KR20080083046A - 7ｈ-피리도[3,4-ｄ]피리미딘-8-온, 이의 제조 및 단백질키나아제 억제제로서의 용도 - Google Patents
7ｈ-피리도[3,4-ｄ]피리미딘-8-온, 이의 제조 및 단백질키나아제 억제제로서의 용도 Download PDFInfo
- Publication number
- KR20080083046A KR20080083046A KR1020087018893A KR20087018893A KR20080083046A KR 20080083046 A KR20080083046 A KR 20080083046A KR 1020087018893 A KR1020087018893 A KR 1020087018893A KR 20087018893 A KR20087018893 A KR 20087018893A KR 20080083046 A KR20080083046 A KR 20080083046A
- Authority
- KR
- South Korea
- Prior art keywords
- pyrido
- alkyl
- pyrimidin
- phenyl
- tolyl
- 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.)
- Ceased
Links
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 229940043355 kinase inhibitor Drugs 0.000 title description 9
- HALYIFFLOBGDNN-UHFFFAOYSA-N 7h-pyrido[3,4-d]pyrimidin-8-one Chemical compound N1=CN=C2C(=O)NC=CC2=C1 HALYIFFLOBGDNN-UHFFFAOYSA-N 0.000 title description 4
- 239000003909 protein kinase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 120
- 125000003545 alkoxy group Chemical group 0.000 claims description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 44
- -1 alkoxy halide Chemical class 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- CFYVVTQGJGMGOR-UHFFFAOYSA-N 2-(1,3-dihydroxypropan-2-ylamino)-7-[(1,5-dimethylpyrazol-3-yl)methyl]-6-(2-methylphenyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound CN1C(C)=CC(CN2C(C3=NC(NC(CO)CO)=NC=C3C=C2C=2C(=CC=CC=2)C)=O)=N1 CFYVVTQGJGMGOR-UHFFFAOYSA-N 0.000 claims description 2
- OBQLNSHAPHUQID-UHFFFAOYSA-N 2-(1,3-dihydroxypropan-2-ylamino)-7-methyl-6-(2-methylphenyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound CC1=CC=CC=C1C1=CC2=CN=C(NC(CO)CO)N=C2C(=O)N1C OBQLNSHAPHUQID-UHFFFAOYSA-N 0.000 claims description 2
- YFAPPBDUKQVPAY-UHFFFAOYSA-N 2-[2-[4-(2-hydroxyethylsulfamoyl)anilino]-6-(2-methylphenyl)-8-oxopyrido[3,4-d]pyrimidin-7-yl]acetamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CC(N)=O)=CC1=CN=C2NC1=CC=C(S(=O)(=O)NCCO)C=C1 YFAPPBDUKQVPAY-UHFFFAOYSA-N 0.000 claims description 2
- YSIDNDBXGCZXIG-UHFFFAOYSA-N 2-[3-(hydroxymethyl)anilino]-7-methyl-6-(2-methylphenyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)C)=CC1=CN=C2NC1=CC=CC(CO)=C1 YSIDNDBXGCZXIG-UHFFFAOYSA-N 0.000 claims description 2
- PVEUVXMDUYUTLE-UHFFFAOYSA-N 2-[4-[2-(diethylamino)ethoxy]anilino]-7-(3-hydroxypropyl)-6-(2-methylphenyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)C)N(CCCO)C2=O)C2=N1 PVEUVXMDUYUTLE-UHFFFAOYSA-N 0.000 claims description 2
- RKZOYIUPOZIVHO-UHFFFAOYSA-N 2-[4-[2-(diethylamino)ethoxy]anilino]-7-[(3-methoxyphenyl)methyl]-6-(2-methylphenyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)C)N(CC=2C=C(OC)C=CC=2)C2=O)C2=N1 RKZOYIUPOZIVHO-UHFFFAOYSA-N 0.000 claims description 2
- RGWPDAJQKZATQH-UHFFFAOYSA-N 2-[4-[2-(diethylamino)ethoxy]anilino]-7-methyl-6-(2-methylphenyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)C)N(C)C2=O)C2=N1 RGWPDAJQKZATQH-UHFFFAOYSA-N 0.000 claims description 2
