公开(公告)号：US20060194756A1

公开(公告)日：2006-08-31

申请号：US11286129

申请日：2005-11-22

申请人： Pier Borea ,  Pier Baraldi ,  Stefania Merighi ,  Stephen MacLennan ,  Edward Leung ,  Allan Moorman

发明人： Pier Borea ,  Pier Baraldi ,  Stefania Merighi ,  Stephen MacLennan ,  Edward Leung ,  Allan Moorman

IPC分类号： A61K31/7076

CPC分类号： A61K31/7076 ,  A61K31/519 ,  C07D487/04 ,  C07D487/14 ,  C07K16/18

摘要： The present invention relates to the use of adenosine receptor agonists, preferably A3 receptor agonists, either alone or in combination with other agents for the treatment, prevention and/or management of diseases or disorders associated with under-expression of HIF-1α and/or decreased HIF-1 α activity (e.g., ischemic related disorders). The methods of the invention are directed to methods of reducing tissue damage (e.g., substantially prevention tissue damage, inducing tissue protection) resulting from ischemia orhypoxia. The invention provides methods for treating, preventing and/or ameliorating one or more symptoms of hypoxic or HIF-1α related disorders by administering an A3 receptor agonist either alone or in combination with other agents.

摘要翻译： 本发明涉及腺苷受体激动剂，优选A 3 N 3受体激动剂，单独使用或与其它药剂组合用于治疗，预防和/或控制与低血糖相关的疾病或病症， HIF-1α的表达和/或降低的HIF-1α活性（例如缺血性相关疾病）。 本发明的方法涉及减少由局部缺血或缺氧引起的组织损伤（例如，基本上预防组织损伤，诱导组织保护）的方法。 本发明提供了通过单独或与其它药剂组合施用A 3 O 3受体激动剂来治疗，预防和/或改善一种或多种缺氧或HIF-1α相关疾病症状的方法。

公开(公告)号：US20070281902A1

公开(公告)日：2007-12-06

申请号：US11757559

申请日：2007-06-04

申请人： Pier Baraldi ,  Pier Borea ,  Allan Moorman ,  Delia Preti

发明人： Pier Baraldi ,  Pier Borea ,  Allan Moorman ,  Delia Preti

IPC分类号： A61K31/7076 ,  C07H19/19

CPC分类号： C07H19/19

摘要： The present invention provides compounds of the formula wherein R1, R2, R3 and n have meaning as described in the specification, as adenosine A2B receptor agonists and, thus, may be employed for the treatment of diseases in mammals that are mediated by the A2B receptor including, but not limited to, septic shock, cystic fibrosis, impotence, diarrhea, and cardiac diseases Cardiac diseases include hyperplasia consequent to hypertension, arteriosclerosis, and heart attack

摘要翻译： 本发明提供下式的化合物，其中R 1，R 2，R 3和n具有如说明书中所述的含义，作为腺苷 2B2受体激动剂，因此可用于治疗哺乳动物由Aβ2A受体介导的疾病，包括但不限于脓毒性休克， 囊性纤维化，阳ence，腹泻和心脏病心脏疾病包括高血压，动脉硬化和心脏病发作的增生

公开(公告)号：US07767685B2

公开(公告)日：2010-08-03

申请号：US11767575

申请日：2007-06-25

申请人： Pier Giovanni Baraldi ,  Pier Andrea Borea ,  Allan Moorman ,  Mojgan Aghazadeh Tabrizi

发明人： Pier Giovanni Baraldi ,  Pier Andrea Borea ,  Allan Moorman ,  Mojgan Aghazadeh Tabrizi

IPC分类号： C07D473/06 ,  A61K31/522 ,  C07D231/14 ,  A61P11/06 ,  A61P3/10 ,  A61P19/02 ,  A61P37/08

CPC分类号： C07D473/06 ,  C07D473/08

摘要： The present invention provides compounds of the formula which are adenosine A2B receptor antagonists and, thus, may be employed for the treatment of conditions and diseases mediated by the adenosine A2B receptor activity. Such conditions include, but are not limited to, chronic and acute inflammatory diseases involving degranulation of mast cells, e.g., asthma, allergic rhinitis and allergic dermatitis; impaired sensitivity to insulin, e.g., type 2 diabetes, pre-diabetic state, and impaired glucose tolerance; diseases in which angiogenesis is a key component of pathogenesis, e.g., solid tumors and angiogenic retinopathies; apnea of preterm infants; myocardial reperfusion injury; inflammatory bowel disease; autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus erythematosis; diseases involving microvascular abnormalities of the retina that are mediated by adenosine A2B receptors, e.g., retinopathy of prematurity, macular degeneration, and diabetic retinopathy; and cardiac diseases including hyperplasia consequent to hypertension, arteriosclerosis, and heart attack.

