MXPA05013550A - Compuestos fusionados que inhiben al receptor de subtipo 1 del receptor vainilloide (vr1). - Google Patents
Compuestos fusionados que inhiben al receptor de subtipo 1 del receptor vainilloide (vr1).Info
- Publication number
- MXPA05013550A MXPA05013550A MXPA05013550A MXPA05013550A MXPA05013550A MX PA05013550 A MXPA05013550 A MX PA05013550A MX PA05013550 A MXPA05013550 A MX PA05013550A MX PA05013550 A MXPA05013550 A MX PA05013550A MX PA05013550 A MXPA05013550 A MX PA05013550A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- formula
- inden
- dihydro
- indazol
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 667
- 108010025083 TRPV1 receptor Proteins 0.000 title abstract description 13
- 102000005962 receptors Human genes 0.000 title description 7
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 123
- 150000003839 salts Chemical class 0.000 claims abstract description 59
- 239000000651 prodrug Substances 0.000 claims abstract description 32
- 229940002612 prodrug Drugs 0.000 claims abstract description 32
- 241000124008 Mammalia Species 0.000 claims abstract description 27
- 230000008569 process Effects 0.000 claims abstract description 24
- 230000036407 pain Effects 0.000 claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 363
- -1 cycloakenyl Chemical group 0.000 claims description 309
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 219
- 125000000217 alkyl group Chemical group 0.000 claims description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims description 112
- 239000000203 mixture Substances 0.000 claims description 112
- 239000001257 hydrogen Substances 0.000 claims description 111
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 99
- 229910001868 water Inorganic materials 0.000 claims description 95
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 88
- 239000002904 solvent Substances 0.000 claims description 73
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 67
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 63
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 62
- 239000004202 carbamide Substances 0.000 claims description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 55
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 49
- 238000004519 manufacturing process Methods 0.000 claims description 45
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 42
- 229910052736 halogen Inorganic materials 0.000 claims description 42
- 150000002367 halogens Chemical class 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 31
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
- 125000001188 haloalkyl group Chemical group 0.000 claims description 28
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 26
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 25
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 239000012298 atmosphere Substances 0.000 claims description 21
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 18
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 16
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 15
- 108010062740 TRPV Cation Channels Proteins 0.000 claims description 14
- 102000011040 TRPV Cation Channels Human genes 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 14
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 13
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 13
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 11
- 125000004967 formylalkyl group Chemical group 0.000 claims description 11
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 11
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 7