- OZSDPBBOARQELU-UHFFFAOYSA-N 2-[6-(2-chlorophenyl)-2-(oxan-4-ylamino)-8-oxopyrido[3,4-d]pyrimidin-7-yl]acetamide Chemical compound N1=C2C(=O)N(CC(=O)N)C(C=3C(=CC=CC=3)Cl)=CC2=CN=C1NC1CCOCC1 OZSDPBBOARQELU-UHFFFAOYSA-N 0.000 claims description 2
- NXBADEZEZICPGN-UHFFFAOYSA-N 2-[6-(2-methylphenyl)-2-(3-methylsulfinylanilino)-8-oxopyrido[3,4-d]pyrimidin-7-yl]acetamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CC(N)=O)=CC1=CN=C2NC1=CC=CC(S(C)=O)=C1 NXBADEZEZICPGN-UHFFFAOYSA-N 0.000 claims description 2
- QDSZTANZRSSYPB-UHFFFAOYSA-N 2-[6-(2-methylphenyl)-2-(oxan-4-ylamino)-8-oxopyrido[3,4-d]pyrimidin-7-yl]acetamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CC(N)=O)=CC1=CN=C2NC1CCOCC1 QDSZTANZRSSYPB-UHFFFAOYSA-N 0.000 claims description 2
- ZTPYDDGSZWLQHO-UHFFFAOYSA-N 3-[2-[3-(hydroxymethyl)anilino]-6-(2-methylphenyl)-8-oxopyrido[3,4-d]pyrimidin-7-yl]propanamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CCC(N)=O)=CC1=CN=C2NC1=CC=CC(CO)=C1 ZTPYDDGSZWLQHO-UHFFFAOYSA-N 0.000 claims description 2
- VRENCUASBPZFLX-UHFFFAOYSA-N 3-[2-[4-(2-hydroxyethylsulfamoyl)anilino]-6-(2-methylphenyl)-8-oxopyrido[3,4-d]pyrimidin-7-yl]propanamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CCC(N)=O)=CC1=CN=C2NC1=CC=C(S(=O)(=O)NCCO)C=C1 VRENCUASBPZFLX-UHFFFAOYSA-N 0.000 claims description 2
- HPJQYYYMYLFCAK-UHFFFAOYSA-N 3-[6-(2-chlorophenyl)-2-(1,3-dihydroxypropan-2-ylamino)-8-oxopyrido[3,4-d]pyrimidin-7-yl]propanamide Chemical compound C=1C2=CN=C(NC(CO)CO)N=C2C(=O)N(CCC(=O)N)C=1C1=CC=CC=C1Cl HPJQYYYMYLFCAK-UHFFFAOYSA-N 0.000 claims description 2
- LYHWGYMJMQAJRQ-UHFFFAOYSA-N 3-[6-(2-methylphenyl)-2-(3-methylsulfinylanilino)-8-oxopyrido[3,4-d]pyrimidin-7-yl]propanamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CCC(N)=O)=CC1=CN=C2NC1=CC=CC(S(C)=O)=C1 LYHWGYMJMQAJRQ-UHFFFAOYSA-N 0.000 claims description 2
- NHWHSOGRLRMVNL-UHFFFAOYSA-N 3-[6-(2-methylphenyl)-2-(oxan-4-ylamino)-8-oxopyrido[3,4-d]pyrimidin-7-yl]propanamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CCC(N)=O)=CC1=CN=C2NC1CCOCC1 NHWHSOGRLRMVNL-UHFFFAOYSA-N 0.000 claims description 2
- RESWMSDAFKNKQB-UHFFFAOYSA-N 4-[[6-(2-chlorophenyl)-7-[(3-methoxyphenyl)methyl]-8-oxopyrido[3,4-d]pyrimidin-2-yl]amino]-n-(2-hydroxyethyl)benzenesulfonamide Chemical compound COC1=CC=CC(CN2C(C3=NC(NC=4C=CC(=CC=4)S(=O)(=O)NCCO)=NC=C3C=C2C=2C(=CC=CC=2)Cl)=O)=C1 RESWMSDAFKNKQB-UHFFFAOYSA-N 0.000 claims description 2
- NGCCXCRUDFXWCY-UHFFFAOYSA-N 4-[[6-(2-chlorophenyl)-8-oxo-7-(oxolan-2-ylmethyl)pyrido[3,4-d]pyrimidin-2-yl]amino]-n-(2-hydroxyethyl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCO)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)Cl)N(CC2OCCC2)C2=O)C2=N1 NGCCXCRUDFXWCY-UHFFFAOYSA-N 0.000 claims description 2
- AVQHHLQKPWZZDK-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-(3-methylsulfinylanilino)-7-(oxolan-2-ylmethyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound CS(=O)C1=CC=CC(NC=2N=C3C(=O)N(CC4OCCC4)C(C=4C(=CC=CC=4)Cl)=CC3=CN=2)=C1 AVQHHLQKPWZZDK-UHFFFAOYSA-N 0.000 claims description 2
