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

描述（由申请人提供）：对抗疟疾药物的需求很大，这些药物既便宜又能有效地对抗耐药菌株。疟疾是世界上最重要的疾病之一，每年有超过2.25亿例病例，约80万人死亡。这些死亡大多发生在撒哈拉以南非洲的儿童和孕妇等较为脆弱的群体中。除了死亡之外，疟疾给流行国家带来了巨大的经济负担，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，由于目前的药物治疗费用昂贵，高达40%的卫生总支出用于治疗疟疾。虽然有几种已获批准的抗疟疾药物，但疟疾寄生虫具有很强的耐药性，其耐药性已达到对目前所有治疗方法都具有耐药性的程度。这种耐药性可能足够强，以至于使这种药物几乎无效，就像氯喹的情况一样，氯喹曾经是疟疾的“金星”治疗方法。DesignMedix开发了一套新的抗疟疾化合物，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，将该方法从实验室规模的研究发展到工厂规模的生产。目的是提高产量，降低生产成本，努力保持药物的总成本尽可能低，因此

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.