TW200300692A - Method for treating or preventing inflammatory diseases - Google Patents
Method for treating or preventing inflammatory diseases Download PDFInfo
- Publication number
- TW200300692A TW200300692A TW091132682A TW91132682A TW200300692A TW 200300692 A TW200300692 A TW 200300692A TW 091132682 A TW091132682 A TW 091132682A TW 91132682 A TW91132682 A TW 91132682A TW 200300692 A TW200300692 A TW 200300692A
- Authority
- TW
- Taiwan
- Prior art keywords
- tetraphosphate
- triphosphate
- group
- alkyl
- urine
- Prior art date
Links
- 208000027866 inflammatory disease Diseases 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title abstract description 37
- 239000001226 triphosphate Substances 0.000 claims abstract description 82
- -1 nucleoside diphosphate Chemical class 0.000 claims abstract description 80
- 235000011178 triphosphate Nutrition 0.000 claims abstract description 73
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 33
- 239000000018 receptor agonist Substances 0.000 claims abstract description 22
- 229940044601 receptor agonist Drugs 0.000 claims abstract description 22
- 229920000388 Polyphosphate Polymers 0.000 claims abstract description 20
- 239000001205 polyphosphate Substances 0.000 claims abstract description 20
- 235000011176 polyphosphates Nutrition 0.000 claims abstract description 20
- 239000001177 diphosphate Substances 0.000 claims abstract description 18
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 16
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 15
- 239000002777 nucleoside Substances 0.000 claims abstract description 15
- 208000015181 infectious disease Diseases 0.000 claims abstract description 14
- 206010039083 rhinitis Diseases 0.000 claims abstract description 14
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 13
- 206010039094 Rhinitis perennial Diseases 0.000 claims abstract description 13
- 235000011180 diphosphates Nutrition 0.000 claims abstract description 13
- 208000022719 perennial allergic rhinitis Diseases 0.000 claims abstract description 13
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims abstract description 11
- 208000002205 allergic conjunctivitis Diseases 0.000 claims abstract description 11
- 208000024998 atopic conjunctivitis Diseases 0.000 claims abstract description 11
- 201000004624 Dermatitis Diseases 0.000 claims abstract description 9
- 208000006673 asthma Diseases 0.000 claims abstract description 7
- 230000002458 infectious effect Effects 0.000 claims abstract description 6
- 201000009890 sinusitis Diseases 0.000 claims abstract description 6
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims abstract description 4
- 208000029147 Collagen-vascular disease Diseases 0.000 claims abstract description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 4
- 208000036284 Rhinitis seasonal Diseases 0.000 claims abstract description 3
- 208000017022 seasonal allergic rhinitis Diseases 0.000 claims abstract description 3
- YDHWWBZFRZWVHO-UHFFFAOYSA-H [oxido-[oxido(phosphonatooxy)phosphoryl]oxyphosphoryl] phosphate Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O YDHWWBZFRZWVHO-UHFFFAOYSA-H 0.000 claims description 73
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 71
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 69
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 210000002700 urine Anatomy 0.000 claims description 55
- 150000001875 compounds Chemical class 0.000 claims description 51
- 206010020751 Hypersensitivity Diseases 0.000 claims description 41
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 37
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 37
- 229940045145 uridine Drugs 0.000 claims description 37
- 150000001412 amines Chemical class 0.000 claims description 36
- 230000002485 urinary effect Effects 0.000 claims description 35
- 239000002253 acid Substances 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 30
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 28
- 206010061218 Inflammation Diseases 0.000 claims description 23
- 230000007815 allergy Effects 0.000 claims description 23
- 230000004054 inflammatory process Effects 0.000 claims description 23