- RYPMPNMNCZHJLH-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[3-(hydroxymethyl)anilino]-7-(oxolan-2-ylmethyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound OCC1=CC=CC(NC=2N=C3C(=O)N(CC4OCCC4)C(C=4C(=CC=CC=4)Cl)=CC3=CN=2)=C1 RYPMPNMNCZHJLH-UHFFFAOYSA-N 0.000 claims description 2
- YCJXYUWUOHIDRN-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-7-(oxolan-2-ylmethyl)pyrido[3,4-d]pyrimidin-8-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)Cl)N(CC2OCCC2)C2=O)C2=N1 YCJXYUWUOHIDRN-UHFFFAOYSA-N 0.000 claims description 2
- OGFWUHSGXBHARP-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-7-[(1,5-dimethylpyrazol-3-yl)methyl]pyrido[3,4-d]pyrimidin-8-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)Cl)N(CC2=NN(C)C(C)=C2)C2=O)C2=N1 OGFWUHSGXBHARP-UHFFFAOYSA-N 0.000 claims description 2
- UVOULCYPXQQYDW-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-7-[(3-methoxyphenyl)methyl]pyrido[3,4-d]pyrimidin-8-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)Cl)N(CC=2C=C(OC)C=CC=2)C2=O)C2=N1 UVOULCYPXQQYDW-UHFFFAOYSA-N 0.000 claims description 2
- NRQGOUAFINXVQZ-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-(3-hydroxypropyl)-2-(oxan-4-ylamino)pyrido[3,4-d]pyrimidin-8-one Chemical compound N1=C2C(=O)N(CCCO)C(C=3C(=CC=CC=3)Cl)=CC2=CN=C1NC1CCOCC1 NRQGOUAFINXVQZ-UHFFFAOYSA-N 0.000 claims description 2
- JWYITBGREPYZJO-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-(3-hydroxypropyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[3,4-d]pyrimidin-8-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)Cl)N(CCCO)C2=O)C2=N1 JWYITBGREPYZJO-UHFFFAOYSA-N 0.000 claims description 2
- PWGFEGBMOWMWQG-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-[(1,5-dimethylpyrazol-3-yl)methyl]-2-(3-methylsulfinylanilino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CN1C(C)=CC(CN2C(C3=NC(NC=4C=C(C=CC=4)S(C)=O)=NC=C3C=C2C=2C(=CC=CC=2)Cl)=O)=N1 PWGFEGBMOWMWQG-UHFFFAOYSA-N 0.000 claims description 2
- AZWCKDWFXLIFRV-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-[(1,5-dimethylpyrazol-3-yl)methyl]-2-(oxan-4-ylamino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CN1C(C)=CC(CN2C(C3=NC(NC4CCOCC4)=NC=C3C=C2C=2C(=CC=CC=2)Cl)=O)=N1 AZWCKDWFXLIFRV-UHFFFAOYSA-N 0.000 claims description 2
- LLIOFPODVJPFGX-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-[(1,5-dimethylpyrazol-3-yl)methyl]-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[3,4-d]pyrimidin-8-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)Cl)N(CC2=NN(C)C(C)=C2)C2=O)C2=N1 LLIOFPODVJPFGX-UHFFFAOYSA-N 0.000 claims description 2
- YQGFOMQKQKZHTP-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-[(3-methoxyphenyl)methyl]-2-(3-methylsulfinylanilino)pyrido[3,4-d]pyrimidin-8-one Chemical compound COC1=CC=CC(CN2C(C3=NC(NC=4C=C(C=CC=4)S(C)=O)=NC=C3C=C2C=2C(=CC=CC=2)Cl)=O)=C1 YQGFOMQKQKZHTP-UHFFFAOYSA-N 0.000 claims description 2
