Prodrug forms of kinase inhibitors and their use in therapy
US9073916B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Mar 11, 2010 |
| Grant date | Jul 7, 2015 |
| Priority date | — |
| Expiry date | Mar 10, 2031 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D405/14
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.