- 208000004454 Hyperalgesia Diseases 0.000 claims description 7
- 239000012279 sodium borohydride Substances 0.000 claims description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 7
- 235000010288 sodium nitrite Nutrition 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- VPSCJCQPUGKRNC-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-1-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4CC3)C(C)(C)C)=CC=CC2=C1 VPSCJCQPUGKRNC-UHFFFAOYSA-N 0.000 claims description 6
- GNRVWTIJRDMIID-UHFFFAOYSA-N 1-(5-tert-butyl-2-fluoro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound FC1CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 GNRVWTIJRDMIID-UHFFFAOYSA-N 0.000 claims description 6
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 claims description 6
- 206010046543 Urinary incontinence Diseases 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- FGZOWQBNDORKQL-UHFFFAOYSA-N 1-[5-(2-cyanopropan-2-yl)-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound C1CC2=CC(C(C)(C#N)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 FGZOWQBNDORKQL-UHFFFAOYSA-N 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 229910052702 rhenium Inorganic materials 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- ZBISBOUCIVCJOF-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(5-methoxy-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1CC2=CC(OC)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 ZBISBOUCIVCJOF-UHFFFAOYSA-N 0.000 claims description 4
- 241000271569 Rhea Species 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000005961 oxazepanyl group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
- YCAAQLHPLMLUQY-UHFFFAOYSA-N 1-(5,6-dimethoxy-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1=2C=C(OC)C(OC)=CC=2CCC1NC(=O)NC1=CC=CC2=C1C=NN2 YCAAQLHPLMLUQY-UHFFFAOYSA-N 0.000 claims description 3
- UJHPWLQNPUIFJU-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-1-yl)-3-(3-methylisoquinolin-5-yl)urea Chemical compound C1CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=C2C=C(C)N=CC2=CC=C1 UJHPWLQNPUIFJU-UHFFFAOYSA-N 0.000 claims description 3
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 3
- YPTLZNNIGSSJPU-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(5-methyl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1CC2=CC(C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 YPTLZNNIGSSJPU-UHFFFAOYSA-N 0.000 claims description 2
- OUIHQJINQZAAFC-UHFFFAOYSA-N 1-(4-bromo-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC=2C(Br)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 OUIHQJINQZAAFC-UHFFFAOYSA-N 0.000 claims description 2
- DEHOJLUMBBKMOD-UHFFFAOYSA-N 1-(5-bromo-2,3-dihydro-1h-inden-1-yl)-3-isoquinolin-5-ylurea Chemical compound N1=CC=C2C(NC(=O)NC3C4=CC=C(C=C4CC3)Br)=CC=CC2=C1 DEHOJLUMBBKMOD-UHFFFAOYSA-N 0.000 claims description 2
- TYOYXJNGINZFET-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 TYOYXJNGINZFET-UHFFFAOYSA-N 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 2
- 229940077388 benzenesulfonate Drugs 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 15
- 201000010099 disease Diseases 0.000 claims 9
- 125000005490 tosylate group Chemical class 0.000 claims 4
- RLFOIUKYGMPPQK-HXUWFJFHSA-N 1-(1-acetylindazol-4-yl)-3-[(1r)-5-tert-butyl-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC2=CC(C(C)(C)C)=CC=C2[C@@H]1NC(=O)NC1=C2C=NN(C(=O)C)C2=CC=C1 RLFOIUKYGMPPQK-HXUWFJFHSA-N 0.000 claims 1
- VEHLEPIVJNKFAH-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-(5-propan-2-yl-2,3-dihydro-1h-inden-1-yl)urea Chemical compound C1CC2=CC(C(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 VEHLEPIVJNKFAH-UHFFFAOYSA-N 0.000 claims 1
