An Efficient, Green Chemical Synthesis of the Malaria\ud Drug, Piperaquine

To provide a robust, efficient synthesis of the malaria drug piperaquine for potential use in resource-poor settings. We used in-process analytical technologies (IPAT; HPLC) and a program of experiments to develop a synthesis of piperaquine that avoids the presence of a toxic impurity in the API and is optimized for overall yield and operational simplicity. A green-chemical synthesis of piperaquine is described that proceeds in 92 – 93 % overall yield. The chemistry is robust and provides very pure piperaquine tetraphosphate salt (> 99.5 %). The overall process utilizes modest amounts (about 8 kg/kg) of 2-propanol and ethyl acetate as the only organic materials not incorporated into the API; roughly 60 % of this waste can be recycled into the production process. This process also completely avoids the formation of a toxic impurity commonly seen in piperaquine that is otherwise difficult to remove. An efficient synthesis of piperaquine is described that may be useful for application in resource-poor settings as a means of expanding access to and reducing the cost of ACTs

African Environmental Ethics: Keys to Sustainable Development Through Agroecological Villages

This essay proposes African-based ethical solutions to profound human problems and a working African model to address those problems. The model promotes sustainability through advanced agroecological and information communication technologies. The essay\u27s first section reviews the ethical ground of that model in the work of the Senegalese scholar, Cheikh Anta Diop. The essay\u27s second section examines an applied African model for translating African ethical speculation into practice. Deeply immersed in European and African ethics, Godfrey Nzamujo developed the Songhaï Centers to solve the problem of rural poverty in seventeen African countries. Harnessing advanced technologies within a holistic agroecological ecosystem, Nzamujo\u27s villages furnish education spanning the fields of ethics, information communication technology, microbiology, international development, and mechanical, electrical, civil and biological engineering in a community-based and centered development enterprise. The essay proposes a global consortium of ecovillages based on Nzamujo\u27s model. The final section explores funding methods for the consortium. The conclusion contemplates a return to Africa to supplement environmental ethics that enhance life\u27s future on earth

4,7-Dichloro­quinoline

The two mol­ecules in the asymmetric unit of the title compound, C9H5Cl2N, are both essentially planar (r.m.s. deviations for all non-H atoms = 0.014 and 0.026 Å). There are no close C—H⋯Cl contacts

Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment

OBJECTIVE: To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). BACKGROUND: TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. METHODS: Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. RESULTS: API costs per kg were $347–$746 for imatinib, $2470 for erlotinib,$4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50$128–$216 for imatinib,$240 for erlotinib, $1450 for sorafenib, and$4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. CONCLUSIONS: Mass generic production of several TKIs could achieve treatment prices in the range of $128–$4020 per person-year, versus current US prices of $75161–$139 138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients

Analysis of minimum target prices for production of entecavir to treat hepatitis B in high- and low-income countries

BACKGROUND: In 2013, an estimated 686,000 people died from hepatitis B virus (HBV) infection worldwide. Mass treatment programmes for hepatitis B will require very low drug costs. International treatment guidelines recommend first-line monotherapy with either entecavir or tenofovir disoproxil fumarate (TDF). While the basic patent on TDF expires in 2017/8, entecavir is already generic in several countries, including the US. The chemical structure of entecavir is related to abacavir, which costs <$200 per person-year in low-income countries. METHODS: The clinical efficacy, chemical structures, daily doses, routes of chemical synthesis, costs of raw materials and patent expiry dates were analysed for entecavir and TDF. Costs of sustainable, generic production were calculated for entecavir, and compared with published originator and generic prices in high- and low-income countries. RESULTS: With a daily dose of 0.5 mg, one year's supply of entecavir treatment requires <0.2 g of active pharmaceutical ingredient (API) per person, estimated to cost$4/year, based on quotations of API production from generic suppliers. With an additional $20 per year for formulation/packaging and a 50$36/person-year, substantially lower than current originator and generic prices. Entecavir is no longer under patent protection in the USA, China, Brazil and South Africa, with European expiry in 2017. Given differences in daily dosing, production volumes for entecavir would be 600 times lower than TDF (300 mg once daily) for treating the same numbers of patients. CONCLUSIONS: Mass treatment for hepatitis B with generic entecavir could be achieved at very low cost in all countries, provided that important projections can be met in terms of pricing for the API and finished dosage form