公开(公告)号：US20060276470A1

公开(公告)日：2006-12-07

申请号：US10522777

申请日：2003-08-18

申请人： Shaun Jackson ,  Alan Robertson ,  Vijaya Kenche ,  Philip Thompson ,  Hishani Prabaharan

发明人： Shaun Jackson ,  Alan Robertson ,  Vijaya Kenche ,  Philip Thompson ,  Hishani Prabaharan

IPC分类号： A61K31/5377 ,  C07D487/04

CPC分类号： C07D401/04 ,  A61K31/4709 ,  A61K31/519 ,  A61K31/5365 ,  A61K31/5375 ,  A61K31/5377 ,  C07D405/04 ,  C07D471/04

摘要： The present invention relates to selective inhibitors of phosphoinositide (PI) 3-kinase β, use of the selective inhibitors in anti-thrombotic therapy, and a method for screening compounds useful for the new anti-thrombotic therapy by detecting selective inhibitory activity of PI 3-kinase β of the compound. The invention also relates to novel compounds that are inhibitors of PI 3-kinase.

摘要翻译： 本发明涉及磷酸肌醇（PI）3-激酶β的选择性抑制剂，选择性抑制剂在抗血栓形成治疗中的应用，以及通过检测PI 3的选择性抑制活性来筛选可用于新的抗血栓形成治疗的化合物的方法 - 化合物的激酶β。 本发明还涉及作为PI3-激酶抑制剂的新化合物。

公开(公告)号：US20050085471A1

公开(公告)日：2005-04-21

申请号：US10961062

申请日：2004-10-12

申请人： Alan Robertson ,  Shaun Jackson ,  Vijaya Kenche ,  Cindy Yaip ,  Hishani Parbaharan ,  Phil Thompson

发明人： Alan Robertson ,  Shaun Jackson ,  Vijaya Kenche ,  Cindy Yaip ,  Hishani Parbaharan ,  Phil Thompson

IPC分类号： A61K9/02 ,  A61K9/08 ,  A61K9/12 ,  A61K9/20 ,  A61K9/48 ,  A61K31/5377 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P37/04 ,  A61P37/06 ,  A61P43/00 ,  C07D215/38 ,  C07D311/22 ,  C07D311/58 ,  C07D311/64 ,  C07D471/04 ,  C07D413/04

CPC分类号： C07D215/38 ,  C07D311/22 ,  C07D311/58 ,  C07D311/64 ,  C07D471/04

摘要： Morpholino-substituted pyridopyrimidine, quinolone, and benzopyranone derivatives inhibit phosphoinositide (PI) 3-kinase, an enzyme that regulates platelet-adhesion processes. As a consequence, the compounds in question have anti-thrombotic activity, as well as other pharmaceutical properties. The compounds claimed are represented by formula (I), (II) and (III). PI 3-kinase generates 3-phosphorylated PI second messengers which stimulate platelet adhesion under blood-flow conditions. Because platelet adhesion is a necessary step in the formation of a thrombus, inhibition by these compounds of PI 3-kinase under such conditions inhibits or prevents thrombus formation. The compounds are useful in treating PI 3-kinase-dependent conditions including cardiovascular diseases such as coronary artery occlusion, stroke, acute coronary syndrome, acute myocardial infarction, vascular restenosis, atherosclerosis, and unstable angina; respiratory diseases such as asthma, chronic obstructive pulmonary diseases (COPD), and bronchitis; inflammatory disorders, neoplasms including cancers such as glioma, prostate cancer, small cell lung cancer, and breast cancer, and diseases linked to disordered white blood cell function, such as autoimmune and inflammatory diseases.

