JP2003505362A - ＩＬ−１βおよびＴＮＦ−αの抑制剤としてのアミノベンゾフェノン - Google Patents
ＩＬ−１βおよびＴＮＦ−αの抑制剤としてのアミノベンゾフェノンInfo
- Publication number
- JP2003505362A JP2003505362A JP2001511410A JP2001511410A JP2003505362A JP 2003505362 A JP2003505362 A JP 2003505362A JP 2001511410 A JP2001511410 A JP 2001511410A JP 2001511410 A JP2001511410 A JP 2001511410A JP 2003505362 A JP2003505362 A JP 2003505362A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- phenyl
- chloro
- alkyl
- phenylamino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108060008682 Tumor Necrosis Factor Proteins 0.000 title description 10
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 title description 10
- 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 description 7
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 title description 4
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 170
- -1 hydroxy, mercapto Chemical class 0.000 claims abstract description 93
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 40
- 125000001424 substituent group Chemical group 0.000 claims abstract description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
- 239000001257 hydrogen Substances 0.000 claims abstract description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 19
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 17
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
- 150000001336 alkenes Chemical group 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 239000012453 solvate Substances 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
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052717 sulfur Chemical group 0.000 claims abstract description 4
- 239000011593 sulfur Chemical group 0.000 claims abstract description 4
- 125000004429 atom Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 63
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 33
- 239000004480 active ingredient Substances 0.000 claims description 19
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 201000004624 Dermatitis Diseases 0.000 claims description 7
- 230000001684 chronic effect Effects 0.000 claims description 7
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 7
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 6
- YWXXLZKYWPWDLY-UHFFFAOYSA-N 4-[1-[[2-[3-chloro-4-(2-methylbenzoyl)anilino]phenyl]carbamoyloxy]ethoxy]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)OC(C)OC(=O)NC1=CC=CC=C1NC(C=C1Cl)=CC=C1C(=O)C1=CC=CC=C1C YWXXLZKYWPWDLY-UHFFFAOYSA-N 0.000 claims description 6
- JJSSWJLJQKHANC-UHFFFAOYSA-N 4-[[5-bromo-2-[3-chloro-4-(2-methylbenzoyl)anilino]phenyl]carbamoyloxymethoxy]-4-oxobutanoic acid Chemical compound CC1=CC=CC=C1C(=O)C(C(=C1)Cl)=CC=C1NC1=CC=C(Br)C=C1NC(=O)OCOC(=O)CCC(O)=O JJSSWJLJQKHANC-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 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 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 5
- 108010003541 Platelet Activating Factor Proteins 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- 208000030507 AIDS Diseases 0.000 claims description 4
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 201000005569 Gout Diseases 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 206010000496 acne Diseases 0.000 claims description 4
- 230000007815 allergy Effects 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 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
- 239000003814 drug Substances 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 201000005671 spondyloarthropathy Diseases 0.000 claims description 4
- 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 3
- AJZDHLHTTJRNQJ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(tetrazol-1-yl)ethyl]benzamide Chemical compound N1(N=NN=C1)CCNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O AJZDHLHTTJRNQJ-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 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
- 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
- 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 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 206010046851 Uveitis Diseases 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
- 239000005557 antagonist Substances 0.000 claims description 3
- 239000003529 anticholesteremic agent Substances 0.000 claims description 3
- 229940127226 anticholesterol agent Drugs 0.000 claims description 3
- 229940125715 antihistaminic agent Drugs 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 3
- 239000000812 cholinergic antagonist Substances 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000003862 glucocorticoid Substances 0.000 claims description 3
- 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 3
- 229960000905 indomethacin Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229960002009 naproxen Drugs 0.000 claims description 3
- 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 3
- 229960001639 penicillamine Drugs 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 150000003751 zinc Chemical class 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- 239000000808 adrenergic beta-agonist Substances 0.000 claims description 2
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 150000002343 gold Chemical class 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003873 salicylate salts Chemical class 0.000 claims description 2
- 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 description 2
- 229960001940 sulfasalazine Drugs 0.000 claims description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 241001024304 Mino Species 0.000 claims 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims 1
