AU2008334457A1 - Nicotinamide derivatives, preparation thereof and therapeutic use thereof - Google Patents
Nicotinamide derivatives, preparation thereof and therapeutic use thereof Download PDFInfo
- Publication number
- AU2008334457A1 AU2008334457A1 AU2008334457A AU2008334457A AU2008334457A1 AU 2008334457 A1 AU2008334457 A1 AU 2008334457A1 AU 2008334457 A AU2008334457 A AU 2008334457A AU 2008334457 A AU2008334457 A AU 2008334457A AU 2008334457 A1 AU2008334457 A1 AU 2008334457A1
- Authority
- AU
- Australia
- Prior art keywords
- group
- alkyl
- ureido
- pyridin
- hydrogen atom
- 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
- 238000002360 preparation method Methods 0.000 title claims description 18
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 150000005480 nicotinamides Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 172
- 125000000217 alkyl group Chemical group 0.000 claims description 112
- 239000011570 nicotinamide Substances 0.000 claims description 80
- 229960003966 nicotinamide Drugs 0.000 claims description 80
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 76
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 66
- -1 -OH Chemical group 0.000 claims description 61
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 38
- 235000005152 nicotinamide Nutrition 0.000 claims description 38
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 33
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
- 125000003386 piperidinyl group Chemical group 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000004193 piperazinyl group Chemical group 0.000 claims description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 150000002500 ions Chemical class 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 239000012190 activator Substances 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 229910003827 NRaRb Inorganic materials 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 229910052700 potassium Inorganic materials 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 claims description 5
- 125000005987 1-oxo-thiomorpholinyl group Chemical group 0.000 claims description 5
- 125000003725 azepanyl group Chemical group 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 3
- 241001409553 Uredo Species 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 229910052796 boron Inorganic materials 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 229910052702 rhenium Inorganic materials 0.000 claims description 3
- 150000003335 secondary amines Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- YNSJXHGTZJTEMM-UHFFFAOYSA-N 2-amino-n-methyl-6-[4-(pyridin-3-ylmethylcarbamoylamino)phenyl]pyridine-3-carboxamide Chemical compound N1=C(N)C(C(=O)NC)=CC=C1C(C=C1)=CC=C1NC(=O)NCC1=CC=CN=C1 YNSJXHGTZJTEMM-UHFFFAOYSA-N 0.000 claims description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical group ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- LELNCJKBCIUSDB-UHFFFAOYSA-N 2-(ethylamino)-6-[4-(pyridin-3-ylmethylcarbamoylamino)phenyl]-n-(2-pyrrolidin-1-ylethyl)pyridine-3-carboxamide Chemical compound CCNC1=NC(C=2C=CC(NC(=O)NCC=3C=NC=CC=3)=CC=2)=CC=C1C(=O)NCCN1CCCC1 LELNCJKBCIUSDB-UHFFFAOYSA-N 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- 239000000243 solution Substances 0.000 description 87
