Optimization of a novel antimalarial drug candidate for plant-scale synthesis

优化用于工厂规模合成的新型抗疟候选药物

基本信息

批准号：
8313665
负责人：
Steven Burgess
金额：
$ 10.26万
依托单位：
DESIGNMEDIX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-05 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8313665
关键词：
Abbreviations Affect Africa South of the Sahara Antimalarials Artemisinins Cessation of life Child Chloroquine Chloroquine resistance Chloroquinoxaline Sulfonamide Combined Modality Therapy Country Dimethyl Sulfoxide Discipline of Nursing Disease Dose Drug Costs Drug resistance Economic Burden Falciparum Malaria Future Goals Gold Health Expenditures In Vitro Inhibitory Concentration 50 Laboratories Laboratory Research Lead Malaria Measures Methods Parasites Parasitic Diseases Pharmaceutical Preparations Pharmacotherapy Phase Plants Plasmodium falciparum Pregnant Women Process Production Reaction Refuse Disposal Research Research Contracts Resistance Resistance development Route Running Safety Techniques Vaccines Vulnerable Populations Woman Work World Health Organization analog artemisinine cost drug candidate drug standard formamide improved in vivo killings novel preclinical evaluation preclinical study pregnant resistant strain response

项目摘要

DESCRIPTION (provided by applicant): There is a great need for anti-malarial drugs that are inexpensive and effective against drug-resistant strains. Malaria is one of the most important diseases worldwide, with over 225 million cases each year, and about 800 thousand deaths. Most of these deaths occur in sub-Saharan Africa among the more vulnerable groups, such as children and pregnant women. In addition to the fatalities, malaria imparts a huge economic burden on the endemic countries, many of which are also the world's poorest. In some of the worst affected countries as much as 40% of their total health expenditure is spent on malaria, as current drug treatments are expensive. Although there are several approved antimalarial drugs, the malaria parasite as a great ability to develop resistance, to such an extent that drug resistance has been identified to every current therapy. This drug resistance can be sufficiently strong as to render the drug almost ineffective, as is the case with chloroquine, once the 'gold star' treatment for malaria. DesignMedix has developed a novel set of antimalarial compounds, the lead of which is currently undergoing preclinical trials. The goal of this proposal is to optimize the synthesis of the lead compound, developing the method from a research laboratory scale, to one ready for plant-scale production. The aim is to improve the yields and reduce production costs in an effort to keep the overall cost of the drug as low as possible and therefore affordable to those who need it. PUBLIC HEALTH RELEVANCE: Malaria is a parasitic disease which kills around 800 thousand people each year, mainly children and pregnant women in sub-Saharan Africa. The parasite has a great ability to develop drug resistance, such that currently there are strains resistant to ever approved drug, so there is a continuing need for new therapies that are less expensive than current drugs. This work is to develop a novel antimalarial drug, from research laboratory scale to a method suitable for full scale production.

描述（由申请人提供）：非常需要廉价且有效对抗耐药菌株的抗疟疾药物。疟疾是全世界最重要的疾病之一，每年有超过 2.25 亿病例，约 80 万人死亡。大多数死亡发生在撒哈拉以南非洲地区的弱势群体中，例如儿童和孕妇。除了造成死亡之外，疟疾还给流行国家带来巨大的经济负担，其中许多国家也是世界上最贫穷的国家。在一些受影响最严重的国家，多达 40% 的卫生总支出用于治疗疟疾，因为目前的药物治疗费用昂贵。尽管有几种已批准的抗疟药物，但疟疾寄生虫具有很强的耐药性，以至于目前的每种疗法都已发现耐药性。这种耐药性可能足够强，以致于使药物几乎无效，就像氯喹的情况一样，氯喹曾是治疗疟疾的“金星”药物。 DesignMedix 开发了一套新型抗疟化合物，其主要成分目前正在进行临床前试验。该提案的目标是优化先导化合物的合成，将该方法从研究实验室规模发展为适合工厂规模生产的方法。目的是提高产量并降低生产成本，以尽可能降低药物的总体成本，从而对于有需要的人来说是负担得起的。公共卫生相关性：疟疾是一种寄生虫病，每年导致约 80 万人死亡，其中主要是撒哈拉以南非洲地区的儿童和孕妇。该寄生虫具有很强的产生耐药性的能力，因此目前存在对曾经批准的药物产生耐药性的菌株，因此持续需要比现有药物更便宜的新疗法。这项工作是开发一种新型抗疟药物，从研究实验室规模到适合大规模生产的方法。