公开(公告)号：US07026328B2

公开(公告)日：2006-04-11

申请号：US10447308

申请日：2003-05-27

申请人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupl ,  Jenifer L. Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

发明人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupl ,  Jenifer L. Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

IPC分类号： C07D239/50 ,  A61K31/505

CPC分类号： C07D401/12 ,  C07D239/50 ,  C07D403/12

摘要： Disclosed are compounds which bind α4 integrins, preferably VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by α4 integrins, preferably VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

公开(公告)号：US07008949B2

公开(公告)日：2006-03-07

申请号：US10447208

申请日：2003-05-27

申请人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer L. Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

发明人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer L. Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

IPC分类号： C07D239/50 ,  A61K31/505

CPC分类号： C07D239/50

摘要： Disclosed are compounds which bind α4 integrins, where the α4 integrin is preferably VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by α4 integrins, where the α4 integrin is preferably VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了结合α4+整联蛋白的化合物，其中α4+整联蛋白优选为VLA-4。 这些化合物中的某些还抑制白细胞粘附，特别是由α4H整联蛋白介导的白细胞粘附，其中α4整联蛋白优选为VLA-4。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US07427628B2

公开(公告)日：2008-09-23

申请号：US11527901

申请日：2006-09-26

申请人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

发明人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

IPC分类号： A61K31/505 ,  A61P19/02 ,  A61P25/00 ,  C07D239/50

CPC分类号： C07D401/12 ,  C07D239/50 ,  C07D403/12

摘要： Disclosed are compounds which bind α4 integrins, preferably VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by α4 integrins, preferably VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了结合α4+整联蛋白，优选VLA-4的化合物。 这些化合物中的某些也抑制白细胞粘附，特别是由α4A整联蛋白（优选VLA-4）介导的白细胞粘附。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US07135477B2

公开(公告)日：2006-11-14

申请号：US10494790

申请日：2003-05-27

申请人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

发明人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

IPC分类号： A61K31/505 ,  A61P19/02 ,  C07D239/50

CPC分类号： C07D401/12 ,  C07D239/50 ,  C07D403/12

摘要： Disclosed are compounds which bind α4 integrins, preferably VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by α4 integrins, preferably VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了结合α4+整联蛋白，优选VLA-4的化合物。 这些化合物中的某些也抑制白细胞粘附，特别是由α4A整联蛋白（优选VLA-4）介导的白细胞粘附。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US07335663B2

公开(公告)日：2008-02-26

申请号：US10494788

申请日：2003-05-27

申请人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

发明人： Andrei W. Konradi ,  Christopher M. Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Brian P. Stupi ,  Jenifer Smith ,  Michael A. Pleiss ,  Eugene D. Thorsett

IPC分类号： A01N43/54

CPC分类号： C07D239/50

摘要： Disclosed are compounds which bind α4 integrins, where the α4 integrin is preferably VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by α4 integrins, where the α4 integrin is preferably VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了结合α4+整联蛋白的化合物，其中α4+整联蛋白优选为VLA-4。 这些化合物中的某些还抑制白细胞粘附，特别是由α4H整联蛋白介导的白细胞粘附，其中α4整联蛋白优选为VLA-4。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US20100267747A1

公开(公告)日：2010-10-21

申请号：US12796441

申请日：2010-06-08

申请人： Xiaocong Michael Ye ,  Albert W. Garofalo ,  Jacek J. Jagodzinski ,  Andrei W. Konradi ,  Christopher M. Semko ,  Jenifer L. Smith ,  Ying-zi Xu

发明人： Xiaocong Michael Ye ,  Albert W. Garofalo ,  Jacek J. Jagodzinski ,  Andrei W. Konradi ,  Christopher M. Semko ,  Jenifer L. Smith ,  Ying-zi Xu

IPC分类号： A61K31/506 ,  C07D471/04 ,  A61K31/437 ,  A61K31/4375 ,  A61P25/28

CPC分类号： C07D491/04 ,  C07D211/96 ,  C07D471/04

摘要： The invention provides N-cyclic sulfonamido compounds of Formula I wherein A, B, R1, R1a, R2, R2a, R3 and R3a are as described in the specification. Compounds of Formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's disease. The invention also encompasses pharmaceutical compositions comprising compounds of Formula I, methods of preparing compounds of formula I, and methods of treating cognitive disorders, such as Alzheimer's disease.

