Approaches to Synthesis and Isolation of Enantiomerically Pure Biologically Active Atropisomers.

Atropisomerism is a stereochemical phenomenon exhibited by molecules containing a rotationally restricted σ bond. Contrary to classical point chirality, the two atropisomeric stereoisomers exist as a dynamic mixture and can be interconverted without the requirement of breaking and reforming a bond. Although this feature increases structural complexity, atropisomers have become frequent targets in medicinal chemistry projects. Their axial chirality, e.g., from axially chiral biaryl motifs, gives access to unique 3D structures. It is often desirable to have access to both enantiomers of the atropisomers via a nonselective reaction during the early discovery phase as it allows the medicinal chemistry team to probe the structure activity relationship in both directions. However, once a single atropisomer is selected, it presents several problems. First, the pure single atropisomer may interconvert to the undesired stereoisomer under certain conditions. Second, separation of atropisomers is nontrivial and often requires expensive chiral stationary phases using chromatography or additives if a salt resolution approach is chosen. Other options can be kinetic resolution using enzymes or chiral catalysts. However, apart from the high cost often associated with the two latter methods, a maximum yield of only 50% of the desired atropisomer can be obtained. The ideal approach is to install the chiral atropisomeric axis enantioselectively or employing a dynamic kinetic resolution approach. In theory, both approaches have the potential to provide a single atropisomer in quantitative yield. This Account will discuss the successes/failures and challenges we have experienced in developing methods for resolution/separation and asymmetric synthesis of atropisomeric drug candidates in one of our early phase drug development projects. Suitability for the different methods at various stages of the drug development phase is discussed. Depending on the scale and time available, a separation of a mixture of atropisomers by chromatography was sometimes preferred, whereas asymmetric- or resolution approaches were desired for long-term supply. With the use of chromatography, the impact on separation efficiency and solvent consumption, depending on the nature of the substrate, is discussed. We hope that with this Account the readers will get a better view on the challenges medicinal and process chemists meet when designing new atropisomeric drug candidates and developing processes for manufacture of a single atropisomer.

School nurses' experience of communicating growth data and weight development to parents of children 8 and 10 years of age.

INTRODUCTION: The prevalence of overweight and obesity among children has risen sharply during recent decades. School nurses are key health professionals in interventions targeting the early onset of overweight and obesity during childhood. Understanding how school nurses experience communication with parents concerning their child´s growth and weight development are essential. The aim of the study is to describe school nurses' experience of communicating growth data and weight development to parents of school children ages 8 and 10 years. METHOD: The design of the study is a descriptive, qualitative design with purposive and snowball sampling. Sixteen interviews with school nurses were conducted and analysed with qualitative content analysis. RESULT: The analysis resulted in three main categories including subcategories. In Challenges in the professional role, the school nurses expressed a lack of knowledge, skills and tools in communication, described a perception of parental responsibility and stated using several different approaches in communicating growth data and weight development to parents. In Sustainable communication with parents, the school nurses described the value of creating a dialogue, a supportive approach to the parents, and the building of a relation between them and the parents as essential. In Barriers in communicating the child´s weight, the school nurses described the experience of stigma concerning the subject of overweight and obesity, increased concern when they detected underweight as well as an ambivalence towards measuring weight. CONCLUSION: The study highlights an educational challenge concerning the need for training, skills, and strategies for communication with parents. A variety of ways in school nurses' communication with parents were identified in the present study and this shows an inconsistency in how School health services was offered and a need for the development of evidence-based procedures for communicating growth data and weight development to parents.

Parents' Experiences of Communication With School Nurses About Their Child's Weight Development in Sweden.

This study aimed to describe parents' experiences of communication with school nurses concerning the growth data and weight development of their children aged 8 and 10 years old in Sweden. Eighteen interviews with parents were conducted and analyzed through qualitative content analysis. The result showed a need for improved dialogue where the parents viewed the health visit's purpose as unclear and lacked feedback. The parents desired access to their child's growth data and described the need for an improved channel for receiving information. The parents moreover experienced the lack of a child-centered perspective, described the child's context as not in focus, and desired collaboration around their child. This study shows the need for the development of evidence-based methods for communicating growth data and weight development between School Health Service (SHS) and parents, as well as the need for a reformed SHS perspective towards parents and children.

Utilisation of formal and informal care and services at home among persons with dementia: a cross-sectional study.

BACKGROUND: The progression of dementia disease implies increasing needs for both informal and formal care and services but also risk of institutionalisation. To better adjust care and services in the phase preceding institutionalisation it is important to find out whether utilisation of formal and informal care and services is determined by increased needs and by who meets the needs. AIM: The aim was to compare persons with dementia (65+) with different levels of cognitive impairment, regarding utilisation of formal and informal care and service at home. METHODS: The participants consisted of 177 persons with dementia ≥65 years old and at risk of nursing home admission, divided into groups according to their cognitive function. Structured interviews were conducted based on questionnaires about type and amount of formal and informal care utilised, as well as questions regarding cognitive impairment, dependency in activities of daily living (ADLs) and neuropsychiatric symptoms. To analyse the data, descriptive and comparative statistics were used. RESULTS: The findings revealed that the group with severe dementia used significantly more help with ADLs and supervision in terms of time (number of hours and days) provided by the informal caregiver, compared with the group with moderate dementia. Utilisation of formal care and services was highest in the group with the most severe cognitive impairments (Standardized Mini-Mental State Examination score of <9). The group with severe dementia were more dependent in ADLs and had more neuropsychiatric symptoms (hallucinations and motor disturbances). They were younger and more often cohabitated with the informal caregiver, compared with the group with moderate dementia. CONCLUSION: This study shows that in the phase preceding institutionalisation the ADL and supervision needs due to progression of dementia appear to tend to be met first and foremost by the informal caregivers.