- ZQOHBQZZPJFTBS-LJQANCHMSA-N 1-(1h-indazol-4-yl)-3-[(1r)-4-piperidin-1-yl-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C([C@H]1NC(=O)NC=2C=3C=NNC=3C=CC=2)CC2=C1C=CC=C2N1CCCCC1 ZQOHBQZZPJFTBS-LJQANCHMSA-N 0.000 claims 1
- ZBISBOUCIVCJOF-INIZCTEOSA-N 1-(1h-indazol-4-yl)-3-[(1s)-5-methoxy-2,3-dihydro-1h-inden-1-yl]urea Chemical compound N([C@@H]1C2=CC=C(C=C2CC1)OC)C(=O)NC1=CC=CC2=C1C=NN2 ZBISBOUCIVCJOF-INIZCTEOSA-N 0.000 claims 1
- AZLLMVYMBZHCFA-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[4-(3-methylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1C(C)CCCN1C1=CC=CC2=C1CCC2NC(=O)NC1=CC=CC2=C1C=NN2 AZLLMVYMBZHCFA-UHFFFAOYSA-N 0.000 claims 1
- XBOINVGXFLCYNR-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[4-(4-methylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC(C)CCN1C1=CC=CC2=C1CCC2NC(=O)NC1=CC=CC2=C1C=NN2 XBOINVGXFLCYNR-UHFFFAOYSA-N 0.000 claims 1
- SQKBVJVKOIQJGQ-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[4-(trifluoromethoxy)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC=2C(OC(F)(F)F)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 SQKBVJVKOIQJGQ-UHFFFAOYSA-N 0.000 claims 1
- OXMKYONMECXXGJ-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[4-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC=2C(C(F)(F)F)=CC=CC=2C1NC(=O)NC1=CC=CC2=C1C=NN2 OXMKYONMECXXGJ-UHFFFAOYSA-N 0.000 claims 1
- NBBJYIVJMJCFCE-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(2-methylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound CC1CCCCN1C1=CC=C(C(CC2)NC(=O)NC=3C=4C=NNC=4C=CC=3)C2=C1 NBBJYIVJMJCFCE-UHFFFAOYSA-N 0.000 claims 1
- FVKWCEQZVSUEJV-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(2-oxopiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=2)CCC1=CC=2N1CCCCC1=O FVKWCEQZVSUEJV-UHFFFAOYSA-N 0.000 claims 1
- PNBWVYYXZCLQRU-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(3-methylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1C(C)CCCN1C1=CC=C(C(CC2)NC(=O)NC=3C=4C=NNC=4C=CC=3)C2=C1 PNBWVYYXZCLQRU-UHFFFAOYSA-N 0.000 claims 1
- QQSNYWRELALBNA-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(4-methylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC(C)CCN1C1=CC=C(C(CC2)NC(=O)NC=3C=4C=NNC=4C=CC=3)C2=C1 QQSNYWRELALBNA-UHFFFAOYSA-N 0.000 claims 1
- UKSFKXHTHRJUIA-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(4-phenylpiperazin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=2)CCC1=CC=2N(CC1)CCN1C1=CC=CC=C1 UKSFKXHTHRJUIA-UHFFFAOYSA-N 0.000 claims 1
- RZFOJZILWOUWLX-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(4-piperidin-1-ylpiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C=1C=CC=2NN=CC=2C=1NC(=O)NC(C1=CC=2)CCC1=CC=2N(CC1)CCC1N1CCCCC1 RZFOJZILWOUWLX-UHFFFAOYSA-N 0.000 claims 1
- QLDCRXZBQVZDEZ-UHFFFAOYSA-N 1-(1h-indazol-4-yl)-3-[5-(trifluoromethyl)-2,3-dihydro-1h-inden-1-yl]urea Chemical compound C1CC2=CC(C(F)(F)F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 QLDCRXZBQVZDEZ-UHFFFAOYSA-N 0.000 claims 1
- JBNOOOTYPGAENR-UHFFFAOYSA-N 1-(5-fluoro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1CC2=CC(F)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 JBNOOOTYPGAENR-UHFFFAOYSA-N 0.000 claims 1
- JMWSQSYRBYDBND-UHFFFAOYSA-N 1-(5-tert-butyl-2,3-dihydro-1h-inden-2-yl)-3-(1h-indazol-4-yl)urea Chemical compound C1C2=CC(C(C)(C)C)=CC=C2CC1NC(=O)NC1=CC=CC2=C1C=NN2 JMWSQSYRBYDBND-UHFFFAOYSA-N 0.000 claims 1
- NHEQTPFLJJJJKT-UHFFFAOYSA-N 1-(6-fluoro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound C12=CC(F)=CC=C2CCC1NC(=O)NC1=CC=CC2=C1C=NN2 NHEQTPFLJJJJKT-UHFFFAOYSA-N 0.000 claims 1
