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1. 发明授权

US06541468B1 Indolocarbazole derivatives useful for the treatment of neurodegenerative diseases and cancer 失效
标题翻译：用于治疗神经变性疾病和癌症的吲哚咔唑衍生物
公开(公告)号：US06541468B1
公开(公告)日：2003-04-01
申请号：US09382539
申请日：1999-08-25
申请人： Hanno Roder , Timothy B. Lowinger , David R. Brittelli , Michael C. VanZandt
发明人： Hanno Roder , Timothy B. Lowinger , David R. Brittelli , Michael C. VanZandt
IPC分类号： A61K3155
CPC分类号： C07D487/16 , C07D487/22
摘要： Novel indolocarbazole derivatives potentially useful for the treatment of dementias characterized by tau hyperphosphorylation [Alzheimer's disease (AD), frontal lobe degeneration (FLD), argyrophilic grains disease, subacute sclerotising panencephalitis (SSPE) as a late complication of viral infections in the CNS], and cancer.
摘要翻译：新型吲哚并咔唑衍生物可用于治疗以tau过度磷酸化为特征的痴呆症[阿尔茨海默病（AD），额叶变性（FLD），嗜酸性粒细胞病，亚急性硬化性全脑炎（SSPE）作为CNS病毒感染的晚期并发症] 和癌症。

2. 发明授权

US06500847B2 Inhibition of matrix metalloproteases by substitued biaryl oxobutyric acids 失效
标题翻译：通过取代的联芳基氧代丁酸抑制基质金属蛋白酶
公开(公告)号：US06500847B2
公开(公告)日：2002-12-31
申请号：US09845392
申请日：2001-04-30
申请人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
发明人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
IPC分类号： A61K3144
CPC分类号： C07D253/08 , A61K31/425 , A61K31/426 , A61K31/4706 , A61K31/502 , A61K31/513 , A61K31/517 , A61K31/53 , A61K31/5513 , C07C62/38 , C07D237/32
摘要： Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have the generalized formulas: wherein r is 0-2, T is selected from and R40 is a mono- or bi-heterocyclic structure. These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from athrosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.
摘要翻译：提出了基质金属蛋白酶抑制化合物，其药物组合物和使用这些化合物的疾病治疗方法。本发明的化合物具有以下通式：其中r为0-2，选自T，R 40为单或双杂环结构。这些化合物可用于抑制基质金属蛋白酶，因此可用于抑制MMP的贡献，如骨关节炎，类风湿关节炎，脓毒性关节炎，牙周病，角膜溃疡，蛋白尿，动脉瘤主动脉疾病，疏水性表皮松解症，大疱疹，导致炎症反应的病症，MMP活性介导的骨质减少，下颌关节病，神经系统脱髓鞘疾病系统，肿瘤转移或创伤性关节损伤后的退行性软骨损失，以及来自动脉粥样硬化斑块破裂的冠状动脉血栓形成。本发明还提供了用于治疗这些病症的药物组合物和方法。

3. 发明授权

US06225314B1 Inhibition of matrix metalloproteases by substituted biaryl oxobutyric acids 失效
标题翻译：通过取代的联芳基氧代丁酸抑制基质金属蛋白酶
公开(公告)号：US06225314B1
公开(公告)日：2001-05-01
申请号：US09343142
申请日：1999-06-29
申请人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
发明人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
IPC分类号： A61K31495
CPC分类号： C07D253/08 , A61K31/425 , A61K31/426 , A61K31/4706 , A61K31/502 , A61K31/513 , A61K31/517 , A61K31/53 , A61K31/5513 , C07C62/38 , C07D237/32
摘要： Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have the generalized formulas: wherein r is 0-2, T is selected from and R40 is a mono- or bi-heterocyclic structure. These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from arteriosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.
摘要翻译：提出了基质金属蛋白酶抑制化合物，其药物组合物和使用这些化合物的疾病治疗方法。本发明的化合物具有以下通式：其中r为0-2，选自T，R 40为单或双杂环结构。这些化合物可用于抑制基质金属蛋白酶，因此可用于抑制MMP的贡献，如骨关节炎，类风湿关节炎，脓毒性关节炎，牙周病，角膜溃疡，蛋白尿，动脉瘤主动脉疾病，疏水性表皮松解症，大疱疹，导致炎症反应的病症，MMP活性介导的骨质减少，下颌关节病，神经系统脱髓鞘疾病系统，肿瘤转移或创伤性关节损伤后的退行性软骨损失，以及动脉硬化斑块破裂引起的冠状动脉血栓形成。本发明还提供了用于治疗这些病症的药物组合物和方法。

