公开(公告)号：US08207167B2

公开(公告)日：2012-06-26

申请号：US13063950

申请日：2009-09-18

申请人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

发明人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

IPC分类号： A61K31/5375 ,  A61K31/18 ,  C07D265/30 ,  C07C311/01

CPC分类号： C07D303/36 ,  C07C311/21 ,  C07C311/39 ,  C07C2601/02 ,  C07D239/26 ,  C07D239/30 ,  C07D263/20 ,  C07D295/135

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-phenyl-sulfonamido-phenylene compounds of the following formula (I) (collectively referred to herein as “APSAP compounds”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in treatment, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, Paget's disease and the like, etc.; and of cancer, such as a haematological malignancy, a solid tumor, etc.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及下列通式（I）的某些芳基 - 苯基 - 亚磺酰氨基 - 亚苯基化合物（本文统称为“APSAP化合物”）。 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体外和体内在治疗例如炎症和/或关节破坏和/或骨丢失中的用途; 由免疫系统的过度和/或不适当和/或延长的激活介导的疾病; 炎性和自身免疫性疾病，例如类风湿性关节炎，牛皮癣，牛皮癣关节炎，慢性阻塞性肺病（COPD），动脉粥样硬化，炎性肠病，强直性脊柱炎等; 与骨丢失相关的疾病，例如与类风湿性关节炎中的过度破骨细胞活性相关的骨丢失，骨质疏松症，癌症相关的骨病，佩吉特氏病等; 和癌症，如血液恶性肿瘤，实体瘤等。

公开(公告)号：US20110190302A1

公开(公告)日：2011-08-04

申请号：US13063950

申请日：2009-09-18

申请人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

发明人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

IPC分类号： A61K31/5375 ,  C07C311/21 ,  C07D303/36 ,  C07D295/135 ,  C07C255/58 ,  C07D263/14 ,  A61K31/18 ,  A61K31/245 ,  A61K31/196 ,  A61K31/336 ,  A61K31/421 ,  A61P29/00 ,  A61P19/02 ,  A61P17/06 ,  A61P11/00 ,  A61P9/10 ,  A61P35/00 ,  A61P35/02 ,  A61P19/08 ,  A61P19/10

CPC分类号： C07D303/36 ,  C07C311/21 ,  C07C311/39 ,  C07C2601/02 ,  C07D239/26 ,  C07D239/30 ,  C07D263/20 ,  C07D295/135

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-phenyl-sulfonamido-phenylene compounds of the following formula (I) (collectively referred to herein as “APSAP compounds”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in treatment, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, Paget's disease and the like, etc.; and of cancer, such as a haematological malignancy, a solid tumour, etc.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及下列通式（I）的某些芳基 - 苯基 - 亚磺酰氨基 - 亚苯基化合物（本文统称为“APSAP化合物”）。 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体外和体内在治疗例如炎症和/或关节破坏和/或骨丢失中的用途; 由免疫系统的过度和/或不适当和/或延长的激活介导的疾病; 炎性和自身免疫性疾病，例如类风湿性关节炎，牛皮癣，牛皮癣关节炎，慢性阻塞性肺病（COPD），动脉粥样硬化，炎性肠病，强直性脊柱炎等; 与骨丢失相关的疾病，例如与类风湿性关节炎中的过度破骨细胞活性相关的骨丢失，骨质疏松症，癌症相关的骨病，佩吉特氏病等; 和癌症，如血液恶性肿瘤，实体瘤等。

公开(公告)号：US20110172189A1

公开(公告)日：2011-07-14

申请号：US13063956

申请日：2009-09-18

申请人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

发明人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

IPC分类号： A61K31/69 ,  C07C311/20 ,  A61K31/18 ,  C07D239/30 ,  A61K31/505 ,  C07D213/61 ,  A61K31/4418 ,  C07F5/02 ,  C07D265/30 ,  A61K31/5375 ,  C07D207/04 ,  A61K31/40 ,  A61K31/235 ,  A61P35/00 ,  A61P19/00 ,  A61P1/00 ,  A61P29/00 ,  A61P7/00 ,  A61P17/06

CPC分类号： A61K31/18 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/505 ,  C07C311/20 ,  C07C311/28 ,  C07C311/29 ,  C07D207/04 ,  C07D213/34 ,  C07D213/52 ,  C07D213/61 ,  C07D239/26 ,  C07D239/30 ,  C07D295/135

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-phenyl-sulfonamido-cycloalkyl compounds of the following formula (collectively referred to herein as “APSAC compounds”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in treatment, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, Paget's disease and the like, etc.; and of cancer, such as a haematological malignancy, a solid tumour, etc. Formula (I).

