NZ337225A - Dinucleotides useful for treating chronic pulmonary obstructive disorder - Google Patents
Dinucleotides useful for treating chronic pulmonary obstructive disorderInfo
- Publication number
- NZ337225A NZ337225A NZ337225A NZ33722598A NZ337225A NZ 337225 A NZ337225 A NZ 337225A NZ 337225 A NZ337225 A NZ 337225A NZ 33722598 A NZ33722598 A NZ 33722598A NZ 337225 A NZ337225 A NZ 337225A
- Authority
- NZ
- New Zealand
- Prior art keywords
- amino
- bru
- cmalkyl
- hydrogen
- hydroxy
- Prior art date
Links
- 230000001684 chronic effect Effects 0.000 title 1
- 230000000414 obstructive effect Effects 0.000 title 1
- 230000002685 pulmonary effect Effects 0.000 title 1
- -1 methylene, difluoromethylene Chemical group 0.000 claims abstract description 67
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001301 oxygen Substances 0.000 claims abstract description 14
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 14
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims abstract description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 6
- 208000000617 lacrimal duct obstruction Diseases 0.000 claims abstract description 5
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims abstract description 5
- 206010013774 Dry eye Diseases 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 70
- 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 58
- 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 40
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 40
- 229940045145 uridine Drugs 0.000 claims description 40
- 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 38
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims description 35
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 29
- 235000011468 Albizia julibrissin Nutrition 0.000 claims description 27
- 241001070944 Mimosa Species 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 21
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 16
- 229940035893 uracil Drugs 0.000 claims description 16
- 229910019142 PO4 Inorganic materials 0.000 claims description 14
- 239000002777 nucleoside Substances 0.000 claims description 14
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 229930024421 Adenine Natural products 0.000 claims description 12
- 229960000643 adenine Drugs 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 239000010452 phosphate Substances 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 11
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 10
- 229940104302 cytosine Drugs 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 229940113082 thymine Drugs 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 206010033078 Otitis media Diseases 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 229940075420 xanthine Drugs 0.000 claims description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 125000003435 aroyl group Chemical group 0.000 claims description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 5
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 201000009890 sinusitis Diseases 0.000 claims description 5
- ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 claims description 4
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-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
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 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 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 3