4. 发明授权

US6013646A Indolocarbazole derivatives useful for the treatment of neurodegenerative diseases and cancer 失效
标题翻译：用于治疗神经变性疾病和癌症的吲哚咔唑衍生物
公开(公告)号：US6013646A
公开(公告)日：2000-01-11
申请号：US109131
申请日：1998-07-02
申请人： Hanno Roder , Timothy B. Lowinger , David R. Brittelli , Michael C. VanZandt
发明人： Hanno Roder , Timothy B. Lowinger , David R. Brittelli , Michael C. VanZandt
IPC分类号： A61K31/551 , A61P25/28 , A61P35/00 , A61P43/00 , C07D487/16 , C07D487/22 , A61K31/55 , C07D487/00 , C07D491/00
CPC分类号： C07D487/16 , C07D487/22
摘要： Novel indolocarbazole derivatives potentially useful for the treatment of dementias characterized by tau hyperphosphorylation [Alzheimer's disease (AD), frontal lobe degeneration (FLD), argyrophilic grains disease, subacute sclerotizing panencephalitis (SSPE) as a late complication of viral infections in the CNS], and cancer.
摘要翻译：新型吲哚咔唑衍生物可用于治疗以tau高磷酸化为特征的痴呆症[阿尔茨海默病（AD），额叶变性（FLD），嗜酸粒细胞病，亚急性发育性全脑炎（SSPE）作为CNS病毒感染的晚期并发症] 和癌症。

5. 发明授权

US06762184B2 Inhibition of matrix metalloproteases by substituted biaryl oxobutyric acids 失效
标题翻译：通过取代的联芳基氧代丁酸抑制基质金属蛋白酶
公开(公告)号：US06762184B2
公开(公告)日：2004-07-13
申请号：US09845379
申请日：2001-04-30
申请人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
发明人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
IPC分类号： A61K3153
CPC分类号： C07D253/08 , A61K31/425 , A61K31/426 , A61K31/4706 , A61K31/502 , A61K31/513 , A61K31/517 , A61K31/53 , A61K31/5513 , C07C62/38 , C07D237/32
摘要： This application relates to matrix metalloprotease inhibitors having the generalized formula in which r is 0-2, T is selected from and R40 is a mono-or bi-heterocyclic structure. More particularly, the present application claims the various stereoisomeric forms of 4-(4′-choloro-biphenyl-4-yl)-4-oxo-2-[2-(4-oxo-4H-benzo[d][1,2,3]triazin-3-yl)ethyl]butyric acid, as well as their pharmaceutically acceptable salts. Pharmaceutical compositions containing these compounds, and methods for inhibiting matrix metalloprotease activity in mammals such as humans and for treating various conditions by administering such compounds are also claimed.
摘要翻译：本申请涉及具有广义结构的基质金属蛋白酶抑制剂，其r为0-2，T选自并且R 40为单或双杂环结构。更具体地说，本申请要求4-（4'-氯 - 联苯-4-基）-4-氧代-2- [2-（4-氧代-4H-苯并[d] [1,3] 2,3]三嗪-3-基）乙基]丁酸，以及它们的药学上可接受的盐。还要求保护含有这些化合物的药物组合物，以及用于抑制哺乳动物如人类中的基质金属蛋白酶活性的方法以及通过施用这些化合物来治疗各种病症。

6. 发明授权

US06911449B2 Inhibition of matrix metalloproteases by substituted biaryl oxobutyric acids 失效
标题翻译：通过取代的联芳基氧代丁酸抑制基质金属蛋白酶
公开(公告)号：US06911449B2
公开(公告)日：2005-06-28
申请号：US10735040
申请日：2003-12-12
申请人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
发明人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
IPC分类号： A61K31/425 , A61K31/426 , A61K31/4706 , A61K31/502 , A61K31/513 , A61K31/517 , A61K31/53 , A61K31/5513 , C07C62/38 , C07D237/32 , C07D253/08 , A61K31/519 , C07D239/72
CPC分类号： C07D253/08 , A61K31/425 , A61K31/426 , A61K31/4706 , A61K31/502 , A61K31/513 , A61K31/517 , A61K31/53 , A61K31/5513 , C07C62/38 , C07D237/32
摘要： Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have the generalized formulas: wherein r is 0-2, T is selected from and R40 is a mono- or bi-heterocyclic structure. These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from athrosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.
摘要翻译：提出了基质金属蛋白酶抑制化合物，其药物组合物和使用这些化合物的疾病治疗方法。本发明的化合物具有以下通式：其中r为0-2，T选自并且R 40是单或双杂环结构。这些化合物可用于抑制基质金属蛋白酶，因此可用于抗MMP的作用，例如骨关节炎，类风湿性关节炎，脓毒性关节炎，牙周病，角膜溃疡，蛋白尿，动脉瘤性主动脉疾病，疏水性表皮松解症，大疱疹，导致炎症的病症反应，MMP活性介导的骨质减少，颞下颌关节疾病，神经系统脱髓鞘疾病，创伤性关节损伤后的肿瘤转移或退行性软骨损失，以及来自动脉粥样硬化斑块破裂的冠状动脉血栓形成。本发明还提供了用于治疗这些病症的药物组合物和方法。

