Tissue non-specific alkaline phosphatase inhibitors and uses thereof for treating vascular calcification 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2009017863 A2 2009-02-05 [WO200917863]WO2009017863 A3 2009-03-19 [WO200917863] / 2009-02-052009-03-19
申请号/申请日
2008WO-US63106 / 2008-05-08
发明人
MILLAN JOSE LUIS;SERGIENKO EDUARD;
申请人
BURNHAM INSTITUTE MEDICAL RESEARCH;
主分类号
IPC分类号
A01N-043/56A61K-031/41
摘要
(WO200917863) Disclosed herein are compounds that are tissue-nonspecific alkaline phosphatase inhibitors.  The disclosed compounds are used to treat, prevent, or abate vascular calcification, arterial calcification and other cardiovascular diseases.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2007US-60928400 2007-05-08
主权利要求
(WO200917863) CLAIMS What is claimed is: 1. A method of treating or preventing vascular calcifcication in a subject, comprising administering to the subject one or more compounds having the formula: wherein R is chosen from: i) hydrogen; ii) C]-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; iii) C2-Ci2substituted or unsubstituted linear or branched alkenyl; iv) C2-Ci2substituted or unsubstituted linear or branched alkynyl; v) substituted or unsubstituted aryl; vi) substituted or unsubstituted heteroaryl; vii) substituted or unsubstituted heterocyclic; viii) -NHC(O)CH3; ix) -C(O)OCH3; or x) -C(O)OH; R1is chosen from: i) hydrogen; ii) Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; iii) C2-Ci2substituted or unsubstituted linear or branched alkenyl; iv) C2-Ci2substituted or unsubstituted linear or branched alkynyl; v) substituted or unsubstituted aryl; vi) substituted or unsubstituted heteroaryl; vii) substituted or unsubstituted heterocyclic; viii) -NHC(O)CH3; ix) -C(O)OCH3; x) -C(O)OH; xi) -OH; or xii) -NH2; R2is: i) hydrogen; ii) halogen; or iii) R and R2or R1and R2can be taken together to form ring A comprising one or more 5 -member or 6-member substituted or unsubstituted cycloalkyl fused rings, substituted or unsubstituted aryl fused rings, 5-member or 6- member heteroaryl fused rings having one or more atoms chosen from nitrogen, oxygen, and sulfur, or substituted or unsubstituted 5-member, 6- member, or 7-member heterocyclic fused rings having one or more atoms chosen from nitrogen, oxygen, and sulfur; L is a linking unit having the formula: -[R5]z[C(R3aR3b)]x[R5]z[C(R4aR4b)]y[R5]z- each R3a, R3b, R4a, and R4bare each independently chosen from: i) hydrogen; ii) Ci-C4linear or branched alkyl; iii) phenyl; iv) hydroxyl; or v) cyano; vi) or two adjacent R3aunits or two adjacent R3bunits can be taken together to form a double bond; R5is chosen from: i) -NR6-; ϋ) -NR6C(O)-; iii) -C(O)NR6-; iv) -C(O)-; v) -OC(O)-; Vi) -C(O)O-; vii) -NHC(O)NH-; viii) -NH(=NR6)NH-; ix) -0-; x) -S-; or Xi) -CR6=CR6-; R6is chosen from hydrogen or methyl; the index x is from O to 6; the index y from O to 6; each index z is 0 or 1 ; L1is a linking unit having the formula: -[R9]r[C(R7aR7b)]p[R9]r[C(R8aR8b)]q[R9]r- each