摘要
背景:近年来,尽管肺动脉高压的治疗已经取得了重大进展,这仍然是一个严重预后不良的疾病,并且寻找新的药物仍然要优先。目前补救措施主要解决血管收缩剂/肺循环血管扩张的失衡,尽管疾病的原因只是适度的影响。最近,受体和非受体激酶在肺动脉高压中的作用已经出现,这些目标被广泛认为是新治疗策略的发展。本文论述了专利小分子靶向激酶参与增殖/凋亡失衡,通常出现在肺动脉高压中。 方法:文献研究发明使用Espacenet和Sci-Finder数据库,以2010-2015年,肺动脉高压和激酶作为研究范围查询。只有发表的英文专利符合。每个专利定性分析的内容用作检查报告的化合物,研究执行和结果讨论。 结果:审查包括大约30个程序。此外,为了说明病理生理疾病和目标机制,大约四十额外的论文报告被报道。考虑到进入临床试验治疗肺动脉高压的伊马替尼,PDGF受体抑制剂,第一个专利是致力于酪氨酸激酶受体抑制剂,如PDGFR和c - kit。随后,除了激酶受体,其他途径参与了肺动脉高压的作用已经出现并且一些研究小组集中把他们的注意力集中在非受体激酶上。关于这一主题的15个专利报道新的目标和新的衍生品。然而,虽然肺动脉高压是可治疗疾病,大多名发明的化合物只服从抗增殖化验而不服从实验动物模型的特定测试。 结论:综述证实连续研究工作旨在确定新的目标和新的药物为治疗肺动脉高压。几种激酶的抑制剂被描述。这些化合物可以主要抑制重要分支流程和病理性血管的生长,从而可能增加病人的寿命。
关键词: 肺动脉高血压,治疗,激酶抑制剂,专利,杂环化合物。
Current Medicinal Chemistry
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.
Export Options
About this article
Cite this article as:
Rita Morigi, Mirella Rambaldi, Alessandra Locatelli, Alberto Leoni , Small-Molecules Targeting Kinases Involved in Pulmonary Hypertension: a Patent Review (2010-2015), Current Medicinal Chemistry 2016; 23 (30) . https://dx.doi.org/10.2174/0929867323666160809093451
DOI https://dx.doi.org/10.2174/0929867323666160809093451 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Peroxisome Proliferator-Activated Receptor (PPAR) in Metabolic Syndrome and Type 2 Diabetes Mellitus
Current Diabetes Reviews New Antihypertensive Drugs Under Development
Current Medicinal Chemistry Editorial [Hot Topic:Central Hemodynamics and Arterial Stiffness: Methodological, Clinical and Pharmaceutical Considerations(Executive Editor: Theodore G. Papaioannou)]
Current Pharmaceutical Design Traditional Cardiovascular Risk Factors in Adolescents with Type 1 Diabetes Mellitus
Current Diabetes Reviews Aliskiren in Patients with Diabetes: A Systematic Review
Current Vascular Pharmacology Toxicological Aspects of Carbon Nanotubes, Fullerenes and Graphenes
Current Pharmaceutical Design Contribution of Catecholamine Reactive Intermediates and Oxidative Stress to the Pathologic Features of Heart Diseases
Current Medicinal Chemistry Current Epidemiological and Clinical Evidence on the Relationship Between Mediterranean Diet and the Metabolic Syndrome
Current Nutrition & Food Science Sex Differences in Biomarkers for Predicting Cardiovascular and Coronary Events
Current Vascular Pharmacology Cardiovascular Morbidity and Mortality in Obstructive Sleep Apnea
Current Pharmaceutical Design Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases
Current Vascular Pharmacology Antioxidant Profile of Home Prepared <i>Taraxacum Officinale</i> Weber Ex Wigg Beverage
Current Nutraceuticals Editorial [Hot Topic: Trends in Vascular Biology; Functional Restoration of Damaged Endothelium (Executive Editors: J.A. Rodriguez-Feo and G. Pasterkamp)]
Current Pharmaceutical Design Endogenous Bufadienolide, Blood Pressure and Alcohol Withdrawal
Current Hypertension Reviews Repurposed Drugs as Potential Therapeutic Candidates for the Management of Alzheimer's Disease
Current Drug Metabolism Vitamin D-Binding Protein Acts in the Actin Scavenge System and Can Have Increased Expression During Aspirin Therapy
Current Neurovascular Research Chemical Investigation of the Root Essential Oil of Stevia rebaudiana (Bert.) Bertoni
Current Bioactive Compounds Editorial [Hot Topic: Targeting Mast Cells and Basophils in Allergy and Beyond: Emerging Concepts (Executive Guest Editor: Petr Heneberg)]
Current Pharmaceutical Design Potential Strategies for Minimizing Mechanism-Based Inhibition of Cytochrome P450 3A4
Current Pharmaceutical Design Pharmacotherapy for the Metabolic Syndrome
Current Vascular Pharmacology