- TVVPDJCZXMQWGT-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-[(3-methoxyphenyl)methyl]-2-(oxan-4-ylamino)pyrido[3,4-d]pyrimidin-8-one Chemical compound COC1=CC=CC(CN2C(C3=NC(NC4CCOCC4)=NC=C3C=C2C=2C(=CC=CC=2)Cl)=O)=C1 TVVPDJCZXMQWGT-UHFFFAOYSA-N 0.000 claims description 2
- VBWRSVIRIYDORD-UHFFFAOYSA-N 6-(2-chlorophenyl)-7-[(3-methoxyphenyl)methyl]-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[3,4-d]pyrimidin-8-one Chemical compound COC1=CC=CC(CN2C(C3=NC(NC=4C=CC(=CC=4)N4CCN(C)CC4)=NC=C3C=C2C=2C(=CC=CC=2)Cl)=O)=C1 VBWRSVIRIYDORD-UHFFFAOYSA-N 0.000 claims description 2
- KVYCTLGELAAPQX-UHFFFAOYSA-N 7-(3-hydroxypropyl)-6-(2-methylphenyl)-2-(3-methylsulfinylanilino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CCCO)=CC1=CN=C2NC1=CC=CC(S(C)=O)=C1 KVYCTLGELAAPQX-UHFFFAOYSA-N 0.000 claims description 2
- OPCDESUYDQTXFA-UHFFFAOYSA-N 7-(3-hydroxypropyl)-6-(2-methylphenyl)-2-(oxan-4-ylamino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)CCCO)=CC1=CN=C2NC1CCOCC1 OPCDESUYDQTXFA-UHFFFAOYSA-N 0.000 claims description 2
- OYXFOQCZUUJTJB-UHFFFAOYSA-N 7-(3-hydroxypropyl)-6-(2-methylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[3,4-d]pyrimidin-8-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)C)N(CCCO)C2=O)C2=N1 OYXFOQCZUUJTJB-UHFFFAOYSA-N 0.000 claims description 2
- IZDSUOKQXXEKOR-UHFFFAOYSA-N 7-[(1,5-dimethylpyrazol-3-yl)methyl]-6-(2-methylphenyl)-2-(4-morpholin-4-ylanilino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CN1C(C)=CC(CN2C(C3=NC(NC=4C=CC(=CC=4)N4CCOCC4)=NC=C3C=C2C=2C(=CC=CC=2)C)=O)=N1 IZDSUOKQXXEKOR-UHFFFAOYSA-N 0.000 claims description 2
- WGUGIZCDBUEOJV-UHFFFAOYSA-N 7-[(1,5-dimethylpyrazol-3-yl)methyl]-6-(2-methylphenyl)-2-(oxan-4-ylamino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CN1C(C)=CC(CN2C(C3=NC(NC4CCOCC4)=NC=C3C=C2C=2C(=CC=CC=2)C)=O)=N1 WGUGIZCDBUEOJV-UHFFFAOYSA-N 0.000 claims description 2
- DJAAILTXUVEZLQ-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methyl]-6-(2-methylphenyl)-2-(3-methylsulfinylanilino)pyrido[3,4-d]pyrimidin-8-one Chemical compound COC1=CC=CC(CN2C(C3=NC(NC=4C=C(C=CC=4)S(C)=O)=NC=C3C=C2C=2C(=CC=CC=2)C)=O)=C1 DJAAILTXUVEZLQ-UHFFFAOYSA-N 0.000 claims description 2
- KRYCEFUADFGKJU-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methyl]-6-(2-methylphenyl)-2-(oxan-4-ylamino)pyrido[3,4-d]pyrimidin-8-one Chemical compound COC1=CC=CC(CN2C(C3=NC(NC4CCOCC4)=NC=C3C=C2C=2C(=CC=CC=2)C)=O)=C1 KRYCEFUADFGKJU-UHFFFAOYSA-N 0.000 claims description 2
- QLNJBPDCZNPQMJ-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methyl]-6-(2-methylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[3,4-d]pyrimidin-8-one Chemical compound COC1=CC=CC(CN2C(C3=NC(NC=4C=CC(=CC=4)N4CCN(C)CC4)=NC=C3C=C2C=2C(=CC=CC=2)C)=O)=C1 QLNJBPDCZNPQMJ-UHFFFAOYSA-N 0.000 claims description 2
- SYAYNWSCLXNBNR-UHFFFAOYSA-N 7-methyl-6-(2-methylphenyl)-2-(3-methylsulfinylanilino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)C)=CC1=CN=C2NC1=CC=CC(S(C)=O)=C1 SYAYNWSCLXNBNR-UHFFFAOYSA-N 0.000 claims description 2