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- 239000002904 solvent Substances 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- 239000012074 organic phase Substances 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 24
- 239000007787 solid Substances 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 20
- 239000002244 precipitate Substances 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 239000012429 reaction media Substances 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 13
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000012300 argon atmosphere Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 8
- AJPKQSSFYHPYMH-UHFFFAOYSA-N 2,6-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1Cl AJPKQSSFYHPYMH-UHFFFAOYSA-N 0.000 description 7
- 230000001093 anti-cancer Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- 230000009435 amidation Effects 0.000 description 6
- 238000007112 amidation reaction Methods 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- ZANPJXNYBVVNSD-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C=C1 ZANPJXNYBVVNSD-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ORBSSWJRHPFEBR-UHFFFAOYSA-N (2-fluoropyridin-3-yl)methanamine Chemical compound NCC1=CC=CN=C1F ORBSSWJRHPFEBR-UHFFFAOYSA-N 0.000 description 3
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 3
- PHBVTMQLXNCAQO-UHFFFAOYSA-N 5-(aminomethyl)pyridin-2-amine Chemical compound NCC1=CC=C(N)N=C1 PHBVTMQLXNCAQO-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- DFLQTVPEIMTXSZ-UHFFFAOYSA-N tert-butyl n-[5-(aminomethyl)pyridin-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(CN)C=N1 DFLQTVPEIMTXSZ-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- RYICOVXDBBDCNT-UHFFFAOYSA-N (5-fluoropyridin-3-yl)methanamine Chemical compound NCC1=CN=CC(F)=C1 RYICOVXDBBDCNT-UHFFFAOYSA-N 0.000 description 2
- ZKAUZQFUIATOQP-UHFFFAOYSA-N (5-methylpyridin-3-yl)methanamine Chemical compound CC1=CN=CC(CN)=C1 ZKAUZQFUIATOQP-UHFFFAOYSA-N 0.000 description 2
- KYRWSLUCAPNJPI-UHFFFAOYSA-N (6-fluoropyridin-3-yl)methanamine Chemical compound NCC1=CC=C(F)N=C1 KYRWSLUCAPNJPI-UHFFFAOYSA-N 0.000 description 2
- NZPFQOXRHLUPRT-UHFFFAOYSA-N (6-methylpyridin-3-yl)methanamine Chemical compound CC1=CC=C(CN)C=N1 NZPFQOXRHLUPRT-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- ATCRIUVQKHMXSH-UHFFFAOYSA-N 2,4-dichlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1Cl ATCRIUVQKHMXSH-UHFFFAOYSA-N 0.000 description 2
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 2
- FESSGGSFQPBJGS-UHFFFAOYSA-N 2-[3-[2-(4-sulfophenyl)tetrazol-5-yl]phenoxy]acetic acid Chemical compound OC(=O)COC1=CC=CC(C2=NN(N=N2)C=2C=CC(=CC=2)S(O)(=O)=O)=C1 FESSGGSFQPBJGS-UHFFFAOYSA-N 0.000 description 2
- NAHHNSMHYCLMON-UHFFFAOYSA-N 2-pyridin-3-ylethanamine Chemical compound NCCC1=CC=CN=C1 NAHHNSMHYCLMON-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- NWDQHUORSVKMQT-UHFFFAOYSA-N 4-(ethylamino)-2-[4-(pyridin-3-ylmethylcarbamoylamino)phenyl]pyrimidine-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(NCC)=NC(C=2C=CC(NC(=O)NCC=3C=NC=CC=3)=CC=2)=N1 NWDQHUORSVKMQT-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- VYPGPUCXQSDVFK-UHFFFAOYSA-N 4-chloro-2-(ethylamino)benzoic acid Chemical compound CCNC1=CC(Cl)=CC=C1C(O)=O VYPGPUCXQSDVFK-UHFFFAOYSA-N 0.000 description 2
