公开(公告)号：US08598353B2

公开(公告)日：2013-12-03

申请号：US12950718

申请日：2010-11-19

申请人： Adnan M. M. Mjalli ,  David R. Jones ,  Devi Reddy Gohimukkula ,  Guoxiang Huang ,  Jeff J. Zhu ,  Mohan Rao ,  Robert C. Andrews ,  Tan Ren

发明人： Adnan M. M. Mjalli ,  David R. Jones ,  Devi Reddy Gohimukkula ,  Guoxiang Huang ,  Jeff J. Zhu ,  Mohan Rao ,  Robert C. Andrews ,  Tan Ren

IPC分类号： C07D401/12 ,  A61K31/4725

CPC分类号： C07D401/14 ,  A61K31/4725 ,  C07D235/30 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D473/00 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04

摘要： The present invention is directed to benzazole compounds that inhibit β-site amyloid precursor protein-cleaving enzyme (BACE) and that may be useful in the treatment or prevention of diseases in which BACE is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which BACE is involved.

摘要翻译： 本发明涉及抑制β-位淀粉样蛋白前体蛋白切割酶（BACE）的苯并唑化合物，其可用于治疗或预防BACE所涉及的疾病如阿尔茨海默氏病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及BACE的疾病中的用途。

公开(公告)号：US07776919B2

公开(公告)日：2010-08-17

申请号：US12019045

申请日：2008-01-24

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Christopher L. Wysong

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Christopher L. Wysong

IPC分类号： A01N37/18 ,  C07C237/00 ,  C07C233/00 ,  C07C235/00

CPC分类号： C07D231/12 ,  C07C235/38 ,  C07C237/20 ,  C07C271/22 ,  C07C2601/08 ,  C07C2603/18 ,  C07D207/16 ,  C07D211/34 ,  C07D217/26 ,  C07D233/56 ,  C07D249/08 ,  C07D309/04

摘要： This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

摘要翻译： 本发明提供某些化合物，其制备方法，包含该化合物的药物组合物及其在治疗人或动物疾病中的用途。 本发明的化合物可用作晚期糖基化终产物（RAGE）的受体与其配体如晚期糖基化终产物（AGE），S100 /钙粒蛋白/ EN-RAGE，淀粉样蛋白和 两性霉素，以及由RAGE引起的人类疾病的管理，治疗，控制或辅助治疗。 这些疾病或疾病状态包括急性和慢性炎症，糖尿病晚期并发症的发展，例如血管通透性增加，肾病，动脉粥样硬化和视网膜病变，阿尔茨海默病的发展，勃起功能障碍和肿瘤侵袭和转移。

公开(公告)号：US07737285B2

公开(公告)日：2010-06-15

申请号：US11800085

申请日：2007-05-03

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Anitha Hari ,  Kwasi A. Avor ,  Ghassan Qabaja ,  Xiao-Chuan Guo ,  Suparna Gupta ,  David R. Jones ,  Xin Chen

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Anitha Hari ,  Kwasi A. Avor ,  Ghassan Qabaja ,  Xiao-Chuan Guo ,  Suparna Gupta ,  David R. Jones ,  Xin Chen

IPC分类号： C07D233/61 ,  A01N43/50

CPC分类号： C07D233/64 ,  C07D235/08 ,  C07D235/12 ,  C07D235/14 ,  C07D235/18 ,  C07D235/30 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D413/12 ,  C07D453/02

摘要： This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

摘要翻译： 本发明提供某些化合物，其制备方法，包含该化合物的药物组合物及其在治疗人或动物疾病中的用途。 本发明的化合物可用作晚期糖基化终产物（RAGE）的受体与其配体如晚期糖基化终产物（AGE），S100 /钙粒蛋白/ EN-RAGE，淀粉样蛋白和 两性霉素，以及由RAGE引起的人类疾病的管理，治疗，控制或辅助治疗。 这些疾病或疾病状态包括急性和慢性炎症，糖尿病晚期并发症的发展，例如血管通透性增加，肾病，动脉粥样硬化和视网膜病变，阿尔茨海默病的发展，勃起功能障碍和肿瘤侵袭和转移。