- 125000005110 aryl thio group Chemical class 0.000 claims description 22
- 125000004104 aryloxy group Chemical group 0.000 claims description 19
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 claims description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000004659 aryl alkyl thio group Chemical class 0.000 claims description 18
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 208000024891 symptom Diseases 0.000 claims description 18
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 17
- 125000004414 alkyl thio group Chemical class 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 102000002298 Purinergic P2Y Receptors Human genes 0.000 claims description 15
- 108010000818 Purinergic P2Y Receptors Proteins 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 15
- 208000026935 allergic disease Diseases 0.000 claims description 14
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 claims description 14
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
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- 239000002245 particle Substances 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 claims description 9
- 229940104302 cytosine Drugs 0.000 claims description 9
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 230000000172 allergic effect Effects 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 210000003205 muscle Anatomy 0.000 claims description 8
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- 235000019640 taste Nutrition 0.000 claims description 8
- 239000005977 Ethylene Substances 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 150000001540 azides Chemical group 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 229960001428 mercaptopurine Drugs 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 6
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 6
- 239000006071 cream Substances 0.000 claims description 6
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 claims description 6
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 5
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 5
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
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- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- FCZOVUJWOBSMSS-UHFFFAOYSA-N 5-[(6-aminopurin-9-yl)methyl]-5-methyl-3-methylideneoxolan-2-one Chemical compound C1=NC2=C(N)N=CN=C2N1CC1(C)CC(=C)C(=O)O1 FCZOVUJWOBSMSS-UHFFFAOYSA-N 0.000 claims description 4
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- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 4
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- QTPILKSJIOLICA-UHFFFAOYSA-N bis[hydroxy(phosphonooxy)phosphoryl] hydrogen phosphate Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(O)=O QTPILKSJIOLICA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- SFYLVTNFLRJWTA-UHFFFAOYSA-N fluoren-1-imine Chemical compound C1=CC=C2C3=CC=CC(=N)C3=CC2=C1 SFYLVTNFLRJWTA-UHFFFAOYSA-N 0.000 claims description 4
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- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 3
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Landscapes
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| US20060177517A1 (en) * | 2003-02-26 | 2006-08-10 | Toshikazu Shiba | Antiinflammtory agent and antiinflammatory medical material |
| GB0417886D0 (en) * | 2004-08-11 | 2004-09-15 | Univ Cardiff | Method and means for enhanced pulmonary delivery |
| SE529064C2 (sv) * | 2005-01-03 | 2007-04-24 | Selectica Pharmaceuticals Ab | Topiska kompositioner |
| GB0502250D0 (en) * | 2005-02-03 | 2005-03-09 | Ic Vec Ltd | Use |
| WO2007041495A2 (en) * | 2005-09-29 | 2007-04-12 | University Of California, San Diego | Dampening humoral and innate immunity by inhibition of ppgalnact-1 |
| US8618074B2 (en) * | 2007-03-15 | 2013-12-31 | Board Of Regents Of The University Of Texas System | GPCR enhanced neuroprotection to treat brain injury |
| US8168597B2 (en) * | 2008-10-22 | 2012-05-01 | Inspire Pharmaceuticals, Inc. | Method for treating cystic fibrosis |
| GB201209244D0 (en) * | 2012-05-25 | 2012-07-04 | Globalacorn Ltd | Compositions |
