CA2465894A1 - Method for treating or preventing inflammatory diseases - Google Patents
Method for treating or preventing inflammatory diseases Download PDFInfo
- Publication number
- CA2465894A1 CA2465894A1 CA002465894A CA2465894A CA2465894A1 CA 2465894 A1 CA2465894 A1 CA 2465894A1 CA 002465894 A CA002465894 A CA 002465894A CA 2465894 A CA2465894 A CA 2465894A CA 2465894 A1 CA2465894 A1 CA 2465894A1
- Authority
- CA
- Canada
- Prior art keywords
- uridine
- tetraphosphate
- triphosphate
- alkyl
- amino
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 54
- 208000027866 inflammatory disease Diseases 0.000 title claims description 23
- -1 nucleoside diphosphate Chemical class 0.000 claims abstract description 87
- 239000001226 triphosphate Substances 0.000 claims abstract description 69
- 235000011178 triphosphate Nutrition 0.000 claims abstract description 69
- 239000002773 nucleotide Substances 0.000 claims abstract description 27
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 27
- 229920000388 Polyphosphate Polymers 0.000 claims abstract description 24
- 239000001205 polyphosphate Substances 0.000 claims abstract description 24
- 235000011176 polyphosphates Nutrition 0.000 claims abstract description 24
- 239000002777 nucleoside Substances 0.000 claims abstract description 23
- 239000000018 receptor agonist Substances 0.000 claims abstract description 22
- 229940044601 receptor agonist Drugs 0.000 claims abstract description 22
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 20
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 16
- 206010039094 Rhinitis perennial Diseases 0.000 claims abstract description 16
- 208000022719 perennial allergic rhinitis Diseases 0.000 claims abstract description 16
- 208000015181 infectious disease Diseases 0.000 claims abstract description 13
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims abstract description 12
- 208000002205 allergic conjunctivitis Diseases 0.000 claims abstract description 12
- 239000001177 diphosphate Substances 0.000 claims abstract description 12
- 208000024998 atopic conjunctivitis Diseases 0.000 claims abstract description 11
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 11
- 201000004624 Dermatitis Diseases 0.000 claims abstract description 9
- 235000011180 diphosphates Nutrition 0.000 claims abstract description 9
- 206010039083 rhinitis Diseases 0.000 claims abstract description 9
- 201000009890 sinusitis Diseases 0.000 claims abstract description 7
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims abstract description 5
- 206010010741 Conjunctivitis Diseases 0.000 claims abstract description 5
- 230000002458 infectious effect Effects 0.000 claims abstract description 5
- 208000029147 Collagen-vascular disease Diseases 0.000 claims abstract description 4
- 206010018364 Glomerulonephritis 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 4
- 208000017022 seasonal allergic rhinitis Diseases 0.000 claims abstract description 4
- 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 150
- 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 117
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 117
- 229940045145 uridine Drugs 0.000 claims description 117
- 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 84
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 53
- 150000001875 compounds Chemical class 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 206010020751 Hypersensitivity Diseases 0.000 claims description 38
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 208000024891 symptom Diseases 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 208000026935 allergic disease Diseases 0.000 claims description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 20
- 230000007815 allergy Effects 0.000 claims description 20
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 20
- 125000005110 aryl thio group Chemical group 0.000 claims description 19
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 claims description 18
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 229960001456 adenosine triphosphate Drugs 0.000 claims description 18
- 125000004104 aryloxy group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 claims description 16
- 125000002102 aryl alkyloxo group Chemical group 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
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical group O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 claims description 14
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 229940097496 nasal spray Drugs 0.000 claims description 13
- 239000007922 nasal spray Substances 0.000 claims description 13
- 229910019142 PO4 Inorganic materials 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 12
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 239000010452 phosphate Substances 0.000 claims description 11