摘要翻译： 吗啉取代的吡啶并嘧啶，喹诺酮和苯并吡喃酮衍生物抑制磷酸肌醇（PI）3-激酶，其是调节血小板粘附过程的酶。 因此，所讨论的化合物具有抗血栓形成活性以及其它药物性质。 所要求的化合物由式（I），（II）和（III）表示。 PI 3激酶产生在血液流动条件下刺激血小板粘附的3-磷酸化PI第二信使。 因为血小板粘附是形成血栓的必要步骤，所以这些条件下这些PI3-激酶化合物的抑制可抑制或预防血栓形成。 该化合物可用于治疗PI 3激酶依赖性疾病，包括心血管疾病如冠状动脉闭塞，中风，急性冠状动脉综合征，急性心肌梗塞，血管再狭窄，动脉粥样硬化和不稳定型心绞痛; 呼吸系统疾病如哮喘，慢性阻塞性肺疾病（COPD）和支气管炎; 炎症性疾病，包括癌症如神经胶质瘤，前列腺癌，小细胞肺癌和乳腺癌的肿瘤，以及与无序白细胞功能如自身免疫性和炎性疾病相关的疾病。

公开(公告)号：US20050070690A1

公开(公告)日：2005-03-31

申请号：US10489739

申请日：2002-09-17

申请人： David Dawbarn ,  Shelly Allen ,  Alan Robertson

发明人： David Dawbarn ,  Shelly Allen ,  Alan Robertson

IPC分类号： C12N15/09 ,  C07K14/705 ,  C07K14/71 ,  C07K19/00 ,  C12P21/00 ,  C12P21/02 ,  C07H21/04 ,  C12N9/12

CPC分类号： C07K14/71

摘要： This invention relates to a purification method, particularly for purifying tyrosine kinase receptor related polypeptides, and to products made by the method. The method comprises a method of producing tyrosine kinase receptor-related polypeptides, the method comprising expressing a tyrosine kinase receptor-related polypeptide in a recombinant expression system and separating expressed monomeric tyrosine kinase receptor-related polypeptide from multimeric form(s) of the expressed polypeptide in a separation step, the separation step allowing refolding of the expressed tyrosine kinase receptor-related polypeptide into a biologically active form.

摘要翻译： 本发明涉及一种纯化方法，特别是用于纯化酪氨酸激酶受体相关多肽的纯化方法以及通过该方法制备的产品。 该方法包括产生酪氨酸激酶受体相关多肽的方法，该方法包括在重组表达系统中表达酪氨酸激酶受体相关多肽，并将所表达的多肽的多聚体形式的表达的单体酪氨酸激酶受体相关多肽分离 在分离步骤中，分离步骤允许表达的酪氨酸激酶受体相关多肽重折叠成生物活性形式。

公开(公告)号：US20060030405A1

公开(公告)日：2006-02-09

申请号：US11198380

申请日：2005-08-05

申请人： Alan Robertson

发明人： Alan Robertson

IPC分类号： A63F9/24

CPC分类号： A63F13/63 ,  A63F13/10 ,  A63F2300/6009 ,  A63F2300/6018

摘要： An apparatus, system, and method are disclosed for generating a reproducible virtual environment in a computer software program. This invention describes a method of generating a realistic virtual environment dependent on a sequence of pseudo-random numbers generated by a pseudo-random number generator initialized by a seed value that may be created by the user. If a user starts with the same initial seed, the same virtual environment is created each time the program is run. However, if a new seed is used, a new virtual environment will be created.

摘要翻译： 公开了用于在计算机软件程序中生成可重现的虚拟环境的装置，系统和方法。 本发明描述了一种根据可由用户创建的种子值初始化的伪随机数生成器产生的伪随机数序列来生成实际虚拟环境的方法。 如果用户以相同的初始种子启动，则每次运行程序时都会创建相同的虚拟环境。 但是，如果使用新的种子，将创建一个新的虚拟环境。

公开(公告)号：US20050159437A1

公开(公告)日：2005-07-21

申请号：US11048959

申请日：2005-02-02

申请人： Bevyn Jarrott ,  Phillip Beart ,  William Jackson ,  Alan Robertson ,  Maree Collis ,  Alexandra Papanikos

发明人： Bevyn Jarrott ,  Phillip Beart ,  William Jackson ,  Alan Robertson ,  Maree Collis ,  Alexandra Papanikos