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及下列通式的某些芳基 - 苯基 - 亚磺酰氨基 - 环烷基化合物（在本文中统称为“APSAC化合物”）。 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体外和体内在治疗例如炎症和/或关节破坏和/或骨丢失中的用途; 由免疫系统的过度和/或不适当和/或延长的激活介导的疾病; 炎性和自身免疫性疾病，例如类风湿性关节炎，牛皮癣，牛皮癣关节炎，慢性阻塞性肺病（COPD），动脉粥样硬化，炎性肠病，强直性脊柱炎等; 与骨丢失相关的疾病，例如与类风湿性关节炎中的过度破骨细胞活性相关的骨丢失，骨质疏松症，癌症相关的骨病，佩吉特氏病等; 和癌症，如血液恶性肿瘤，实体肿瘤等。式（I）。

公开(公告)号：US20090209494A1

公开(公告)日：2009-08-20

申请号：US12094240

申请日：2006-12-22

申请人： Christine Janet Martin ,  Barrie Wilkinson ,  Sabine Gaisser ,  Ming-Oiang Zhang ,  Rose Mary Sheridan ,  Lesley Sarah Sheehan ,  Rachel Edith Lill ,  Mohammed Nur-E-Alam ,  William Alexander Vousden

发明人： Christine Janet Martin ,  Barrie Wilkinson ,  Sabine Gaisser ,  Ming-Oiang Zhang ,  Rose Mary Sheridan ,  Lesley Sarah Sheehan ,  Rachel Edith Lill ,  Mohammed Nur-E-Alam ,  William Alexander Vousden

IPC分类号： A61K31/66 ,  C12P17/10 ,  C12N1/21 ,  A61K31/395 ,  A61K31/4745 ,  A61K31/175 ,  A61K31/135 ,  C07D225/06

CPC分类号： C07D225/06

摘要： The present invention relates to 21-deoxymacbecin analogues that are useful, e.g. in the treatment of cancer, B-cell malignancies, malaria, fungal infection, diseases of the central nervous system and neurodegenerative diseases, diseases dependent on angiogenesis, autoimmune diseases or as a prophylactic pretreatment for cancer. The present invention also provides methods for the production of these compounds and their use in medicine, in particular in the treatment and or prophylaxis of cancer or B-cell malignancies.

摘要翻译： 本发明涉及21-脱氧山梨醇类似物，其可用于，例如， 在治疗癌症，B细胞恶性肿瘤，疟疾，真菌感染，中枢神经系统疾病和神经变性疾病，依赖于血管生成的疾病，自身免疫性疾病或作为癌症的预防性预处理。 本发明还提供了这些化合物的制备方法及其在医药中的用途，特别是治疗和/或预防癌症或B细胞恶性肿瘤的方法。

公开(公告)号：US08435968B2

公开(公告)日：2013-05-07

申请号：US13063956

申请日：2009-09-18

申请人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

发明人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

IPC分类号： A61K31/69 ,  A61K31/18 ,  A61K31/505 ,  A61K31/5375 ,  A61K31/40 ,  C07D239/30 ,  C07D213/61 ,  C07D265/30 ,  C07D207/04

CPC分类号： A61K31/18 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/505 ,  C07C311/20 ,  C07C311/28 ,  C07C311/29 ,  C07D207/04 ,  C07D213/34 ,  C07D213/52 ,  C07D213/61 ,  C07D239/26 ,  C07D239/30 ,  C07D295/135

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-phenyl-sulfonamido-cycloalkyl compounds of the following formula (collectively referred to herein as “APSAC compounds”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in treatment, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, Paget's disease and the like, etc.; and of cancer, such as a haematological malignancy, a solid tumour, etc. Formula (I).