- PQMSNGBEYXMPJH-UHFFFAOYSA-N 7-methyl-6-(2-methylphenyl)-2-(4-morpholin-4-ylanilino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)C)=CC1=CN=C2NC1=CC=C(N2CCOCC2)C=C1 PQMSNGBEYXMPJH-UHFFFAOYSA-N 0.000 claims description 2
- ZPMRVEWUTMHHTR-UHFFFAOYSA-N 7-methyl-6-(2-methylphenyl)-2-(oxan-4-ylamino)pyrido[3,4-d]pyrimidin-8-one Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)C)=CC1=CN=C2NC1CCOCC1 ZPMRVEWUTMHHTR-UHFFFAOYSA-N 0.000 claims description 2
- GYHFZUDOHXHCOR-UHFFFAOYSA-N 7-methyl-6-(2-methylphenyl)-2-[4-(4-methylpiperazin-1-yl)anilino]pyrido[3,4-d]pyrimidin-8-one Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2)C)N(C)C2=O)C2=N1 GYHFZUDOHXHCOR-UHFFFAOYSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 235000012054 meals Nutrition 0.000 claims description 2
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- YUDXESFEIFXSIV-UHFFFAOYSA-N n-(2-hydroxyethyl)-4-[[7-[(3-methoxyphenyl)methyl]-6-(2-methylphenyl)-8-oxopyrido[3,4-d]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound COC1=CC=CC(CN2C(C3=NC(NC=4C=CC(=CC=4)S(=O)(=O)NCCO)=NC=C3C=C2C=2C(=CC=CC=2)C)=O)=C1 YUDXESFEIFXSIV-UHFFFAOYSA-N 0.000 claims description 2
- MJESOYWMNDKUPV-UHFFFAOYSA-N n-(2-hydroxyethyl)-4-[[7-methyl-6-(2-methylphenyl)-8-oxopyrido[3,4-d]pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CC1=CC=CC=C1C(N(C(=O)C1=N2)C)=CC1=CN=C2NC1=CC=C(S(=O)(=O)NCCO)C=C1 MJESOYWMNDKUPV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 239000000203 mixture Substances 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- 101150001535 SRC gene Proteins 0.000 description 27
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 238000000034 method Methods 0.000 description 23
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- ORFSSYGWXNGVFB-UHFFFAOYSA-N sodium 4-amino-6-[[4-[4-[(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl]-3-methoxyphenyl]-2-methoxyphenyl]diazenyl]-5-hydroxynaphthalene-1,3-disulfonic acid Chemical compound COC1=C(C=CC(=C1)C2=CC(=C(C=C2)N=NC3=C(C4=C(C=C3)C(=CC(=C4N)S(=O)(=O)O)S(=O)(=O)O)O)OC)N=NC5=C(C6=C(C=C5)C(=CC(=C6N)S(=O)(=O)O)S(=O)(=O)O)O.[Na+] ORFSSYGWXNGVFB-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000009221 stress response pathway Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 238000001685 time-resolved fluorescence spectroscopy Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-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
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/22—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06001915 | 2006-01-31 | ||
| EP06001915.5 | 2006-01-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080083046A true KR20080083046A (ko) | 2008-09-12 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| KR1020087018893A Ceased KR20080083046A (ko) | 2006-01-31 | 2007-01-29 | 7ｈ-피리도[3,4-ｄ]피리미딘-8-온, 이의 제조 및 단백질키나아제 억제제로서의 용도 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8058283B2 (https=) |
| EP (1) | EP1981886B1 (https=) |