- 206010036790 Productive cough Diseases 0.000 claims description 3
- 206010038848 Retinal detachment Diseases 0.000 claims description 3
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 3
- 230000004264 retinal detachment Effects 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 3
- 108091023231 Ap4A Proteins 0.000 claims description 2
- AAXYAFFKOSNMEB-UHFFFAOYSA-N Gp3G Natural products C1=NC(C(N=C(N)N2)=O)=C2N1C(C(O)C1O)OC1COP(O)(=O)OP(O)(=O)OP(O)(=O)OCC(C(O)C1O)OC1N1C=NC2=C1NC(N)=NC2=O AAXYAFFKOSNMEB-UHFFFAOYSA-N 0.000 claims description 2
- QCICUPZZLIQAPA-XPWFQUROSA-N P(1),P(3)-bis(5'-adenosyl) triphosphate Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=CN=C2N)=C2N=C1 QCICUPZZLIQAPA-XPWFQUROSA-N 0.000 claims description 2
- YOAHKNVSNCMZGQ-XPWFQUROSA-J P(1),P(4)-bis(5'-adenosyl) tetraphosphate(4-) Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=CN=C2N)=C2N=C1 YOAHKNVSNCMZGQ-XPWFQUROSA-J 0.000 claims description 2
- OIMACDRJUANHTJ-XPWFQUROSA-I P(1),P(5)-bis(5'-adenosyl) pentaphosphate(5-) Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=CN=C2N)=C2N=C1 OIMACDRJUANHTJ-XPWFQUROSA-I 0.000 claims description 2
- SJXJAXXRDJWRCR-INFSMZHSSA-N P(1)-(5'-adenosyl),P(4)-(5'-guanosyl) tetraphosphate Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=C(NC2=O)N)=C2N=C1 SJXJAXXRDJWRCR-INFSMZHSSA-N 0.000 claims description 2
- BSOFHAKJEKMWPE-FZNBVPMYSA-N [(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl [(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [hydroxy(phosphonooxy)phosphoryl] phosphate Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2O)O)N2C=3N=CN=C(C=3N=C2)N)OP(O)(=O)OP(O)(O)=O)C=CC(=O)NC1=O BSOFHAKJEKMWPE-FZNBVPMYSA-N 0.000 claims description 2
- JPNWHMPVXHYIKN-VRXVDWQRSA-K [[(2r,3r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [[(2s,3s,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] phosphate Chemical compound N1([C@@H]2O[C@@H]([C@@H](C2O)O)COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OC[C@@H]2O[C@H](C(O)[C@@H]2O)N2C(NC(=O)C=C2)=O)C=CC(=O)NC1=O JPNWHMPVXHYIKN-VRXVDWQRSA-K 0.000 claims description 2
- ADWZBTIGCZHWBW-KPKSGTNCSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@@H]([C@@H]2O)O)N2C=3N=CN=C(C=3N=C2)N)C=CC(=O)NC1=O ADWZBTIGCZHWBW-KPKSGTNCSA-N 0.000 claims description 2
- OLGWXCQXRSSQPO-UHFFFAOYSA-N diguanosine tetraphosphate Natural products C1=NC(C(N=C(N)N2)=O)=C2N1C(C(O)C1O)OC1COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OCC(C(O)C1O)OC1N1C=NC2=C1NC(N)=NC2=O OLGWXCQXRSSQPO-UHFFFAOYSA-N 0.000 claims description 2
- 230000006698 induction Effects 0.000 claims description 2
- 208000024794 sputum Diseases 0.000 claims description 2
- 210000003802 sputum Anatomy 0.000 claims description 2
- OWTGMPPCCUSXIP-FNXFGIETSA-J tetrasodium;[[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [[[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate Chemical compound [Na+].[Na+].[Na+].[Na+].N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C(NC(=O)C=C2)=O)O)O)C=CC(=O)NC1=O OWTGMPPCCUSXIP-FNXFGIETSA-J 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 12
- 150000002431 hydrogen Chemical group 0.000 claims 9
- DYWBDRKFYPLULC-UHFFFAOYSA-N cyano(nitrosulfonyl)sulfamic acid Chemical compound C(#N)N(S(=O)(=O)[N+](=O)[O-])S(=O)(=O)O DYWBDRKFYPLULC-UHFFFAOYSA-N 0.000 claims 7
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 claims 6