- GNRVWTIJRDMIID-LPHOPBHVSA-N 1-[(1s,2s)-5-tert-butyl-2-fluoro-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound N([C@H]1C2=CC=C(C=C2C[C@@H]1F)C(C)(C)C)C(=O)NC1=CC=CC2=C1C=NN2 GNRVWTIJRDMIID-LPHOPBHVSA-N 0.000 claims 1
- VTVZETXZBPJECM-UHFFFAOYSA-N 1-[4-(3,3-difluoropiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound C1C(F)(F)CCCN1C1=CC=CC2=C1CCC2NC(=O)NC1=CC=CC2=C1C=NN2 VTVZETXZBPJECM-UHFFFAOYSA-N 0.000 claims 1
- CJHYHNWJRPRTDB-UHFFFAOYSA-N 1-[4-(4-fluoropiperidin-1-yl)-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound C1CC(F)CCN1C1=CC=CC2=C1CCC2NC(=O)NC1=CC=CC2=C1C=NN2 CJHYHNWJRPRTDB-UHFFFAOYSA-N 0.000 claims 1
- SDNXJZYKIUFPFE-UHFFFAOYSA-N 1-[4-(cyanomethyl)-2,3-dihydro-1h-inden-1-yl]-3-(1h-indazol-4-yl)urea Chemical compound C1CC(C(=CC=C2)CC#N)=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 SDNXJZYKIUFPFE-UHFFFAOYSA-N 0.000 claims 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-O Pyrrolidinium ion Chemical compound C1CC[NH2+]C1 RWRDLPDLKQPQOW-UHFFFAOYSA-O 0.000 claims 1
- 125000005626 carbonium group Chemical group 0.000 claims 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 103
- 238000005481 NMR spectroscopy Methods 0.000 description 102
- 239000000243 solution Substances 0.000 description 88
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 77
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 64
- 239000007787 solid Substances 0.000 description 61
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 55
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- ZQJYTTPJYLKTTI-UHFFFAOYSA-M zinc;2h-pyridin-2-ide;bromide Chemical compound Br[Zn+].C1=CC=N[C-]=C1 ZQJYTTPJYLKTTI-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/06—Anti-spasmodics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Materials For Photolithography (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/459,925 US7015233B2 (en) | 2003-06-12 | 2003-06-12 | Fused compounds that inhibit vanilloid subtype 1 (VR1) receptor |
| US10/864,068 US7375126B2 (en) | 2003-06-12 | 2004-06-09 | Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
| PCT/US2004/018590 WO2004111009A1 (en) | 2003-06-12 | 2004-06-10 | Fused compounds that inhibit vanilloid receptor subtype 1 (vr1) receptor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA05013550A true MXPA05013550A (es) | 2006-04-05 |
Family
ID=33555102
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA05013550A MXPA05013550A (es) | 2003-06-12 | 2004-06-10 | Compuestos fusionados que inhiben al receptor de subtipo 1 del receptor vainilloide (vr1). |
Country Status (20)
| Country | Link |
|---|---|
| EP (2) | EP1658269B1 (enExample) |
| JP (2) | JP4857113B2 (enExample) |
| KR (2) | KR101138216B1 (enExample) |
| CN (1) | CN102617464A (enExample) |
| AT (2) | ATE510824T1 (enExample) |
| AU (2) | AU2004247721C1 (enExample) |
| BR (1) | BRPI0411116A (enExample) |
| CA (2) | CA2526872C (enExample) |
| CY (2) | CY1108713T1 (enExample) |
| DE (1) | DE602004017329D1 (enExample) |
| DK (2) | DK1658269T3 (enExample) |
| ES (1) | ES2318308T3 (enExample) |
| IL (4) | IL172457A (enExample) |
| MX (1) | MXPA05013550A (enExample) |
| NZ (3) | NZ590234A (enExample) |
| PL (2) | PL2017265T3 (enExample) |
| PT (2) | PT1658269E (enExample) |
| SI (2) | SI2017265T1 (enExample) |
| TW (3) | TW201300361A (enExample) |
| WO (1) | WO2004111009A1 (enExample) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004089296A2 (en) | 2003-04-03 | 2004-10-21 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide hydrolase |
