DE69920455T2 - Bis-indolederivate und ihre verwendung als entzündungshemmende mittel - Google Patents
Bis-indolederivate und ihre verwendung als entzündungshemmende mittel Download PDFInfo
- Publication number
- DE69920455T2 DE69920455T2 DE69920455T DE69920455T DE69920455T2 DE 69920455 T2 DE69920455 T2 DE 69920455T2 DE 69920455 T DE69920455 T DE 69920455T DE 69920455 T DE69920455 T DE 69920455T DE 69920455 T2 DE69920455 T2 DE 69920455T2
- Authority
- DE
- Germany
- Prior art keywords
- inflammatory
- compounds
- compound
- bis
- alkyl
- 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.)
- Expired - Fee Related
Links
- 230000002757 inflammatory effect Effects 0.000 title claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 49
- 230000001272 neurogenic effect Effects 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 31
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 17
- 206010061218 Inflammation Diseases 0.000 claims description 16
- 230000004054 inflammatory process Effects 0.000 claims description 16
- 208000002193 Pain Diseases 0.000 claims description 11
- 230000036407 pain Effects 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 230000002163 immunogen Effects 0.000 claims description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 230000000259 anti-tumor effect Effects 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 230000000840 anti-viral effect Effects 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 208000018937 joint inflammation Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- 206010010741 Conjunctivitis Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 150000001412 amines Chemical group 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 208000003455 anaphylaxis Diseases 0.000 claims description 2
- 230000000843 anti-fungal effect Effects 0.000 claims description 2
- 229940121375 antifungal agent Drugs 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 208000024693 gingival disease Diseases 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 201000008383 nephritis Diseases 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 206010039083 rhinitis Diseases 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000028774 intestinal disease Diseases 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
- TYGUTURXHKSOBP-UHFFFAOYSA-N 10-bromo-5,12-dihydroindolo[2,3-g]carbazole-2,3-diol Chemical class C1=C(Br)C=C2NC3=C(C4=C(C=C(C(=C4)O)O)N4)C4=CC=C3C2=C1 TYGUTURXHKSOBP-UHFFFAOYSA-N 0.000 abstract 1
- 230000000676 anti-immunogenic effect Effects 0.000 abstract 1
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 14
- 206010030113 Oedema Diseases 0.000 description 13
- 210000005069 ears Anatomy 0.000 description 10
- 239000002260 anti-inflammatory agent Substances 0.000 description 9
- 229940121363 anti-inflammatory agent Drugs 0.000 description 9
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 9
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 8
- 229960002504 capsaicin Drugs 0.000 description 7
- 235000017663 capsaicin Nutrition 0.000 description 7
- 230000028709 inflammatory response Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- DSDNAKHZNJAGHN-MXTYGGKSSA-N resiniferatoxin Chemical compound C1=C(O)C(OC)=CC(CC(=O)OCC=2C[C@]3(O)C(=O)C(C)=C[C@H]3[C@@]34[C@H](C)C[C@@]5(O[C@@](O4)(CC=4C=CC=CC=4)O[C@@H]5[C@@H]3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-MXTYGGKSSA-N 0.000 description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 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
- 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 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- IKYCZSUNGFRBJS-UHFFFAOYSA-N Euphorbia factor RL9 = U(1) = Resiniferatoxin Natural products COC1=CC(O)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 IKYCZSUNGFRBJS-UHFFFAOYSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- DSDNAKHZNJAGHN-UHFFFAOYSA-N resinferatoxin Natural products C1=C(O)C(OC)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-UHFFFAOYSA-N 0.000 description 5