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 3
- HVPQJGPSDXISJA-UHFFFAOYSA-N 1h-imidazo[1,2-c]pyrimidin-5-one Chemical class O=C1N=CC=C2NC=CN12 HVPQJGPSDXISJA-UHFFFAOYSA-N 0.000 claims 2
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims 2
- 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 2
- 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 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 2
- 229940104230 thymidine Drugs 0.000 claims 2
- UBORTCNDUKBEOP-UUOKFMHZSA-N xanthosine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UUOKFMHZSA-N 0.000 claims 2
- WIYQAQIDVXSPMY-DBIOUOCHSA-N 3-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]benzamide Chemical compound NC(=O)C1=CC=CC([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1 WIYQAQIDVXSPMY-DBIOUOCHSA-N 0.000 claims 1
- AGFIRQJZCNVMCW-UAKXSSHOSA-N 5-bromouridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 AGFIRQJZCNVMCW-UAKXSSHOSA-N 0.000 claims 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 claims 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims 1
- HAEJPQIATWHALX-KQYNXXCUSA-N ITP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CNC2=O)=C2N=C1 HAEJPQIATWHALX-KQYNXXCUSA-N 0.000 claims 1
- PZCFFCOJNXGTIM-XPWFQUROSA-N P(1),P(6)-bis(5'-adenosyl)hexaphosphate Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]([C@@H](O)[C@H]1O)O[C@H]1N1C(N=CN=C2N)=C2N=C1 PZCFFCOJNXGTIM-XPWFQUROSA-N 0.000 claims 1
- 229960005305 adenosine Drugs 0.000 claims 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 229940029575 guanosine Drugs 0.000 claims 1
- 239000011570 nicotinamide Substances 0.000 claims 1
- 229960003966 nicotinamide Drugs 0.000 claims 1
- 235000005152 nicotinamide Nutrition 0.000 claims 1
- 239000011618 nicotinamide riboside Substances 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 abstract description 4
- 206010009137 Chronic sinusitis Diseases 0.000 abstract 1
- 208000024035 chronic otitis media Diseases 0.000 abstract 1
- 208000027157 chronic rhinosinusitis Diseases 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 31
- 238000005481 NMR spectroscopy Methods 0.000 description 28
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Otolaryngology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/797,472 US5900407A (en) | 1997-02-06 | 1997-02-06 | Method of treating dry eye disease with uridine triphosphates and related compounds |
| US08/798,508 US5837861A (en) | 1997-02-10 | 1997-02-10 | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
| PCT/US1998/002702 WO1998034942A2 (en) | 1997-02-06 | 1998-02-06 | Dinucleotides and their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ337225A true NZ337225A (en) | 2002-03-28 |
Family
ID=27121880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ337225A NZ337225A (en) | 1997-02-06 | 1998-02-06 | Dinucleotides useful for treating chronic pulmonary obstructive disorder |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US6348589B1 (enExample) |
| EP (1) | EP0981534B1 (enExample) |
| JP (1) | JP4531867B2 (enExample) |
| KR (1) | KR100606131B1 (enExample) |
| CN (1) | CN1262556C (enExample) |
| AT (1) | ATE325129T1 (enExample) |
| AU (1) | AU738907C (enExample) |
| BR (1) | BR9807169A (enExample) |
| CA (1) | CA2279963C (enExample) |
| DE (1) | DE69834392T2 (enExample) |
| DK (1) | DK0981534T3 (enExample) |
| ES (1) | ES2264197T3 (enExample) |