R7a, R7b, R8a, and R8bare each independently chosen from: i) hydrogen; ϋ) Ci-C4linear or branched alkyl; iii) phenyl; iv) hydroxyl; or v) cyano; each R9is chosen from: i) -NR10-; ϋ) -NR10C(O)-; iii) -C(O)NR10-; iv) -C(O)-; v) -OC(O)-; vi) -C(O)O-; vii) -NHC(O)NH-; viii) -C(O)NHC(O)NH-; IX) -NH(=NR10)NH-;x) -0-; Xi) -S-; or xii) -CR10=CR10-; each R10is chosen from hydrogen or methyl; the index p is from O to 6; the index q from O to 6; and each index r is O or 1. 2. The method of claim 1, wherein R, R1, and R2can be substituted by one or more units chosen from: i) Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; ii) C2-Ci2substituted or unsubstituted linear, branched, or cyclic alkenyl; iii) C2-Ci2substituted or unsubstituted linear or branched alkynyl; iv) C6or Cio substituted or unsubstituted aryl; v) C1-Cg substituted or unsubstituted heterocyclic; vi) Ci-Cn substituted or unsubstituted heteroaryl; vii) -[C(R14a)(R14b)]kOR15; wherein R15is chosen from: a) -H; b) Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl or C1-C12substituted or unsubstituted linear, branched, or cyclic haloalkyl; c) C6or Cio substituted or unsubstituted aryl or C7-C2O alkylenearyl; d) Ci -Cg substituted or unsubstituted heterocyclic; and e) Ci-Cn substituted or unsubstituted heteroaryl; viii) -[C(R14a)(R14b)]kN(R16a)(R16b); wherein R16aand R16bare each independently chosen from: a) -H; b) -OR17; R17is hydrogen or Q-C4 linear alkyl; c) C1-C12substituted or unsubstituted linear, branched, or cyclic alkyl; d) C6or Cio substituted or unsubstituted aryl; e) Ci-Cg substituted or unsubstituted heterocyclic; f) Ci-Cn substituted or unsubstituted heteroaryl; and g) R16aand R16bcan be taken together to form a substituted or unsubstituted ring having from 3 to 10 carbon atoms and from 0 to 3 heteroatoms chosen from oxygen, nitrogen, and sulfur; ix) -[C(R14a)(R14b)]kC(O)R18; wherein R is chosen from: a) Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; b) -OR19; wherein R19is hydrogen, substituted or unsubstituted Ci-C4linear alkyl, C6or Cio substituted or unsubstituted aryl, Ci-Cg substituted or unsubstituted heterocyclic, C]-Cn substituted or unsubstituted heteroaryl; and c) -N(R20a)(R20b); wherein R20aand R20bare each independently hydrogen, C]-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; C6or Cio substituted or unsubstituted aryl; C1-C9 substituted or unsubstituted heterocyclic; Ci-Cn substituted or unsubstituted heteroaryl; or R20aand R20bcan be taken together to form a substituted or unsubstituted ring having from 3 to 10 carbon atoms and from 0 to 3 heteroatoms chosen from oxygen, nitrogen, and sulfur; -[C(R14a)(R14b)]kOC(O)R21; wherein R21is chosen from: a) Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; and b) -N(R22a)(R22b); R22aand R22bare each independently hydrogen, Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; C6or C10substituted or unsubstituted aryl; C1-C9substituted or unsubstituted heterocyclic; Ci-Cn substituted or unsubstituted heteroaryl; or Raand R22bcan be taken together to form a substituted or unsubstituted ring having from 3 to 10 carbon atoms and from 0 to 3 heteroatoms chosen from oxygen, nitrogen, and sulfur; -[C(R14a)(R14b)]kNR23C(O)R24; wherein R23is chosen from: a) -H; and b) Ci-C4substituted or unsubstituted linear, branched, or cyclic alkyl; wherein R24is chosen from: a) Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; and b) -N(R25a)(R25b); R25aand R25bare each independently hydrogen, Ci-Ci2substituted or unsubstituted linear, branched, or cyclic alkyl; C6or Ci0substituted or unsubstituted aryl; C1-C9substituted or unsubstituted heterocyclic; Ci-Cn substituted or unsubstituted heteroaryl; or R25aand R25bcan be taken together to form a substituted or unsubstituted ring having from 3 to 10 carbon atoms and from 0 to 3 heteroatoms chosen from oxygen, nitrogen, and sulfur; xii) -[C(R14a)(R14b)]kCN; xiii) -[C(R14a)(R14b)]kNO2; xiv) -[C(R14a)(R14b)]kSO2R26; R26is hydrogen, hydroxyl, substituted or unsubstituted Ci-C4linear or branched alkyl; substituted or unsubstituted C6, C10, or Ci4aryl; C7-Ci5alkylenearyl; C1-Cg substituted or unsubstituted heterocyclic; or Ci-Cn substituted or unsubstituted heteroaryl; and xv) halogen; R14aand R14bare each independently hydrogen or CpC4alkyl; and the index k is from 0 to 5. 3. The method of claim 2, having the formula: wherein R is i) hydrogen; ii) substituted or unsubstituted aryl; or iii) substituted or unsubstituted heteroaryl; R1is chosen from: i) hydrogen; ii) substituted or unsubstituted aryl; iii) substituted or unsubstituted heteroaryl; and iv) substituted or unsubstituted heterocyclic; each R9is independently chosen from: i) -NHC(O)-; ii) -C(O)NH-; iii) -C(O)-; iv) -NHC(O)NH-; v) -C(O)NHC(O)NH-; vi) -NH(=NR10)NH-; or vii) -O-; the index p is from 1 to 3; the index q is from 1 to 3; and the index r is 1 or 0. 4. The method of claim 1, having the formula: wherein Rais from 0 to 5 substitutions for hydrogen chosen from: i) chloro; ii) fluoro; iii) bromo; iv) methoxy; and v) cyano; R1is chosen from: i) substituted or unsubstituted aryl; or ii) substituted or unsubstituted heteroaryl each R9is chosen from: 1) -NHC(O)-; ii) -C(O)NH-; iϋ) -C(O)-; iv) -C(O)NHC(O)NH-; or v) -O-; the index p is from 1 to 3; the index q is from 1 to 3; and the index r is 1 or O. 5. The method of claim 1, wherein R is chosen from 2-fluorophenyl, 3 -fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-methoxyphenyl, 3-methoxyphenyl, A- methoxyphenyl, 2-methylphenyl, 3-methylphenyl, and 4-methylphenyl. 