- 229940073454 resiniferatoxin Drugs 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 240000001307 Myosotis scorpioides Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229960000890 hydrocortisone Drugs 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 229960000905 indomethacin Drugs 0.000 description 3
- 230000004968 inflammatory condition Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 2
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 2
- 102400000097 Neurokinin A Human genes 0.000 description 2
- 101800000399 Neurokinin A Proteins 0.000 description 2
- 108090000189 Neuropeptides Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 102400000096 Substance P Human genes 0.000 description 2
- 101800003906 Substance P Proteins 0.000 description 2
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 2
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000001640 nerve ending Anatomy 0.000 description 2
- 230000003040 nociceptive effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- TVPNFKRGOFJQOO-UHFFFAOYSA-N topsentin b1 Chemical compound C1=CC=C2C(C3=CN=C(N3)C(=O)C=3C4=CC=C(C=C4NC=3)O)=CNC2=C1 TVPNFKRGOFJQOO-UHFFFAOYSA-N 0.000 description 2
- SQTCTJUGYBKNCX-UHFFFAOYSA-N (6-hydroxy-1h-indol-3-yl)-[5-(1h-indol-2-yl)-1h-imidazol-2-yl]methanone Chemical compound C1=CC=C2NC(C=3N=C(NC=3)C(=O)C=3C4=CC=C(C=C4NC=3)O)=CC2=C1 SQTCTJUGYBKNCX-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- AUJKXAIGSXKZBR-SJORKVTESA-N 6,7-dibromo-3-[(2s,5r)-5-(6-bromo-1h-indol-3-yl)-4-methylpiperazin-2-yl]-1h-indol-4-ol Chemical compound BrC1=CC(O)=C2C([C@H]3CN([C@@H](CN3)C=3C4=CC=C(Br)C=C4NC=3)C)=CNC2=C1Br AUJKXAIGSXKZBR-SJORKVTESA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 235000002283 Capsicum annuum var aviculare Nutrition 0.000 description 1
- 235000013303 Capsicum annuum var. frutescens Nutrition 0.000 description 1
- 235000002284 Capsicum baccatum var baccatum Nutrition 0.000 description 1
- 235000002568 Capsicum frutescens Nutrition 0.000 description 1
- 208000009043 Chemical Burns Diseases 0.000 description 1
- AUJKXAIGSXKZBR-UHFFFAOYSA-N Dragmacidin Natural products BrC1=CC(O)=C2C(C3CN(C(CN3)C=3C4=CC=C(Br)C=C4NC=3)C)=CNC2=C1Br AUJKXAIGSXKZBR-UHFFFAOYSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000026816 acute arthritis Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- -1 hydrocortisone Chemical class 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000001962 neuropharmacologic effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000036575 thermal burns Effects 0.000 description 1
- ONYVJPZNVCOAFF-UHFFFAOYSA-N topsentin Natural products Oc1ccc2cc([nH]c2c1)C(=O)c3ncc([nH]3)c4c[nH]c5ccccc45 ONYVJPZNVCOAFF-UHFFFAOYSA-N 0.000 description 1
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9199198P | 1998-07-08 | 1998-07-08 | |
| US91991P | 1998-07-08 | ||
| PCT/US1999/015376 WO2000002857A1 (en) | 1998-07-08 | 1999-07-08 | Bis-indole derivatives and their use as antiinflammatory agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69920455D1 DE69920455D1 (de) | 2004-10-28 |
| DE69920455T2 true DE69920455T2 (de) | 2005-01-20 |
Family
ID=22230663
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69920455T Expired - Fee Related DE69920455T2 (de) | 1998-07-08 | 1999-07-08 | Bis-indolederivate und ihre verwendung als entzündungshemmende mittel |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US6323233B1 (https=) |
| EP (1) | EP1093455B1 (https=) |
| JP (1) | JP2002520315A (https=) |
| AT (1) | ATE277010T1 (https=) |
| CA (1) | CA2335254A1 (https=) |
| DE (1) | DE69920455T2 (https=) |
| ES (1) | ES2229736T3 (https=) |
