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

描述(申请人提供)：非常需要廉价且对耐药菌株有效的抗疟疾药物。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。其中大多数死亡发生在撒哈拉以南非洲的较脆弱群体中，如儿童和孕妇。除了死亡之外，疟疾还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，高达40%的总卫生支出用于疟疾，因为目前的药物治疗很昂贵。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抗药性，以至于目前的每一种治疗方法都已发现抗药性。这种抗药性可能足以使该药物几乎无效，就像氯喹一样，氯喹曾是治疗疟疾的“金星”。DesignMedex已经开发出一套新的抗疟疾化合物，其先导目前正在进行临床前试验。这项提议的目标是优化先导化合物的合成，将该方法从研究性实验室规模发展到准备用于工厂规模生产的方法。其目的是提高产量和降低生产成本，以努力保持药物的总成本尽可能低，因此 对那些需要它的人来说负担得起。 与公共卫生相关：疟疾是一种寄生虫病，每年导致约80万人死亡，主要是撒哈拉以南非洲的儿童和孕妇。这种寄生虫具有很强的抗药性，因此目前存在对任何批准的药物具有抗药性的菌株，因此持续需要比当前药物更便宜的新疗法。这项工作是为了开发一种新型的抗疟疾药物，从研究性的实验室规模到适合大规模生产的方法。

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.