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 2
- PNCVDUNITYPRNG-UHFFFAOYSA-N 5-(aminomethyl)-3-methylpyridin-2-amine Chemical compound CC1=CC(CN)=CN=C1N PNCVDUNITYPRNG-UHFFFAOYSA-N 0.000 description 2
- YJIDKQVYACIBPR-UHFFFAOYSA-N 5-(aminomethyl)-n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=C(CN)C=N1 YJIDKQVYACIBPR-UHFFFAOYSA-N 0.000 description 2
- MVJDUNKELBBNKM-UHFFFAOYSA-N 6-(ethylamino)pyridine-3-carbonitrile Chemical compound CCNC1=CC=C(C#N)C=N1 MVJDUNKELBBNKM-UHFFFAOYSA-N 0.000 description 2
- OFCRHTLXDCWARW-UHFFFAOYSA-N 6-(methylamino)pyridine-3-carbonitrile Chemical compound CNC1=CC=C(C#N)C=N1 OFCRHTLXDCWARW-UHFFFAOYSA-N 0.000 description 2
- SAGPWEDGPJWJDT-UHFFFAOYSA-N 6-chloro-2-(ethylamino)pyridine-3-carboxylic acid Chemical compound CCNC1=NC(Cl)=CC=C1C(O)=O SAGPWEDGPJWJDT-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 101150003085 Pdcl gene Proteins 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004807 desolvation Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
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- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- DSGFMJHVLKGOBJ-UHFFFAOYSA-N pyridin-3-ylmethyl n-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate Chemical compound O1C(C)(C)C(C)(C)OB1C(C=C1)=CC=C1NC(=O)OCC1=CC=CN=C1 DSGFMJHVLKGOBJ-UHFFFAOYSA-N 0.000 description 1
- ZZLBMYCVJGKGOF-UHFFFAOYSA-N pyridin-3-ylmethyl n-[4-[6-(ethylamino)-5-(methylcarbamoyl)pyridin-2-yl]phenyl]carbamate Chemical compound C1=C(C(=O)NC)C(NCC)=NC(C=2C=CC(NC(=O)OCC=3C=NC=CC=3)=CC=2)=C1 ZZLBMYCVJGKGOF-UHFFFAOYSA-N 0.000 description 1
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- RBDZEJHRPTUXLF-UHFFFAOYSA-N tert-butyl n-[5-[[[4-[6-(ethylamino)-5-(2-piperidin-1-ylethylcarbamoyl)pyridin-2-yl]phenyl]carbamoylamino]methyl]pyridin-2-yl]carbamate Chemical compound CCNC1=NC(C=2C=CC(NC(=O)NCC=3C=NC(NC(=O)OC(C)(C)C)=CC=3)=CC=2)=CC=C1C(=O)NCCN1CCCCC1 RBDZEJHRPTUXLF-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- ZXYAAVBXHKCJJB-UHFFFAOYSA-N uracil-5-carboxylic acid Chemical compound OC(=O)C1=CNC(=O)NC1=O ZXYAAVBXHKCJJB-UHFFFAOYSA-N 0.000 description 1
- 239000004066 vascular targeting agent Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0706799 | 2007-09-28 | ||
| FR0706799A FR2921657A1 (fr) | 2007-09-28 | 2007-09-28 | Derives de nicotinamide, leur preparation et leur application en therapeutique |
| PCT/FR2008/001338 WO2009074749A2 (fr) | 2007-09-28 | 2008-09-26 | Dérives de nicotinamide. leur préparation et leur application en thérapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2008334457A1 true AU2008334457A1 (en) | 2009-06-18 |
Family
ID=39356668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008334457A Abandoned AU2008334457A1 (en) | 2007-09-28 | 2008-09-26 | Nicotinamide derivatives, preparation thereof and therapeutic use thereof |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US20100222319A1 (https=) |
| EP (1) | EP2205566A2 (https=) |
| JP (1) | JP2010540504A (https=) |
| KR (1) | KR20100065165A (https=) |
| CN (1) | CN101808996A (https=) |
| AR (1) | AR066171A1 (https=) |
| AU (1) | AU2008334457A1 (https=) |
| BR (1) | BRPI0817973A2 (https=) |
| CA (1) | CA2700559A1 (https=) |
| CL (1) | CL2008002893A1 (https=) |
| FR (1) | FR2921657A1 (https=) |
| IL (1) | IL204663A0 (https=) |
