公开(公告)号：US07705042B2

公开(公告)日：2010-04-27

申请号：US11255043

申请日：2005-10-20

申请人： Carl R. Illig ,  Shelley K. Ballentine ,  Jinsheng Chen ,  Sanath Meegalla ,  Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee DesJarlais ,  Carl L. Manthey ,  Christopher M. Flores ,  Christopher J. Molloy

发明人： Carl R. Illig ,  Shelley K. Ballentine ,  Jinsheng Chen ,  Sanath Meegalla ,  Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee DesJarlais ,  Carl L. Manthey ,  Christopher M. Flores ,  Christopher J. Molloy

IPC分类号： A61K31/34

CPC分类号： C07D263/34 ,  C07D207/34 ,  C07D233/90 ,  C07D307/68 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12

摘要： The invention relates to arylamide and hetereoarylamide compounds of Formula I: wherein A, X, R2 and W are set forth in the specification, as well as tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

摘要翻译： 本发明涉及式I的芳基酰胺和hetereoarylamide化合物：其中A，X，R 2和W在说明书中列出，以及其互变异构体和药学上可接受的盐，其抑制蛋白酪氨酸激酶，特别是c-fms激酶。 治疗自身免疫性疾病的方法 和具有炎症成分的疾病; 治疗卵巢癌，子宫癌，乳腺癌，结肠癌，胃癌，毛细胞白血病和非小细胞肺癌的转移; 并治疗疼痛，包括由肿瘤转移或骨关节炎引起的骨骼疼痛，或内脏，炎症和神经源性疼痛; 还提供了骨质疏松症，佩吉特氏病和其它骨吸收介导关节炎，假体失败，溶骨性骨肉瘤，骨髓瘤以及与式I化合物对骨的肿瘤转移的其它疾病。

公开(公告)号：US07645755B2

公开(公告)日：2010-01-12

申请号：US11408096

申请日：2006-04-20

申请人： Carl R. Illig ,  Shelley K. Ballentine ,  Jinsheng Chen ,  Sanath K. Meegalla ,  M. Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee L. Desjarlais ,  Carl L. Manthey ,  Christopher Flores ,  Christopher J. Molloy

发明人： Carl R. Illig ,  Shelley K. Ballentine ,  Jinsheng Chen ,  Sanath K. Meegalla ,  M. Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee L. Desjarlais ,  Carl L. Manthey ,  Christopher Flores ,  Christopher J. Molloy

IPC分类号： A61K31/5377 ,  A61K31/454 ,  C07D413/14 ,  C07D401/02

CPC分类号： C07D307/71 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14

摘要： The invention is directed to compounds of Formula I: wherein A, X, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

公开(公告)号：US07662837B2

公开(公告)日：2010-02-16

申请号：US11254276

申请日：2005-10-20

申请人： Carl R. Illig ,  Shelley K. Ballentine ,  Jinsheng Chen ,  Sanath K. Meegalla ,  M. Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee L. Desjarlais ,  Carl L. Manthey ,  Christopher Flores ,  Christopher J. Molloy

发明人： Carl R. Illig ,  Shelley K. Ballentine ,  Jinsheng Chen ,  Sanath K. Meegalla ,  M. Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee L. Desjarlais ,  Carl L. Manthey ,  Christopher Flores ,  Christopher J. Molloy

IPC分类号： A61K31/454 ,  C07D401/02

CPC分类号： C07D307/71 ,  C07D401/12 ,  C07D401/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14

摘要： The invention is directed to compounds of Formula I: wherein A, X, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

摘要翻译： 本发明涉及式I化合物：其中A，X，R 2和W在本说明书中阐述，以及其抑制蛋白酪氨酸激酶，特别是c-fms激酶的溶剂合物，水合物，互变异构体及其药学上可接受的盐 。 治疗自身免疫性疾病的方法 和具有炎症成分的疾病; 治疗卵巢癌，子宫癌，乳腺癌，结肠癌，胃癌，毛细胞白血病和非小细胞肺癌的转移; 并治疗疼痛，包括由肿瘤转移或骨关节炎引起的骨骼疼痛，或内脏，炎症和神经源性疼痛; 还提供了骨质疏松症，佩吉特氏病和其它骨吸收介导包括关节炎，假体失败，溶骨性骨肉瘤，骨髓瘤以及与式I化合物对骨的肿瘤转移的其它疾病。