摘要翻译： 本发明提供了具有腺苷A2B受体拮抗剂的下式的化合物，因此可用于治疗由腺苷A2B受体活性介导的病症和疾病。 这些病症包括但不限于涉及肥大细胞脱颗粒的慢性和急性炎性疾病，例如哮喘，过敏性鼻炎和过敏性皮炎; 对胰岛素的敏感性降低，例如2型糖尿病，糖尿病前期状态和葡萄糖耐量异常; 血管发生是发病机理的关键组分的疾病，例如实体瘤和血管生成视网膜病变; 早产儿呼吸暂停; 心肌再灌注损伤; 炎症性肠病; 自身免疫性疾病，例如类风湿性关节炎，多发性硬化症和狼疮性红斑狼疮; 涉及由腺苷A2B受体介导的视网膜的微血管异常的疾病，例如早产儿视网膜病变，黄斑变性和糖尿病性视网膜病变; 心脏病，包括高血压，动脉硬化和心脏病发作的增生。

公开(公告)号：US20080045549A1

公开(公告)日：2008-02-21

申请号：US11767575

申请日：2007-06-25

申请人： Pier Giovanni Baraldi ,  Pier Andrea Borea ,  Allan Moorman ,  Mojgan Aghazadeh Tabrizi

发明人： Pier Giovanni Baraldi ,  Pier Andrea Borea ,  Allan Moorman ,  Mojgan Aghazadeh Tabrizi

IPC分类号： A61K31/522 ,  A61P1/00 ,  A61P11/06 ,  A61P17/00 ,  A61P19/02 ,  A61P29/00 ,  A61P3/10 ,  A61P9/00 ,  C07D473/04

CPC分类号： C07D473/06 ,  C07D473/08

摘要： The present invention provides compounds of the formula which are adenosine A2B receptor antagonists and, thus, may be employed for the treatment of conditions and diseases mediated by the adenosine A2B receptor activity. Such conditions include, but are not limited to, chronic and acute inflammatory diseases involving degranulation of mast cells, e.g., asthma, allergic rhinitis and allergic dermatitis; impaired sensitivity to insulin, e.g., type 2 diabetes, non-insulin dependent diabetes, pre-diabetic state, and impaired glucose tolerance; diseases in which angiogenesis is a key component of pathogenesis, e.g., solid tumors and angiogenic retinopathies; apnea of preterm infants; myocardial reperfusion injury; inflammatory bowel disease; autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus erythematosis; diseases involving microvascular abnormalities of the retina that are mediated by adenosine A2B receptors, e.g., retinopathy of prematurity, macular degeneration, and diabetic retinopathy; and cardiac diseases including hyperplasia consequent to hypertension, arteriosclerosis, and heart attack.

摘要翻译： 本发明提供下式的化合物，其为腺苷A 2B2受体拮抗剂，因此可用于治疗由腺苷A 2B受体介导的病症和疾病 活动。 这些病症包括但不限于涉及肥大细胞脱颗粒的慢性和急性炎性疾病，例如哮喘，过敏性鼻炎和过敏性皮炎; 对胰岛素的敏感性降低，例如2型糖尿病，非胰岛素依赖性糖尿病，糖尿病前期状态和葡萄糖耐量降低; 血管发生是发病机理的关键组分的疾病，例如实体瘤和血管生成视网膜病变; 早产儿呼吸暂停; 心肌再灌注损伤; 炎症性肠病; 自身免疫性疾病，例如类风湿性关节炎，多发性硬化症和狼疮性红斑狼疮; 涉及由腺苷A 2B受体介导的视网膜的微血管异常的疾病，例如早产儿视网膜病变，黄斑变性和糖尿病性视网膜病变; 心脏病，包括高血压，动脉硬化和心脏病发作的增生。

公开(公告)号：US20060204502A1

公开(公告)日：2006-09-14

申请号：US11286127

申请日：2005-11-22

申请人： Pier Borea ,  Pier Baraldi ,  Stefania Merighi ,  Stephen MacLennan ,  Edward Leung ,  Allan Moorman

发明人： Pier Borea ,  Pier Baraldi ,  Stefania Merighi ,  Stephen MacLennan ,  Edward Leung ,  Allan Moorman