| JP (1) | JP2009525292A (https=) |
| KR (1) | KR20080083046A (https=) |
| CN (1) | CN101374840B (https=) |
| AT (1) | ATE439361T1 (https=) |
| AU (1) | AU2007211684A1 (https=) |
| BR (1) | BRPI0706781A2 (https=) |
| CA (1) | CA2636981A1 (https=) |
| DE (1) | DE602007001952D1 (https=) |
| ES (1) | ES2329419T3 (https=) |
| IL (1) | IL191748A0 (https=) |
| WO (1) | WO2007088014A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200100429A (ko) * | 2019-02-18 | 2020-08-26 | 한국과학기술연구원 | 단백질 키나아제 저해 활성을 갖는 신규한 피리도[3,4-d]피리미딘-8-온 유도체 및 이를 포함하는 암의 예방, 개선 또는 치료용 약학 조성물 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009525292A (ja) | 2006-01-31 | 2009-07-09 | エフ．ホフマン−ラ ロシュ アーゲー | ７ｈ−ピリド［３，４−ｄ］ピリミジン−８−オン、それらの製造及びプロテインキナーゼ阻害剤としての使用 |
| SA111320200B1 (ar) * | 2010-02-17 | 2014-02-16 | ديبيوفارم اس ايه | مركبات ثنائية الحلقة واستخداماتها كمثبطات c-src/jak مزدوجة |
| CN104271576A (zh) | 2012-02-23 | 2015-01-07 | 艾伯维公司 | 激酶的吡啶并嘧啶酮抑制剂 |
| JP6280546B2 (ja) | 2012-06-26 | 2018-02-14 | デル マー ファーマシューティカルズ | ジアンヒドロガラクチトール、ジアセチルジアンヒドロガラクチトール、ジブロモズルシトール、又はこれらの類似体若しくは誘導体を用いた、遺伝子多型又はａｈｉ１の調節不全若しくは変異を有する患者におけるチロシンキナーゼインヒビター抵抗性悪性腫瘍を処置するための方法 |
| CN105130986B (zh) | 2015-09-30 | 2017-07-18 | 广州科擎新药开发有限公司 | 嘧啶或吡啶并吡啶酮类化合物及其应用 |
| CN110016026B (zh) * | 2018-01-08 | 2022-11-25 | 上海凌济生物科技有限公司 | 一类具有抗肿瘤活性的嘧啶并吡啶酮类化合物、制备方法和用途 |
| KR102329720B1 (ko) * | 2019-08-30 | 2021-11-23 | 한국과학기술연구원 | 단백질 키나아제 저해 활성을 갖는 신규한 피리미도[4,5-d]피리미딘-2-온 유도체 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUT76853A (en) | 1994-11-14 | 1997-12-29 | Warner Lambert Co | 6-aryl pyrido[2,3-d]pyrimidines and naphthyridines for inhibiting protein tyrosine kinase mediated cellular proliferation and pharmaceutical compositions containing the same |
| IL117923A (en) | 1995-05-03 | 2000-06-01 | Warner Lambert Co | Anti-cancer pharmaceutical compositions containing polysubstituted pyrido¬2,3-d¾pyrimidine derivatives and certain such novel compounds |
| RS49779B (sr) * | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| AU763839B2 (en) | 1998-05-26 | 2003-07-31 | Warner-Lambert Company | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
| NZ510760A (en) | 1998-10-23 | 2003-08-29 | F | Bicyclic nitrogen heterocycles |
| KR100537241B1 (ko) | 1999-10-21 | 2005-12-19 | 에프. 호프만-라 로슈 아게 | Ｐ38 단백질 키나제의 억제제로서의 알킬아미노 치환된이중고리 질소 헤테로고리 화합물 |
| DE60033307T2 (de) | 1999-10-21 | 2007-07-12 | F. Hoffmann-La Roche Ag | Heteroalkylamino-substituierte bicyclische stickstoffheterocyclen als p38-proteinkinase-inhibitoren |
| CA2420122A1 (en) | 2000-08-31 | 2002-03-07 | F. Hoffmann-La Roche Ag | 7-oxo pyridopyrimidines |
| WO2002018380A1 (en) | 2000-08-31 | 2002-03-07 | F. Hoffmann-La Roche Ag | 7-oxo pyridopyrimidines as inhibitors of a cellular proliferation |
| US7196090B2 (en) | 2002-07-25 | 2007-03-27 | Warner-Lambert Company | Kinase inhibitors |
| US7112676B2 (en) | 2002-11-04 | 2006-09-26 | Hoffmann-La Roche Inc. | Pyrimido compounds having antiproliferative activity |