IPC分类号： C07D251/48 ,  A61K31/505 ,  A61K31/506 ,  A61K31/53 ,  A61P1/08 ,  A61P9/02 ,  A61P9/10 ,  A61P9/12 ,  A61P11/06 ,  A61P13/10 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P43/00 ,  C07D239/48 ,  C07D239/49 ,  C07D239/50 ,  C07D251/70 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D409/06 ,  C07D409/12 ,  C07D417/06 ,  C07D417/12 ,  C07D417/02 ,  C07D43/02 ,  C07D49/02

CPC分类号： C07D239/48 ,  C07D239/50 ,  C07D405/12

摘要： This invention relates to compounds of formula (1) wherein B is optionally substituted aryl; R1 and R2 are the same or different and are independently selected from hydrogen or C1-3 alkyl; n is 1 or 2, preferably n is 1; m is 0 or 1; R3 is hydrogen or acyl; R4 and R5 are the same or different and are independently selected from amino, alkylamino, dialkylamino, arylamino and C2-C8 cycloalkylamino; X and Y are independently selected from C, H or N provided at least one of X and Y is N; and salts thereof, solvates thereof, pharmaceutically acceptable derivatives thereof, prodrugs thereof, tautomers thereof and/or isomers thereof; and processes for their preparation and methods of treatment, pharmaceutical formulations and uses involving them.

摘要翻译： 本发明涉及式（1）化合物，其中B为任选取代的芳基; R 1和R 2相同或不同，并且独立地选自氢或C 1-3烷基; n为1或2，优选n为1; m为0或1; R 3是氢或酰基; R 4和R 5相同或不同，并且独立地选自氨基，烷基氨基，二烷基氨基，芳基氨基和C 2 -C 3 > 8个环烷基氨基; X和Y独立地选自C，H或N，其中X和Y中的至少一个是N; 及其盐，其溶剂合物，其药学上可接受的衍生物，其前药，其互变异构体和/或其异构体; 及其制备方法和治疗方法，药物制剂和涉及它们的用途。

公开(公告)号：US07648966B2

公开(公告)日：2010-01-19

申请号：US10557773

申请日：2004-05-20

申请人： William Butler Cowden ,  Gavin James Bartell ,  Bart Michael Eschler ,  Darren Ray March ,  Alan Robertson

发明人： William Butler Cowden ,  Gavin James Bartell ,  Bart Michael Eschler ,  Darren Ray March ,  Alan Robertson

IPC分类号： A61K31/70 ,  A61K31/7028

CPC分类号： C07H19/04 ,  C07H11/04

摘要： Novel phosphotetrahydropyran compounds that mimic mannose-6-phosphate but that are more resistant to phosphatases and mannosidases, and pharmaceutical compositions thereof, are disclosed. These compounds and compositions inhibit T lymphocyte migration from blood to tissues or to other extravascular sites. By inhibiting such migration, these compounds are useful for treating diseases or disorders that are mediated at least in part by such T lymphocyte migration. Such diseases and disorders include rheumatoid arthritis, multiple sclerosis, acute disseminated encephalomyelitis, psoriasis, inflammatory bowel disease, T cell-mediated dermatitis, stromal keratitis, uveitis, thyroiditis, sialitis and type I diabetes.

摘要翻译： 公开了新型磷酸四氢吡喃化合物，其模拟甘露糖-6-磷酸，但对磷酸酶和甘露糖苷酶更具抗性，以及其药物组合物。 这些化合物和组合物抑制T淋巴细胞从血液迁移到组织或其他血管外部位。 通过抑制这种迁移，这些化合物可用于治疗至少部分通过这种T淋巴细胞迁移介导的疾病或病症。 这些疾病和病症包括类风湿性关节炎，多发性硬化症，急性播散性脑脊髓炎，牛皮癣，炎性肠病，T细胞介导的皮炎，基质角膜炎，葡萄膜炎，甲状腺炎，唾液炎和I型糖尿病。

公开(公告)号：US20070082850A1

公开(公告)日：2007-04-12

申请号：US10557773

申请日：2004-05-20

申请人： William Cowden ,  Gavin Bartell ,  Bart Eschler ,  Darren March ,  Alan Robertson

