公开(公告)号：US20050227997A1

公开(公告)日：2005-10-13

申请号：US11120376

申请日：2005-05-03

申请人： Mark Noe ,  Michael Letavic ,  Louis Chupak ,  Kim McClure

发明人： Mark Noe ,  Michael Letavic ,  Louis Chupak ,  Kim McClure

IPC分类号： A61K45/00 ,  A61K31/445 ,  A61K31/495 ,  A61P1/00 ,  A61P1/02 ,  A61P1/04 ,  A61P3/10 ,  A61P7/00 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P17/00 ,  A61P17/02 ,  A61P19/02 ,  A61P19/10 ,  A61P21/00 ,  A61P25/00 ,  A61P25/02 ,  A61P25/04 ,  A61P25/06 ,  A61P25/14 ,  A61P25/16 ,  A61P25/24 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P31/04 ,  A61P31/18 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D211/42 ,  C07D211/96 ,  C07D241/04 ,  C07D241/08 ,  C07D333/34

CPC分类号： C07D241/04 ,  C07D211/96 ,  C07D241/08

摘要： This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R1 and R2 is methyl; R3 and R4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R3 and R4 may be taken together to form a carbonyl group; and R5 and R6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R7 and R8 are both hydrogen and at least one of R1, R2, R3, and R4 is hydroxy; when X is carbon and R5 is para-halo, then at least one of R6, R3, and R4 is not hydrogen; when X is nitrogen, then R8 is not present and R7 is hydrogen or a group of the formula: wherein, Y is —CH2—NH2 or —NH—CH3; and when X is nitrogen and R7 is H, then R3 and R4 are taken together to form a carbonyl group.

公开(公告)号：US20050277630A1

公开(公告)日：2005-12-15

申请号：US10772860

申请日：2004-02-06

申请人： Louis Chupak ,  Wenhua Jiao ,  Vera Prasad Josyula ,  Takushi Kaneko

发明人： Louis Chupak ,  Wenhua Jiao ,  Vera Prasad Josyula ,  Takushi Kaneko

IPC分类号： A61P31/04 ,  C07D413/04 ,  C07D413/14 ,  C07D491/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  A61K31/551 ,  C07D491/14

CPC分类号： C07D413/04 ,  C07D413/14 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04

摘要： Compounds of formula I and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula I as well as pharmaceutically acceptable compositions comprising compounds of formula I. Compounds of formula I as disclosed herein can be used in a variety of applications including use as antibacterial agents.

公开(公告)号：US20050288273A1

公开(公告)日：2005-12-29

申请号：US10774241

申请日：2004-02-06

申请人： Frederick Boyer ,  Allison Choy ,  Louis Chupak ,  Susan Hagen ,  Joysula Venkata Prasad ,  Takushi Kaneko ,  Ji-Young Kim

发明人： Frederick Boyer ,  Allison Choy ,  Louis Chupak ,  Susan Hagen ,  Joysula Venkata Prasad ,  Takushi Kaneko ,  Ji-Young Kim

IPC分类号： A61K31/55 ,  A61P31/04 ,  C07D263/38 ,  C07D413/04 ,  C07D413/06 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04

CPC分类号： C07D263/38 ,  C07D413/04 ,  C07D413/06 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04

摘要： Compounds of formula I and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula I as well as pharmaceutically acceptable compositions comprising compounds of formula I. Compounds of formula I as disclosed herein can be used in a variety of applications including use as antibacterial agents.

公开(公告)号：US20060135447A1

公开(公告)日：2006-06-22

申请号：US11313523

申请日：2005-12-21

申请人： Louis Chupak ,  Mark Flanagan ,  Takushi Kaneko ,  Thomas Magee ,  Mark Noe ,  Usa Reilly

发明人： Louis Chupak ,  Mark Flanagan ,  Takushi Kaneko ,  Thomas Magee ,  Mark Noe ,  Usa Reilly

IPC分类号： A61K31/7052 ,  C07H17/08

CPC分类号： C07H17/08

摘要： Macrolide compounds per se, as shown below and defined herein, and their use, e.g., as antibacterial and antiprotozoal agents in animals, including humans: Also disclosed are methods of preparing the compounds, intermediates, and pharmaceutical compositions thereof, and methods of treating or preventing disease by administering the compounds to subjects in need. This abstract is only an excerpt and is not limiting of the invention.

摘要翻译： 大环内酯类化合物本身，如下文所示和定义，以及它们在动物（包括人）中作为抗细菌剂和抗原虫药的用途：还公开了制备化合物，中间体及其药物组合物的方法，以及治疗或 通过将化合物给予需要的受试者来预防疾病。 该摘要仅是摘录而不是本发明的限制。

公开(公告)号：US20050215549A1

公开(公告)日：2005-09-29

申请号：US11120846

申请日：2005-05-03

申请人： Kim McClure ,  Mark Noe ,  Michael Letavic ,  Louis Chupak

发明人： Kim McClure ,  Mark Noe ,  Michael Letavic ,  Louis Chupak

IPC分类号： A61K31/5355 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/54 ,  A61P1/00 ,  A61P1/02 ,  A61P9/04 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P17/00 ,  A61P19/02 ,  A61P19/10 ,  A61P25/14 ,  A61P25/16 ,  A61P25/24 ,  A61P27/02 ,  A61P29/00 ,  A61P31/04 ,  A61P31/18 ,  A61P35/00 ,  A61P37/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D211/96 ,  C07D265/30 ,  C07D279/12 ,  C07D413/12 ,  A61K31/495

CPC分类号： C07D265/30 ,  C07D211/96 ,  C07D279/12

摘要： A compound of the formula wherein R1, R2 R3, R4, R5, R6 and Q are as defined above, useful in the treatment of arthritis, cancer, and other diseases involving the dysregulated production/release of reprolysins such as TNF and other diseases characterized by matrix metalloproteinase activity. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID's), COX-2 inhibitors and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.

摘要翻译： 下式的化合物其中R 1，R 2，R 3，R 4，R 5，R 5， Q 6和Q如上所定义，可用于治疗关节炎，癌症和涉及生殖调节的生殖/释放诸如TNF和其它特征为基质的疾病的其它疾病 金属蛋白酶活性。 此外，本发明的化合物可以与标准非甾体抗炎药（NSAID），COX-2抑制剂和镇痛药组合使用，并与细胞毒性药物如阿霉素，道诺霉素，顺式铂 ，依托泊苷，紫杉醇，泰索帝等生物碱，如长春新碱，用于治疗癌症。