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 241001061127 Thione Species 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 239000002245 particle Substances 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 2'-dA Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 claims description 8
- PCDQPRRSZKQHHS-UHFFFAOYSA-N Cytidine 5'-triphosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-UHFFFAOYSA-N 0.000 claims description 8
- 125000004442 acylamino group Chemical group 0.000 claims description 8
- 208000010668 atopic eczema Diseases 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- PCDQPRRSZKQHHS-ZAKLUEHWSA-N cytidine-5'-triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-ZAKLUEHWSA-N 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Natural products NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 7
- 229940104302 cytosine Drugs 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 7
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2'-deoxyguanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000005035 acylthio group Chemical group 0.000 claims description 6
- 125000003368 amide group Chemical group 0.000 claims description 6
- 125000005251 aryl acyl group Chemical group 0.000 claims description 6
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 6
- 125000001769 aryl amino group Chemical group 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- SZTWKXQGCGRUHR-UHFFFAOYSA-N c1nc2ncn3cc[nH]c3c2n1 Chemical class c1nc2ncn3cc[nH]c3c2n1 SZTWKXQGCGRUHR-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000006071 cream Substances 0.000 claims description 6
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 6
- 125000004986 diarylamino group Chemical group 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000003835 nucleoside group Chemical group 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 239000006194 liquid suspension Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 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 4
- DUCZQUFMCSTEHH-PEBGCTIMSA-N 6-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]imidazo[1,2-c]pyrimidin-5-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N2C=CN=C2C=C1 DUCZQUFMCSTEHH-PEBGCTIMSA-N 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- UBORTCNDUKBEOP-UHFFFAOYSA-N L-xanthosine Natural products OC1C(O)C(CO)OC1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UHFFFAOYSA-N 0.000 claims description 4
- UBORTCNDUKBEOP-HAVMAKPUSA-N Xanthosine Natural products O[C@@H]1[C@H](O)[C@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-HAVMAKPUSA-N 0.000 claims description 4
- 239000000443 aerosol Substances 0.000 claims description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 4
- 125000003106 haloaryl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229940100662 nasal drops Drugs 0.000 claims description 4
- 125000004999 nitroaryl group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 150000008223 ribosides Chemical class 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 230000000699 topical effect Effects 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 claims description 3
- 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
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 3
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 3
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000003843 furanosyl group Chemical group 0.000 claims description 3
- 239000002674 ointment Substances 0.000 claims description 3
- 201000003646 skin sarcoidosis Diseases 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 229940104230 thymidine Drugs 0.000 claims description 3
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- HVPQJGPSDXISJA-UHFFFAOYSA-N 1h-imidazo[1,2-c]pyrimidin-5-one Chemical class O=C1N=CC=C2NC=CN12 HVPQJGPSDXISJA-UHFFFAOYSA-N 0.000 claims description 2
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 2
- 206010012434 Dermatitis allergic Diseases 0.000 claims description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 2
- JNGIJPMMHVVZSU-VJUNAUMWSA-N P(O)(=O)(OP(=O)(O)OP(=O)(O)O)OC[C@@H]1[C@]([C@]2([C@@](O1)(N1C(=O)N=C(N)C=C1)C=C2)O)(O)C1=CC=C(C=C1)[N+](=O)[O-] Chemical compound P(O)(=O)(OP(=O)(O)OP(=O)(O)O)OC[C@@H]1[C@]([C@]2([C@@](O1)(N1C(=O)N=C(N)C=C1)C=C2)O)(O)C1=CC=C(C=C1)[N+](=O)[O-] JNGIJPMMHVVZSU-VJUNAUMWSA-N 0.000 claims description 2
- GKVHYBAWZAYQDO-XVFCMESISA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-(2-oxo-4-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@@H](O)[C@@H]1N1C(=O)NC(=S)C=C1 GKVHYBAWZAYQDO-XVFCMESISA-N 0.000 claims description 2
- 125000000328 arabinofuranosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 2
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 claims 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims 1
- 125000006501 nitrophenyl group Chemical group 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 238000009472 formulation Methods 0.000 abstract description 4
- 201000000306 sarcoidosis Diseases 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 description 21
- 206010061218 Inflammation Diseases 0.000 description 19
- 230000000694 effects Effects 0.000 description 17