| NO (1) | NO326718B1 (enExample) |
| NZ (1) | NZ337225A (enExample) |
| PT (1) | PT981534E (enExample) |
| WO (1) | WO1998034942A2 (enExample) |
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| US6673779B2 (en) | 1996-03-27 | 2004-01-06 | Inspire Pharmaceuticals, Inc. | Method of treating ciliary dyskinesia with dinucleoside polyphosphate compounds or UTP analogues |
| US6319908B1 (en) | 1996-07-03 | 2001-11-20 | Inspire Pharmaceuticals, Inc. | Method for large-scale production of di(uridine 5′-tetraphosphate) and salts thereof |
| 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 |
| DK0981534T3 (da) | 1997-02-06 | 2006-09-04 | Inspire Pharmaceuticals Inc | Dinukleotider og deres anvendelser |
| US7078391B2 (en) * | 1997-02-10 | 2006-07-18 | Inspire Pharmaceuticals, Inc. | Method of treating edematous retinal disorders |
| US6818629B2 (en) * | 1997-02-10 | 2004-11-16 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising P1-(2'-deoxycytidine 5'-)P4-(uridine 5'-) tetraphosphate |
| US7223744B2 (en) * | 1997-02-10 | 2007-05-29 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof |
| US6596725B2 (en) | 1997-02-10 | 2003-07-22 | Inspire Pharmaceuticals, Inc. | Use of certain dinucleotides to stimulate removal of fluid in retinal detachment and retinal edema |
| US6462028B2 (en) | 1997-07-25 | 2002-10-08 | Inspire Pharmaceuticals, Inc. | Method of promoting cervical and vaginal secretions |
| US6872710B2 (en) * | 1997-07-25 | 2005-03-29 | Inspire Pharmaceuticals, Inc. | Di(uridine 5′)-tetraphosphate and salts thereof |
| US6548658B2 (en) * | 1997-07-25 | 2003-04-15 | Inspire Pharmaceuticals, Inc. | Di-(uridine 5′)-tetraphosphate and salts thereof |
| TW593331B (en) | 1997-07-25 | 2004-06-21 | Inspire Pharmaceuticals Inc | Method for large-scale production of di(uridine 5')-tetraphosphate and salts thereof |
| DE69822482T2 (de) * | 1997-07-25 | 2005-03-03 | Inspire Pharmaceuticals, Inc. | Salze von di(uridine 5'-tetraphosphate), verfahren zur herstellung und verwendungen davon |
| EP1011688B1 (en) * | 1997-08-29 | 2005-02-02 | The University of North Carolina at Chapel Hill | Use of uridine 5'-diphosphate and analogs thereof for the treatment of lung diseases |
| ATE232733T1 (de) * | 1998-05-22 | 2003-03-15 | Inspire Pharmaceuticals Inc | Therapeutische dinucleotide und deren derivate |
| JP2002533110A (ja) * | 1998-12-23 | 2002-10-08 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | Ｇタンパク質共役レセプターを使用した目的とする遺伝子の導入 |
| BR0008498A (pt) | 1999-02-26 | 2002-02-05 | Inspire Pharmaceuticals Inc | Método de promoção de hidratação de mucosas com certos difosfatos de uridina, adenina e citidina e seus análogos |
| DE60006814T2 (de) | 1999-06-30 | 2004-05-19 | Yamasa Corp., Choshi | Dinucleotid-kristalle |
| AU6551800A (en) * | 1999-08-17 | 2001-03-13 | Adani, Alexander | Dinucleoside 5',5'-tetraphosphates as inhibitors of viral reverse transcriptasesand viruses |
| EP1261323A2 (en) * | 1999-12-22 | 2002-12-04 | Inspire Pharmaceuticals, Inc. | Method of treating gastrointestinal tract disease with purinergic receptor agonists |
| RU2161982C1 (ru) * | 2000-01-20 | 2001-01-20 | Общество с ограниченной ответственностью "Клиника Института биорегуляции и геронтологии" | Тетрапептид, стимулирующий функцию сетчатой оболочки глаза, фармакологическое средство на его основе и способ его применения |