| US10111904B2 (en) * | 2013-01-09 | 2018-10-30 | Berlock Aps | Micron-sized gold, kit comprising said gold and its use as a non-toxic immune suppressor |
| US20150031712A1 (en) * | 2013-03-12 | 2015-01-29 | Moshe Rogosnitzky | Therapeutic Compositions Containing Dipyridamole and Treatment Packs Including Such Compositions and Methods for Producing Same |
| GB201320962D0 (en) * | 2013-11-27 | 2014-01-08 | Globalacorn Ltd | Compositions |
| GB201320959D0 (en) * | 2013-11-27 | 2014-01-08 | Globalacorn Ltd | Compositions |
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| US6255059B1 (en) | 1993-03-31 | 2001-07-03 | Cadus Pharmaceutical Corporation | Methods for identifying G protein coupled receptor effectors |
| US5656256A (en) | 1994-12-14 | 1997-08-12 | The University Of North Carolina At Chapel Hill | Methods of treating lung disease by an aerosol containing benzamil or phenamil |
| US6147056A (en) * | 1995-06-06 | 2000-11-14 | Trustees Of Boston University | Use of locally applied DNA fragments |
| US5635160A (en) | 1995-06-07 | 1997-06-03 | The University Of North Carolina At Chapel Hill | Dinucleotides useful for the treatment of cystic fibrosis and for hydrating mucus secretions |
| US5628984A (en) | 1995-07-31 | 1997-05-13 | University Of North Carolina At Chapel Hill | Method of detecting lung disease |
| US6423694B1 (en) | 1996-02-21 | 2002-07-23 | Inspire Pharmaceuticals, Inc. | Method of treating otitis media with uridine triphosphates and related compounds |
| US5900407A (en) | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
| AU727314B2 (en) | 1996-03-27 | 2000-12-07 | Inspire Pharmaceuticals, Inc. | Method of treating ciliary dyskinesia with uridine triphosphates and related compounds |
| US5837861A (en) | 1997-02-10 | 1998-11-17 | Inspire Pharmaceuticals, Inc. | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
| US5789391A (en) | 1996-07-03 | 1998-08-04 | Inspire Pharmaceuticals, Inc. | Method of treating sinusitis with uridine triphosphates and related compounds |
| US5968913A (en) | 1996-07-03 | 1999-10-19 | Inspire Pharmaceuticals, Inc. | Pharmaceutical compositions of uridine triphosphate |
| US5763447C1 (en) | 1996-07-23 | 2002-05-07 | Inspire Pharmaceuticals | Method of preventing or treating pneumonia in immobilized patients with uridine triphosphates and related compounds |
| WO1998015835A1 (en) | 1996-10-08 | 1998-04-16 | Inspire Pharmaceuticals, Inc. | Method of early lung cancer detection via sputum induction and analysis of sputum to detect cancer associated substances |
| EP0929218A4 (en) * | 1996-10-30 | 2001-05-16 | Univ North Carolina | P2Y RECEPTOR ANTAGONISTS |
| US6159952A (en) | 1996-11-07 | 2000-12-12 | Inspire Pharmaceuticals, Inc. | Method of treating bronchitis with uridine triphosphate and related compounds |
| ES2264197T3 (es) * | 1997-02-06 | 2006-12-16 | Inspire Pharmaceuticals, Inc. | Dinucleotidos y sus usos. |
| US6372724B1 (en) * | 1997-03-25 | 2002-04-16 | Duska Scientific Co. | Modulation of human mast cell activation |
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| US6143279A (en) * | 1997-08-29 | 2000-11-07 | The University Of North Carolina At Chapel Hill | Uridine 5'-diphosphate and analogs useful for treating lung diseases |
| JP4633927B2 (ja) * | 1998-05-22 | 2011-02-16 | インスパイアー ファーマシューティカルズ,インコーポレイティド | 治療用ジヌクレオチドおよび誘導体 |
| US6264975B1 (en) * | 1998-10-20 | 2001-07-24 | The University Of North Carolina At Chapel Hill | Methods of hydrating mucosal surfaces |
| WO2000050024A2 (en) * | 1999-02-26 | 2000-08-31 | Inspire Pharmaceuticals, Inc. | Method of promoting mucosal hydration with certain uridine, adenine and cytidine diphosphates and analogs thereof |
| CN1413113A (zh) * | 1999-12-22 | 2003-04-23 | 印斯拜尔药品股份有限公司 | 使用嘌呤能受体激动剂治疗胃肠道疾病的方法 |
| US6610274B1 (en) * | 2000-12-22 | 2003-08-26 | Wallace J. Gardner | Anti-inflammatory composition comprising tetracycline |
| EP1432426A2 (en) * | 2001-09-05 | 2004-06-30 | ACTIAL Farmaceutica Lda. | USE OF UNMETHYLATED CpG |
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| US20030125299A1 (en) | 2003-07-03 |
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