| MX (1) | MX2010003445A (https=) |
| PA (1) | PA8797301A1 (https=) |
| PE (1) | PE20091033A1 (https=) |
| RU (1) | RU2010116765A (https=) |
| TW (1) | TW200918056A (https=) |
| UY (1) | UY31367A1 (https=) |
| WO (1) | WO2009074749A2 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102775396B (zh) | 2005-11-08 | 2014-10-08 | 沃泰克斯药物股份有限公司 | Atp-结合弹夹转运蛋白的杂环调控剂 |
| CN104447716A (zh) | 2007-05-09 | 2015-03-25 | 沃泰克斯药物股份有限公司 | Cftr调节剂 |
| MX365732B (es) | 2007-12-07 | 2019-06-12 | Vertex Pharma | Procesos para producir acidos cicloalquilcarboxamido-piridin benzoicos. |
| EP3683218B1 (en) | 2007-12-07 | 2024-09-18 | Vertex Pharmaceuticals Incorporated | Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid |
| NZ720282A (en) | 2008-02-28 | 2017-12-22 | Vertex Pharma | Heteroaryl derivatives as cftr modulators |
| FR2943675A1 (fr) * | 2009-03-24 | 2010-10-01 | Sanofi Aventis | Composes anticancereux, leur preparation et leur application en therapeutique |
| FR2943670B1 (fr) * | 2009-03-24 | 2011-05-06 | Sanofi Aventis | Derives anticancereux,leur preparation et leur application en therapeutique |
| FR2943669B1 (fr) * | 2009-03-24 | 2011-05-06 | Sanofi Aventis | Derives de nicotinamide,leur preparation et leur application en therapeutique |
| EP2440204B1 (en) * | 2009-06-12 | 2013-12-18 | Bristol-Myers Squibb Company | Nicotinamide compounds useful as kinase modulators |
| AU2011223790A1 (en) * | 2010-03-01 | 2012-08-30 | Myrexis, Inc. | Compounds and therapeutic uses thereof |
| US8912184B1 (en) | 2010-03-01 | 2014-12-16 | Alzheimer's Institute Of America, Inc. | Therapeutic and diagnostic methods |
| JP2013523833A (ja) | 2010-04-07 | 2013-06-17 | バーテックス ファーマシューティカルズ インコーポレイテッド | ３−（６−（１−（２，２−ジフルオロベンゾ［ｄ］［１，３］ジオキソール−５−イル）シクロプロパンカルボキサミド）−３−メチルピリジン−２−イル）安息香酸の医薬組成物およびその投与 |
| US8827372B2 (en) | 2010-07-07 | 2014-09-09 | Frontis Corp. | Blowing system |
| FR2965263A1 (fr) * | 2010-09-24 | 2012-03-30 | Sanofi Aventis | Derives de thienopyridine nicotinamide, leur preparation et leur application en therapeutique |
| US9169246B2 (en) | 2011-09-26 | 2015-10-27 | Sanofi | Pyrazoloquinolinone derivatives, preparation thereof and therapeutic use thereof |
| CN103012397B (zh) * | 2011-09-26 | 2017-03-01 | 赛诺菲 | 吡唑并喹啉酮衍生物、其制备方法及其治疗用途 |
| PT2573073E (pt) * | 2011-09-26 | 2015-02-05 | Sanofi Sa | Derivados de pirazoloquinolinona, sua preparação e sua utilização terapêutica |
| NZ727015A (en) | 2012-01-25 | 2017-12-22 | Vertex Pharma | Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid |
| AU2014349010C1 (en) | 2013-11-12 | 2020-08-06 | Vertex Pharmaceuticals Incorporated | Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases |
| CN103804270B (zh) * | 2014-01-23 | 2016-06-22 | 中国药科大学 | 5-(4-甲脒基苄氧基)色氨酸衍生物、其制法及应用 |
| RU2691136C2 (ru) | 2014-11-18 | 2019-06-11 | Вертекс Фармасьютикалз Инкорпорейтед | Способ проведения высокопроизводительной тестовой высокоэффективной жидкостной хроматографии |
| JP7092356B2 (ja) * | 2016-06-22 | 2022-06-28 | フーダン ユニヴァーシティ | ビアリール尿素誘導体またはそれらの塩、およびそれらの調製方法および使用 |
| CN107522641B (zh) * | 2016-06-22 | 2020-05-05 | 复旦大学 | 联芳基脲类衍生物或其盐及其制备方法和用途 |
| KR102831570B1 (ko) | 2018-05-04 | 2025-07-10 | 레미디 플랜, 인크. | 암 줄기 세포를 표적화하는 암 치료 |
| CN110396065A (zh) * | 2019-06-25 | 2019-11-01 | 南京普锐达医药科技有限公司 | 一种2,4-二氯-5-嘧啶甲酰氯的合成方法 |