| US6864243B1 (en) * | 2000-05-12 | 2005-03-08 | Inspire Pharmaceuticals, Inc. | Method for treating retinal degeneration with purinergic receptor agonists |
| BR0111297A (pt) * | 2000-05-30 | 2004-01-06 | Santen Pharmaceutical Co Ltd | Promotor de migração epitelial corneana |
| US7115585B2 (en) * | 2000-08-21 | 2006-10-03 | Inspire Pharmaceuticals, Inc. | Compositions for treating epithelial and retinal tissue diseases |
| US6555675B2 (en) * | 2000-08-21 | 2003-04-29 | Inspire Pharmaceuticals, Inc. | Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists |
| US7132408B2 (en) * | 2000-08-21 | 2006-11-07 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
| US7452870B2 (en) * | 2000-08-21 | 2008-11-18 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with P2Y12 receptor antagonist compound |
| US6867199B2 (en) | 2000-08-21 | 2005-03-15 | Inspire Pharmaceuticals, Inc. | Dinucleoside polyphosphate compositions and their therapeutic use |
| US7018985B1 (en) | 2000-08-21 | 2006-03-28 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
| US20040266723A1 (en) * | 2000-12-15 | 2004-12-30 | Otto Michael J. | Antiviral agents for treatment of Flaviviridae infections |
| EP1368366A1 (en) * | 2001-02-07 | 2003-12-10 | Celltech R & D Limited | Non-natural nucleotides and dinucleotides |
| AR034635A1 (es) | 2001-06-25 | 2004-03-03 | Inspire Pharmaceuticals Inc | Lubricacion de las articulaciones con agonistas del receptor purinergico p2y |
| US20050009777A1 (en) * | 2001-07-25 | 2005-01-13 | Mack Stephen Robert | Non-natural carbon-linked nucleotides and dinucleotides |
| US20030109488A1 (en) * | 2001-10-11 | 2003-06-12 | Alcon, Inc. | Methods for treating dry eye |
| CN1612739A (zh) * | 2001-11-06 | 2005-05-04 | 印斯拜尔药品股份有限公司 | 治疗或预防炎性疾病的方法 |
| US7084128B2 (en) * | 2002-01-18 | 2006-08-01 | Inspire Pharmaceuticals, Inc. | Method for reducing intraocular pressure |
| JP2006505585A (ja) * | 2002-10-18 | 2006-02-16 | モリケム メディシンズ， インコーポレイテッド | ランチビオティクスで眼乾燥症を処置する方法 |
| US6984628B2 (en) * | 2003-07-15 | 2006-01-10 | Allergan, Inc. | Ophthalmic compositions comprising trefoil factor family peptides |
| WO2005107787A1 (en) * | 2004-05-06 | 2005-11-17 | Molichem Medicines, Inc. | Treatment of membrane-associated diseases and disorders using lantibiotic containing compositions |
| US7479481B2 (en) * | 2004-05-06 | 2009-01-20 | Molichem Medicines, Inc. | Treatment of ocular diseases and disorders using lantibiotic compositions |
| GB0417886D0 (en) * | 2004-08-11 | 2004-09-15 | Univ Cardiff | Method and means for enhanced pulmonary delivery |
| GB0502250D0 (en) * | 2005-02-03 | 2005-03-09 | Ic Vec Ltd | Use |
| US7368439B2 (en) * | 2005-06-15 | 2008-05-06 | Bar - Ilan University | Dinucleoside poly(borano)phosphate derivatives and uses thereof |
| US7851456B2 (en) * | 2005-06-29 | 2010-12-14 | Inspire Pharmaceuticals, Inc. | P2Y6 receptor agonists for treating lung diseases |
| EP1959968A2 (en) | 2005-12-06 | 2008-08-27 | P2-Science APS | Modulation of the p2y2 receptor pathway |
| US20070249556A1 (en) * | 2006-04-21 | 2007-10-25 | Brubaker Kurt E | Method of treating inflammation |
| EP2045257B1 (en) * | 2006-07-26 | 2016-08-17 | Yamasa Corporation | Process for producing di(pyrimidine nucleoside 5'-)polyphosphate |
| EP2049665A2 (en) * | 2006-07-28 | 2009-04-22 | Applera Corporation | Dinucleotide mrna cap analogs |
| AU2008310734B2 (en) | 2007-10-10 | 2014-06-05 | Parion Sciences, Inc. | Delivering osmolytes by nasal cannula |
