NZ516825A - Aminobenzophenones as inhibitors of IL-1beta and TNF-alpha - Google Patents
Aminobenzophenones as inhibitors of IL-1beta and TNF-alpha Download PDFInfo
- Publication number
- NZ516825A NZ516825A NZ516825A NZ51682500A NZ516825A NZ 516825 A NZ516825 A NZ 516825A NZ 516825 A NZ516825 A NZ 516825A NZ 51682500 A NZ51682500 A NZ 51682500A NZ 516825 A NZ516825 A NZ 516825A
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- NZ
- New Zealand
- Prior art keywords
- compound
- phenyl
- alkyl
- chloro
- carbamate
- Prior art date
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- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 title 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 title 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 175
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 92
- -1 (C1-C3alkoxycarbonyl Chemical group 0.000 claims abstract description 86
- 125000001424 substituent group Chemical group 0.000 claims abstract description 47
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 27
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 25
- 150000002367 halogens Chemical class 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 25
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 17
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 16
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 15
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 9
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims abstract description 7
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 7
- 230000001684 chronic effect Effects 0.000 claims abstract description 7
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 5
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 5
- 208000030507 AIDS Diseases 0.000 claims abstract description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 4
- 201000005569 Gout Diseases 0.000 claims abstract description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 4
- 206010040070 Septic Shock Diseases 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000005864 Sulphur Chemical group 0.000 claims abstract description 4
- 208000026935 allergic disease Diseases 0.000 claims abstract description 4
- 230000007815 allergy Effects 0.000 claims abstract description 4
- 206010003246 arthritis Diseases 0.000 claims abstract description 4
- 230000002062 proliferating effect Effects 0.000 claims abstract description 4
- 230000036303 septic shock Effects 0.000 claims abstract description 4
- 208000017520 skin disease Diseases 0.000 claims abstract description 4
- RTAPDZBZLSXHQQ-UHFFFAOYSA-N 8-methyl-3,7-dihydropurine-2,6-dione Chemical class N1C(=O)NC(=O)C2=C1N=C(C)N2 RTAPDZBZLSXHQQ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 3
- 229930003316 Vitamin D Natural products 0.000 claims abstract description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims abstract description 3
- 239000005557 antagonist Substances 0.000 claims abstract description 3
- 230000001387 anti-histamine Effects 0.000 claims abstract description 3
- 229940125715 antihistaminic agent Drugs 0.000 claims abstract description 3
- 239000000739 antihistaminic agent Substances 0.000 claims abstract description 3
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims abstract description 3
- 235000019166 vitamin D Nutrition 0.000 claims abstract description 3
- 239000011710 vitamin D Substances 0.000 claims abstract description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 claims abstract description 3
- 229940046008 vitamin d Drugs 0.000 claims abstract description 3
- 150000003751 zinc Chemical class 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 94
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 20
- 239000004480 active ingredient Substances 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 claims description 4
- 108010003541 Platelet Activating Factor Proteins 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 150000001925 cycloalkenes Chemical group 0.000 claims description 4
- 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 4
- 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 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 claims description 3
- IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 3
- POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 claims description 3
- 208000007156 Spondylarthritis Diseases 0.000 claims description 3
- 201000002661 Spondylitis Diseases 0.000 claims description 3
- 206010046851 Uveitis Diseases 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 claims description 3
- 201000008937 atopic dermatitis Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 claims description 2
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 2
