EA013968B1 - СПОСОБЫ ПОЛУЧЕНИЯ ПИРАЗОЛО[3,4-d]ПИРИМИДИНОВЫХ ЭФИРОВ - Google Patents
СПОСОБЫ ПОЛУЧЕНИЯ ПИРАЗОЛО[3,4-d]ПИРИМИДИНОВЫХ ЭФИРОВ Download PDFInfo
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- EA013968B1 EA013968B1 EA200701500A EA200701500A EA013968B1 EA 013968 B1 EA013968 B1 EA 013968B1 EA 200701500 A EA200701500 A EA 200701500A EA 200701500 A EA200701500 A EA 200701500A EA 013968 B1 EA013968 B1 EA 013968B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- formula
- compound
- specified
- alkyl
- compounds
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- -1 pyrazolo(3,4-d)pyrimidine ethers Chemical class 0.000 title claims abstract description 162
- 238000000034 method Methods 0.000 title claims abstract description 89
- 230000008569 process Effects 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 142
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 48
- 239000002904 solvent Substances 0.000 claims description 44
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 26
- 230000003993 interaction Effects 0.000 claims description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 21
- 125000002252 acyl group Chemical group 0.000 claims description 20
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 16
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 230000026030 halogenation Effects 0.000 claims description 16
- 238000005658 halogenation reaction Methods 0.000 claims description 16
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 16
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 15
- 125000003282 alkyl amino group Chemical group 0.000 claims description 15
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 14
- 125000004423 acyloxy group Chemical group 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 150000003839 salts Chemical group 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 150000003003 phosphines Chemical class 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical group C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 5
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical group [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 5
- 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 claims description 4
- 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 claims description 4
- 239000003125 aqueous solvent Substances 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- 150000003512 tertiary amines Chemical class 0.000 claims description 4
- 238000005660 chlorination reaction Methods 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 claims description 2
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 claims 1
- 230000008520 organization Effects 0.000 claims 1
- IKNCGYCHMGNBCP-UHFFFAOYSA-N propan-1-olate Chemical compound CCC[O-] IKNCGYCHMGNBCP-UHFFFAOYSA-N 0.000 claims 1
- OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 abstract description 6
- 238000011282 treatment Methods 0.000 abstract description 6
- 208000008589 Obesity Diseases 0.000 abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 3
- 235000020824 obesity Nutrition 0.000 abstract description 3
- 230000004153 glucose metabolism Effects 0.000 abstract description 2
- 239000011541 reaction mixture Substances 0.000 description 33
- 125000004432 carbon atom Chemical group C* 0.000 description 26
- 239000000047 product Substances 0.000 description 26
- 239000002253 acid Substances 0.000 description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 18
- 125000001072 heteroaryl group Chemical group 0.000 description 16
