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：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：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：US07794700B2

公开(公告)日：2010-09-14

申请号：US11177748

申请日：2005-07-08

申请人： Andrei Konradi ,  Michael A. Pleiss ,  Christopher M. Semko ,  Theodore Yednock ,  Jenifer L. Smith

发明人： Andrei Konradi ,  Michael A. Pleiss ,  Christopher M. Semko ,  Theodore Yednock ,  Jenifer L. Smith

IPC分类号： A61K31/74

CPC分类号： A61K45/06 ,  A61K31/785 ,  A61K47/60 ,  A61Q5/00

摘要： Disclosed are conjugates exhibiting VLA-4 antagonistic properties. Certain of these conjugates also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. The conjugates of this invention are characterized as containing more than one VLA-4 inhibiting compound covalently attached to a bio-compatible polymer, such as polyethylene glycol. Conjugates of the invention are defined by formula I, wherein A, B, and q are described in the specification. Such conjugates 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 conjugates can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了表现出VLA-4拮抗性质的缀合物。 这些缀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。 本发明的缀合物的特征在于含有多于一种共价连接到生物相容性聚合物如聚乙二醇的VLA-4抑制化合物。 本发明的缀合物由式I定义，其中A，B和q在说明书中描述。 这样的缀合物可用于治疗哺乳动物患者（例如人，例如哮喘，阿尔茨海默病，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）中的炎性疾病。 也可以将缀合物用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US07595318B2

公开(公告)日：2009-09-29

申请号：US11042734

申请日：2005-01-24

申请人： Andrei Konradi ,  Michael A. Pleiss ,  Jenifer L. Smith ,  Christopher M. Semko ,  Chris Vandevert

发明人： Andrei Konradi ,  Michael A. Pleiss ,  Jenifer L. Smith ,  Christopher M. Semko ,  Chris Vandevert

IPC分类号： A61K31/497 ,  A61K31/425 ,  C07D295/00 ,  C07D277/04

CPC分类号： C08G63/91 ,  A61K47/60 ,  C07D295/205 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed are conjugates which bind VLA-4. Certain of these conjugates also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such conjugates 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 conjugates can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了结合VLA-4的缀合物。 这些缀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。 这样的缀合物可用于治疗哺乳动物患者（例如人，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）中的炎性疾病。 也可以将缀合物用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US20120329807A1

公开(公告)日：2012-12-27

申请号：US13606783

申请日：2012-09-07

申请人： Andrei Konradi ,  Michael A. Pleiss ,  Christopher M. Semko ,  Theodore Yednock ,  Jenifer L. Smith

发明人： Andrei Konradi ,  Michael A. Pleiss ,  Christopher M. Semko ,  Theodore Yednock ,  Jenifer L. Smith

IPC分类号： C07D417/14 ,  A61P25/00 ,  C07D401/14 ,  A61K31/506 ,  A61K31/496 ,  A61K31/444

CPC分类号： A61K45/06 ,  A61K31/785 ,  A61K47/60 ,  A61Q5/00

摘要： Disclosed are conjugates which bind VLA-4. Certain of these conjugates also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such conjugates 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 conjugates can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了结合VLA-4的缀合物。 这些缀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。 这样的缀合物可用于治疗哺乳动物患者（例如人，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）中的炎性疾病。 也可以将缀合物用于治疗炎性脑疾病如多发性硬化症。

公开(公告)号：US20130018187A1

公开(公告)日：2013-01-17

申请号：US13622037

申请日：2012-09-18

申请人： Andrei W. Konradi ,  Jenifer L. Smith ,  Michael S. Dappen ,  Christopher M. Semko

发明人： Andrei W. Konradi ,  Jenifer L. Smith ,  Michael S. Dappen ,  Christopher M. Semko

IPC分类号： C07D471/04

CPC分类号： C07D471/04 ,  A61K31/444 ,  A61K31/506 ,  A61K47/60

摘要： Disclosed is a process for preparing polymer conjugates of agricultural, therapeutic, and food additive compounds using Mitsunobu conditions.

摘要翻译： 公开了使用Mitsunobu条件制备农业，治疗和食品添加剂化合物的聚合物共轭物的方法。

公开(公告)号：US08263063B2

公开(公告)日：2012-09-11

申请号：US12877496

申请日：2010-09-08

申请人： Andrei W. Konradi ,  Michael A. Pleiss ,  Christopher M. Semko ,  Theodore Yednock ,  Jenifer L. Smith

发明人： Andrei W. Konradi ,  Michael A. Pleiss ,  Christopher M. Semko ,  Theodore Yednock ,  Jenifer L. Smith

IPC分类号： A61K31/74

CPC分类号： A61K45/06 ,  A61K31/785 ,  A61K47/60 ,  A61Q5/00

摘要： Disclosed are conjugates exhibiting VLA-4 antagonistic properties. Certain of these conjugates also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. The conjugates of this invention are characterized as containing more than one VLA-4 inhibiting compound covalently attached to a bio-compatible polymer, such as polyethylene glycol. Conjugates of the invention are defined by formula I, wherein A, B, and q are described in the specification. Such conjugates 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 conjugates can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

摘要翻译： 公开了表现出VLA-4拮抗性质的缀合物。 这些缀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。 本发明的缀合物的特征在于含有多于一种共价连接到生物相容性聚合物如聚乙二醇的VLA-4抑制化合物。 本发明的缀合物由式I定义，其中A，B和q在说明书中描述。 这样的缀合物可用于治疗哺乳动物患者（例如人，例如哮喘，阿尔茨海默病，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）中的炎性疾病。 也可以将缀合物用于治疗炎性脑疾病如多发性硬化症。