发明人： William Cowden ,  Gavin Bartell ,  Bart Eschler ,  Darren March ,  Alan Robertson

IPC分类号： A61K31/7024 ,  A61K31/7052 ,  C07H19/04

CPC分类号： C07H19/04 ,  C07H11/04

摘要： Novel phosphotetrahydropyran compounds that mimic mannose-6-phosphate but that are more resistant to phosphatases and mannosidases, and pharmaceutical compositions thereof, are disclosed. These compounds and compositions inhibit T lymphocyte migration from blood to tissues or to other extravascular sites. By inhibiting such migration, these compounds are useful for treating diseases or disorders that are mediated at least in part by such T lymphocyte migration. Such diseases and disorders include rheumatoid arthritis, multiple sclerosis, acute disseminated encephalomyelitis, psoriasis, inflammatory bowel disease, T cell-mediated dermatitis, stromal keratitis, uveitis, thyroiditis, sialitis and type I diabetes.

摘要翻译： 公开了新型磷酸四氢吡喃化合物，其模拟甘露糖-6-磷酸，但对磷酸酶和甘露糖苷酶更具抗性，以及其药物组合物。 这些化合物和组合物抑制T淋巴细胞从血液迁移到组织或其他血管外部位。 通过抑制这种迁移，这些化合物可用于治疗至少部分通过这种T淋巴细胞迁移介导的疾病或病症。 这些疾病和病症包括类风湿性关节炎，多发性硬化症，急性播散性脑脊髓炎，牛皮癣，炎性肠病，T细胞介导的皮炎，基质角膜炎，葡萄膜炎，甲状腺炎，唾液炎和I型糖尿病。

公开(公告)号：US20060065797A1

公开(公告)日：2006-03-30

申请号：US10951160

申请日：2004-09-27

申请人： Alan Robertson ,  Mildred Robertson ,  Shelby Robertson

发明人： Alan Robertson ,  Mildred Robertson ,  Shelby Robertson

IPC分类号： A47K1/00

CPC分类号： A47G29/10

摘要： An attachment for cooperation with an associated electric switch mounting box and an associated faceplate which includes an elongated bolt; a plurality of beads, each having an internal bore dimensioned for allowing passage of an axial portion of the elongated bolt, and first and second finish washers, the beads being disposed on the elongated bolt when each of the beads being disposed in adjacent relationship to at least one other of the beads, the plurality of beads comprising an elongated stack, the first and second finish washers being disposed respectively at the axial extremities of the stack. In some forms of the invention the finish washers have cupped peripheral edges which may be disposed in facing relationship whereby the axial extremities of the stack have smooth surfaces. The beads may have respective colors associated with a country. The colors may be red, white and blue. Other forms of the apparatus include an electric switch mounting box having at least one threaded bore therein; a faceplate dimensioned and configured for mounting on the electric switch mounting box; an elongated bolt dimensioned and configured for passing through the faceplate into the threaded bore; a plurality of beads, each having an internal bore dimensioned for allowing passage of an axial portion of the elongated bolt; and first and second finish washers.

摘要翻译： 用于与相关联的电开关安装盒和相关联的面板配合的附件，其包括细长螺栓; 多个珠，每个具有内孔，其尺寸适于允许细长螺栓的轴向部分通过，以及第一和第二精磨垫圈，当每个珠子以与之相邻的关系设置时，珠被设置在细长螺栓上 珠子中的至少一个，多个珠粒包括细长的叠层，第一和第二精磨垫圈分别设置在堆叠的轴向末端。 在本发明的某些形式中，精加工垫圈具有杯状的周边边缘，其可以以面对的关系设置，从而堆叠的轴向端部具有光滑的表面。 珠可以具有与国家相关联的各自的颜色。 颜色可能是红色，白色和蓝色。 该装置的其他形式包括其中具有至少一个螺纹孔的电开关安装盒; 一个面板尺寸和配置用于安装在电气开关安装盒上; 细长螺栓的尺寸和构造适于穿过面板进入螺纹孔; 多个珠，每个具有内孔，其尺寸适于允许所述细长螺栓的轴向部分通过; 第一和第二洗衣机。