- 125000000623 heterocyclic group Chemical group 0.000 description 16
- 238000010992 reflux Methods 0.000 description 14
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 125000003342 alkenyl group Chemical group 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- 238000009835 boiling Methods 0.000 description 10
- 150000003857 carboxamides Chemical class 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000007792 addition Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- 229940124530 sulfonamide Drugs 0.000 description 9
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 150000003456 sulfonamides Chemical class 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 125000004663 dialkyl amino group Chemical group 0.000 description 7
- 125000005432 dialkylcarboxamide group Chemical group 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- NVMHDJQDTCMXLH-UHFFFAOYSA-N propan-2-yl piperidine-1-carboxylate Chemical compound CC(C)OC(=O)N1CCCCC1 NVMHDJQDTCMXLH-UHFFFAOYSA-N 0.000 description 7
- DVWZGMMXZAAOLA-UHFFFAOYSA-N 5-amino-1-(2-fluoro-4-methylsulfonylphenyl)pyrazole-4-carbonitrile Chemical compound FC1=CC(S(=O)(=O)C)=CC=C1N1C(N)=C(C#N)C=N1 DVWZGMMXZAAOLA-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 description 6
- 125000004995 haloalkylthio group Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 5
- JXPDNDHCMMOJPC-UHFFFAOYSA-N 2-hydroxybutanedinitrile Chemical compound N#CC(O)CC#N JXPDNDHCMMOJPC-UHFFFAOYSA-N 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- OHZUEFKOZYWUFF-UHFFFAOYSA-N 4-hydroxypiperidine-1-carboxylic acid Chemical compound OC1CCN(C(O)=O)CC1 OHZUEFKOZYWUFF-UHFFFAOYSA-N 0.000 description 5
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical class CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- IOOKDEPCDHCNSK-UHFFFAOYSA-N (2-fluoro-4-methylsulfonylphenyl)hydrazine Chemical compound CS(=O)(=O)C1=CC=C(NN)C(F)=C1 IOOKDEPCDHCNSK-UHFFFAOYSA-N 0.000 description 4
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 4
- OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
- 125000003636 chemical group Chemical group 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 125000004971 nitroalkyl group Chemical group 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 235000005985 organic acids Nutrition 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- 125000004771 (C1-C4) haloalkylsulfinyl group Chemical group 0.000 description 3
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000010575 fractional recrystallization Methods 0.000 description 3
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- ASQOQJYHIYYTEJ-GBESFXJTSA-N (1r,7s,9as)-7-decyl-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizin-1-ol Chemical compound O[C@@H]1CCCN2C[C@@H](CCCCCCCCCC)CC[C@H]21 ASQOQJYHIYYTEJ-GBESFXJTSA-N 0.000 description 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N 1,3-Dimethylbenzene Natural products CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 2
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- JAWQTFNPXGAMGH-UHFFFAOYSA-N CS(=O)(=O)C1=CC(=C(C=C1)N2C(=C(C=N2)C(=O)O)N)F Chemical compound CS(=O)(=O)C1=CC(=C(C=C1)N2C(=C(C=N2)C(=O)O)N)F JAWQTFNPXGAMGH-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
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- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64371205P | 2005-01-13 | 2005-01-13 | |
| PCT/US2006/001020 WO2006076455A2 (en) | 2005-01-13 | 2006-01-12 | Processes for preparing pyrazolo[3,4-d]pyrimidine ethers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200701500A1 EA200701500A1 (ru) | 2007-12-28 |
