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41. 发明授权

US06686347B2 Phthalazine derivatives for treating inflammatory diseases 失效
标题翻译：用于治疗炎性疾病的酞嗪衍生物
公开(公告)号：US06686347B2
公开(公告)日：2004-02-03
申请号：US09964025
申请日：2001-09-26
申请人： Guido Bold , Janet Dawson King , Jörg Frei , Richard Heng , Paul William Manley , Bernhard Wietfeld , Jeanette Marjorie Wood
发明人： Guido Bold , Janet Dawson King , Jörg Frei , Richard Heng , Paul William Manley , Bernhard Wietfeld , Jeanette Marjorie Wood
IPC分类号： A61K3133
CPC分类号： C07D401/06 , A61K31/501 , A61K31/502 , C07D401/14
摘要： The invention relates to the treatment of an inflammatory disease, especially an inflammatory rheumatoid or rheumatic disease, and/or pain with an inhibitor of the activity of VEGF receptor tyrosine kinase of the formula I, the substituents being defined in the specification; as well as to new phthalazine derivatives; processes for the preparation thereof; the application thereof in a process for the treatment of the human or animal body; the use thereof for the treatment of a disease, especially a disease caused by ocular neovascularization, such as age-related macula degeneration or diabetic retinopathy, or other diseases that respond to the inhibition of tyrosine kinases, such as a proliferative disease; a method for the treatment of such disease in mammals; and the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment especially of a disease as mentioned above.
摘要翻译：本发明涉及治疗炎症性疾病，特别是炎性类风湿病或风湿性疾病，和/或具有式I的VEGF受体酪氨酸激酶的活性抑制剂的疼痛，所述取代基在本说明书中定义;以及新的酞嗪衍生物; 制备方法; 其用于治疗人或动物体的过程中的应用; 其用于治疗疾病，特别是由眼睛新生血管形成引起的疾病，例如年龄相关性黄斑变性或糖尿病性视网膜病，或其它对酪氨酸激酶（例如增殖性疾病）的抑制作用的疾病; 哺乳动物治疗这种疾病的方法; 以及这种化合物用于制造特别是上述疾病的药物制剂的用途。

42. 发明申请

US20130310395A1 COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF ABL1, ABL2 AND BCR-ABL1 有权
标题翻译：抑制ABL1，ABL2和BCR-ABL1活性的化合物和组合物
公开(公告)号：US20130310395A1
公开(公告)日：2013-11-21
申请号：US13892769
申请日：2013-05-13
申请人： Stephanie Kay DODD , Pascal FURET , Robert Martin GROTZFELD , Darryl Brynley JONES , Paul William MANLEY , Andreas MARZINZIK , Xavier Francois Andre PELLE , Bahaa SALEM , Joseph SCHOEPFER
发明人： Stephanie Kay DODD , Pascal FURET , Robert Martin GROTZFELD , Darryl Brynley JONES , Paul William MANLEY , Andreas MARZINZIK , Xavier Francois Andre PELLE , Bahaa SALEM , Joseph SCHOEPFER
IPC分类号： C07D401/10 , A61K31/4439 , C07D405/14 , C07D401/14 , C07D403/10 , A61K45/06 , A61K31/506 , C07F9/58
CPC分类号： C07D213/82 , A61K31/4439 , A61K31/506 , A61K45/06 , C07D401/04 , C07D401/10 , C07D401/14 , C07D403/10 , C07D405/14 , C07F9/58
摘要： The present invention relates to compounds of formula (I): in which Y, Y1, R1, R2, R3 and R4 are defined in the Summary of the Invention; capable of inhibiting the activity of BCR-ABL1 and mutants thereof. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.
摘要翻译：本发明涉及式（I）化合物：其中Y，Y 1，R 1，R 2，R 3和R 4在发明概述中定义; 能够抑制BCR-ABL1及其突变体的活性。本发明还提供了制备本发明化合物的方法，包含这些化合物的药物制剂和使用这些化合物治疗癌症的方法。