| AU2020378067A1 (en) * | 2019-11-06 | 2022-05-26 | Remedy Plan, Inc. | Cancer treatments targeting cancer stem cells |
| WO2021219513A1 (en) | 2020-04-28 | 2021-11-04 | Basf Se | Pesticidal compounds |
| JP2024518089A (ja) * | 2021-05-13 | 2024-04-24 | リメディー プラン，インコーポレーテッド | Ｎａｍｐｔ阻害剤とその使用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4301110A1 (de) * | 1993-01-18 | 1994-07-21 | Bayer Ag | Verfahren zur Herstellung von 2-Amino-5-aminomethyl-pyridin |
| CZ20012185A3 (cs) * | 1998-12-16 | 2001-10-17 | Bayer Aktiengesellschaft | Nové bifenylové sloučeniny a sloučeniny analogické bifenylovým sloučeninám, způsob jejich přípravy, farmaceutické prostředky a pouľití těchto sloučenin a prostředků jako antagonistů integrinu |
| DE10063008A1 (de) * | 2000-12-16 | 2002-06-20 | Merck Patent Gmbh | Carbonsäureamidderivate |
| US20040067985A1 (en) * | 2002-10-04 | 2004-04-08 | Fortuna Haviv | Method of inhibiting angiogenesis |
| JP2007515400A (ja) * | 2003-11-28 | 2007-06-14 | ノバルティス アクチエンゲゼルシャフト | タンパク質キナーゼ依存性疾患の処置におけるジアリール尿素誘導体 |
| US20060216288A1 (en) * | 2005-03-22 | 2006-09-28 | Amgen Inc | Combinations for the treatment of cancer |
-
2007
- 2007-09-28 FR FR0706799A patent/FR2921657A1/fr not_active Withdrawn
-
2008
- 2008-09-24 TW TW097136703A patent/TW200918056A/zh unknown
- 2008-09-26 JP JP2010526335A patent/JP2010540504A/ja not_active Withdrawn
- 2008-09-26 KR KR1020107006595A patent/KR20100065165A/ko not_active Withdrawn
- 2008-09-26 EP EP08859496A patent/EP2205566A2/fr not_active Withdrawn
- 2008-09-26 BR BRPI0817973-5A patent/BRPI0817973A2/pt not_active IP Right Cessation
- 2008-09-26 CA CA2700559A patent/CA2700559A1/fr not_active Abandoned
- 2008-09-26 PE PE2008001687A patent/PE20091033A1/es not_active Application Discontinuation
- 2008-09-26 MX MX2010003445A patent/MX2010003445A/es not_active Application Discontinuation
- 2008-09-26 CN CN200880109332A patent/CN101808996A/zh active Pending
- 2008-09-26 CL CL2008002893A patent/CL2008002893A1/es unknown
- 2008-09-26 AU AU2008334457A patent/AU2008334457A1/en not_active Abandoned
- 2008-09-26 UY UY31367A patent/UY31367A1/es not_active Application Discontinuation
- 2008-09-26 RU RU2010116765/04A patent/RU2010116765A/ru not_active Application Discontinuation
- 2008-09-26 PA PA20088797301A patent/PA8797301A1/es unknown
- 2008-09-26 AR ARP080104193A patent/AR066171A1/es unknown
- 2008-09-26 WO PCT/FR2008/001338 patent/WO2009074749A2/fr not_active Ceased
-
2010
- 2010-03-22 IL IL204663A patent/IL204663A0/en unknown
- 2010-03-26 US US12/732,749 patent/US20100222319A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009074749A2 (fr) | 2009-06-18 |
| WO2009074749A3 (fr) | 2009-08-20 |
| CN101808996A (zh) | 2010-08-18 |
| RU2010116765A (ru) | 2011-11-27 |
| PA8797301A1 (es) | 2009-05-15 |
| FR2921657A1 (fr) | 2009-04-03 |
| MX2010003445A (es) | 2010-04-27 |
| CA2700559A1 (fr) | 2009-06-18 |
| EP2205566A2 (fr) | 2010-07-14 |
| PE20091033A1 (es) | 2009-08-17 |
| US20100222319A1 (en) | 2010-09-02 |
| UY31367A1 (es) | 2009-04-30 |
| CL2008002893A1 (es) | 2009-10-16 |
| KR20100065165A (ko) | 2010-06-15 |
| IL204663A0 (en) | 2010-11-30 |
| AR066171A1 (es) | 2009-07-29 |
| JP2010540504A (ja) | 2010-12-24 |
| BRPI0817973A2 (pt) | 2019-04-09 |
| TW200918056A (en) | 2009-05-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |