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1.发明授权公开(公告)号：US08138225B2
公开(公告)日：2012-03-20
申请号：US12545712
申请日：2009-08-21
IPC分类号： A61K31/336
CPC分类号： C07D303/32
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, for example, an alpha-ketoepoxide group, such as an alpha-ketothio group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, autosomal dominant disorders, e.g. spinal muscular atrophy and Huntington's disease, genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy, or to stimulate hematopoietic cells ex vivo.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如α-酮氧化物基团，例如α-酮硫基，可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶抑制可抑制基因表达，包括与肿瘤抑制相关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供治疗癌症的替代途径，血液学病症，例如血红蛋白病，常染色体显性疾病，例如常染色体显性疾病。 脊髓性肌肉萎缩和亨廷顿病，遗传相关的代谢紊乱，例如囊性纤维化和肾上腺脑白质营养不良，或离体刺激造血细胞。
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公开(公告)号：US20110288168A1
公开(公告)日：2011-11-24
申请号：US12955470
申请日：2010-11-29
IPC分类号： A61K31/202 , A61K31/19 , A61P25/00 , A61K31/21 , A61K31/11 , A61K31/336 , A61K31/195 , A61K31/12
CPC分类号： A61K31/19 , A61K31/202 , A61K31/336 , A61K31/34 , A61K31/381
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, genetic disorders, e.g. Huntington's disease and spinal muscular atrophy and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如异羟肟酸基或羧酸基可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶抑制可抑制基因表达，包括与肿瘤抑制相关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供治疗癌症的替代途径，血液病症，例如血红蛋白病，遗传疾病， 亨廷顿氏病和脊髓性肌肉萎缩以及遗传相关的代谢紊乱，例如囊性纤维化和肾上腺脑白质营养不良。
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公开(公告)号：US06495719B2
公开(公告)日：2002-12-17
申请号：US09812944
申请日：2001-03-27
IPC分类号： C07C25906
CPC分类号： C07C57/42 , A61K31/16 , C07C57/60 , C07C259/06 , C07D307/54
摘要： Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Inhibition of histone deacetylase can lead to the histone deacetylase-mediated transcriptional repression of tumor suppressor genes. For example, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, such as hematopoiesis, and genetic related metabolic disorders, such as, cystic fibrosis and adrenoleukodystrophy.
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公开(公告)号：US08026280B2
公开(公告)日：2011-09-27
申请号：US10025947
申请日：2001-12-26
IPC分类号： A61K31/20 , A61K31/195 , A61K31/19 , C07C63/33 , C07C63/64
CPC分类号： A61K31/16 , C07C57/42 , C07C57/60 , C07C259/06 , C07D307/54
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy. Carboxylic acid-containing compounds having a terminal cyclic moiety, a carboxylic acid group, and a C3-12 hydrocarbon chain optionally containing at least one double bond, at least one triple bond, or at least one double bond and one triple bond linking the cyclic moiety and the carboxylic acid group are inhibitors of histone deacetylase.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分（例如羧酸基团）的化合物可抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶抑制可抑制基因表达，包括与肿瘤抑制相关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供用于治疗癌症，血液学疾病，例如血红蛋白病和遗传相关代谢紊乱（例如囊性纤维化和肾上腺脑白质营养不良）的替代途径。 含有末端环状部分的羧酸化合物，羧酸基团和任选含有至少一个双键的C3-12烃链，至少一个三键，或至少一个双键和一个三键，连接环状 部分和羧酸基团是组蛋白脱乙酰酶的抑制剂。
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公开(公告)号：US07858664B2
公开(公告)日：2010-12-28
申请号：US11019303
申请日：2004-12-23
IPC分类号： A61K31/185
CPC分类号： A61K31/16 , C07C57/42 , C07C57/60 , C07C259/06 , C07D307/54
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如异羟肟酸基或羧酸基可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶可抑制基因表达，包括与肿瘤抑制有关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供用于治疗癌症，血液学疾病，例如血红蛋白病和遗传相关代谢紊乱（例如囊性纤维化和肾上腺脑白质营养不良）的替代途径。
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公开(公告)号：US07312247B2
公开(公告)日：2007-12-25
申请号：US09812945
申请日：2001-03-27
IPC分类号： A61K31/19
CPC分类号： A61K31/16 , C07C57/42 , C07C57/60 , C07C259/06 , C07D307/54
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如异羟肟酸基或羧酸基可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶抑制可抑制基因表达，包括与肿瘤抑制相关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供用于治疗癌症，血液学疾病，例如血红蛋白病和遗传相关代谢紊乱（例如囊性纤维化和肾上腺脑白质营养不良）的替代途径。
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公开(公告)号：US20110287535A1
公开(公告)日：2011-11-24
申请号：US12977335
申请日：2010-12-23
IPC分类号： C12N5/071
CPC分类号： A61K31/16 , C07C57/42 , C07C57/60 , C07C259/06 , C07D307/54
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如异羟肟酸基或羧酸基可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶可抑制基因表达，包括与肿瘤抑制有关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供用于治疗癌症，血液学疾病例如血红蛋白病和遗传相关代谢紊乱（例如囊性纤维化和肾上腺嗜甲基营养不良）的替代途径。
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8.发明授权公开(公告)号：US07579372B2
公开(公告)日：2009-08-25
申请号：US11198293
申请日：2005-08-08
IPC分类号： A61K31/336
CPC分类号： C07D303/32
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, for example, an alpha-ketoepoxide group, such as an alpha-ketothio group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, autosomal dominant disorders, e.g. spinal muscular atrophy and Huntington's disease, genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy, or to stimulate hematopoietic cells ex vivo.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如α-酮氧化物基团，例如α-酮硫基，可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶抑制可抑制基因表达，包括与肿瘤抑制相关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供治疗癌症的替代途径，血液学病症，例如血红蛋白病，常染色体显性疾病，例如常染色体显性疾病。 脊髓性肌肉萎缩和亨廷顿病，遗传相关的代谢紊乱，例如囊性纤维化和肾上腺脑白质营养不良，或离体刺激造血细胞。
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公开(公告)号：US20120035257A1
公开(公告)日：2012-02-09
申请号：US13041666
申请日：2011-03-07
IPC分类号： A61K31/341 , C07D307/54 , A61P43/00 , A61P35/00 , A61P7/00 , A61P3/00 , C07C259/06 , A61K31/165
CPC分类号： A61K31/16 , C07C57/42 , C07C57/60 , C07C259/06 , C07D307/54
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如异羟肟酸基或羧酸基可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶可抑制基因表达，包括与肿瘤抑制有关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供用于治疗癌症，血液学疾病，例如血红蛋白病和遗传相关代谢紊乱（例如囊性纤维化和肾上腺脑白质营养不良）的替代途径。
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公开(公告)号：US07842727B2
公开(公告)日：2010-11-30
申请号：US11489519
申请日：2006-07-20
IPC分类号： A61K31/20 , A61K31/195 , A61K31/19
CPC分类号： A61K31/19 , A61K31/202 , A61K31/336 , A61K31/34 , A61K31/381
摘要： Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a hydroxamic acid group or a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, genetic disorders, e.g. Huntington's disease and spinal muscular atrophy and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy.
摘要翻译： 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分的化合物，例如异羟肟酸基或羧酸基可以抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶抑制可抑制基因表达，包括与肿瘤抑制相关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供治疗癌症的替代途径，血液病症，例如血红蛋白病，遗传疾病， 亨廷顿氏病和脊髓性肌肉萎缩以及遗传相关的代谢紊乱，例如囊性纤维化和肾上腺脑白质营养不良。
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