43. 发明授权

US08445479B2 Staurosporine derivatives as inhibitors of FLT3 receptor tyrosine kinase activity 有权
标题翻译：星形孢菌素衍生物作为FLT3受体酪氨酸激酶活性的抑制剂
公开(公告)号：US08445479B2
公开(公告)日：2013-05-21
申请号：US13524340
申请日：2012-06-15
申请人： James Douglas Griffin , Paul William Manley
发明人： James Douglas Griffin , Paul William Manley
IPC分类号： A61P35/02 , A61K31/55 , A61K31/535 , C07D498/22 , C07D487/04 , C07D487/14 , C07D519/00
CPC分类号： A61K31/407 , A61K31/535 , A61K31/55 , A61K31/553
摘要： The present invention relates to the use of staurosporines derivatives for the preparation of a drug for the treatment of diseases involving deregulated FLT3 receptor tyrosine kinase activity, especially for the curative and/or prophylactic treatment of leukemias and myelodysplastic syndromes, and to a method of treating diseases involving deregulated FLT3 receptor tyrosine kinase activity.
摘要翻译：本发明涉及星形孢菌素衍生物在制备用于治疗涉及失调的FLT3受体酪氨酸激酶活性的疾病的药物中的用途，特别是用于治疗和/或预防性治疗白血病和骨髓增生异常综合征，以及治疗方法涉及失调的FLT3受体酪氨酸激酶活性的疾病。

44. 发明申请

US20110294820A1 N-Oxides of n-Phenyl-2-pyrimidine-amine Derivatives 审中-公开
标题翻译：正 - 苯基-2-嘧啶 - 胺衍生物的N-氧化物
公开(公告)号：US20110294820A1
公开(公告)日：2011-12-01
申请号：US13176289
申请日：2011-07-05
申请人： Klaus Olaf Börnsen , Peter End , Gerhard Gross , Ulrike Pfaar , Paul William Manley , Jürg Zimmerman
发明人： Klaus Olaf Börnsen , Peter End , Gerhard Gross , Ulrike Pfaar , Paul William Manley , Jürg Zimmerman
IPC分类号： A61K31/506 , A61P11/06 , A61P9/10 , C07D401/14 , A61P35/00
CPC分类号： C07D401/04 , C07D401/14
摘要： The invention relates to N-phenyl-2-pyrimidine-amine derivatives derivatives in which at least one nitrogen atom carries an oxygen atom to form the corresponding N-oxides, to processes for the preparation thereof, to pharmaceutical compositions comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.
摘要翻译：本发明涉及N-苯基-2-嘧啶 - 胺衍生物衍生物，其中至少一个氮原子携带氧原子以形成相应的N-氧化物，其制备方法，包含这些化合物的药物组合物，以及其用于制备用于治疗性治疗温血动物（包括人）的药物组合物。

45. 发明申请

US20110224194A1 Staurosporine Derivatives as Inhibitors of FLT3 Receptor Tyrosine Kinase Activity 有权
标题翻译：星形孢菌素衍生物作为FLT3受体酪氨酸激酶活性的抑制剂
公开(公告)号：US20110224194A1
公开(公告)日：2011-09-15
申请号：US13109511
申请日：2011-05-17
申请人： James Douglas Griffin , Paul William Manley
发明人： James Douglas Griffin , Paul William Manley
IPC分类号： A61K31/551 , A61P35/02
CPC分类号： A61K31/407 , A61K31/535 , A61K31/55 , A61K31/553
摘要： The present invention relates to the use of staurosporines derivatives for the preparation of a drug for the treatment of diseases involving deregulated FLT3 receptor tyrosine kinase activity, especially for the curative and/or prophylactic treatment of leukemias and myelodysplastic syndromes, and to a method of treating diseases involving deregulated FLT3 receptor tyrosine kinase activity.
摘要翻译：本发明涉及星形孢菌素衍生物在制备用于治疗涉及失调的FLT3受体酪氨酸激酶活性的疾病的药物中的用途，特别是用于治疗和/或预防性治疗白血病和骨髓增生异常综合征，以及治疗方法涉及失调的FLT3受体酪氨酸激酶活性的疾病。

46. 发明申请

US20110218187A1 INHIBITORS OF TYROSINE KINASES 审中-公开
标题翻译： TYROSINE KINASES的抑制剂
公开(公告)号：US20110218187A1
公开(公告)日：2011-09-08
申请号：US13106582
申请日：2011-05-12
申请人： Werner BREITENSTEIN , Pascal FURET , Sandra JACOB , Paul William MANLEY
发明人： Werner BREITENSTEIN , Pascal FURET , Sandra JACOB , Paul William MANLEY
IPC分类号： A61K31/55 , C07D401/04 , A61K31/506 , A61K31/496 , C07D401/14 , C07D413/14 , A61K31/5377 , A61P35/02
CPC分类号： C07D401/14 , C07D405/14
摘要： The invention relates to compounds of formula wherein the substituents R1, R2 and R4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, especially a neoplastic disease, in particular leukaemia, and a method for the treatment of such a disease.
摘要翻译：本发明涉及下式的化合物，其中取代基R 1，R 2和R 4具有本发明说明书中阐述和解释的含义，制备这些化合物的方法，含有它们的药物组合物，其任选组合的用途与一种或多种用于治疗对蛋白激酶活性，特别是肿瘤性疾病，特别是白血病的抑制作出反应的疾病的其它药学活性化合物，以及治疗这种疾病的方法。