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及下列通式的某些芳基 - 苯基 - 亚磺酰氨基 - 环烷基化合物（在本文中统称为“APSAC化合物”）。 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体外和体内在治疗例如炎症和/或关节破坏和/或骨丢失中的用途; 由免疫系统的过度和/或不适当和/或延长的激活介导的疾病; 炎性和自身免疫性疾病，例如类风湿性关节炎，牛皮癣，牛皮癣关节炎，慢性阻塞性肺病（COPD），动脉粥样硬化，炎性肠病，强直性脊柱炎等; 与骨丢失相关的疾病，例如与类风湿性关节炎中的过度破骨细胞活性相关的骨丢失，骨质疏松症，癌症相关的骨病，佩吉特氏病等; 和癌症，如血液恶性肿瘤，实体肿瘤等。式（I）。

公开(公告)号：US20130245018A1

公开(公告)日：2013-09-19

申请号：US13886799

申请日：2013-05-03

申请人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

发明人： Iain Robert Greig ,  Rose Mary Sheridan ,  Raymond Fisher ,  Matthew John Tozer ,  Juha Andrew Clase ,  Andrew Smith ,  Andrew Robert Tuffnell ,  Robert Jurgen Van 't Hof

IPC分类号： C07C311/20 ,  C07D239/26 ,  C07D213/61 ,  C07D239/30 ,  C07D207/04 ,  C07D295/135

CPC分类号： A61K31/18 ,  A61K31/44 ,  A61K31/4418 ,  A61K31/505 ,  C07C311/20 ,  C07C311/28 ,  C07C311/29 ,  C07D207/04 ,  C07D213/34 ,  C07D213/52 ,  C07D213/61 ,  C07D239/26 ,  C07D239/30 ,  C07D295/135

摘要： The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl-phenyl-sulfonamido-cycloalkyl compounds of the following formula (collectively referred to herein as “APSAC compounds”). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in treatment, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, Paget's disease and the like, etc.; and of cancer, such as a haematological malignancy, a solid tumour, etc.

摘要翻译： 本发明一般涉及治疗化合物领域，更具体地涉及下列通式的某些芳基 - 苯基 - 亚磺酰氨基 - 环烷基化合物（在本文中统称为“APSAC化合物”）。 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体外和体内在治疗例如炎症和/或关节破坏和/或骨丢失中的用途; 由免疫系统的过度和/或不适当和/或延长的激活介导的疾病; 炎性和自身免疫性疾病，例如类风湿性关节炎，牛皮癣，牛皮癣关节炎，慢性阻塞性肺病（COPD），动脉粥样硬化，炎性肠病，强直性脊柱炎等; 与骨丢失相关的疾病，例如与类风湿性关节炎中的过度破骨细胞活性相关的骨丢失，骨质疏松症，癌症相关的骨病，佩吉特氏病等; 和癌症，如血液恶性肿瘤，实体瘤等。

公开(公告)号：US20090209572A1

公开(公告)日：2009-08-20

申请号：US12273990

申请日：2008-11-19

申请人： Barrie Wilkinson ,  Ming-Qiang Zhang ,  Rose Mary Sheridan ,  Christoph Beckmann

发明人： Barrie Wilkinson ,  Ming-Qiang Zhang ,  Rose Mary Sheridan ,  Christoph Beckmann

IPC分类号： A61K31/436 ,  C07D491/153

CPC分类号： C07D493/18

摘要： The present invention relates to novel 36-des(3-methoxy-4-hydroxycyclohexyl)-36-(3-hydroxycycloheptyl)rapamycin derivatives, methods for their production, and uses thereof. In a further aspect the present invention provides for the use of these 36-des(3-methoxy-4-hydroxycyclohexyl)-36-(3-hydroxycycloheptyl)rapamycin derivatives in the treatment of cancer and/or B-cell malignancies, the induction or maintenance of immunosuppression, the treatment of transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation, vascular disease and fibrotic diseases, the stimulation of neuronal regeneration or the treatment of fungal infections.

摘要翻译： 本发明涉及新的36-des（3-甲氧基-4-羟基环己基）-36-（3-羟基环庚基）雷帕霉素衍生物，其制备方法及其应用。 在另一方面，本发明提供了这些36-des（3-甲氧基-4-羟基环己基）-36-（3-羟基环庚基）雷帕霉素衍生物在治疗癌症和/或B细胞恶性肿瘤中的用途，诱导 或维持免疫抑制，移植排斥，移植物抗宿主病，自身免疫性疾病，炎症疾病，血管疾病和纤维化疾病的治疗，刺激神经元再生或治疗真菌感染。