6. The method of claim 1, wherein the compound is chosen from: 2-(4H-l,2,4-triazol-3-ylthio)-l,2-diphenylethanone; 2-(4H-l,2,4-triazol-3-ylthio)-N-(2-phenoxyethyl)acetamide; 2-(5-benzyl-4H-l,2,4-triazol-3-yl)-3a,4,7,7a-tetrahydro-lH-isoindole-l,3(2H)- dione; methyl 3-(4-bromophenyl)- lΗ-pyrazole-5-carboxylate; 3-(2-chlorophenyl)-lH-pyrazole-5-carboxylic acid; 7V-[5-(propylthio)-4H-l,2,4-triazol-3-yl]acetamide; methyl 5-(lΗ-indol-3-yl)-lΗ-pyrazole-3-carboxylate; 3-(4-chlorophenyl)-lH-pyrazole-5-carboxylic acid; methyl 3-phenyl-lH-pyrazole-5-carboxylate; (Z)-4-[5-(2-bromophenyl)-4H-l,2,4-triazol-3-ylthio]-3-hydroxy-2-(l- iminoethyl)but-2-enenitrile; 7V-(furan-2-ylmethylcarbamoyl)-2-(5-phenyl-4H-l,2,4-triazol-3-ylthio)acetamide; iV-[5-(2-methoxyphenyl)-4H-l,2,4-triazol-3-yl]acetamide; N2-phenyl-6-[(5-phenyl-lH-l,2,4-triazol-3-ylthio)methyl]-l,3,5-triazine-2,4- diamine; 3 ,4,5-trimethoxy-N-(3 -phenyl- 1 Η-pyrazol-5-yl)benzamide 3-(2-chlorophenyl)-5-phenyl-lH-l,2,4-triazole; 2-[5-(2-bromophenyl)-4H-l,2,4-triazol-3-ylthio]-7V-(furan-2- ylmethylcarbamoyl)acetamide; 3-(naphthalen- 1 -yl)- lΗ-pyrazol-5-ol; 2-{[5-(2-methoxyphenyl)-4H-l,2,4-triazol-3-ylthio]methyl}pyridine; 5-(allylthio)-3-(4-methoxyphenyl)-lΗ-l,2,4-triazole; ethyl 4-cyano-5-(2-(5-(2-methoxyphenyl)-4H-l,2,4-triazol-3-ylthio)acetamido)-3- methylthiophene-2-carboxylate; and 3 -( 1 -methyl- 1 H-pyrrol-2-yl)- 1 H-pyrazole-5 -carboxylic acid. 7. The method of claim 1 , wherein R and R2or R1and R2are taken together to form a heteroaryl or heterocyclic fused ring chosen from indazolyl, pyrazole[3,4- ό]pyridine, pyrano[2,3-c]pyrazol-6-olyl, pyrano[2,3-c]pyrazol-6-onyl, 6,7-dihydro- 2H-indazol-4(5H)-only, 2,4-dihydrochromeno[3,4-c]pyrazolyl; 5Η- [l,2,4]triazole[5,l-δ][l,3]thiazin-7-(6H)-one, l,5,6,7-tetrahydropyrano[3,2- cjpyrazolyl, and 7H-pyrazolo[4,3-e][l,2,4]triazole[4,3-c]pyrimidinyl. 8. The method of claim 1, wherein the compound is chosen from: 7-methoxy-4,5-dihydro-2H-benzo[g]indazole-3-carboxylic acid; 3-benzyl-6,6-dimethyl-6,7-dihydro-2H-indazol-4(5H)-one; methyl 5-(lH-indol-3-yl)-lH-pyrazole-3-carboxylate; 4-methyl-3-phenylpyrano[2,3-c]pyrazol-6-ol; 3-phenyl-lH-indazole; 3-(4-methoxyphenyl)-4-methylpyrano[2,3-c]pyrazol-6-ol; 2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylic acid; 3-butyl-6,6-dimethyl-6,7-dihydro-2H-indazol-4(5H)-one; 6,6-dimethyl-3-(thiophen-2-yl)-6,7-dihydro-2H-indazol-4(5H)-one; 5-(furan-2-yl)-2-(4-methoxyphenyl)-5H-[l,2,4]triazolo[5,l-b][l,3]thiazin-7(6H)- one; 2-(4H-imidazo[4,5-b]pyridin-2-ylthio)-l-(2,5-dimethoxyphenyl)ethanone; 6-amino-4-(4-hydroxy-3,5-dimethoxyphenyl)-3-(methoxymethyl)-l,4- dihydropyrano[2,3-c]pyrazole-5-carbonitrile; 5-chloro-l-phenyl-lH-benzo[d]imidazol-2-ol; 3-(2-chlorophenyl)-7-methyl-7H-pyrazolo[4,3-e][l,2,4]triazolo[4,3-c]pyrimidine; 2-(4H-imidazo[4,5-b]pyridin-2-ylthio)-l-(4-fluorophenyl)ethanone; 3-((2,6-dimethylphenoxy)methyl)-7-methyl-7H-pyrazolo[4,3-e][l,2,4]triazolo[4,3- cjpyrimidine; 7-(3,4-dimethylphenyl)-3-methyl-7H-pyrrolo[3,2-e][l,2,4]triazolo[4,3- cjpyrimidine; 2-(5-methylisoxazol-3-ylamino)-2-oxoethyl 2H-indazole-3-carboxylate; 5-(2-(3,4-dihydroxyphenyl)-2-oxoethylthio)-2-isopropylimidazo[l,2-c]quinazolin- 3(2H)-one; (Z)-5-((3-methylthiophen-2-yl)methylene)thiazolo[3,2-b][l,2,4]triazol-6(5H)-one; 7-(3,4-dimethylphenyl)-2-methyl-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5- cjpyrimidine; and 7-methyl-2-phenethyl-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine. 9. A method of treating or preventing vascular calcifcication in a subject, comprising administering one or more compounds having the formula: wherein C is a substituted or unsubstituted C6of Ci0aryl ring; D is a substituted or unsubstituted C6or C10aryl ring, or a substituted or unsubstituted C5-C9 heteroaryl ring; wherein further the substitutions are each independently chosen from: i) halogen; ii) hydroxy iii) Ci-C4alkyl; iv) CpC4alkoxy; v) substituted or unsubstituted heterocyclic; vi) substituted or unsubstituted heteroaryl; vii) substituted or unsubstituted aryl; viii) amino; ix) mono-Ci-C4alkylamino; x) di-Ci-C4alkylamino; xi) nitro; and xii) cyano. 10. The method of claim 9, wherein the compound is chosen from: 2-dimethoxy-N-(quinolin-3-yl)benzene-sulfonamide; 2-methoxy-5-methyl-N-(pyridine-3-yl)benzenesulfonamide; 2-ethoxy-5-methyl-N-(pyridine-3-yl)benzenesulfonamide; and N-[3-lH-l,2,4,-triazol-3-ylthio)-4-hydroxyphenyl)-2,5- dimethyoxybenzenesulfonamide. 11. A method of treating or preventing vascular calcifcication in a subject, comprising administering one or more compounds having the formula: wherein L represents a polyalkylene or polyalkyleneoxy linking unit having from 2 to 20 carbon atoms and from 1 to 10 oxygen atoms. 12. The method of claim 11 , wherein the one or more compounds are chosen from: 2,2'-[2,2'-oxybis(ethane-2,l-diyl)bis(oxy)]bis(2,l-phenylene)diphosphonic acid; and 2,2'-(pentane-l,5-diylbis(oxy))bis(2,l-phenylene)diphosphonic acid. 13. A method of treating or preventing vascular calcifcication in a subject, comprising administering one or more compounds chosen from: 4-{2-[2-(3,4-dihydroxyρhenyl)-2-oxoethylthio]-4-oxoquinazolin-3(4H)-yl}-N- [(tetrahydrofuran-2-yl)methyl]butanamide; and (£')-2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-phenylpropyl)acrylamide. 14. A method of treating or preventing vascular calcifcication in a subject, comprising administering one or more compounds chosen from: 3-(2-chlorophenyl)-lH-pyrazole-5-carboxylic acid; methyl 3-(lH-indol-3-yl)-lH-pyrazole-5-carboxylate; 3-(4-chlorophenyl)-lH-pyrazole-5-carboxylic acid; methyl 3-phenyl- lH-pyrazole-5-carboxylate; 3-(napthalen-l-yl)-lH-pyrazol-5-ol; 3-(4-bromophenyl)-4-chloro-l-H-pyrazol-5-amine; 3-(l-methyl-lH-pyrrol-2-yl)-lH-pyrazole-5-carboxylate; methyl 3-(4-bromophenyl)-lH-pyrazole-5-carboxylate; 3-butyl-6,6-dimethyl-6,7-dihydro-2H-indazol-4(5H)-one; 6,6-dimethyl-3-(thiophen-2-yl)-6,7-dihydro-2H-indazol-4(5H)-one; 3-benzyl-6,6-dimethyl-6,7-dihydro-2H-indazol-4(5H)-one; 4-methyl-3-phenylpyrano[2,3-c]pyrazol-6-ol; 3-(4-methoxyphenyl)-4-methylpyrano[2,3-c]pyrazol-6-ol; 6-amino-4-(4-hydroxy-3,5-dimethoxyphenyl)-3-(methoxymethyl)-l,4- dihydropyrano[2,3-c]pyrazole-5-carbonitrile; 3-phenyl-l,4,5,6-tetrahydrocyclopenta[c]pyrazole; 2-(5-methylisoxazol-3-ylamino)-2-oxoethyl 2H-indazole-3-carboxylate; 7-methoxy-4,5-dihydro-2Η-benzo[g]indazole-3-carboxylic acid; 