公开(公告)号：US07205310B2

公开(公告)日：2007-04-17

申请号：US11118862

申请日：2005-04-29

申请人： Andrei W. Konradi ,  Frank Stappenbeck ,  Michael A. Pleiss ,  Christopher Semko ,  Jenifer L. Smith

发明人： Andrei W. Konradi ,  Frank Stappenbeck ,  Michael A. Pleiss ,  Christopher Semko ,  Jenifer L. Smith

IPC分类号： C07D239/48 ,  C07D239/49 ,  A61K31/4166 ,  A61K31/506 ,  A61P11/06 ,  A61P19/02

CPC分类号： C07D487/04 ,  C07D403/10 ,  C07D403/12 ,  C07D405/14

摘要： Disclosed are compounds which bind VLA-4 and/or LPAM-1. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4 and/or LPAM-1. 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VLA-4和/或LPAM-1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VLA-4和/或LPAM-1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：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：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：US07365073B2

公开(公告)日：2008-04-29

申请号：US10898576

申请日：2004-07-23

申请人： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Darren B. Dressen ,  Francine S. Farouz ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

发明人： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Darren B. Dressen ,  Francine S. Farouz ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

IPC分类号： A61K31/497 ,  C07D401/12 ,  C07D403/12

CPC分类号： C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed are certain 3-(heteroaryl)alanine derivatives which bind VLA-4 and inhibit 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： 公开了结合VLA-4并抑制由VLA-4介导的白细胞粘附的某些3-（杂芳基）丙氨酸衍生物。 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：US06794506B2

公开(公告)日：2004-09-21

申请号：US09910466

申请日：2001-07-19

申请人： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

发明人： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

IPC分类号： A01N4358

CPC分类号： C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed are certain 3-(heteroaryl)alanine derivatives which bind VLA-4 and inhibit 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.

公开(公告)号：US20080182850A1

公开(公告)日：2008-07-31

申请号：US11873358

申请日：2007-10-16

申请人： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

发明人： Andrei W. Konradi ,  Michael A. Pleiss ,  Eugene D. Thorsett ,  Susan Ashwell ,  Gregory S. Welmaker ,  Anthony Kreft ,  Dimitrios Sarantakis ,  Darren B. Dressen ,  Francine S. Grant ,  Christopher Semko ,  Ying-Zi Xu ,  Frank Stappenbeck

IPC分类号： A61K31/41 ,  C07D403/02 ,  A61K31/435 ,  A61K31/501 ,  A61K31/504

CPC分类号： C07D239/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed are certain 3-(heteroaryl)alanine derivatives which bind VLA-4 and inhibit 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： 公开了结合VLA-4并抑制由VLA-4介导的白细胞粘附的某些3-（杂芳基）丙氨酸衍生物。 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：US08158642B2

公开(公告)日：2012-04-17

申请号：US12579828

申请日：2009-10-15

申请人： Christopher Michael Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Jenifer Lea Smith ,  Kassandra Inez Rossiter ,  Juri Y. Fukuda ,  Andrei W. Konradi

发明人： Christopher Michael Semko ,  Ying-zi Xu ,  Frank Stappenbeck ,  Jenifer Lea Smith ,  Kassandra Inez Rossiter ,  Juri Y. Fukuda ,  Andrei W. Konradi

IPC分类号： A01N43/54 ,  A61K31/505 ,  C07D239/02

CPC分类号： C07D417/12 ,  C07D239/50 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14

摘要： Disclosed are compounds which bind VLA-4. Certain of these compounds 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： 公开了结合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。