The four-membered oxetane ring has been increasingly exploited for its contrasting behaviors: its influence on physicochemical properties as a stable motif in medicinal chemistry and its propensity to undergo ring-opening reactions as a synthetic intermediate. These applications have driven numerous studies into the synthesis of new oxetane derivatives. This review takes an overview of the literature for the synthesis of oxetane derivatives, concentrating on advances in the last five years up to the end of 2015. These methods are clustered by strategies for preparation of the ring and further derivatization of preformed oxetane-containing building blocks. Examples of the use of oxetanes in medicinal chemistry are reported, including a collation of oxetane derivatives appearing in recent patents for medicinal chemistry applications. Finally, examples of oxetane derivatives in ring-opening and ring-expansion reactions are described.

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The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis, and cancer. Germline mutations of several Wnt pathway components, such as Axin, APC, and ß-catenin, can lead to oncogenesis. Inhibition of the poly(ADP-ribose) polymerase (PARP) catalytic domain of the tankyrases (TNKS1 and TNKS2) is known to inhibit the Wnt pathway via increased stabilization of Axin. In order to explore the consequences of tankyrase and Wnt pathway inhibition in preclinical models of cancer and its impact on normal tissue, we sought a small molecule inhibitor of TNKS1/2 with suitable physicochemical properties and pharmacokinetics for hypothesis testing in vivo. Starting from a 2-phenyl quinazolinone hit (compound 1), we discovered the pyrrolopyrimidinone compound 25 (AZ6102), which is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows 5 nM Wnt pathway inhibition in DLD-1 cells. Moreover, compound 25 can be formulated well in a clinically relevant intravenous solution at 20 mg/mL, has demonstrated good pharmacokinetics in preclinical species, and shows low Caco2 efflux to avoid possible tumor resistance mechanisms.

A small survey was carried out in two areas of northern Bangladesh to assess and compare the level of knowledge, attitude and practice towards leprosy and tuberculosis (TB) among two communities that differed widely in the amount of health education received about these diseases. The results indicate that without a health education programme, levels of knowledge about the cause and treatability of the diseases are poor, worse for leprosy than TB , with correspondingly negative attitudes. Only 16% of the respondents in the 'uninformed' area mentioned 'skin patch' in a question about what they knew about leprosy; and only 44% mentioned 'cough' as a symptom of TB. In the area that had received health education, 90% mentioned, respectively, 'skin patch' and 'cough'. Seventy-eight percent of the respondents would not buy goods from a shopkeeper known to have leprosy, 76% if he had TB in the uninformed area; but in the community who had received health education the proportions were reversed, with three-quarters agreeing to purchase from a diseased shopkeeper. The implications of these findings for the DBLM and National Health Education programmes are discussed. Leprosy and tuberculosis (TB) are considered to be major public health problems in Bangladesh, and both are the subject of very active control programmes in which the Government of Bangladesh (GoB) and Non-Government Organisations (NGOs) are sharing resources to achieve the aim of disease control. Both the GoB and NGOs are involved in health education campaigns to the population. Since 1993, the GoB Leprosy and TB Control Services have been involved in IEC (Information, Education and Communication) activities with the general public through radio, TV, newspaper advertising, advocacy meetings, handbills, stickers and posters. The aim has been to present succinctly the signs and symptoms of TB and leprosy, and the availability of treatment at health posts and clinics. Leprosy and TB NGOs assist the GoB in certain specified districts in the country, under a Memorandum of Understanding signed in 1994. These NGOs have developed their own

The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study designed to investigate epidemiological, diagnostic, therapeutic and operational aspects of acute nerve function impairment in leprosy. The study is based at a single centre in Bangladesh, in an area with a high prevalence of leprosy. The centre, Danish Bangladesh Leprosy Mission, has a well-established vertical leprosy control programme. In this paper, the study design and methodology are described, together with definitions of nerve function impairment (NFl) used in this and subsequent papers. The study recruited 2664 new leprosy cases in a 12-month period. The male:femaJe ratio is 1•25: I, and 17•61 % of the cohort are under 15 years of age. In all, 83•33% of the cohort are paucibacillary (PB), and 16•67% multibacillary (MB). However, the MB rate amongst males is 19•72%, and amongst females is 12•85%, despite an equal period of delay to diagnosis. 55% of patients presented for treatment within 12 months of developing symptoms. 6• 12% of the total number of cases were smear positive, and 36•71% of the MB cases were smear positive. 9•61% of the total number of cases were graded as having World Health Organisation (WHO) disability grade I, and 5•97% had grade 2. Amongst MB cases, 27-48% had WHO grade 1 disability present, and 18•24% had grade 2 present, compared with 6•04% and 3 •5 1 %, respectively, amongst PB cases. A total of 11•90% of the cohort had sensory NFl of any kind, and 7•39% had motor NFL Ninety patients presented with NFl needing treatment (3•38%), and of these, 61 (67•78%) had silent NFL MB patients had a prevalence of reactionlNFI needing treatment nearly 7 times higher than PB cases (15•32% amongst MB; 2•30% amongst PB), and males nearly double that of females (5•67% amongst males, 2•96% amongst females). The most