JP2008526975A - ピラゾロ［３，４−ｄ］ピリミジンエーテルを調製するための方法 - Google Patents
ピラゾロ［３，４−ｄ］ピリミジンエーテルを調製するための方法 Download PDFInfo
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- JP2008526975A JP2008526975A JP2007551363A JP2007551363A JP2008526975A JP 2008526975 A JP2008526975 A JP 2008526975A JP 2007551363 A JP2007551363 A JP 2007551363A JP 2007551363 A JP2007551363 A JP 2007551363A JP 2008526975 A JP2008526975 A JP 2008526975A
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- alkyl
- alkoxy
- formula
- compound
- cycloalkyl
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- -1 pyrazolo [3,4-d] pyrimidine ethers Chemical class 0.000 title claims abstract description 205
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 238000000034 method Methods 0.000 claims abstract description 122
- 150000001875 compounds Chemical class 0.000 claims description 161
- 125000000217 alkyl group Chemical group 0.000 claims description 153
- 125000004414 alkyl thio group Chemical group 0.000 claims description 98
- 125000003545 alkoxy group Chemical group 0.000 claims description 91
- 229910052736 halogen Inorganic materials 0.000 claims description 85
- 238000006243 chemical reaction Methods 0.000 claims description 76
- 150000002367 halogens Chemical class 0.000 claims description 73
- 125000001188 haloalkyl group Chemical group 0.000 claims description 70
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 69
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 66
- 125000002252 acyl group Chemical group 0.000 claims description 64
- 125000003282 alkyl amino group Chemical group 0.000 claims description 61
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 61
- 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 60
- 125000001072 heteroaryl group Chemical group 0.000 claims description 60
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 58
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 57
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 56
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 55
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 53
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 53
- 125000004423 acyloxy group Chemical group 0.000 claims description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims description 50
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 50
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 48
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 46
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 46
- 125000000304 alkynyl group Chemical group 0.000 claims description 45
- 229910052799 carbon Inorganic materials 0.000 claims description 44
- 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 44
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 239000002904 solvent Substances 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 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 38
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 claims description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 239000003153 chemical reaction reagent Substances 0.000 claims description 29
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- 125000003342 alkenyl group Chemical group 0.000 claims description 23
- 230000002140 halogenating effect Effects 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 19
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 18
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 18
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 18
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 18
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 18
- 125000005363 dialkylsulfonamide group Chemical group 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 17
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical group CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 16
- 239000002585 base Substances 0.000 claims description 16
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 14
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 14
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 12
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000005223 heteroarylcarbonyl 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
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 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
- 150000001408 amides Chemical class 0.000 claims description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
- 125000004771 (C1-C4) haloalkylsulfinyl group Chemical group 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical group [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 5
- 239000003125 aqueous solvent Substances 0.000 claims description 5
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical group ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 5
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical class CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000003460 sulfonic acids Chemical group 0.000 claims description 4
- 239000012320 chlorinating reagent Substances 0.000 claims description 3
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 3
- 150000003512 tertiary amines Chemical class 0.000 claims description 3
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 claims description 2
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical group [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 claims description 2
- IKNCGYCHMGNBCP-UHFFFAOYSA-N propan-1-olate Chemical compound CCC[O-] IKNCGYCHMGNBCP-UHFFFAOYSA-N 0.000 claims description 2
- OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 claims description 2
- LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000005392 carboxamide group Chemical class NC(=O)* 0.000 claims 44
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 11
- 208000030159 metabolic disease Diseases 0.000 abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 5
- 208000008589 Obesity Diseases 0.000 abstract description 4
- 235000020824 obesity Nutrition 0.000 abstract description 4
- 150000008378 aryl ethers Chemical class 0.000 abstract description 3
- 230000004153 glucose metabolism Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- 239000002253 acid Substances 0.000 description 24
- 125000004432 carbon atom Chemical group C* 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 19
- 238000010992 reflux Methods 0.000 description 16
- BYHLFEBBMMRQTF-UHFFFAOYSA-N 1-(2-fluoro-4-methylsulfonylphenyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound FC1=CC(S(=O)(=O)C)=CC=C1N1C(N=CNC2=O)=C2C=N1 BYHLFEBBMMRQTF-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- 150000003857 carboxamides Chemical class 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 150000003839 salts Chemical group 0.000 description 11
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- UKVIBHRSFKWRPA-UHFFFAOYSA-N propan-2-yl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)OC(=O)N1CCC(O)CC1 UKVIBHRSFKWRPA-UHFFFAOYSA-N 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 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 8
- XTRUQJBVQBUKSQ-UHFFFAOYSA-N propan-2-yl 4-[1-(2-fluoro-4-methylsulfonylphenyl)pyrazolo[3,4-d]pyrimidin-4-yl]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1OC1=NC=NC2=C1C=NN2C1=CC=C(S(C)(=O)=O)C=C1F XTRUQJBVQBUKSQ-UHFFFAOYSA-N 0.000 description 8
- 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 7
- 0 *c(c(C#N)c1N)n[n]1-c1c(*)c(*)c(*)c(*)c1* Chemical compound *c(c(C#N)c1N)n[n]1-c1c(*)c(*)c(*)c(*)c1* 0.000 description 7
- PRCRQTARUHCPGS-UHFFFAOYSA-N 4-chloro-1-(2-fluoro-4-methylsulfonylphenyl)pyrazolo[3,4-d]pyrimidine Chemical compound FC1=CC(S(=O)(=O)C)=CC=C1N1C2=NC=NC(Cl)=C2C=N1 PRCRQTARUHCPGS-UHFFFAOYSA-N 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 229940124530 sulfonamide Drugs 0.000 description 7
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 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
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 150000003456 sulfonamides Chemical class 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 description 4
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- QQQBHMLMLJOSSQ-UHFFFAOYSA-N 5-amino-1-(2-fluoro-4-methylsulfonylphenyl)pyrazole-4-carboxamide Chemical compound FC1=CC(S(=O)(=O)C)=CC=C1N1C(N)=C(C(N)=O)C=N1 QQQBHMLMLJOSSQ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-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
- 150000004703 alkoxides Chemical class 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 125000003636 chemical group Chemical group 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000000593 degrading effect Effects 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 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
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 2
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 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
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-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
- GATVIKZLVQHOMN-UHFFFAOYSA-N Chlorodibromomethane Chemical compound ClC(Br)Br GATVIKZLVQHOMN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000001391 thioamide group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 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 |
|---|---|
| JP2008526975A true JP2008526975A (ja) | 2008-07-24 |
| JP2008526975A5 JP2008526975A5 (enExample) | 2009-02-19 |
Family
ID=36463499
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007551363A Withdrawn JP2008526975A (ja) | 2005-01-13 | 2006-01-12 | ピラゾロ［３，４−ｄ］ピリミジンエーテルを調製するための方法 |
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 |
|---|---|---|---|---|
| KR20200103694A (ko) | 2018-01-04 | 2020-09-02 | 엔티엔 가부시키가이샤 | 스위칭 전원의 역률 개선용 pwm 제어 장치 |
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 |
| HK1243936A1 (zh) * | 2014-12-06 | 2018-07-27 | Intra-Cellular Therapies, Inc. | 有机化合物 |
| 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 |
| 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 |
Family Cites Families (11)
| 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 |
| 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 |
| 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 |
| JP4022271B2 (ja) * | 1995-10-31 | 2007-12-12 | 富士フイルム株式会社 | ピラゾリルアゾフエノール色素 |
| DE60004685T2 (de) * | 1999-09-17 | 2004-07-29 | Abbott Gmbh & Co. Kg | Pyrazolopyrimidine als arzneimittel |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| DE10219435A1 (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 |
| 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 |
| GB0425035D0 (en) | 2004-11-12 | 2004-12-15 | Novartis Ag | Organic compounds |
-
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
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200103694A (ko) | 2018-01-04 | 2020-09-02 | 엔티엔 가부시키가이샤 | 스위칭 전원의 역률 개선용 pwm 제어 장치 |
Also Published As
| Publication number | Publication date |
|---|---|
| EA013968B1 (ru) | 2010-08-30 |
| 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 |
| 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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