- 229930003316 Vitamin D Natural products 0.000 claims 1
- 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 1
- 230000003213 activating effect Effects 0.000 claims 1
- 239000000464 adrenergic agent Substances 0.000 claims 1
- 229940067594 flufenamate Drugs 0.000 claims 1
- 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 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 150000004492 retinoid derivatives Chemical class 0.000 claims 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims 1
- 229960001860 salicylate Drugs 0.000 claims 1
- SDKPSXWGRWWLKR-UHFFFAOYSA-M sodium;9,10-dioxoanthracene-1-sulfonate Chemical compound [Na+].O=C1C2=CC=CC=C2C(=O)C2=C1C=CC=C2S(=O)(=O)[O-] SDKPSXWGRWWLKR-UHFFFAOYSA-M 0.000 claims 1
- 235000019166 vitamin D Nutrition 0.000 claims 1
- 239000011710 vitamin D Substances 0.000 claims 1
- 150000003710 vitamin D derivatives Chemical class 0.000 claims 1
- 229940046008 vitamin d Drugs 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 abstract description 4
- 239000004215 Carbon black (E152) Substances 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 3
- 125000003282 alkyl amino group Chemical group 0.000 abstract 2
- 125000004414 alkyl thio group Chemical group 0.000 abstract 2
- 239000007858 starting material Substances 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 32
- 239000000203 mixture Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- 238000004587 chromatography analysis Methods 0.000 description 22
- 238000009472 formulation Methods 0.000 description 20
- 238000000746 purification Methods 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 238000005859 coupling reaction Methods 0.000 description 18
- 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 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 16
- 238000002425 crystallisation Methods 0.000 description 16
- 230000008025 crystallization Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 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
- 238000002360 preparation method Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 239000003480 eluent Substances 0.000 description 14
- WXUAQHNMJWJLTG-VKHMYHEASA-N (S)-methylsuccinic acid Chemical compound OC(=O)[C@@H](C)CC(O)=O WXUAQHNMJWJLTG-VKHMYHEASA-N 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZFQCRLNKHHXELH-UHFFFAOYSA-N cyclopentyl carbonochloridate Chemical compound ClC(=O)OC1CCCC1 ZFQCRLNKHHXELH-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 10
- 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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 125000000524 functional group Chemical group 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
- 230000008878 coupling Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
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Classifications
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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
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- 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
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- 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
-
- 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
-
- 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
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Landscapes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Cardiology (AREA)
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- 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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14406399P | 1999-07-16 | 1999-07-16 | |
| US60/144,063 | 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 (2)
| Publication Number | Publication Date |
|---|---|
| JP2003505362A true JP2003505362A (ja) | 2003-02-12 |
| JP2003505362A5 JP2003505362A5 (enExample) | 2007-09-06 |
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| JP2001511410A Pending JP2003505362A (ja) | 1999-07-16 | 2000-07-11 | ＩＬ−１βおよびＴＮＦ−αの抑制剤としてのアミノベンゾフェノン |
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| 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) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011529885A (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 | アジド組成物並びにその製造及び使用方法 |
Families Citing this family (18)
| 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 |
| 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 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1998032730A1 (en) * | 1997-01-24 | 1998-07-30 | Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) | Aminobenzophenones as inhibitors of interleukin and tnf |
Family Cites Families (2)
| 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 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998032730A1 (en) * | 1997-01-24 | 1998-07-30 | Leo Pharmaceutical Products Ltd. A/S (Løvens Kemiske Fabrik Produktionsaktieselskab) | Aminobenzophenones as inhibitors of interleukin and tnf |
| JP2001511771A (ja) * | 1997-01-24 | 2001-08-14 | レオ・ファーマシューティカル・プロダクツ・リミテッド・アクティーゼルスカブ（レーベンス・ケミスケ・ファブリック・プロデュクチオンスアクティーゼルスカブ） | インターロイキンおよびｔｎｆの阻害剤としてのアミノベンゾフェノン類 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011529885A (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 | アジド組成物並びにその製造及び使用方法 |
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 |
| HUP0201911A3 (en) | 2002-11-28 |
| HK1048303A1 (zh) | 2003-03-28 |
| EP1202959A1 (en) | 2002-05-08 |
| CA2379286A1 (en) | 2001-01-25 |
| NZ516825A (en) | 2004-05-28 |
| ATE277897T1 (de) | 2004-10-15 |
| RU2240995C2 (ru) | 2004-11-27 |
| PL353646A1 (en) | 2003-12-01 |
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