- SQVNITZYWXMWOG-UHFFFAOYSA-N 2-cyclohexyl-1-(2-methylquinolin-4-yl)-3-(1,3-thiazol-2-yl)guanidine Chemical compound C=12C=CC=CC2=NC(C)=CC=1NC(=NC1CCCCC1)NC1=NC=CS1 SQVNITZYWXMWOG-UHFFFAOYSA-N 0.000 claims description 2
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 2
- 206010000496 acne Diseases 0.000 claims description 2
- 239000000464 adrenergic agent Substances 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 229940067594 flufenamate Drugs 0.000 claims description 2
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003862 glucocorticoid Substances 0.000 claims description 2
- 150000002343 gold Chemical class 0.000 claims description 2
- 229960000905 indomethacin Drugs 0.000 claims description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 2
- 229960002009 naproxen Drugs 0.000 claims description 2
- 229960001639 penicillamine Drugs 0.000 claims description 2
- 150000003873 salicylate salts Chemical class 0.000 claims description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 claims description 2
- 229950006828 timegadine Drugs 0.000 claims description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 6
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims 1
- MMOXZBCLCQITDF-UHFFFAOYSA-N N,N-diethyl-m-toluamide Chemical compound CCN(CC)C(=O)C1=CC=CC(C)=C1 MMOXZBCLCQITDF-UHFFFAOYSA-N 0.000 claims 1
- 238000009775 high-speed stirring Methods 0.000 claims 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003529 anticholesteremic agent Substances 0.000 abstract 1
- 229940127226 anticholesterol agent Drugs 0.000 abstract 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 abstract 1
- 239000010931 gold Substances 0.000 abstract 1
- 229910052737 gold Inorganic materials 0.000 abstract 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 abstract 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 abstract 1
- 238000000034 method Methods 0.000 description 66
- 239000007858 starting material Substances 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 29
- 238000000746 purification Methods 0.000 description 27
- 238000009472 formulation Methods 0.000 description 21
- 238000005859 coupling reaction Methods 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 18
- 125000001246 bromo group Chemical group Br* 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 238000002425 crystallisation Methods 0.000 description 16
- 230000008025 crystallization Effects 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- ZFQCRLNKHHXELH-UHFFFAOYSA-N cyclopentyl carbonochloridate Chemical compound ClC(=O)OC1CCCC1 ZFQCRLNKHHXELH-UHFFFAOYSA-N 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- WXUAQHNMJWJLTG-VKHMYHEASA-N (S)-methylsuccinic acid Chemical compound OC(=O)[C@@H](C)CC(O)=O WXUAQHNMJWJLTG-VKHMYHEASA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- MSXZXFPYTVQJIL-UHFFFAOYSA-N [4-(2-aminoanilino)-2-chlorophenyl]-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)C(C(=C1)Cl)=CC=C1NC1=CC=CC=C1N MSXZXFPYTVQJIL-UHFFFAOYSA-N 0.000 description 7
- AOGYCOYQMAVAFD-UHFFFAOYSA-M carbonochloridate Chemical compound [O-]C(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-M 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- JURXNAXIOWTHFP-UHFFFAOYSA-M silver;4-methoxy-4-oxobutanoate Chemical compound [Ag+].COC(=O)CCC([O-])=O JURXNAXIOWTHFP-UHFFFAOYSA-M 0.000 description 5
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- INSOCLAQJMTMEO-UHFFFAOYSA-N (4-nitrophenoxy)carbonyloxymethyl hexanoate Chemical compound CCCCCC(=O)OCOC(=O)OC1=CC=C([N+]([O-])=O)C=C1 INSOCLAQJMTMEO-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 201000004624 Dermatitis Diseases 0.000 description 4
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/32—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C271/38—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
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- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
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- Pain & Pain Management (AREA)
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- Urology & Nephrology (AREA)
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- Molecular Biology (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- AIDS & HIV (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14406399P | 1999-07-16 | 1999-07-16 | |
| PCT/DK2000/000386 WO2001005749A1 (en) | 1999-07-16 | 2000-07-11 | AMINOBENZOPHENONES AS INHIBITORS OF IL-1β AND TNF-$g(a) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ516825A true NZ516825A (en) | 2004-05-28 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ516825A NZ516825A (en) | 1999-07-16 | 2000-07-11 | Aminobenzophenones as inhibitors of IL-1beta and TNF-alpha |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP1202959B1 (enExample) |
| JP (1) | JP2003505362A (enExample) |
| KR (1) | KR20020022774A (enExample) |