公开(公告)号：US08697716B2

公开(公告)日：2014-04-15

申请号：US11737517

申请日：2007-04-19

申请人： Carl R. Illig ,  Shelley K. Balltentine ,  Jinsheng Chen ,  Sanath K. Meegalla ,  M. Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee L. DesJarlais ,  Carl L. Manthey ,  Christopher J. Molloy

发明人： Carl R. Illig ,  Shelley K. Balltentine ,  Jinsheng Chen ,  Sanath K. Meegalla ,  M. Jonathan Rudolph ,  Mark J. Wall ,  Kenneth J. Wilson ,  Renee L. DesJarlais ,  Carl L. Manthey ,  Christopher J. Molloy

IPC分类号： A61K31/41 ,  A61K31/435

CPC分类号： A61K31/5377 ,  A61K31/4178 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K45/06 ,  A61N5/10 ,  A61N2005/1098 ,  C07D307/68 ,  C07D401/12 ,  C07D401/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C12N9/99

摘要： A method of reducing or inhibiting kinase activity of C-KIT in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to C-KIT using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.

摘要翻译： 降低或抑制细胞或受试者中C-KIT的激酶活性的方法，以及使用这些化合物在受试者中预防或治疗细胞增殖性疾病和/或与C-KIT相关的病症的方法， 本发明：或其溶剂合物，水合物，互变异构体或其药学上可接受的盐。 本发明还涉及治疗诸如癌症和其它细胞增殖性疾病的病症的方法。

公开(公告)号：US06291514B1

公开(公告)日：2001-09-18

申请号：US09372748

申请日：1999-08-11

申请人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Juan José Marugán

发明人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Juan José Marugán

IPC分类号： A61K3138

CPC分类号： C07D409/04 ,  C07D333/38 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

摘要： The present invention is directed to compounds of Formula I: wherein X is O, S or NR7 and R1-R7, Y and Z are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, plasmin and urokinase. Certain of the compounds exhibit direct, selective inhibition of urokinase, or are intermediates useful for forming compounds having such activity.

摘要翻译： 本发明涉及式I化合物：其中X是O，S或NR 7，R 1 -R 7，Y和Z在说明书中列出，以及其水合物，溶剂合物或其药学上可接受的盐。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，纤溶酶和尿激酶。 某些化合物表现出对尿激酶的直接选择性抑制，或者是用于形成具有这种活性的化合物的中间体。

公开(公告)号：US06562840B1

公开(公告)日：2003-05-13

申请号：US10082127

申请日：2002-02-26

申请人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Juan José Marugán

发明人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Juan José Marugán

IPC分类号： A61K3147

CPC分类号： C07D409/04 ,  C07D333/38 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

摘要： The present invention is directed to compounds of Formula I: wherein X is O, S or NR7 and R1—R7, Y and Z are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, plasmin and urokinase. Certain of the compounds exhibit direct, selective inhibition of urokinase, or are intermediates useful for forming compounds having such activity.

摘要翻译： 本发明涉及式I化合物：其中X是O，S或NR 7，R 1 -R 7，Y和Z在说明书中列出，以及其水合物，溶剂合物或其药学上可接受的盐。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，纤溶酶和尿激酶。 某些化合物表现出对尿激酶的直接选择性抑制，或者是用于形成具有这种活性的化合物的中间体。

公开(公告)号：US06515002B2

公开(公告)日：2003-02-04

申请号：US09962304

申请日：2001-09-26

申请人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Roger F. Bone ,  Scott L. Klein ,  Troy L. Randle

发明人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Roger F. Bone ,  Scott L. Klein ,  Troy L. Randle

IPC分类号： C07D41718

CPC分类号： C07D409/04 ,  A61K31/427 ,  C07D333/38 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, X, Y and Z are defined in the specification.

摘要翻译： 公开了一种治疗由补体级联的经典途径介导的急性或慢性障碍的症状的方法，其包括向需要这种治疗的哺乳动物施用治疗有效量的式I化合物或溶剂合物，水合物或药学上 其可接受的盐; 其中R1，R2，R3，R4，X，Y和Z在说明书中定义。

公开(公告)号：US06403633B2

公开(公告)日：2002-06-11

申请号：US09828783

申请日：2001-04-10

申请人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Juan José Marugán

发明人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Juan José Marugán

IPC分类号： A61K3138

CPC分类号： C07D409/04 ,  C07D333/38 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

摘要： The present invention is directed to compounds of Formula I: wherein X is O, S or NR7 and R1-R7, Y and Z are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. Also described are methods for preparing the compounds of Formula I. The novel compounds of the present invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, plasmin and urokinase. Certain of the compounds exhibit direct, selective inhibition of urokinase, or are intermediates useful for forming compounds having such activity.

摘要翻译： 本发明涉及式I化合物：其中X是O，S或NR 7，R 1 -R 7，Y和Z在说明书中列出，以及其水合物，溶剂合物或其药学上可接受的盐。 还描述了制备式I化合物的方法。本发明的新化合物是蛋白酶的有效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，例如胰凝乳蛋白酶，胰蛋白酶，纤溶酶和尿激酶。 某些化合物表现出对尿激酶的直接选择性抑制，或者是用于形成具有这种活性的化合物的中间体。

公开(公告)号：US06492403B1

公开(公告)日：2002-12-10

申请号：US09500783

申请日：2000-02-09

申请人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Roger F. Bone ,  Scott L. Klein ,  Troy L. Randle

发明人： Carl R. Illig ,  Nalin L. Subasinghe ,  James B. Hoffman ,  Kenneth J. Wilson ,  M. Jonathan Rudolph ,  Roger F. Bone ,  Scott L. Klein ,  Troy L. Randle

IPC分类号： A61K31427

CPC分类号： C07D409/04 ,  A61K31/427 ,  C07D333/38 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, X, Y and Z are defined in the specification.

摘要翻译： 公开了一种治疗由补体级联的经典途径介导的急性或慢性障碍的症状的方法，其包括向需要这种治疗的哺乳动物施用治疗有效量的式I化合物或溶剂合物，水合物或药学上 其可接受的盐; 其中R1，R2，R3，R4，X，Y和Z在说明书中定义。

公开(公告)号：USH1890H

公开(公告)日：2000-10-03

申请号：US226615

申请日：1998-12-22

申请人： Timothy P. Parr ,  Klaus Schadow ,  Kenneth J. Wilson ,  Robert A. Smith ,  Kenneth Yu

发明人： Timothy P. Parr ,  Klaus Schadow ,  Kenneth J. Wilson ,  Robert A. Smith ,  Kenneth Yu

IPC分类号： F23C15/00 ,  F23G7/06 ,  F23C11/04

CPC分类号： F23C15/00 ,  F23C2205/10 ,  F23G7/065

摘要： This invention involves an improved technique for the modulation of waste an actively controlled compact waste incinerator afterburner. This improved technique utilizes acoustic driving to affect indirect modulation of waste flow velocities. The waste surrogate gases are modulated indirectly by periodic entrainment created by the roll-up of the main air vortex as well as indirect acoustic excitation of secondary air injection. One of the main advantages of this new configuration is the acoustic drivers used to phase inject the waste into the vortex for proper combustion are not in direct contact with the hot waste and therefore can be less expensive and more durable over the long term.

摘要翻译： 本发明涉及用于在主动控制的紧凑型垃圾焚烧炉后燃器中调节废物的改进技术。 这种改进的技术利用声学驱动来影响废物流速的间接调制。 通过主空气涡流的卷起以及二次空气喷射的间接声激发产生的周期夹带间接地调节废弃代用气体。 这种新配置的主要优点之一是用于将废物相位注入涡流以用于适当燃烧的声学驱动器不与热废物直接接触，因此可以在长期内更便宜并且更耐用。