| TW200413381A (en) | 2002-11-04 | 2004-08-01 | Hoffmann La Roche | Novel amino-substituted dihydropyrimido [4,5-d]pyrimidinone derivatives, their manufacture and use as pharmaceutical agents |
| CL2004000366A1 (es) | 2003-02-26 | 2005-01-07 | Pharmacia Corp Sa Organizada B | USO DE UNA COMBINACION DE UN COMPUESTO DERIVADO DE PIRAZOL INHIBIDOR DE QUINASA p38, Y UN INHIBIDOR DE ACE PARA TRATAR DISFUNCION RENAL, ENFERMEDAD CARDIOVASCULAR Y VASCULAR, RETINOPATIA, NEUROPATIA, EDEMA, DISFUNCION ENDOTELIAL O INSULINOPATIA. |
| JP2006522756A (ja) | 2003-04-10 | 2006-10-05 | エフ．ホフマン−ラ ロシュ アーゲー | ピリミド化合物 |
| MXPA06001098A (es) | 2003-07-29 | 2006-04-24 | Irm Llc | Compuestos y composiciones utiles como inhibidores de proteina cinasa. |
| AU2004279427B2 (en) * | 2003-10-08 | 2008-07-03 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| WO2006012577A2 (en) * | 2004-07-22 | 2006-02-02 | Bayer Pharmaceuticals Corporation | Quinazolinone derivatives useful for the regulation of glucose homeostasis and food intake |
| JP2009525292A (ja) | 2006-01-31 | 2009-07-09 | エフ．ホフマン−ラ ロシュ アーゲー | ７ｈ−ピリド［３，４−ｄ］ピリミジン−８−オン、それらの製造及びプロテインキナーゼ阻害剤としての使用 |
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- 2007-01-29 AU AU2007211684A patent/AU2007211684A1/en not_active Abandoned
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- 2007-01-29 CN CN2007800035988A patent/CN101374840B/zh not_active Expired - Fee Related
- 2007-01-29 AT AT07703091T patent/ATE439361T1/de not_active IP Right Cessation
- 2007-01-29 CA CA002636981A patent/CA2636981A1/en not_active Abandoned
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- 2007-01-29 EP EP07703091A patent/EP1981886B1/en not_active Not-in-force
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200100429A (ko) * | 2019-02-18 | 2020-08-26 | 한국과학기술연구원 | 단백질 키나아제 저해 활성을 갖는 신규한 피리도[3,4-d]피리미딘-8-온 유도체 및 이를 포함하는 암의 예방, 개선 또는 치료용 약학 조성물 |
| WO2020171499A1 (ko) * | 2019-02-18 | 2020-08-27 | 한국과학기술연구원 | 단백질 키나아제 저해 활성을 갖는 신규한 피리도[3,4-d]피리미딘-8-온 유도체 및 이를 포함하는 암의 예방, 개선 또는 치료용 약학 조성물 |
| AU2020225048B2 (en) * | 2019-02-18 | 2023-02-23 | Pharos Ibio Co., Ltd | Novel pyrido(3,4-d)pyrimidin-8-one derivative having protein kinase inhibitory activity, and pharmaceutical composition for preventing, alleviating, or treating cancer, comprising same |
Also Published As
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|---|---|
| EP1981886A1 (en) | 2008-10-22 |
| BRPI0706781A2 (pt) | 2011-04-05 |
| CN101374840B (zh) | 2011-09-28 |
| AU2007211684A1 (en) | 2007-08-09 |
| JP2009525292A (ja) | 2009-07-09 |
| ATE439361T1 (de) | 2009-08-15 |
| EP1981886B1 (en) | 2009-08-12 |
| ES2329419T3 (es) | 2009-11-25 |
| US20090030020A1 (en) | 2009-01-29 |
| US8058283B2 (en) | 2011-11-15 |
| WO2007088014A1 (en) | 2007-08-09 |
| IL191748A0 (en) | 2008-12-29 |
| DE602007001952D1 (de) | 2009-09-24 |
| CN101374840A (zh) | 2009-02-25 |
| CA2636981A1 (en) | 2007-08-09 |
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