| EA013968B1 true EA013968B1 (ru) | 2010-08-30 |
Family
ID=36463499
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200701500A EA013968B1 (ru) | 2005-01-13 | 2006-01-12 | СПОСОБЫ ПОЛУЧЕНИЯ ПИРАЗОЛО[3,4-d]ПИРИМИДИНОВЫХ ЭФИРОВ |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US7425630B2 (enExample) |
| EP (1) | EP1838713A2 (enExample) |
| JP (1) | JP2008526975A (enExample) |
| KR (1) | KR20070114126A (enExample) |
| CN (1) | CN101142216A (enExample) |
| AR (1) | AR052557A1 (enExample) |
| AU (1) | AU2006204940A1 (enExample) |
| BR (1) | BRPI0606115A2 (enExample) |
| CA (1) | CA2593345A1 (enExample) |
| CR (1) | CR9224A (enExample) |
| DO (1) | DOP2006000009A (enExample) |
| EA (1) | EA013968B1 (enExample) |
| GT (1) | GT200600011A (enExample) |
| HN (1) | HN2006001493A (enExample) |
| IL (1) | IL184365A0 (enExample) |
| MX (1) | MX2007008381A (enExample) |
| NO (1) | NO20074052L (enExample) |
| PA (1) | PA8659701A1 (enExample) |
| PE (1) | PE20061118A1 (enExample) |
| TW (1) | TW200637865A (enExample) |
| WO (1) | WO2006076455A2 (enExample) |
| ZA (1) | ZA200705279B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2709786C2 (ru) * | 2014-12-06 | 2019-12-20 | Интра-Селлулар Терапиз, Инк. | Органические соединения |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10238722A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| DE602004009295T2 (de) | 2003-01-14 | 2008-07-03 | Arena Pharmaceuticals, Inc., San Diego | 1,2,3-trisubstituierte aryl- und heteroarylderivate als modulatoren des metabolismus zur vorbeugung und behandlung von metabolismus-bedingten krankheiten wie diabetes oder hyperglykämie |
| EP2292620A3 (en) * | 2003-07-14 | 2011-06-22 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prohylaxis and treatment of disorders related thereto |
| US7923465B2 (en) * | 2005-06-02 | 2011-04-12 | Glenmark Pharmaceuticals S.A. | Cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
| JP5498392B2 (ja) | 2007-11-30 | 2014-05-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | １，５−ジヒドロ−ピラゾロ［３，４−ｄ］ピリミジン−４−オン誘導体及びｃｎｓ障害の治療のためのｐｄｅ９ａモジュレーターとしてのそれらの使用 |
| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| US8822480B2 (en) | 2008-07-16 | 2014-09-02 | Merck Sharp & Dohme Corp. | Bicyclic heterocycle derivatives and use thereof as GPR119 modulators |
| WO2010026214A1 (en) | 2008-09-08 | 2010-03-11 | Boehringer Ingelheim International Gmbh | Pyrazolopyrimidines and their use for the treatment of cns disorders |
| DK2414363T3 (da) | 2009-03-31 | 2014-01-27 | Boehringer Ingelheim Int | 1-heterocyklyl-1,5-dihydro-pyrazol[3,4-d]pyrimidin-4-on-derivater og anvendelse af disse som PDE9A-modulatorer. |
| US20100285145A1 (en) * | 2009-05-08 | 2010-11-11 | Pfizer Inc | Gpr 119 modulators |
| NZ596467A (en) * | 2009-06-05 | 2014-01-31 | Pfizer | L- ( piperidin-4-yl) -pyrazole derivatives as gpr 119 modulators |
| SG10201500639TA (en) | 2010-01-27 | 2015-03-30 | Arena Pharm Inc | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
| WO2012020022A1 (en) | 2010-08-12 | 2012-02-16 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a inhibitors |
| PH12013500547A1 (en) | 2010-09-22 | 2013-06-10 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US8809345B2 (en) | 2011-02-15 | 2014-08-19 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders |
| EA031618B1 (ru) | 2011-06-09 | 2019-01-31 | Ризен Фармасьютикалз Са | Соединения-модуляторы gpr-119 |
| JP6567276B2 (ja) | 2014-05-13 | 2019-08-28 | ソニーセミコンダクタソリューションズ株式会社 | 固体撮像素子、および電子機器 |