IPC分类号： A61K39/395 ,  A61K31/519

CPC分类号： A61K31/7076 ,  A61K31/519 ,  C07D487/04 ,  C07D487/14 ,  C07K16/18

摘要： The present invention relates to the use of adenosine receptor antagonists, preferably A3 receptor antagonists, either alone or in combination with other agents for the treatment, prevention and/or management of diseases or disorders associated with overexpression of HIF-1α and/or increased HIF-1α activity (e.g., cancer, respiratory disease). The methods and compositions of the invention are particularly useful for preventing, treating, or ameliorating symptoms associated with a cancer, disease or disorder associated with hypoxia-inducible factor 1α (HIF-1α) using the A3 receptor antagonists of the invention. The present invention provides methods to inhibit the growth of tumors, particularly solid tumors and more particularly hypoxic tumors.

摘要翻译： 本发明涉及腺苷受体拮抗剂，优选Aβ3受体拮抗剂，其单独使用或与其它药物组合用于治疗，预防和/或控制与过表达相关的疾病或病症 HIF-1α和/或增加的HIF-1α活性（如癌症，呼吸系统疾病）。 本发明的方法和组合物特别可用于预防，治疗或改善与使用Aβ受体相关的与缺氧诱导因子1α（HIF-1α）相关的癌症，疾病或病症相关症状。 本发明的拮抗剂。 本发明提供抑制肿瘤，特别是实体瘤，特别是缺氧性肿瘤生长的方法。

公开(公告)号：US20060183921A1

公开(公告)日：2006-08-17

申请号：US11402240

申请日：2006-04-11

申请人： Allan Moorman ,  Romeo Romagnoli ,  Pier Baraldi

发明人： Allan Moorman ,  Romeo Romagnoli ,  Pier Baraldi

IPC分类号： C07D333/76 ,  A61K31/38

CPC分类号： A61K31/4365 ,  A61K31/381 ,  A61K31/4743

摘要： New fused thiophene compounds are provided and methods of using those compounds for a variety of therapeutic indications. Compounds of the invention are particularly useful for treatment of neuropathic pain.

公开(公告)号：US20060135466A1

公开(公告)日：2006-06-22

申请号：US11155212

申请日：2005-06-16

申请人： Allan Moorman ,  Michael Scannell ,  Thiagarajan Balasubramanian ,  Russell Outcalt

发明人： Allan Moorman ,  Michael Scannell ,  Thiagarajan Balasubramanian ,  Russell Outcalt

IPC分类号： A61K31/7076 ,  C07H19/16

CPC分类号： C07H19/16 ,  C07H19/167 ,  Y02P20/55

摘要： Provided is a method for the synthesis of an aralkyloxyadenosine or an alkoxyadenosine. The method includes protecting the hydroxyl sugar groups with a protecting group to produce a protected halogenated adenosine. The protected halogenated adenosine is alkoxylated, and the hydroxyl sugar groups of the protected halogenated adenosine are deprotected to provide the aralkyloxyadenosine or alkoxyadenosine.

摘要翻译： 提供了合成芳烷氧基腺苷或烷氧基腺苷的方法。 该方法包括用保护基保护羟基糖基团以产生被保护的卤代腺苷。 保护的卤代腺苷被烷氧基化，被保护的卤代腺苷的羟基糖基脱保护，得到芳烷氧基腺苷或烷氧基腺苷。

公开(公告)号：US20050250729A1

公开(公告)日：2005-11-10

申请号：US10944245

申请日：2004-09-17

申请人： Pier Baraldi ,  Allan Moorman ,  Pier Borea

发明人： Pier Baraldi ,  Allan Moorman ,  Pier Borea

IPC分类号： A61K31/7076 ,  C07H20060101 ,  C07H1/00 ,  C07H19/16 ,  G01N33/74

CPC分类号： C07H19/16 ,  A61K31/7076 ,  C07H1/00 ,  G01N33/74 ,  G01N2333/726

摘要： The compounds of the following formula: wherein Ar, R and R1 have the meanings given in the specification. This series of sulfonamido derivatives with a conserved uronamide group at the 5′ position provide superior A3 receptor affinity as well as selectivity. These new adenosine agonists are sulfonamido derivatives N-substituted with aliphatic groups (cyclic or linear) or aromatic radicals.

摘要翻译： 下式的化合物：其中Ar，R和R 1具有说明书中给出的含义。 该系列具有5'位保守脲酰胺基团的亚磺酰氨基衍生物提供了优异的A3受体亲和力以及选择性。 这些新的腺苷激动剂是用脂肪族（环状或直链）或芳族基团N-取代的亚磺酰氨基衍生物。