公开(公告)号：US07714013B2

公开(公告)日：2010-05-11

申请号：US11511163

申请日：2006-08-28

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Anitha Hari ,  Kwasi A. Avor ,  Ghassan Qabaja ,  Xiao-Chuan Guo ,  Suparna Gupta ,  David R. Jones ,  Xin Chen

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Anitha Hari ,  Kwasi A. Avor ,  Ghassan Qabaja ,  Xiao-Chuan Guo ,  Suparna Gupta ,  David R. Jones ,  Xin Chen

IPC分类号： A61K31/4164 ,  A61K31/4178 ,  C07D233/64 ,  C07D403/02

CPC分类号： C07D233/64 ,  C07D235/08 ,  C07D235/12 ,  C07D235/14 ,  C07D235/18 ,  C07D235/30 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D413/12 ,  C07D453/02

摘要： This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

公开(公告)号：US07361678B2

公开(公告)日：2008-04-22

申请号：US10382203

申请日：2003-03-05

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Anitha Hari ,  Kwasi S. Avor ,  Ghassan Qabaja ,  Xiao-Chuan Guo ,  Suparna Gupta ,  David R. Jones ,  Xin Chen

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Anitha Hari ,  Kwasi S. Avor ,  Ghassan Qabaja ,  Xiao-Chuan Guo ,  Suparna Gupta ,  David R. Jones ,  Xin Chen

IPC分类号： A61K31/4164 ,  A61K31/4178 ,  C07D233/64 ,  C07D403/02

CPC分类号： C07D233/64 ,  C07D235/08 ,  C07D235/12 ,  C07D235/14 ,  C07D235/18 ,  C07D235/30 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/12 ,  C07D413/12 ,  C07D453/02

摘要： This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

摘要翻译： 本发明提供某些化合物，其制备方法，包含该化合物的药物组合物及其在治疗人或动物疾病中的用途。 本发明的化合物可用作晚期糖基化终产物（RAGE）的受体与其配体如晚期糖基化终产物（AGE），S100 /钙粒蛋白/ EN-RAGE，β-淀粉样蛋白和两性蛋白之间相互作用的调节剂 ，以及由RAGE引起的人类疾病的管理，治疗，控制或辅助治疗。 这些疾病或疾病状态包括急性和慢性炎症，糖尿病晚期并发症的发展，例如血管通透性增加，肾病，动脉粥样硬化和视网膜病变，阿尔茨海默病的发展，勃起功能障碍和肿瘤侵袭和转移。

公开(公告)号：US07122580B2

公开(公告)日：2006-10-17

申请号：US10637900

申请日：2003-08-08

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Xiao-Chuan Guo ,  Daniel Peter Christen ,  Devi Reddy Gohimmukkula ,  Guoxiang Huang ,  Robert Rothlein ,  Sameer Tyagi ,  Tripura Yaramasu ,  Christopher Behme

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Xiao-Chuan Guo ,  Daniel Peter Christen ,  Devi Reddy Gohimmukkula ,  Guoxiang Huang ,  Robert Rothlein ,  Sameer Tyagi ,  Tripura Yaramasu ,  Christopher Behme