| ES2995737T3 (en) | 2015-01-06 | 2025-02-11 | Arena Pharm Inc | Compound for use in treating conditions related to the s1p1 receptor |
| MA42807A (fr) | 2015-06-22 | 2018-07-25 | Arena Pharm Inc | Sel l-arginine cristallin d'acide (r)-2-(7-(4-cyclopentyl-3-(trifluorométhyl)benzyloxy)-1,2,3,4-tétrahydrocyclo-penta[b]indol-3-yl)acétique (composé 1) pour une utilisation dans des troubles associés au récepteur de s1p1 |
| WO2018151873A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| JP2019122134A (ja) | 2018-01-04 | 2019-07-22 | Ntn株式会社 | スイッチング電源の力率改善用ｐｗｍ制御装置 |
| EP3801459B1 (en) | 2018-06-06 | 2024-08-07 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
| CA3219597A1 (en) * | 2021-06-23 | 2022-12-29 | F. Hoffmann-La Roche Ag | Novel process |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0053678A1 (de) * | 1980-12-05 | 1982-06-16 | BASF Aktiengesellschaft | 5-Amino-1-phenyl-4-cyanpyrazole, diese enthaltende herbizide Mittel, Verfahren zu ihrer Herstellung und ihre Anwendung als Herbizide |
| EP0772087A1 (en) * | 1995-10-31 | 1997-05-07 | Fuji Photo Film Co., Ltd. | Pyrazolylazophenol dye |
| WO2003093269A2 (de) * | 2002-05-02 | 2003-11-13 | Bayer Cropscience Ag | Substituierte pyrazolo-pyrimidin-4-one |
| US6660744B1 (en) * | 1999-09-17 | 2003-12-09 | Abbott Gmbh & Co. Kg | Pyrazolopyrimidines as therapeutic agents |
| WO2004009602A1 (en) * | 2002-07-23 | 2004-01-29 | Smithkline Beecham Corporation | Pyrazolopyrimidines as kinase inhibitors |
| WO2005007658A2 (en) * | 2003-07-14 | 2005-01-27 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| WO2006050946A1 (en) * | 2004-11-12 | 2006-05-18 | Novartis Ag | 1,4 substituted pyrazolopyrimidines as kinase inhibitors |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3070304D1 (en) | 1980-04-28 | 1985-04-25 | Teijin Ltd | Thiazolo(3,2-a)pyrimidine derivatives, process for preparing same, and drug containing same |
| US4612376A (en) | 1983-03-25 | 1986-09-16 | Fujisawa Pharmaceutical Co., Ltd. | Substituted-3,4-dihydro-4-(2,4,6-trimethoxyphenylimino)-2(1H)-pyrimidones useful as cardiotonic, antihypertensive, cerebrovascular vasodilator and anti-platelet agent |
| GB9114760D0 (en) | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
-
2006
- 2006-01-05 DO DO2006000009A patent/DOP2006000009A/es unknown
- 2006-01-09 TW TW095100806A patent/TW200637865A/zh unknown
- 2006-01-10 PE PE2006000054A patent/PE20061118A1/es not_active Application Discontinuation
- 2006-01-11 GT GT200600011A patent/GT200600011A/es unknown
- 2006-01-12 JP JP2007551363A patent/JP2008526975A/ja not_active Withdrawn
- 2006-01-12 AU AU2006204940A patent/AU2006204940A1/en not_active Withdrawn
- 2006-01-12 BR BRPI0606115-0A patent/BRPI0606115A2/pt not_active IP Right Cessation
- 2006-01-12 CA CA002593345A patent/CA2593345A1/en not_active Withdrawn
- 2006-01-12 PA PA20068659701A patent/PA8659701A1/es unknown
- 2006-01-12 EP EP06718131A patent/EP1838713A2/en not_active Withdrawn
- 2006-01-12 MX MX2007008381A patent/MX2007008381A/es active IP Right Grant
- 2006-01-12 WO PCT/US2006/001020 patent/WO2006076455A2/en not_active Ceased
- 2006-01-12 HN HN2006001493A patent/HN2006001493A/es unknown
- 2006-01-12 CN CNA2006800064543A patent/CN101142216A/zh not_active Withdrawn
- 2006-01-12 EA EA200701500A patent/EA013968B1/ru not_active IP Right Cessation
- 2006-01-12 AR ARP060100122A patent/AR052557A1/es not_active Application Discontinuation
- 2006-01-12 KR KR1020077018365A patent/KR20070114126A/ko not_active Withdrawn
- 2006-01-12 US US11/331,372 patent/US7425630B2/en not_active Expired - Fee Related