摘要翻译： 本发明提供式I的N-环磺酰氨基化合物，其中A，B，R 1，R 1a，R 2，R 2a，R 3和R 3a如说明书中所述。 式I的化合物可用于治疗或预防认知障碍，例如阿尔茨海默病。 本发明还包括包含式I化合物，制备式I化合物的方法和治疗认知障碍如阿尔茨海默氏病的方法的药物组合物。

公开(公告)号：US07732609B2

公开(公告)日：2010-06-08

申请号：US11566070

申请日：2006-12-01

申请人： Xiaocong Michael Ye ,  Albert W. Garofalo ,  Jacek J. Jagodinski ,  Andrei W. Konradi ,  Christopher M. Semko ,  Jenifer L. Smith ,  Ying-zi Xu

发明人： Xiaocong Michael Ye ,  Albert W. Garofalo ,  Jacek J. Jagodinski ,  Andrei W. Konradi ,  Christopher M. Semko ,  Jenifer L. Smith ,  Ying-zi Xu

IPC分类号： C07D471/04 ,  A61K31/437

CPC分类号： C07D491/04 ,  C07D211/96 ,  C07D471/04

摘要： The invention provides N-cyclic sulfonamido compounds of Formula I wherein A, B, R1, R1a, R2, R2a, R3 and R3a are as described in the specification. Compounds of Formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's disease. The invention also encompasses pharmaceutical compositions comprising compounds of Formula I, methods of preparing compounds of formula I, and methods of treating cognitive disorders, such as Alzheimer's disease.

摘要翻译： 本发明提供式I的N-环磺酰氨基化合物，其中A，B，R 1，R 1a，R 2，R 2a，R 3和R 3a如说明书中所述。 式I的化合物可用于治疗或预防认知障碍，例如阿尔茨海默病。 本发明还包括包含式I化合物，制备式I化合物的方法和治疗认知障碍如阿尔茨海默氏病的方法的药物组合物。

公开(公告)号：US08030328B2

公开(公告)日：2011-10-04

申请号：US11438659

申请日：2006-05-22

申请人： Frank Stappenbeck ,  Andrei Konradi ,  Jacek Jagodzinski ,  Christopher M. Semko ,  Ying-zi Xu ,  Jenifer L. Smith ,  Kassandra Rossiter

发明人： Frank Stappenbeck ,  Andrei Konradi ,  Jacek Jagodzinski ,  Christopher M. Semko ,  Ying-zi Xu ,  Jenifer L. Smith ,  Kassandra Rossiter

IPC分类号： A61K31/4166 ,  A61K31/437 ,  C07D235/26 ,  C07D471/04

CPC分类号： C07D471/04

摘要： Disclosed are compounds of the formula: and the pharmaceutically acceptable salts thereof wherein the variables A, n, R5, R21-R24 and Q are defined herein. These compounds bind VLA-4. Certain of these compound also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了下式的化合物及其药学上可接受的盐，其中变量A，n，R5，R21-R24和Q在本文中定义。 这些化合物结合VLA-4。 这些化合物中的某些也抑制白细胞粘附，特别是由VLA-4介导的白细胞粘附。 这样的化合物可用于治疗哺乳动物患者，例如人类例如哮喘，阿尔茨海默氏病，动脉粥样硬化，艾滋病痴呆，糖尿病，炎性肠病，类风湿性关节炎，组织移植，肿瘤转移和心肌缺血等炎性疾病。 化合物也可以用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US07754712B2

公开(公告)日：2010-07-13

申请号：US11951097

申请日：2007-12-05

申请人： Simeon Bowers ,  Albert W. Garofalo ,  Roy K. Hom ,  Andrei W. Konradi ,  Matthew N. Mattson ,  Martin L. Neitzel ,  Christopher M. Semko ,  Anh P. Truong ,  Jing Wu ,  Ying-zi Xu