- 238000011282 treatment Methods 0.000 description 16
- XCCTYIAWTASOJW-UHFFFAOYSA-N UDP-Glc Natural products OC1C(O)C(COP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-UHFFFAOYSA-N 0.000 description 15
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 14
- 229940068196 placebo Drugs 0.000 description 13
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- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 239000000126 substance Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 210000003630 histaminocyte Anatomy 0.000 description 9
- 229960001120 levocabastine Drugs 0.000 description 9
- 235000021317 phosphate Nutrition 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 8
- 108010058846 Ovalbumin Proteins 0.000 description 8
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Landscapes
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- Heart & Thoracic Surgery (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US33782801P | 2001-11-06 | 2001-11-06 | |
| US60/337,828 | 2001-11-06 | ||
| PCT/US2002/035775 WO2003039473A2 (en) | 2001-11-06 | 2002-11-06 | Method for treating or preventing inflammatory diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2465894A1 true CA2465894A1 (en) | 2003-05-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002465894A Abandoned CA2465894A1 (en) | 2001-11-06 | 2002-11-06 | Method for treating or preventing inflammatory diseases |
Country Status (11)
| Country | Link |
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| US (1) | US7256183B2 (https=) |
| EP (1) | EP1450820A4 (https=) |
| JP (1) | JP2005532254A (https=) |
| KR (1) | KR20050043761A (https=) |
| CN (1) | CN1612739A (https=) |
| AR (1) | AR037263A1 (https=) |
| BR (1) | BR0213897A (https=) |
| CA (1) | CA2465894A1 (https=) |
| MX (1) | MXPA04004215A (https=) |
| TW (1) | TW200300692A (https=) |
| WO (1) | WO2003039473A2 (https=) |
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| WO2003028712A2 (en) * | 2001-09-28 | 2003-04-10 | Universite Libre De Bruxelles | Purinergic and pyrimidinergic receptor agonists for the treatment of activated cd4+ t lymphocyte-mediated immune diseases |
| JPWO2004075906A1 (ja) * | 2003-02-26 | 2006-06-01 | リジェンティス株式会社 | 抗炎症剤及び抗炎症性医療材料 |
| 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 |
| WO2008113072A2 (en) * | 2007-03-15 | 2008-09-18 | Board Of Regents, 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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| US5292498A (en) | 1991-06-19 | 1994-03-08 | The University Of North Carolina At Chapel Hill | Method of treating lung disease with uridine triphosphates |
| 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 |
| US5837861A (en) | 1997-02-10 | 1998-11-17 | Inspire Pharmaceuticals, Inc. | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
| US5900407A (en) | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
| NZ332426A (en) | 1996-03-27 | 2000-09-29 | Univ North Carolina | Method of treating diseases involving dysfunction of ciliary movement such as ciliary dyskinesia and infertility with uridine triphosphates (UTP) and related compounds |
| 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 |
| DK0981534T3 (da) * | 1997-02-06 | 2006-09-04 | Inspire Pharmaceuticals Inc | Dinukleotider og deres anvendelser |
| EP1011686B9 (en) * | 1997-03-25 | 2011-02-09 | Duska Scientific Co | Modulation of human mast cell activation |
| US6462028B2 (en) | 1997-07-25 | 2002-10-08 | Inspire Pharmaceuticals, Inc. | Method of promoting cervical and vaginal secretions |
| ID29198A (id) * | 1997-08-29 | 2001-08-09 | Univ North Carolina | Pemakaian uridin 5'-difosfat dan persamaannya untuk mengobati penyakit paru-paru |
| CA2332540A1 (en) * | 1998-05-22 | 1999-12-02 | Benjamin R. Yerxa | Therapeutic dinucleotide and derivatives |
| EP1143896B1 (en) * | 1998-10-20 | 2006-12-13 | The University of North Carolina at Chapel Hill | Methods of hydrating the nasal mucosal surface |
| 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 |
| AU2603101A (en) * | 1999-12-22 | 2001-07-03 | Inspire Pharmaceuticals, Inc. | Method of treating gastrointestinal tract disease with purinergic receptor agonists |
| US6610274B1 (en) * | 2000-12-22 | 2003-08-26 | Wallace J. Gardner | Anti-inflammatory composition comprising tetracycline |
| WO2003022255A2 (en) * | 2001-09-05 | 2003-03-20 | Vsl Pharmaceuticals, Inc. | Lactic acid bacteria comprising unmethylated cytosine-guanine dinucleotides for use in therapy |
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| EP1450820A4 (en) | 2009-02-18 |
| US7256183B2 (en) | 2007-08-14 |
| KR20050043761A (ko) | 2005-05-11 |
| JP2005532254A (ja) | 2005-10-27 |
| AR037263A1 (es) | 2004-11-03 |
| CN1612739A (zh) | 2005-05-04 |
| EP1450820A2 (en) | 2004-09-01 |
| US20030125299A1 (en) | 2003-07-03 |
| WO2003039473A2 (en) | 2003-05-15 |
| BR0213897A (pt) | 2006-05-23 |
| WO2003039473A3 (en) | 2003-10-23 |
| TW200300692A (en) | 2003-06-16 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |