Invention Grant
- Patent Title: Prodrug forms of kinase inhibitors and their use in therapy
- Patent Title (中): 激酶抑制剂的前体形式及其在治疗中的应用
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Application No.: US13138429Application Date: 2010-03-11
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Publication No.: US09073916B2Publication Date: 2015-07-07
- Inventor: Jeffrey Bruce Smaill , Adam Vorn Patterson , Michael Patrick Hay , William Alexander Denny , William Robert Wilson , Guo-Liang Lu , Robert Forbes Anderson , Ho Huat Lee , Amir Ashoorzadeh
- Applicant: Jeffrey Bruce Smaill , Adam Vorn Patterson , Michael Patrick Hay , William Alexander Denny , William Robert Wilson , Guo-Liang Lu , Robert Forbes Anderson , Ho Huat Lee , Amir Ashoorzadeh
- Applicant Address: NZ Auckland
- Assignee: AUCKLAND UNISERVICES LIMITED
- Current Assignee: AUCKLAND UNISERVICES LIMITED
- Current Assignee Address: NZ Auckland
- Agency: Kilpatrick Townsend & Stockton LLP
- Priority: NZ575490 20090311; NZ579458 20090902; NZ581170 20091112
- International Application: PCT/NZ2010/000040 WO 20100311
- International Announcement: WO2010/104406 WO 20100916
- Main IPC: A61K31/5377
- IPC: A61K31/5377 ; A61K31/519 ; A61K31/4178 ; A61K31/517 ; A61K31/4709 ; C07D403/12 ; C07D403/14 ; C07D401/12 ; C07D405/14 ; C07D471/04 ; C07D239/94

Abstract:
The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R1 is a group of the formula —(CH2)nTr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3 and R4 may be absent and two of R2, R3 and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.
Public/Granted literature
- US20120077811A1 PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY Public/Granted day:2012-03-29
Information query
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