| US20090018092A1 (en) | 2004-03-16 | 2009-01-15 | The Regents Of The University Of California | Reducing Nephropathy with Inhibitors of Soluble Epoxide Hydrolase and Epoxyeicosanoids |
| AU2005295167B2 (en) | 2004-10-20 | 2012-05-10 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide hydrolase |
| WO2006062982A2 (en) | 2004-12-07 | 2006-06-15 | Locus Pharmaceuticals, Inc. | Urea inhibitors of map kinases |
| JP2008523072A (ja) | 2004-12-07 | 2008-07-03 | ルーカス ファーマシューティカルズ， インコーポレイテッド | タンパク質キナーゼの阻害剤 |
| CA2624307C (en) | 2005-10-07 | 2014-04-29 | Glenmark Pharmaceuticals S.A. | Substituted benzofused derivatives and their use as vanilloid receptor ligands |
| CA2626579A1 (en) * | 2005-10-25 | 2007-05-03 | Abbott Laboratories | Formulation comprising a drug of low water solubility and method of use thereof |
| AU2006306146A1 (en) | 2005-10-28 | 2007-05-03 | Abbott Laboratories | Indazole derivatives that inhibit TRPV1 receptor |
| TW200808723A (en) | 2006-03-13 | 2008-02-16 | Univ California | Conformationally restricted urea inhibitors of soluble epoxide hydrolase |
| RU2450006C2 (ru) * | 2006-04-18 | 2012-05-10 | Эбботт Лэборетриз | Антагонисты ванилоидного рецептора подтипа 1(vr1) и их применение |
| WO2009081222A1 (en) | 2007-12-21 | 2009-07-02 | Glenmark Pharmaceuticals, S.A. | Substituted tricyclic pyridine or pyrimidine vanilloid receptor ligands |
| CN101925575B (zh) | 2008-01-28 | 2014-06-18 | 株式会社爱茉莉太平洋 | 作为香草酸受体拮抗剂的化合物、其异构体或其药物学可接受的盐、及包含这些化合物的药物组合物 |
| CN102137851B (zh) | 2008-07-02 | 2014-08-27 | 株式会社爱茉莉太平洋 | 作为香草素受体拮抗剂的化合物、其异构体或其药学可接受的盐以及包含它们的药物组合物 |
| AR073631A1 (es) * | 2008-10-17 | 2010-11-17 | Abbott Lab | Antagonistas del receptor transitorio potencial de vanilloides 1 ( trpv1) utiles para tratar inflamacion y dolor |
| US9296693B2 (en) | 2010-01-29 | 2016-03-29 | The Regents Of The University Of California | Acyl piperidine inhibitors of soluble epoxide hydrolase |
| HRP20161786T1 (hr) | 2011-05-13 | 2017-03-10 | Array Biopharma, Inc. | Pirolidinil urea, pirolidinil tiourea i pirolidinil gvanidin spojevi kao inhibitori trka kinaze |
| CN104364236B (zh) * | 2012-05-09 | 2018-01-16 | 拜尔农作物科学股份公司 | 5‑卤代吡唑二氢茚基甲酰胺 |
| WO2014078372A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| UA117573C2 (uk) | 2012-11-13 | 2018-08-27 | Ерей Біофарма Інк. | Біциклічні сполуки сечовини, тіосечовини, гуанідину й ціаногуанідину, придатні для лікування болю |
| WO2014078328A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078331A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(arylalkyl)-n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| US9809578B2 (en) | 2012-11-13 | 2017-11-07 | Array Biopharma Inc. | Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trkA kinase inhibitors |
| US9981959B2 (en) | 2012-11-13 | 2018-05-29 | Array Biopharma Inc. | Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| US9828360B2 (en) | 2012-11-13 | 2017-11-28 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| WO2014078325A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(monocyclic aryl),n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| UA116455C2 (uk) | 2012-11-13 | 2018-03-26 | Еррей Біофарма Інк. | Сполуки n-піролідинілсечовини, n'-піразолілсечовини, тіосечовини, гуанідину та ціаногуанідину як інгібітори кінази trka |
| US9822118B2 (en) | 2012-11-13 | 2017-11-21 | Array Biopharma Inc. | Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| CN109970614B (zh) | 2014-05-15 | 2023-01-13 | 阵列生物制药公司 | 作为trka激酶抑制剂的化合物及其用途 |
| WO2017190107A1 (en) * | 2016-04-29 | 2017-11-02 | Board Of Regents, The University Of Texas System | Sigma receptor binders |