| WO (1) | WO2000002857A1 (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6589975B2 (en) | 1998-07-08 | 2003-07-08 | The Regents Of The University Of California | Synthetic compounds for treatment of inflammation |
| WO2000002857A1 (en) * | 1998-07-08 | 2000-01-20 | Harbor Branch Oceanographic Institution, Inc. | Bis-indole derivatives and their use as antiinflammatory agents |
| WO2003022274A2 (en) | 2001-09-13 | 2003-03-20 | Synta Pharmaceuticals Corp. | 2-aroylimidazole compounds for treating cancer |
| US6800655B2 (en) * | 2002-08-20 | 2004-10-05 | Sri International | Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents |
| US7074938B2 (en) * | 2002-11-19 | 2006-07-11 | The Regents Of The University Of California | Method for the synthesis of soritin compounds |
| US7232771B2 (en) * | 2003-11-04 | 2007-06-19 | Regents Of The University Of Minnesota | Method and apparatus for depositing charge and/or nanoparticles |
| US7592269B2 (en) * | 2003-11-04 | 2009-09-22 | Regents Of The University Of Minnesota | Method and apparatus for depositing charge and/or nanoparticles |
| CA2593084C (en) | 2004-12-30 | 2014-03-18 | Bioresponse, Llc | Use of diindolylmethane-related indoles for the treatment and prevention of respiratory syncytial virus associated conditions |
| EP1893576A4 (en) * | 2005-05-27 | 2010-03-17 | Univ Kingston | TREATMENT OF PROTEIN DISORDERING |
| UA95788C2 (en) | 2005-12-15 | 2011-09-12 | Ф. Хоффманн-Ля Рош Аг | Fused pyrrole derivatives |
| BRPI0717753B1 (pt) | 2006-10-27 | 2022-04-12 | Bioresponse, Llc | Uso de uma composição compreendendo 50-250 mg de um ou mais indóis relacionados com dim e um ou mais agentes anti-protozoários, e, composição |
| US20080220175A1 (en) * | 2007-01-22 | 2008-09-11 | Lorenzo Mangolini | Nanoparticles wtih grafted organic molecules |
| CA2982162C (en) | 2015-04-10 | 2023-10-10 | Bioresponse, L.L.C. | Self-emulsifying formulations of dim-related indoles |
| CN108822116A (zh) * | 2018-06-04 | 2018-11-16 | 南京中医药大学 | 具有抗肿瘤活性的吲哚生物碱及其制备方法和应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1403617A (fr) | 1962-04-02 | 1965-06-25 | Rhone Poulenc Sa | Nouveaux dérivés de l'indole et leur préparation |
| US4866084A (en) * | 1987-07-17 | 1989-09-12 | Harbor Branch Oceanographic Institution, Inc. | Topsentin compounds effective against viruses and certain tumors |
| CA2015996C (en) * | 1989-05-05 | 2001-08-28 | Hartmut Osswald | Bis-(1h-indol-3-yl)-maleinimide derivatives and their use as pharmaceuticals |
| US4970226A (en) | 1989-10-03 | 1990-11-13 | Harbor Branch Oceanographic Institution, Inc. | Bis-indole imidazole compounds which are useful antitumor and antimicrobial agents |
| CA2046801C (en) | 1990-08-07 | 2002-02-26 | Peter D. Davis | Substituted pyrroles |
| US5290777A (en) | 1993-02-24 | 1994-03-01 | Regents Of The Univ. Of California | Use for topsentin compounds and pharmaceutical compositions containing same |
| US5955462A (en) * | 1996-10-31 | 1999-09-21 | Harbor Branch Oceanographic Institution, Inc. | Anti-neurogenic inflammatory compounds and compositions and methods of use thereof |
| EP0887348A1 (en) * | 1997-06-25 | 1998-12-30 | Boehringer Mannheim Italia S.p.A. | Bis-Indole derivatives having antimetastatic activity, a process for their preparation and pharmaceutical compositions containing them |
| WO2000002857A1 (en) * | 1998-07-08 | 2000-01-20 | Harbor Branch Oceanographic Institution, Inc. | Bis-indole derivatives and their use as antiinflammatory agents |
-
1999
- 1999-07-08 WO PCT/US1999/015376 patent/WO2000002857A1/en not_active Ceased
- 1999-07-08 US US09/349,316 patent/US6323233B1/en not_active Expired - Lifetime
- 1999-07-08 ES ES99933759T patent/ES2229736T3/es not_active Expired - Lifetime
- 1999-07-08 JP JP2000559088A patent/JP2002520315A/ja active Pending