47. 发明申请

US20080188451A1 INHIBITORS OF TYROSINE KINASES 有权
标题翻译： TYROSINE KINASES的抑制剂
公开(公告)号：US20080188451A1
公开(公告)日：2008-08-07
申请号：US12061334
申请日：2008-04-02
申请人： Werner Breitenstein , Pascal Furet , Sandra Jacob , Paul William Manley
发明人： Werner Breitenstein , Pascal Furet , Sandra Jacob , Paul William Manley
IPC分类号： A61K31/337 , C07D239/24 , A61K31/505 , C07D403/14 , A61P35/00 , A61K31/496 , C07D413/14 , A61K31/5377
CPC分类号： C07D401/14 , C07D405/14
摘要： The invention relates to compounds of formula wherein the substituents R1, R2 and R4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, especially a neoplastic disease, in particular leukaemia, and a method for the treatment of such a disease.
摘要翻译：本发明涉及下式的化合物，其中取代基R 1，R 2和R 4具有本发明说明书中阐述和解释的含义，制备这些化合物的方法，含有它们的药物组合物，其任选组合的用途与一种或多种用于治疗对蛋白激酶活性，特别是肿瘤性疾病，特别是白血病的抑制作出反应的疾病的其它药学活性化合物，以及治疗这种疾病的方法。

48. 发明授权

US06878720B2 VEGF receptor tyrosine kinase inhibitors 失效
标题翻译： VEGF受体酪氨酸激酶抑制剂
公开(公告)号：US06878720B2
公开(公告)日：2005-04-12
申请号：US10180289
申请日：2002-06-26
申请人： Karl-Heinz Altmann , Guido Bold , Pascal Furet , Paul William Manley , Jeanette Marjorie Wood , Stefano Ferrari , Francesco Hofmann , Jürgen Mestan , Andreas Huth , Martin Krüger , Dieter Seidelmann , Andreas Menrad , Martin Haberey , Karl-Heinz Thierauch
发明人： Karl-Heinz Altmann , Guido Bold , Pascal Furet , Paul William Manley , Jeanette Marjorie Wood , Stefano Ferrari , Francesco Hofmann , Jürgen Mestan , Andreas Huth , Martin Krüger , Dieter Seidelmann , Andreas Menrad , Martin Haberey , Karl-Heinz Thierauch
IPC分类号： C07D233/64 , A61K20060101 , A61K31/00 , A61K31/166 , A61K31/167 , A61K31/415 , A61K31/417 , A61K31/44 , A61K31/4409 , A61K31/443 , A61K31/444 , A61K31/47 , A61K31/4745 , A61K31/497 , A61K31/505 , A61P20060101 , A61P17/00 , A61P27/02 , A61P35/00 , A61P43/00 , C07C20060101 , C07C223/02 , C07C237/30 , C07C317/26 , C07D20060101 , C07D211/22 , C07D213/04 , C07D213/38 , C07D213/40 , C07D213/61 , C07D213/64 , C07D213/89 , C07D215/12 , C07D215/14 , C07D215/36 , C07D215/58 , C07D233/54 , C07D265/26 , C07D401/12 , C07D401/14 , C07D405/12 , C07D407/12 , C07D409/12 , C07D413/12 , C07D471/02
CPC分类号： A61K31/415 , A61K31/44 , A61K31/47 , C07D213/38 , C07D213/56 , C07D213/64 , C07D213/89 , C07D215/12 , C07D233/54 , C07D405/12
摘要： Described are compunds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10—(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO2; R1 is aryl; R2 is a bicyclic heteroaryl group comprising one ring nitrogen atom with the exception that R2 cannot represent 2-phthalimidyl; any of R3, R4, R5 and R6, independently of the other, is H or a substituent other than hydrogen; and R7 and R8, independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.
摘要翻译：描述的是式（I）的化合物，其中W是O或S; X为NR8; Y为CR 9 R 10 - （CH 2）n，其中R 9和R 10彼此独立地为氢或低级烷基，n为0〜3的整数。或Y为SO2; R1是芳基; R2是包含一个环氮原子的二环杂芳基，不同的是R 2不能代表2-邻苯二酰亚氨基; R 3，R 4，R 5和R 6中的任何一个独立地为H或氢以外的取代基; 且R 7和R 8彼此独立地为H或低级烷基; 或N-氧化物或其药学上可接受的盐在制备用于治疗对VEGF受体酪氨酸激酶活性的抑制作出反应的肿瘤疾病的药物产品中的用途。式（I）化合物可用于治疗，例如，的肿瘤疾病，如肿瘤疾病，视网膜病变和年龄相关性黄斑变性。

49. 发明授权

US06706731B2 Pyridine derivatives inhibiting angiogenesis and/or VEGF receptor tyrosine kinase 失效
标题翻译：抑制血管发生和/或VEGF受体酪氨酸激酶的吡啶衍生物
公开(公告)号：US06706731B2
公开(公告)日：2004-03-16
申请号：US10203579
申请日：2002-10-11
申请人： Guido Bold , Paul William Manley
发明人： Guido Bold , Paul William Manley
IPC分类号： C07D47104
CPC分类号： C07D401/06 , C07D471/04
摘要： The invention relates to pyridine derivatives of formula I: wherein the substituents and symbols are defined as indicated in the description, processes for the preparation thereof, their usage in the preparation of a pharmaceutical composition for the treatment of a disease which responds to an inhibition of angiogenesis, and pharmaceutical compositions containing such compounds.
摘要翻译：本发明涉及式I的吡啶衍生物：其中取代基和符号如说明书所述定义，其制备方法，它们在制备用于治疗对抑制作用的疾病的药物组合物中的用途血管生成和含有这些化合物的药物组合物。

50. 发明授权

US06624174B2 2-amino-nicotinamide derivatives and their use as VEGF-receptor tyrosine kinase inhibitors 有权
标题翻译： 2-氨基 - 烟酰胺衍生物及其作为VEGF-受体酪氨酸激酶抑制剂的用途
公开(公告)号：US06624174B2
公开(公告)日：2003-09-23
申请号：US10181005
申请日：2002-07-11
申请人： Paul William Manley , Guido Bold
发明人： Paul William Manley , Guido Bold
IPC分类号： C07D21382
CPC分类号： C07D213/82 , A61K31/445 , C07D213/89 , C07D401/14 , C07D417/14
摘要： The invention relates to the use of 2 amino-nicotinamide derivatives of formula I wherein n is from 1 up to and including 6; W is O or S; R1 and R3 represent independently of each other hydrogen, lower alkyl or lower acyl; R2 represents a cycloalkyl group, an aryl group, or a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms and 0, 1 or 2 heteroatoms independently from each other selected from the group consisting of oxygen and sulfur, which groups in each case are unsubstituted or mono- or polysubstituted; R and R′ are independently of each other hydrogen or lower alkyl; X represents an aryl group, or a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms and 0, 1 or 2 heteroatoms independently from each other selected from the group consisting of oxygen and sulfur, which groups in each case are unsubstituted or mono- or polysubstituted; or a N-oxide, a possible tautomer thereof or a pharmaceutically acceptable salt of such a compound, alone or in combination with one or more other pharmaceutically active compounds for the preparation of a pharmaceutical composition for use for therapy of a disease which responds to an inhibition of the VEGF-receptor tyrosine kinase activity; and to new 2-amino-nicotinamide derivatives of formula I and processes for the preparation thereof.
摘要翻译：本发明涉及式I的2种氨基 - 烟酰胺衍生物的用途，其中n为1至6，W为O或S; R 1和R 3彼此独立地为氢，低级烷基或低级酰基; R 2表示环烷基，芳基或包含一个或多个环氮原子和0,1或2个彼此独立地选自氧和硫的杂原子的单环或双环杂芳基，这些基团在每种情况下是未取代的或单取代或多取代; R和R'彼此独立地为氢或低级烷基; X表示芳基，或单环或双环杂芳基，其包含一个或多个环氮原子和0,1或2个独立地为彼此选自氧和硫，这些基团在每种情况下都是未取代的或单取代或多取代的;或N-氧化物，其可能的互变异构体或这种化合物的药学上可接受的盐，alo ne或与一种或多种其它药学活性化合物组合用于制备用于治疗对VEGF-受体酪氨酸激酶活性的抑制作出反应的疾病的药物组合物;以及新的2-氨基 - 烟酰胺衍生物式I及其制备方法。

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