-
2007
- 2007-07-02 IL IL184365A patent/IL184365A0/en unknown
- 2007-07-03 CR CR9224A patent/CR9224A/es unknown
- 2007-07-06 ZA ZA200705279A patent/ZA200705279B/xx unknown
- 2007-08-06 NO NO20074052A patent/NO20074052L/no not_active Application Discontinuation
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0053678A1 (de) * | 1980-12-05 | 1982-06-16 | BASF Aktiengesellschaft | 5-Amino-1-phenyl-4-cyanpyrazole, diese enthaltende herbizide Mittel, Verfahren zu ihrer Herstellung und ihre Anwendung als Herbizide |
| EP0772087A1 (en) * | 1995-10-31 | 1997-05-07 | Fuji Photo Film Co., Ltd. | Pyrazolylazophenol dye |
| US6660744B1 (en) * | 1999-09-17 | 2003-12-09 | Abbott Gmbh & Co. Kg | Pyrazolopyrimidines as therapeutic agents |
| WO2003093269A2 (de) * | 2002-05-02 | 2003-11-13 | Bayer Cropscience Ag | Substituierte pyrazolo-pyrimidin-4-one |
| WO2004009602A1 (en) * | 2002-07-23 | 2004-01-29 | Smithkline Beecham Corporation | Pyrazolopyrimidines as kinase inhibitors |
| WO2005007658A2 (en) * | 2003-07-14 | 2005-01-27 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| WO2006050946A1 (en) * | 2004-11-12 | 2006-05-18 | Novartis Ag | 1,4 substituted pyrazolopyrimidines as kinase inhibitors |
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| Title |
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| ANDREW J. PEAT ET AL.: "Novel pyrazolopyrimidine derivatives as GSK-3 inhibitors". BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 14, 2004, pages 2121-2125, XP002399434, the whole document * |
| CHENG AND ROBINS: "Potential Purine Antagonists. XII. Synthesis of 1-Alkyl(aryl)-4,6-disubstituted Pyrazolo[3,4-d]pyrimidines". J. ORG. CHEM., vol. 23, 1958, pages 852-861, XP002385022, the whole document * |
| CHENG C.C. ET AL.: "POTENTIAL PURINE ANTAGONISTS". JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 21, 1 November, 1956 (1956-11-01), pages 1240-1256, XP000575948, ISSN: 0022-3263, examples; table I * |
| JAY A. MARKWALDER ET AL.: "Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Inhibitors of Cyclin-dependent Kinases". J. MED. CHEM., vol. 47, 2004, pages 5894-5911, XP002399637, examples; table I * |
| MITSUNOBU O.: "The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products". SYNTHESIS, GEORG THIEME VERLAG, STUTTGART, DE, 1981, pages 1-28, XP002123593, ISSN: 0039-7881, the whole document * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2709786C2 (ru) * | 2014-12-06 | 2019-12-20 | Интра-Селлулар Терапиз, Инк. | Органические соединения |
Also Published As
| Publication number | Publication date |
|---|---|
| IL184365A0 (en) | 2007-10-31 |
| KR20070114126A (ko) | 2007-11-29 |
| DOP2006000009A (es) | 2006-08-15 |
| US20060154940A1 (en) | 2006-07-13 |
| US7425630B2 (en) | 2008-09-16 |
| CR9224A (es) | 2007-10-23 |
| AR052557A1 (es) | 2007-03-21 |
| HN2006001493A (es) | 2010-08-19 |
| WO2006076455A2 (en) | 2006-07-20 |
| NO20074052L (no) | 2007-09-12 |
| PE20061118A1 (es) | 2006-10-13 |
| EP1838713A2 (en) | 2007-10-03 |
| BRPI0606115A2 (pt) | 2009-06-02 |
| CA2593345A1 (en) | 2006-07-20 |
| WO2006076455A8 (en) | 2006-11-02 |
| CN101142216A (zh) | 2008-03-12 |
| TW200637865A (en) | 2006-11-01 |
| GT200600011A (es) | 2006-08-10 |
| EA200701500A1 (ru) | 2007-12-28 |
| JP2008526975A (ja) | 2008-07-24 |
| PA8659701A1 (es) | 2006-09-08 |
| ZA200705279B (en) | 2008-11-26 |
| MX2007008381A (es) | 2007-09-07 |
| AU2006204940A1 (en) | 2006-07-20 |
| WO2006076455A3 (en) | 2006-12-07 |
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