| WO2010048341A1 (en) * | 2008-10-22 | 2010-04-29 | Inspire Pharmaceuticals, Inc. | Method for treating cystic fibrosis |
| US9067964B2 (en) | 2008-12-18 | 2015-06-30 | Oligomer Sciences Ab | Complex and method for enhancing nuclear delivery |
| US9011909B2 (en) | 2010-09-03 | 2015-04-21 | Wisconsin Pharmacal Company, Llc | Prebiotic suppositories |
| EP2614838B1 (en) | 2010-09-10 | 2016-04-20 | Santen Pharmaceutical Co., Ltd. | Diquafosol and hyaluronic acid or salts thereof for the treatment of dry eye |
| CN103732213A (zh) | 2011-06-07 | 2014-04-16 | 帕里昂科学公司 | 治疗方法 |
| US8945605B2 (en) | 2011-06-07 | 2015-02-03 | Parion Sciences, Inc. | Aerosol delivery systems, compositions and methods |
| AR086745A1 (es) | 2011-06-27 | 2014-01-22 | Parion Sciences Inc | 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida |
| ES2702575T3 (es) | 2012-03-26 | 2019-03-04 | Santen Pharmaceutical Co Ltd | Solución oftálmica que comprende diquafosol |
| EP3366680B1 (en) | 2012-05-29 | 2020-05-13 | Parion Sciences, Inc. | Dendrimer like amino amides possessing sodium channel blocker activity for the treatment of dry eye and other mucosal diseases |
| RU2015129065A (ru) | 2012-12-17 | 2017-01-25 | Пэрион Сайенсиз, Инк. | Производные хлор-пиразинкарбоксамида, обладающие активностью блокирования эпителиальных натриевых каналов |
| ES2674665T3 (es) | 2012-12-17 | 2018-07-03 | Parion Sciences, Inc. | Compuestos de 3,5-diamino-6-cloro-N-(N-(4-fenilbutilo)carbamimidoilo)-pirazina-2-carboxamida |
| CN104995178B (zh) | 2012-12-17 | 2018-06-26 | 帕里昂科学公司 | 3，5-二氨基-6-氯-n-(n-(4-苯基丁基)甲脒基)吡嗪-2-甲酰胺化合物 |
| WO2016014927A2 (en) | 2014-07-24 | 2016-01-28 | W.R. Grace & Co.-Conn. | Crystalline form of nicotinamide riboside |
| CN107428791B (zh) | 2015-03-09 | 2024-05-28 | 格雷斯公司 | 烟酰胺核苷的结晶形式 |
| US20180125876A1 (en) | 2015-05-20 | 2018-05-10 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and Pharmaceutical Composition for Modulation Polarization and Activation of Macrophages |
| WO2019126482A1 (en) | 2017-12-22 | 2019-06-27 | Elysium Health, Inc. | Crystalline forms of nicotinamide riboside chloride |
| WO2021245107A2 (en) | 2020-06-02 | 2021-12-09 | Institut Gustave Roussy | Modulators of purinergic receptors and related immune checkpoint for treating acute respiratory distress syndrom |
| EP3919062A1 (en) | 2020-06-02 | 2021-12-08 | Institut Gustave-Roussy | Modulators of purinergic receptors and related immune checkpoint for treating acute respiratory distress syndrom |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4855304A (en) | 1985-01-10 | 1989-08-08 | Repligen Corporation | Dinucleoside pyrophosphates and pyrophosphate homologs as plant antivirals |
| US5049550A (en) | 1987-11-05 | 1991-09-17 | Worcester Foundation For Experimental Biology | Diadenosine 5', 5'"-p1, p4,-tetraphosphate analogs as antithrombotic agents |
| US5292498A (en) * | 1991-06-19 | 1994-03-08 | The University Of North Carolina At Chapel Hill | Method of treating lung disease with uridine triphosphates |
| AU688552B2 (en) * | 1994-07-15 | 1998-03-12 | Biosearch Italia S.P.A. | Dinucleoside-5',5'-pyrophosphates |
| 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 |
| US5837861A (en) * | 1997-02-10 | 1998-11-17 | Inspire Pharmaceuticals, Inc. | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