| DE102022104759A1 (de) | 2022-02-28 | 2023-08-31 | SCi Kontor GmbH | Co-Kristall-Screening Verfahren, insbesondere zur Herstellung von Co-Kristallen |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW536734B (en) * | 2000-07-31 | 2003-06-11 | Clariant Int Ltd | Process for manufacturing a microelectronic device |
| WO2003014064A1 (en) * | 2001-07-31 | 2003-02-20 | Bayer Healthcare Ag | Naphthylurea and naphthylacetamide derivatives as vanilloid receptor 1 (vr1) antagonists |
| JP2003192587A (ja) * | 2001-12-26 | 2003-07-09 | Bayer Ag | 尿素誘導体 |
| WO2003070247A1 (en) * | 2002-02-20 | 2003-08-28 | Abbott Laboratories | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (vr1) receptor |
| GB0206876D0 (en) * | 2002-03-22 | 2002-05-01 | Merck Sharp & Dohme | Therapeutic agents |
| WO2003097586A1 (en) * | 2002-05-17 | 2003-11-27 | Janssen Pharmaceutica N.V. | Aminotetralin-derived urea modulators of vanilloid vr1 receptor |
-
2004
- 2004-06-10 BR BRPI0411116-8A patent/BRPI0411116A/pt not_active IP Right Cessation
- 2004-06-10 AU AU2004247721A patent/AU2004247721C1/en not_active Ceased
- 2004-06-10 DE DE602004017329T patent/DE602004017329D1/de not_active Expired - Lifetime
- 2004-06-10 PT PT04754996T patent/PT1658269E/pt unknown
- 2004-06-10 DK DK04754996T patent/DK1658269T3/da active
- 2004-06-10 DK DK08166079.7T patent/DK2017265T3/da active
- 2004-06-10 SI SI200431715T patent/SI2017265T1/sl unknown
- 2004-06-10 EP EP04754996A patent/EP1658269B1/en not_active Expired - Lifetime
- 2004-06-10 CN CN2012100573625A patent/CN102617464A/zh active Pending
- 2004-06-10 KR KR1020057023829A patent/KR101138216B1/ko not_active Expired - Fee Related
- 2004-06-10 AT AT08166079T patent/ATE510824T1/de active
- 2004-06-10 PL PL08166079T patent/PL2017265T3/pl unknown
- 2004-06-10 PL PL04754996T patent/PL1658269T3/pl unknown
- 2004-06-10 NZ NZ590234A patent/NZ590234A/en not_active IP Right Cessation
- 2004-06-10 SI SI200430995T patent/SI1658269T1/sl unknown
- 2004-06-10 NZ NZ543713A patent/NZ543713A/en not_active IP Right Cessation
- 2004-06-10 JP JP2006533722A patent/JP4857113B2/ja not_active Expired - Fee Related
- 2004-06-10 NZ NZ578264A patent/NZ578264A/en not_active IP Right Cessation
- 2004-06-10 CA CA2526872A patent/CA2526872C/en not_active Expired - Fee Related
- 2004-06-10 CA CA2756058A patent/CA2756058A1/en not_active Abandoned
- 2004-06-10 EP EP08166079A patent/EP2017265B1/en not_active Expired - Lifetime
- 2004-06-10 ES ES04754996T patent/ES2318308T3/es not_active Expired - Lifetime
- 2004-06-10 PT PT08166079T patent/PT2017265E/pt unknown
- 2004-06-10 WO PCT/US2004/018590 patent/WO2004111009A1/en not_active Ceased
- 2004-06-10 AT AT04754996T patent/ATE411982T1/de active
- 2004-06-10 KR KR1020117017610A patent/KR101150324B1/ko not_active Expired - Fee Related
- 2004-06-10 MX MXPA05013550A patent/MXPA05013550A/es active IP Right Grant
- 2004-06-14 TW TW101107398A patent/TW201300361A/zh unknown
- 2004-06-14 TW TW093117059A patent/TWI394569B/zh not_active IP Right Cessation
- 2004-06-14 TW TW099119548A patent/TWI366461B/zh not_active IP Right Cessation
-
2005
- 2005-12-08 IL IL172457A patent/IL172457A/en not_active IP Right Cessation
-
2009
- 2009-01-14 CY CY20091100044T patent/CY1108713T1/el unknown
-
2010
- 2010-08-01 IL IL207335A patent/IL207335A/en not_active IP Right Cessation
- 2010-12-17 AU AU2010257277A patent/AU2010257277B2/en not_active Ceased
-
2011
- 2011-03-07 JP JP2011049274A patent/JP2011153148A/ja active Pending
- 2011-07-28 CY CY20111100738T patent/CY1111945T1/el unknown
- 2011-10-27 IL IL215997A patent/IL215997A0/en unknown
- 2011-10-30 IL IL216046A patent/IL216046A0/en unknown
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