- 1999-07-08 DE DE69920455T patent/DE69920455T2/de not_active Expired - Fee Related
- 1999-07-08 CA CA002335254A patent/CA2335254A1/en not_active Abandoned
- 1999-07-08 AT AT99933759T patent/ATE277010T1/de not_active IP Right Cessation
- 1999-07-08 EP EP99933759A patent/EP1093455B1/en not_active Expired - Lifetime
-
2001
- 2001-07-27 US US09/916,470 patent/US6444697B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US6323233B1 (en) | 2001-11-27 |
| ES2229736T3 (es) | 2005-04-16 |
| CA2335254A1 (en) | 2000-01-20 |
| EP1093455B1 (en) | 2004-09-22 |
| WO2000002857A1 (en) | 2000-01-20 |
| WO2000002857A9 (en) | 2000-07-20 |
| US6444697B2 (en) | 2002-09-03 |
| DE69920455D1 (de) | 2004-10-28 |
| EP1093455A1 (en) | 2001-04-25 |
| JP2002520315A (ja) | 2002-07-09 |
| US20010056112A1 (en) | 2001-12-27 |
| ATE277010T1 (de) | 2004-10-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0214058B1 (fr) | Composition pharmaceutique contenant des dérivés de l'histamine | |
| DE69920455T2 (de) | Bis-indolederivate und ihre verwendung als entzündungshemmende mittel | |
| DE69431568T2 (de) | Inhibierung der migration und proliferation glatter muskeln mit hydroxycarbazolverbindungen | |
| DE19814838C2 (de) | Indolyl-3-glyoxylsäure-Derivate mit Antitumorwirkung | |
| EP0527736B1 (de) | Isoxazol-4-carbonsäureamide und hydroxyalkyliden-cyanessigsäureamide, diese verbindungen enthaltende arzneimittel und deren verwendung | |
| DE69809726T2 (de) | Substituierte analoge von indol-3-carbinol und von diindolmethan als antiestrogene | |
| DE60014361T2 (de) | Zyklische aminderivate und ihre verwendung | |
| DE69813839T2 (de) | Verwendung von n,n-bis (phenylcarbamoylmethyl) dimethylammoniumchlorid und derivaten davon zur behandlung von chronischem schmerz | |
| DE3590035T1 (de) | Diphenhydramin enthaltende, analgetische und anti-inflammatorische Mittel und Verfahren zu ihrer Verwendung | |
| HUT73434A (en) | Process for preparing pharmaceutical compositions containing lamotrigine for treating aids-related neural disorders | |
| DE69409796T2 (de) | Neue verwendung bis-heterocyclische verbindungen und dessen zusammensetzungen | |
| DE4321444A1 (de) | Pharmazeutische Zubereitung | |
| DE68904462T2 (de) | 4-chinolincarbonsaeure-derivate, brauchbar zur behandlung von haut- und muco-epithelial-gewebekrankheiten. | |
| EP0752246A2 (de) | Kappa-Opiate für entzündliche Darmerkrankungen | |
| DE69727305T2 (de) | Verwendung neurogen-entzuendungshemmender verbindungen und zusammensetzungen | |
| DE19602964A1 (de) | Neue Morphinderivate, Verfahren zu deren Herstellung und deren Verwendung | |
| DE10139410A1 (de) | Verwendung von BIBN4096 in Kombination mit anderen Arzneistoffen gegen Migräne für die Behandlung von Migräne | |
| US4208417A (en) | Indole derivatives and their use as anxiolytics | |
| EP0761650A1 (de) | Thermostabile und lagerfähige Kristallmodifikation von N-Methyl-N-((1S)-1-phenyl-2-((3S)-3-hydroxypyrrolidin-1-yl)-ethyl)-2,2-diphenyl-acetamid und Verfahren zu dessen Herstellung | |
| EP0607777B1 (de) | Verwendung von Leflunomid zur Hemmung von Interleukin 8 | |
| DE69001526T2 (de) | Verwendung von Trifluormethylphenyltetrahydropyridinen zur Herstellung von Arzneimitteln zur Bekämpfung intestinaler Motilitätsstörungen. | |
| JPH0532635A (ja) | ヒスタミン誘導体の治療への応用と、新規なヒスタミン誘導体と、この誘導体の医薬としての使用 | |
| DE60318561T2 (de) | Kombinierte tumortherapie auf der basis von distamycin-acryloyl derivaten und radiotherapie | |
| DE1911467A1 (de) | Mittel zum Senken des Cholesterinspiegels | |
| WO2004087134A1 (de) | Verwendung des hydrochlorids der wirkstoffbase 1-[n2-[3,5-dibrom-n-[[4 (3,4-dihydro-2(1h)-oxochinazolin-3-yl)-1-piperidinyl]-carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazin in kombination mit sumatriptan zur behandlung von migräne |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |