Invention Grant
US09101632B2 Kinase inhibitors, prodrug forms thereof and their use in therapy
有权
激酶抑制剂,其前药形式及其在治疗中的用途
- Patent Title: Kinase inhibitors, prodrug forms thereof and their use in therapy
- Patent Title (中): 激酶抑制剂,其前药形式及其在治疗中的用途
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Application No.: US13390398Application Date: 2010-09-02
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Publication No.: US09101632B2Publication Date: 2015-08-11
- Inventor: Jeffrey Bruce Smaill , Adam Vorn Patterson , Guo-Liang Lu , Ho Huat Lee , Amir Ashoorzadeh , Robert Forbes Anderson , William Robert Wilson , William Alexander Denny , Huai-Ling Annie Hsu , Andrej Maroz , Stephen Michael Frazer Jamieson , Alexandra Marie Mowday , Kendall Marie Carlin
- Applicant: Jeffrey Bruce Smaill , Adam Vorn Patterson , Guo-Liang Lu , Ho Huat Lee , Amir Ashoorzadeh , Robert Forbes Anderson , William Robert Wilson , William Alexander Denny , Huai-Ling Annie Hsu , Andrej Maroz , Stephen Michael Frazer Jamieson , Alexandra Marie Mowday , Kendall Marie Carlin
- Applicant Address: NZ Auckland
- Assignee: AUCKLAND UNISERVICES LIMITED
- Current Assignee: AUCKLAND UNISERVICES LIMITED
- Current Assignee Address: NZ Auckland
- Agency: Kilpatrick Townsend & Stockton LLP
- Priority: NZ579458 20090902
- International Application: PCT/NZ2010/000174 WO 20100902
- International Announcement: WO2011/028135 WO 20110310
- Main IPC: A61K31/519
- IPC: A61K31/519 ; A61P35/00 ; C07D471/04

Abstract:
The invention provides kinase inhibitors of Formula I: wherein either: (1) R1 is H, and (a) R2 is (3-chlorobenzyl)oxy-and R3 is chloro; (b) R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; (c) R2 is 2-pyridinylmethoxy and R3 is chloro; (d) R2 and R3 are both chloro; (e) R2 is chloro and R1 is bromo; (f) R2 and R3 are both bromo; (g) R2 is fluoro and R3 is ethynyl; (h) R2 is chloro and R3 is ethynyl; (i) R2 is bromo and R3 is ethynyl; (j) other than when R1 is in the 3-position in combination with R3, in the 4-position, R2 is bromo and R3 is fluoro; (k) R2 is 2-pyridinylmethoxy and R3 is fluoro; or (l) R2 is 2-pyridinylmethoxy and R1 is bromo; or (2) at least one of R1, R2 and R3 is selected from benzyloxy, 3-chlorobenzyloxy and 2-pyridinylmethoxy and when at least one of R1, R2 and R3 is not benzyloxy, 3-chlorobenzyloxy or 2-pyridinylmethoxy, each of the others is independently selected from H, halogen, and C2-C4 alkynyl, with the proviso that when one of R1, R2 and R3 is benzyloxy or 2-pyridinylmethoxy, the other two of R1, R2 and R3 are not H; or (3) two of R1, R2 and R3, together with the carbon atoms to which they are attached, form 1-(3-fluorobenzyl)-1H-pyrazole; and the other is selected from H, halogen and C2-C4 alkynyl. Also provided are reductive prodrugs, comprising a kinase inhibitor as defined above and a reductive trigger linked directly or indirectly to a nitrogen of the kinase inhibitor. Further provided are pharmaceutical compositions, comprising the kinase inhibitors or the prodrugs, and the use of such compositions in therapy, in particular for treating cancer.
Public/Granted literature
- US20120202832A1 KINASE INHIBITORS, PRODRUG FORMS THEREOF AND THEIR USE IN THERAPY Public/Granted day:2012-08-09
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