IPC分类号： A61K31/245 ,  C07C233/87

CPC分类号： C07D207/267 ,  C07C233/29 ,  C07C233/87 ,  C07C235/42 ,  C07C235/52 ,  C07C235/60 ,  C07C235/66 ,  C07C237/36 ,  C07C237/42 ,  C07C237/44 ,  C07C255/60 ,  C07C257/18 ,  C07C271/20 ,  C07C271/44 ,  C07C311/18 ,  C07C311/19 ,  C07C311/44 ,  C07C317/14 ,  C07C317/28 ,  C07C317/36 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2603/74 ,  C07D207/09 ,  C07D211/26 ,  C07D213/30 ,  C07D213/70 ,  C07D213/71 ,  C07D213/74 ,  C07D213/81 ,  C07D217/02 ,  C07D217/16 ,  C07D217/22 ,  C07D231/12 ,  C07D231/14 ,  C07D231/18 ,  C07D233/84 ,  C07D239/94 ,  C07D249/08 ,  C07D261/10 ,  C07D263/32 ,  C07D271/10 ,  C07D277/46 ,  C07D285/08 ,  C07D295/088 ,  C07D295/155 ,  C07D307/66 ,  C07D307/79 ,  C07D307/85 ,  C07D317/60 ,  C07D333/24 ,  C07D333/38 ,  C07D333/70 ,  C07D401/04 ,  C07D409/04 ,  C07D409/06 ,  C07D413/04

摘要： This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as antagonists, or more preferably, partial antagonist of factor IX and thus, may be used to inhibit the intrinsic pathway of blood coagulation. The compounds are useful in a variety of applications including the management, treatment and/or control of diseases caused in part by the intrinsic clotting pathway utilizing factor IX. Such diseases or disease states include stroke, myocardial infarction, aneurysm surgery, and deep vein thrombosis associated with surgical procedures, long periods of confinement, and acquired or inherited pro-coagulant states.

摘要翻译： 本发明提供某些化合物，其制备方法，包含该化合物的药物组合物及其在治疗人或动物疾病中的用途。 本发明的化合物可用作拮抗剂，或更优选为因子IX的部分拮抗剂，因此可用于抑制血液凝固的内在途径。 该化合物可用于各种应用，包括通过利用因子IX的内在凝血途径部分引起的疾病的管理，治疗和/或控制。 这些疾病或疾病状态包括中风，心肌梗死，动脉瘤手术以及与外科手术相关的深部静脉血栓形成，长时间的约束，以及获得性或遗传的促凝血状态。

公开(公告)号：US07582673B2

公开(公告)日：2009-09-01

申请号：US11255000

申请日：2005-10-20

申请人： Adnan M. M. Mjalli ,  Bapu Gaddam ,  Mohan Rao ,  Muralidhar Bondlela ,  Ramesh Gopalaswamy ,  Robert C. Andrews ,  Stephen Davis ,  Suvi Simila ,  Tan Ren

发明人： Adnan M. M. Mjalli ,  Bapu Gaddam ,  Mohan Rao ,  Muralidhar Bondlela ,  Ramesh Gopalaswamy ,  Robert C. Andrews ,  Stephen Davis ,  Suvi Simila ,  Tan Ren

IPC分类号： A61K31/381 ,  A61K31/18 ,  C07D333/66 ,  C07C311/21

CPC分类号： C07D213/42 ,  C07C311/29 ,  C07D233/54 ,  C07D307/82 ,  C07D333/34 ,  C07D333/62 ,  C07D409/12 ,  C07D413/04 ,  C07D413/12 ,  C07D495/04

摘要： Embodiments of the present invention provide bissulfonamide compounds that are agonists of GalR1. The present invention further provides compositions comprising bissulfonamide compounds that are agonists of GalR1, and methods of use of such compounds and compositions.

摘要翻译： 本发明的实施方案提供作为GalR1的激动剂的双磺酰胺化合物。 本发明还提供了包含作为GalR1的激动剂的双磺酰胺化合物的组合物，以及这些化合物和组合物的使用方法。

公开(公告)号：US07544699B2

公开(公告)日：2009-06-09

申请号：US10913168

申请日：2004-08-06

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Xiao-Chuan Guo ,  Daniel Peter Christen ,  Devi Reddy Gohimmukkula ,  Guoxiang Huang ,  Robert Rothlein ,  Sameer Tyagi ,  Tripura Yaramasu ,  Christopher Behme

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Xiao-Chuan Guo ,  Daniel Peter Christen ,  Devi Reddy Gohimmukkula ,  Guoxiang Huang ,  Robert Rothlein ,  Sameer Tyagi ,  Tripura Yaramasu ,  Christopher Behme