2,4-dihydrochromeno[4,3-c]pyrazole-3-carboxylic acid; 3-phenyl- 1 ,4,5,6-tetrahydrocyclopenta[c]pyrazole; N2-phenyl-6-[(5-phenyl-lH-l,2,4-triazol-3-ylthio)methyl]-l,3,5-triazine-2,4- diamine; 2-((5-(2-methoxyphenyl)-4H-l,2,4-triazol-3-ylthio)methyl)pyridine; ethyl 4-cyano-5- {2-[5-(2-methoxyphenyl)-4/τT- 1 ,2,4-triazol-3-ylthio]acetamide} -3- methylthiophene-2-carboxylate; 2-[5-(2-bromophenyl)-4Η- 1 ,2,4-triazol-3-ylthio]-N-(furan-2- ylmethylcarbamoyl)acetamide; 7V-(furan-2-ylmethylcarbamoyl)-2-(5-phenyl-4H-l,2,4-triazol-3-ylthio)acetamide; N2-phenyl-6-[(5-ρhenyl-lH-l,2,4-triazol-3-ylthio)methyl]-l,3,5-triazine-2,4- diamine; 2-((5-(2-methoxyphenyl)-4H-l,2,4-triazol-3-ylthio)methyl)pyridine; 6-(l -methyl- lH-imidazol-2-ylthio)-τV2,7V4-diphenyl-l, 3, 5-triazine-2,4-diamine; 2-(5-benzyl-4H-l,2,4-triazol-3-yl)-3a,4,7,7a-tetrahydro-lH-isoindole-l,3(2H)- dione; N-(5-(propylthio)-4H- 1 ,2,4-triazol-3-yl)acetamide; (Z)-4-(5-(2-bromophenyl)-4H-l,2,4-triazol-3-ylthio)-3-hydroxy-2-(l- iminoethyl)but-2-enenitrile; 7V-(5-(2-methoxyphenyl)-4H- 1 ,2,4-triazol-3-yl)acetamide; 3,3'-(2,5-dimethoxy-l,4-phenylene)-bis(methylene)bis(sulfanediyl)bis(4H-l,2,4- triazole); 3,4,5-trimethoxy-N-(3-phenyl-lH-pyrazol-5-yl)benzamide; 3-(2-chlorophenyl)-5-phenyl-lH-l,2,4-triazole; 5-(fiiran-2-yl)-2-(4-methoxyphenyl)-5H-[ 1 ,2,4]triazolo[5 , l-b][l ,3]thiazin-7(6H)- one; 5-(allylthio)-3-(4-methoxyphenyl)-lΗ-l,2,4-triazole; 2-(4H-imidazo[4,5-έ]pyridin-2-ylthio)-l-(2,5-dimethoxyphenyl)ethanone; 5-chloro-l-phenyl-lH-benzo[d]imidazol-2-ol; 3-(2-chlorophenyl)-7-methyl-7H-pyrazolo[4,3-e][l,2,4]triazolo[4,3-c]pyrimidine; 2-(4H-imidazo[4,5-ό]pyridin-2-ylthio)-l-(4-fluorophenyl)ethanone; 3-((2,6-dimethylphenoxy)methyl)-7-methyl-7H-pyrazolo[4,3-e] [ 1 ,2,4]triazolo[4,3- cjpyrimidine; 7-(3,4-dimethylphenyl)-3-methyl-7H-pyrrolo[3,2-e][l,2,4]triazolo[4,3- cjpyrimidine; 5-(2-(3,4-dihydroxyphenyl)-2-oxoethylthio)-2-isopropylimidazo[l,2-c]quinazolin- 3(2H)-one; (Z)-5-((3-methylthiophen-2-yl)methylene)thiazolo[3,2-δ] [ 1 ,2,4]triazol-6(5H)-one; 7-(3,4-dimethylphenyl)-2-methyl-7Η-pyrazolo[4,3-e] [ 1 ,2,4]triazolo[ 1 ,5- c]pyrimidine; 7-methyl-2-phenethyl-7H-pyrazolo[4,3-e][l,2,4]triazolo[l,5-c]pyrimidine; 2-dimethoxy-N-(quinolin-3-yl)benzene-sulfonamide; 2-methoxy-5-methyl-N-(pyridine-3-yl)benzenesulfonamide; 2-ethoxy-5-methyl-N-(pyridine-3-yl)benzenesulfonamide; 7V-[3-lH-l,2,4,-triazol-3-ylthio)-4-hydroxyphenyl)-2,5- dimethyoxybenzenesulfonamide; 2,2'-[2,2'-oxybis(ethane-2,l-diyl)bis(oxy)]bis(2,l-phenylene)diphosphonic acid; 2,2'-(pentane-l,5-diylbis(oxy))bis(2,l-phenylene)diphosphonic acid; 4-{2-[2-(3,4-dihydroxyphenyl)-2-oxoethylthio]-4-oxoquinazolin-3(4H)-yl}-N- [(tetrahydrofuran-2-yl)methyl]butanamide; and (E)-2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-phenylpropyl)acrylamide. 15. A method of treating or preventing vascular calcifcication in a subj ect, comprising administering one or more compounds chosen from:
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