发明人： Simeon Bowers ,  Albert W. Garofalo ,  Roy K. Hom ,  Andrei W. Konradi ,  Matthew N. Mattson ,  Martin L. Neitzel ,  Christopher M. Semko ,  Anh P. Truong ,  Jing Wu ,  Ying-zi Xu

IPC分类号： A61K31/5365 ,  A61K31/437 ,  A61K31/4985 ,  A61P25/28 ,  C07D497/04 ,  C07D497/14 ,  C07D471/14

CPC分类号： C07D451/14 ,  C07D471/08 ,  C07D471/18 ,  C07D471/22 ,  C07D498/08

摘要： The invention provides N-cyclic sulfonamido compounds and salts of Formula I: wherein A is as described in the specification and R1 and R2 combine to form a [3.3.1] or a [3.2.1] ring system, where the nitrogen is attached to the two bridgehead carbons, and the [3.3.1] or [3.2.1] ring systems are optionally fused with an heteroaryl or heterocycloalkyl ring. Compounds of Formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's Disease. The invention also encompasses pharmaceutical compositions comprising compounds of Formula I, methods of treating cognitive disorders, such as Alzheimer's disease, and the intermediates useful in preparing the compounds of Formula I.

摘要翻译： 本发明提供了N-环磺酰氨基化合物和式I的盐：其中A如说明书中所述，并且R 1和R 2结合形成[3.3.1]或[3.2.1]环体系，其中氮被连接 并且[3.3.1]或[3.2.1]环体系任选地与杂芳基或杂环烷基环稠合。 式I的化合物可用于治疗或预防认知障碍，例如阿尔茨海默病。 本发明还包括含有式I化合物的药物组合物，治疗认知障碍的方法，例如阿尔茨海默氏病，以及可用于制备式I化合物的中间体。

公开(公告)号：US20110003802A1

公开(公告)日：2011-01-06

申请号：US12830914

申请日：2010-07-06

申请人： Simeon Bowers ,  Albert W. Garofalo ,  Roy K. Hom ,  Andrei W. Konradi ,  Matthew N. Mattson ,  Martin L. Neitzel ,  Christopher M. Semko ,  Anh P. Truong ,  Jing Wu ,  Ying-zi Xu

发明人： Simeon Bowers ,  Albert W. Garofalo ,  Roy K. Hom ,  Andrei W. Konradi ,  Matthew N. Mattson ,  Martin L. Neitzel ,  Christopher M. Semko ,  Anh P. Truong ,  Jing Wu ,  Ying-zi Xu

IPC分类号： A61K31/5383 ,  C07D498/06 ,  C07D498/16 ,  C07D453/02 ,  C07D471/16 ,  C07D487/06 ,  C07D487/16 ,  A61K31/439 ,  A61K31/4995 ,  A61P25/28

CPC分类号： C07D451/14 ,  C07D471/08 ,  C07D471/18 ,  C07D471/22 ,  C07D498/08

摘要： The invention provides N-cyclic sulfonamido compounds and salts of Formula I: wherein A is as described in the specification and R1 and R2 combine to form a [3.3.1] or a [3.2.1] ring system, where the nitrogen is attached to the two bridgehead carbons, and the [3.3.1] or [3.2.1] ring systems are optionally fused with an heteroaryl or heterocycloalkyl ring. Compounds of Formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's Disease. The invention also encompasses pharmaceutical compositions comprising compounds of Formula I, methods of treating cognitive disorders, such as Alzheimer's disease, and the intermediates useful in preparing the compounds of Formula I.

摘要翻译： 本发明提供了N-环磺酰氨基化合物和式I的盐：其中A如说明书中所述，并且R 1和R 2结合形成[3.3.1]或[3.2.1]环体系，其中氮被连接 并且[3.3.1]或[3.2.1]环体系任选地与杂芳基或杂环烷基环稠合。 式I的化合物可用于治疗或预防认知障碍，例如阿尔茨海默病。 本发明还包括含有式I化合物的药物组合物，治疗认知障碍的方法，例如阿尔茨海默氏病，以及可用于制备式I化合物的中间体。