 2009-01-27 | The Procter & Gamble Company | Bicyclic pyrazolone cytokine inhibitors |
KR20070086188A (ko) * | 2004-11-17 | 2007-08-27 | 미카나 테라퓨틱스, 인크. | 키나제 억제제 |
AU2006279794B2 (en) * | 2005-08-12 | 2011-04-07 | Synta Pharmaceuticals Corp. | Pyrazole compounds that modulate HSP90 activity |
BRPI0616630B8 (pt) * | 2005-09-30 | 2021-05-25 | Miikana Therapeutics Inc | compostos de pirazol substituídos |
JP2010529193A (ja) * | 2007-06-11 | 2010-08-26 | ミイカナ セラピューティクス インコーポレイテッド | 置換ピラゾール化合物 |
WO2018192793A1 (en) | 2017-04-20 | 2018-10-25 | Basf Se | Substituted rhodanine derivatives |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4663327A (en) * | 1984-05-23 | 1987-05-05 | Bayer Aktiengesellschaft | 1-heteroaryl-4-aryl-pyrazolin-5-ones |
US5559137A (en) * | 1994-05-16 | 1996-09-24 | Smithkline Beecham Corp. | Compounds |
EP1343781B1 (en) * | 2000-12-05 | 2008-09-03 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases |
AU2002308748A1 (en) * | 2001-05-16 | 2002-11-25 | Vertex Pharmaceuticals Incorporated | Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases |
US6566357B1 (en) * | 2001-09-20 | 2003-05-20 | The Procter & Gamble Co. | Spirocyclic-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-ones which control inflammatory cytokines |
-
2003
- 2003-03-05 US US10/382,060 patent/US6677337B2/en not_active Expired - Fee Related
- 2003-03-12 IL IL16371203A patent/IL163712A0/xx unknown
- 2003-03-12 BR BR0308579-1A patent/BR0308579A/pt not_active IP Right Cessation
- 2003-03-12 JP JP2003578007A patent/JP2006502093A/ja active Pending
- 2003-03-12 NZ NZ534869A patent/NZ534869A/en unknown
- 2003-03-12 CN CNA038062003A patent/CN1642600A/zh active Pending
- 2003-03-12 PL PL03372882A patent/PL372882A1/xx not_active Application Discontinuation
- 2003-03-12 WO PCT/US2003/007635 patent/WO2003080184A1/en active Application Filing
- 2003-03-12 KR KR10-2004-7014642A patent/KR20040093158A/ko active IP Right Grant
- 2003-03-12 EP EP03716512A patent/EP1485167A1/en not_active Withdrawn
- 2003-03-12 AU AU2003220216A patent/AU2003220216A1/en not_active Abandoned
- 2003-03-12 RU RU2004130843/04A patent/RU2004130843A/ru not_active Application Discontinuation
- 2003-03-12 MX MXPA04009088A patent/MXPA04009088A/es unknown
- 2003-03-12 CA CA002477091A patent/CA2477091A1/en not_active Abandoned
- 2003-03-14 TW TW092105683A patent/TW200306182A/zh unknown
- 2003-03-14 PE PE2003000262A patent/PE20040160A1/es not_active Application Discontinuation
- 2003-03-18 MY MYPI20030939A patent/MY134226A/en unknown
- 2003-03-18 AR ARP030100936A patent/AR039001A1/es not_active Application Discontinuation
-
2004
- 2004-09-07 ZA ZA200407135A patent/ZA200407135B/en unknown
- 2004-09-09 MA MA27850A patent/MA27784A1/fr unknown
- 2004-09-23 CO CO04094890A patent/CO5611175A2/es not_active Application Discontinuation
- 2004-10-18 NO NO20044413A patent/NO20044413L/no unknown
Also Published As
Publication number | Publication date |
---|---|
AR039001A1 (es) | 2005-02-02 |
RU2004130843A (ru) | 2005-08-27 |
US20030225082A1 (en) | 2003-12-04 |
JP2006502093A (ja) | 2006-01-19 |
EP1485167A1 (en) | 2004-12-15 |
PE20040160A1 (es) | 2004-04-30 |
US6677337B2 (en) | 2004-01-13 |
CA2477091A1 (en) | 2003-10-02 |
NZ534869A (en) | 2006-09-29 |
WO2003080184A1 (en) | 2003-10-02 |
MA27784A1 (fr) | 2006-03-01 |
CN1642600A (zh) | 2005-07-20 |
MXPA04009088A (es) | 2004-12-06 |
CO5611175A2 (es) | 2006-02-28 |
BR0308579A (pt) | 2005-01-25 |
IL163712A0 (en) | 2005-12-18 |
MY134226A (en) | 2007-11-30 |
TW200306182A (en) | 2003-11-16 |
NO20044413L (no) | 2004-10-18 |
KR20040093158A (ko) | 2004-11-04 |
PL372882A1 (en) | 2005-08-08 |
AU2003220216A1 (en) | 2003-10-08 |
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