Title:Small-Molecules Targeting Kinases Involved in Pulmonary Hypertension: a Patent Review (2010-2015)
Volume: 23
Issue: 30
Author(s): Rita Morigi, Mirella Rambaldi, Alessandra Locatelli, Alberto Leoni
Affiliation:
关键词:
肺动脉高血压，治疗，激酶抑制剂，专利，杂环化合物。
摘要: Background: Despite the fact that in recent years, a substantial progress
has been made in the treatment of pulmonary hypertension, it is still a
severe disease characterized by poor prognosis, and the search for new drugs
remains a priority. Current remedies address mainly the vasoconstrictor/
vasodilator imbalance in the pulmonary circulation, while the causes of the
disease are only moderately affected. Recently, the role of receptor and non
receptor kinases in pulmonary hypertension has emerged and these targets were
extensively considered for the development of new therapeutic strategies. This
review discusses the patents on small-molecules targeting kinases involved in
the proliferation/apoptosis imbalance, typically present in pulmonary hypertension.
Methods: Bibliographic research for the inventions was carried out using Espacenet and Sci-Finder databases, “pulmonary hypertension and kinases” as research query and the range from
2010 to 2015. Only patents published in English were considered. A qualitative analysis of the
contents of each patent was made to examine the reported compounds, the studies performed and
the resulting conclusions.
Results: The review includes about thirty applications. Moreover, in order to illustrate the pathophisiology
of the disease and the mechanisms of the targets, about forty additional papers were
reported. Considering that imatinib, a PDGF receptor inhibitor, entered the clinical trials for the
treatment of pulmonary hypertension, the first patents were devoted to inhibitors of tyrosine
kinase receptors, such as PDGFR and c-Kit. Subsequently, in addition to kinase receptors, the role
of other pathways involved in pulmonary hypertension has emerged, and some research groups
have focused their attention also on non-receptor kinases. Fifteen patents on this topic reported
these new targets and new derivatives. However, in most of the inventions, although the pulmonary
hypertension is among the treatable diseases, the compounds were subjected only to antiproliferative
assays and not to specific tests on animal models.
Conclusion: The studies reported in this review confirm the continuous research efforts aimed to
identify new targets and new drugs for the treatment of pulmonary hypertension. Several inhibitors
of kinase were described. These compounds could inhibit mainly important branching processes
and pathological growth of blood vessels, thereby might increase the lifespan of patients.