7. 发明授权

US5932577A Substituted oxobutyric acids as matrix metalloprotease inhibitors 失效
标题翻译：取代的氧代丁酸作为基质金属蛋白酶抑制剂
公开(公告)号：US5932577A
公开(公告)日：1999-08-03
申请号：US857053
申请日：1997-05-15
申请人： Brian R. Dixon , Jinshan Chen , Michael C. VanZandt , David R. Brittelli
发明人： Brian R. Dixon , Jinshan Chen , Michael C. VanZandt , David R. Brittelli
IPC分类号： C07C59/90 , C07D209/48 , C07D253/08 , A61K31/53 , C07C65/32 , C07D251/00
CPC分类号： C07D209/48 , C07C59/90 , C07D253/08
摘要： The present invention provides pharmaceutical compositions and methods for treating certain conditions associated with matrix metalloproteases comprising administering an amount of a compound or composition of the invention which is effective to inhibit the activity of at least one matrix metalloprotease, resulting in achievement of the desired effect. The compounds of the present invention are either of the generalized formula: ##STR1## wherein y is 0, 2, or, 3, r is 0-6, Z is (CH.sub.2).sub.7 or (CH.sub.2).sub.e --C.sub.6 H.sub.4 --(CH.sub.2).sub.f, wherein e is 0-1 and f is 0-5, and R.sup.15 is --H, --Cl, --OMe or ##STR2## wherein n is 0-4, R.sup.17 is C.sub.2 H.sub.5, alkyl, benzyl, and R.sup.16 is ##STR3## wherein t is 0-2, x is 0-4, and R.sup.4 is one of the following: halide, alkyl of 1-6 carbons, OR, NR.sub.2, NO.sub.2 (R=H or alkyl of 1-6 carbons).
摘要翻译：本发明提供用于治疗与基质金属蛋白酶相关的某些病症的药物组合物和方法，其包括给予一定量的有效抑制至少一种基质金属蛋白酶活性的本发明化合物或组合物，从而达到预期的效果。本发明的化合物是以下通式：其中y是0,1或3，r是0-6，Z是（CH2）7或（CH2）e-C6H4-（CH2）f，其中 e为0-1，f为0-5，R15为-H，-Cl，-OMe或其中n为0-4，R17为C2H5，烷基，苄基，R16为其中t为0-2，x 是0-4，R4是以下之一：卤化物，1-6个碳的烷基，OR，NR2，NO2（R = H或1-6个碳原子的烷基）。

8. 发明授权

US5925637A Inhibition of matrix metalloproteases by substituted biaryl oxobutyric acids 失效
标题翻译：通过取代的联芳基氧代丁酸抑制基质金属蛋白酶
公开(公告)号：US5925637A
公开(公告)日：1999-07-20
申请号：US856693
申请日：1997-05-15
申请人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
发明人： Michael C. VanZandt , David R. Brittelli , Brian R. Dixon
IPC分类号： A61K31/425 , A61K31/426 , A61K31/4706 , A61K31/502 , A61K31/513 , A61K31/517 , A61K31/53 , A61K31/5513 , C07C62/38 , C07D237/32 , C07D253/08 , C07C63/64 , C07D253/10
CPC分类号： C07D253/08 , A61K31/425 , A61K31/426 , A61K31/4706 , A61K31/502 , A61K31/513 , A61K31/517 , A61K31/53 , A61K31/5513 , C07C62/38 , C07D237/32
摘要： Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have the generalized formulas: ##STR1## wherein r is 0-2, T is selected from ##STR2## and R.sup.40 is a mono- or bi-heterocyclic structure. These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, comeal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibularjoint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from athrosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.
摘要翻译：提出了基质金属蛋白酶抑制化合物，其药物组合物和使用这些化合物的疾病治疗方法。本发明的化合物具有以下通式：其中r为0-2，选自T，R 40为单或双杂环结构。这些化合物可用于抑制基质金属蛋白酶，因此可用于抗MMP的作用，例如骨关节炎，类风湿关节炎，脓毒性关节炎，牙周病，溃疡性溃疡，蛋白尿，动脉瘤性主动脉疾病，疏水性表皮松解症，大疱疹，导致炎症的病症反应，MMP活性介导的骨质减少，颞下颌关节疾病，神经系统脱髓鞘疾病，创伤性关节损伤后的肿瘤转移或退行性软骨损失，以及来自动脉粥样硬化斑块破裂的冠状动脉血栓形成。本发明还提供了用于治疗这些病症的药物组合物和方法。

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