| US5681823A (en) | 1996-05-02 | 1997-10-28 | Prp Inc. | P1, P4 -dithio-P2 -P3 -monochloromethylene 5', 5'"-diadenosine P1, P4 -tetraphosphate as antithrombotic agent |
| US5789391A (en) * | 1996-07-03 | 1998-08-04 | Inspire Pharmaceuticals, Inc. | Method of treating sinusitis with uridine triphosphates and related compounds |
| 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 |
| JP4118958B2 (ja) | 1996-10-09 | 2008-07-16 | ファーマセット，リミティド | テトラホスホネート二環式トリス無水物 |
| DK0981534T3 (da) | 1997-02-06 | 2006-09-04 | Inspire Pharmaceuticals Inc | Dinukleotider og deres anvendelser |
-
1998
- 1998-02-06 DK DK98907435T patent/DK0981534T3/da active
- 1998-02-06 PT PT98907435T patent/PT981534E/pt unknown
- 1998-02-06 ES ES98907435T patent/ES2264197T3/es not_active Expired - Lifetime
- 1998-02-06 CN CNB988032597A patent/CN1262556C/zh not_active Expired - Fee Related
- 1998-02-06 AU AU63242/98A patent/AU738907C/en not_active Ceased
- 1998-02-06 KR KR1019997007070A patent/KR100606131B1/ko not_active Expired - Fee Related
- 1998-02-06 NZ NZ337225A patent/NZ337225A/en not_active IP Right Cessation
- 1998-02-06 WO PCT/US1998/002702 patent/WO1998034942A2/en not_active Ceased
- 1998-02-06 BR BR9807169-6A patent/BR9807169A/pt active Search and Examination
- 1998-02-06 US US09/101,395 patent/US6348589B1/en not_active Expired - Lifetime
- 1998-02-06 AT AT98907435T patent/ATE325129T1/de active
- 1998-02-06 JP JP53505598A patent/JP4531867B2/ja not_active Expired - Fee Related
- 1998-02-06 CA CA002279963A patent/CA2279963C/en not_active Expired - Fee Related
- 1998-02-06 EP EP98907435A patent/EP0981534B1/en not_active Expired - Lifetime
- 1998-02-06 DE DE69834392T patent/DE69834392T2/de not_active Expired - Lifetime
-
1999
- 1999-08-04 NO NO19993776A patent/NO326718B1/no not_active IP Right Cessation
-
2001
- 2001-11-06 US US10/007,451 patent/US6977246B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998034942A3 (en) | 2000-01-06 |
| ATE325129T1 (de) | 2006-06-15 |
| AU6324298A (en) | 1998-08-26 |
| KR20000070807A (ko) | 2000-11-25 |
| US6977246B2 (en) | 2005-12-20 |
| CN1262556C (zh) | 2006-07-05 |
| CA2279963A1 (en) | 1998-08-13 |
| DE69834392T2 (de) | 2007-02-08 |
| JP2001526635A (ja) | 2001-12-18 |
| AU738907B2 (en) | 2001-09-27 |
| AU738907C (en) | 2002-05-16 |
| DK0981534T3 (da) | 2006-09-04 |
| US6348589B1 (en) | 2002-02-19 |
| BR9807169A (pt) | 2000-06-06 |
| US20020082417A1 (en) | 2002-06-27 |
| CA2279963C (en) | 2008-04-22 |
| JP4531867B2 (ja) | 2010-08-25 |
| EP0981534B1 (en) | 2006-05-03 |
| NO993776L (no) | 1999-10-06 |
| CN1292795A (zh) | 2001-04-25 |
| NO993776D0 (no) | 1999-08-04 |
| WO1998034942A2 (en) | 1998-08-13 |
| NO326718B1 (no) | 2009-02-02 |
| PT981534E (pt) | 2006-09-29 |
| KR100606131B1 (ko) | 2006-07-31 |
| DE69834392D1 (de) | 2006-06-08 |
| ES2264197T3 (es) | 2006-12-16 |
| EP0981534A2 (en) | 2000-03-01 |
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Owner name: MERCK SHARP + DOHME CORP., NZ Effective date: 20141218 |
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Free format text: THE AGENT HAS BEEN CORRECTED TO 600102, BALDWINS INTELLECTUAL PROPERTY, LEVEL 15, VODAFONE ON THE QUAY, 157 LAMBTON QUAY, WELLINGTON 6011, NZ; THE CONTACT HAS BEEN CORRECTED TO 600102, BALDWINS INTELLECTUAL PROPERTY, LEVEL 15, VODAFONE ON THE QUAY, 157 LAMBTON QUAY, WELLINGTON 6011, NZ Effective date: 20150216 |
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| EXPY | Patent expired |