| CN (1) | CN1167667C (enExample) |
| AT (1) | ATE277897T1 (enExample) |
| AU (1) | AU768512B2 (enExample) |
| CA (1) | CA2379286A1 (enExample) |
| DE (1) | DE60014394T2 (enExample) |
| ES (1) | ES2230118T3 (enExample) |
| HU (1) | HUP0201911A3 (enExample) |
| NZ (1) | NZ516825A (enExample) |
| PL (1) | PL353646A1 (enExample) |
| PT (1) | PT1202959E (enExample) |
| RU (1) | RU2240995C2 (enExample) |
| WO (1) | WO2001005749A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2270194C2 (ru) | 2000-05-22 | 2006-02-20 | Лео Фарма А/С | Бензофеноны как ингибиторы il-1бета и tnf-альфа, фармацевтическая композиция и способ лечения |
| US7232924B2 (en) | 2001-06-11 | 2007-06-19 | Xenoport, Inc. | Methods for synthesis of acyloxyalkyl derivatives of GABA analogs |
| US8048917B2 (en) | 2005-04-06 | 2011-11-01 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US7186855B2 (en) | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US6818787B2 (en) | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| KR100896667B1 (ko) * | 2001-08-28 | 2009-05-14 | 레오 파마 에이/에스 | 신규한 아미노벤조페논 및 이를 포함하는 약제학적 조성물 |
| US20030225089A1 (en) * | 2002-04-10 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and p38 kinase inhibitors |
| DE60310730T2 (de) | 2002-07-09 | 2007-05-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmazeutische zusammensetzungen aus anticholinergica und p38 kinase hemmern zur behandlung von erkrankungen der atemwege |
| AU2003262911A1 (en) | 2002-08-29 | 2004-03-19 | Scios Inc. | Methods of promoting osteogenesis |
| PL377377A1 (pl) * | 2002-12-20 | 2006-02-06 | Leo Pharma A/S | Nowe związki aminobenzofenonu |
| ZA200510137B (en) | 2003-07-24 | 2007-04-25 | Leo Pharma As | Novel aminobenzophenone compounds |
| US7244441B2 (en) | 2003-09-25 | 2007-07-17 | Scios, Inc. | Stents and intra-luminal prostheses containing map kinase inhibitors |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| JP5015005B2 (ja) | 2004-12-13 | 2012-08-29 | レオ ファーマ アクティーゼルスカブ | トリアゾール置換アミノベンゾフェノン化合物 |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| WO2010014276A1 (en) * | 2008-07-31 | 2010-02-04 | 3M Innovative Properties Company | Azide compositions and methods of making and using thereof |
| JP2011529977A (ja) | 2008-07-31 | 2011-12-15 | スリーエム イノベイティブ プロパティズ カンパニー | フルオロポリマー組成物並びにその製造及び使用方法 |
| EP2206534A1 (de) | 2008-10-09 | 2010-07-14 | c-a-i-r biosciences GmbH | Dibenzocycloheptanonderivate und pharmazeutische Mittel, welche diese Verbindungen enthalten |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1535401A (en) * | 1977-07-28 | 1978-12-13 | Holliday & Co Ltd L | Nitrodiphenylamine carboxylic acid disperse dyes |
| JPH0776303B2 (ja) * | 1986-11-21 | 1995-08-16 | 株式会社リコー | 呈色性フタリド化合物及びその製造法及びこのものを発色成分とした記録材料 |
| GB9701453D0 (en) * | 1997-01-24 | 1997-03-12 | Leo Pharm Prod Ltd | Aminobenzophenones |
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2000
- 2000-07-11 NZ NZ516825A patent/NZ516825A/en unknown
- 2000-07-11 PT PT00943700T patent/PT1202959E/pt unknown
- 2000-07-11 CN CNB008121516A patent/CN1167667C/zh not_active Expired - Fee Related
- 2000-07-11 PL PL00353646A patent/PL353646A1/xx not_active Application Discontinuation
- 2000-07-11 HU HU0201911A patent/HUP0201911A3/hu unknown
- 2000-07-11 AU AU58069/00A patent/AU768512B2/en not_active Ceased
- 2000-07-11 RU RU2002103876/04A patent/RU2240995C2/ru not_active IP Right Cessation
- 2000-07-11 AT AT00943700T patent/ATE277897T1/de not_active IP Right Cessation
- 2000-07-11 KR KR1020027000619A patent/KR20020022774A/ko not_active Ceased
- 2000-07-11 DE DE60014394T patent/DE60014394T2/de not_active Expired - Fee Related
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- 2000-07-11 EP EP00943700A patent/EP1202959B1/en not_active Expired - Lifetime
- 2000-07-11 CA CA002379286A patent/CA2379286A1/en not_active Abandoned
- 2000-07-11 ES ES00943700T patent/ES2230118T3/es not_active Expired - Lifetime
- 2000-07-11 JP JP2001511410A patent/JP2003505362A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| KR20020022774A (ko) | 2002-03-27 |
| ES2230118T3 (es) | 2005-05-01 |
| CN1167667C (zh) | 2004-09-22 |
| AU5806900A (en) | 2001-02-05 |
| WO2001005749A1 (en) | 2001-01-25 |
| DE60014394D1 (de) | 2004-11-04 |
| PT1202959E (pt) | 2005-01-31 |
| EP1202959B1 (en) | 2004-09-29 |
| HUP0201911A2 (en) | 2002-10-28 |
| DE60014394T2 (de) | 2005-12-22 |
| CN1371359A (zh) | 2002-09-25 |
| AU768512B2 (en) | 2003-12-18 |
| JP2003505362A (ja) | 2003-02-12 |
| HUP0201911A3 (en) | 2002-11-28 |
| HK1048303A1 (zh) | 2003-03-28 |
| EP1202959A1 (en) | 2002-05-08 |
| CA2379286A1 (en) | 2001-01-25 |
| ATE277897T1 (de) | 2004-10-15 |
| RU2240995C2 (ru) | 2004-11-27 |
| PL353646A1 (en) | 2003-12-01 |
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| RENW | Renewal (renewal fees accepted) |