IPC分类号： C07D217/00 ,  A61K31/47

CPC分类号： C07D295/155 ,  C07C233/87 ,  C07C235/42 ,  C07C235/52 ,  C07C235/60 ,  C07C235/66 ,  C07C237/36 ,  C07C237/42 ,  C07C271/20 ,  C07C311/08 ,  C07C311/09 ,  C07C311/21 ,  C07C311/44 ,  C07C317/32 ,  C07C323/36 ,  C07C2601/08

摘要： This invention provides aryl and heteroaryl compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention may be antagonists, or partial antagonist of factor IX and/or factor XI and thus, may be useful for inhibiting the intrinsic pathway of blood coagulation. The compounds may be useful in a variety of applications including the management, treatment and/or control of diseases caused in part by the intrinsic clotting pathway.

摘要翻译： 本发明提供芳基和杂芳基化合物，其制备方法，包含该化合物的药物组合物及其在治疗人或动物病症中的用途。 本发明的化合物可以是拮抗剂或因子IX和/或因子XI的部分拮抗剂，因此可用于抑制凝血的内在途径。 所述化合物可用于各种应用，包括部分由内在凝血途径引起的疾病的管理，治疗和/或控制。

公开(公告)号：US20090035302A1

公开(公告)日：2009-02-05

申请号：US12238087

申请日：2008-09-25

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Jane M. Shen ,  Robert Rothlein

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Jane M. Shen ,  Robert Rothlein

IPC分类号： A61K39/395 ,  A61K31/4164 ,  A61K31/4184 ,  A61K31/16 ,  A61K38/00

CPC分类号： A61K31/4164 ,  A61K31/4184 ,  A61K31/425

摘要： Disclosed are RAGE antagonist compounds that have the ability to reverse pre-existing amyloidosis. Treatment with the RAGE antagonist compounds described herein may be used to reduce plaque size and improve cognition for subjects in the later stages of Alzheimer's disease. Additionally, the RAGE antagonists described herein may be used to reduce the onset of plaque formation and thereby prevent loss of cognition and other symptoms associated with Alzheimer's Disease and other diseases of amyloid deposition.

摘要翻译： 公开了具有逆转预先存在的淀粉样变性的能力的RAGE拮抗剂化合物。 本文所述的RAGE拮抗剂化合物的治疗可用于减少斑块大小并改善阿尔茨海默病后期受试者的认知。 此外，本文所述的RAGE拮抗剂可用于减少斑块形成的发作，从而防止与阿尔茨海默病和其他淀粉样蛋白沉积疾病相关的认知和其它症状的丧失。

公开(公告)号：US07423177B2

公开(公告)日：2008-09-09

申请号：US10091759

申请日：2002-03-05

申请人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Chris Wysong

发明人： Adnan M. M. Mjalli ,  Robert C. Andrews ,  Ramesh Gopalaswamy ,  Chris Wysong

IPC分类号： C07C237/00 ,  C07C233/00 ,  C07C235/00 ,  A01N37/18

CPC分类号： C07D231/12 ,  C07C235/38 ,  C07C237/20 ,  C07C271/22 ,  C07C2601/08 ,  C07C2603/18 ,  C07D207/16 ,  C07D211/34 ,  C07D217/26 ,  C07D233/56 ,  C07D249/08 ,  C07D309/04

摘要： This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

摘要翻译： 本发明提供某些化合物，其制备方法，包含该化合物的药物组合物及其在治疗人或动物疾病中的用途。 本发明的化合物可用作晚期糖基化终产物（RAGE）的受体与其配体如晚期糖基化终产物（AGE），S100 /钙粒蛋白/ EN-RAGE，β-淀粉样蛋白和两性蛋白之间相互作用的调节剂 ，以及由RAGE引起的人类疾病的管理，治疗，控制或辅助治疗。 这些疾病或疾病状态包括急性和慢性炎症，糖尿病晚期并发症的发展，例如血管通透性增加，肾病，动脉粥样硬化和视网膜病变，阿尔茨海默病的发展，勃起功能障碍和肿瘤侵袭和转移。