Trends in treatment with antipsychotic medication in relation to national directives, in people with dementia - a review of the Swedish context.

BACKGROUND: The aim of this study was to explore trends in treatment with antipsychotic medication in Swedish dementia care in nursing homes as reported in the most recent empirical studies on the topic, and to relate these trends to directives from the national authorities. METHODS: The study included two scoping review studies based on searches of electronic databases as well as the Swedish directives in the field. RESULTS: During the past decade, directives have been developed for antipsychotic medication in Sweden. These directives were generic at first, but have become increasingly specific and restrictive with time. The scoping review showed that treatment with antipsychotic drugs varied between 6% and 38%, and was higher in younger older persons and in those with moderate cognitive impairment and living in nursing homes for people with dementia. A decreasing trend in antipsychotic use has been seen over the last 15 years. CONCLUSIONS: Directives from the authorities in Sweden may have had an impact on treatment with antipsychotic medication for people with dementia. Treatment with antipsychotic medication has decreased, while treatment with combinations of psychotropic medications is common. National directives may possibly be even more effective, if applied in combination with systematic follow-ups.

Psychological well-being over time among informal caregivers caring for persons with dementia living at home.

OBJECTIVES: To investigate informal caregivers' psychological well-being and predicted increase in psychological well-being, when caring for persons with dementia (PwDs) living at home, related to caregiver, PwD and formal care (FC) factors. METHOD: A cohort study at baseline and 3 months' follow-up in eight European countries. Caregivers included (n = 1223) were caring for PwDs aged ≥ 65 years at home. Data on caregivers, PwDs and FC were collected using standardized instruments. Regression analysis of factors associated with caregiver psychological well-being at baseline and 3 months later was performed. RESULTS: Factors associated with caregiver psychological well-being at baseline were positive experience of caregiving, low caregiver burden, high quality of life (QoL) for caregivers, male gender of PwD, high QoL of PwD, few neuropsychiatric symptoms and depressive symptoms for the PwD. At follow-up, caregivers with increased psychological well-being experienced of quality of care (QoC) higher and were more often using dementia specific service. Predicting factors for caregivers' increased psychological well-being were less caregiver burden, positive experience of caregiving, less supervision of the PwD and higher caregiver QoL, if PwD were male, had higher QoL and less neuropsychiatric symptoms. Furthermore, higher QoC predicted increased caregivers' psychological well-being. CONCLUSION: Informal caregiving for PwDs living at home is a complex task. Our study shows that caregivers' psychological well-being was associated with, among other things, less caregiver burden and higher QoL. Professionals should be aware of PwD neuropsychiatric symptoms that might affect caregivers' psychological well-being, and provide proper care and treatment for caregivers and PwDs.

Significance of quality of care for quality of life in persons with dementia at risk of nursing home admission: a cross-sectional study.

BACKGROUND: Quality of life in persons with dementia is, in large part, dependent on the quality of care they receive. Investigating both subjective and objective aspects of quality of care may reveal areas for improvement regarding their care, which information may ultimately enable persons with dementia to remain living in their own homes while maintaining quality of life. The aim of this study was to 1) describe self-reported quality of life in persons with dementia at risk of nursing home admission. 2) describe subjective and objective aspects of quality of care, 3) investigate the significance of quality of care for quality of life. METHODS: A cross-sectional interview study design was used, based on questionnaires about quality of life (QoL-AD) and different aspects of quality of care (CLINT and quality indicators). The sample consisted of 177 persons with dementia living in urban and rural areas in Skåne County, Sweden. Descriptive and comparative statistics (Mann-Whitney U-test) were used to analyse the data. RESULTS: Based upon Lawton's conceptual framework for QoL in older people, persons with pain showed significantly lower quality of life in the dimensions behavioural competence (p = 0.026) and psychological wellbeing (p = 0.006) compared with those without pain. Satisfaction with care seemed to have a positive effect on quality of life. The overall quality of life was perceived high even though one-third of the persons with dementia had daily pain and had had a weight loss of ≥4% during the preceding year. Furthermore, 23% of the persons with dementia had fallen during the last month and 40% of them had sustained an injury when falling. CONCLUSION: This study indicates need for improvements in home care and services for persons with dementia at risk for nursing home admission. Registered nurses are responsible for nursing interventions related to pain, patient safety, skin care, prevention of accidents, and malnutrition. Therefore, it is of great importance for nurses to have knowledge about areas that can be improved to be able to tailor interventions and thereby improve quality of care outcomes such as quality of life in persons with dementia living at home.

Formal support for informal caregivers to older persons with dementia through the course of the disease: an exploratory, cross-sectional study.

BACKGROUND: In European countries, knowledge about availability and utilization of support for informal caregivers caring for older persons (≥65 years) with dementia (PwD) is lacking. To be able to evaluate and develop the dementia support system for informal caregivers to PwD, a survey of European support systems and professionals involved is needed. The aim of this study was to explore support for informal caregivers to PwD in European countries. We investigated the availability and utilization of support in each of the participating countries, and the professional care providers involved, through the dementia disease. METHODS: A mapping system was used in 2010-2011 to gather information about estimations of availability, utilization, and professional providers of support to informal caregivers caring for PwD. Data collected was representing each country as a whole. RESULTS: There was high availability of counselling, caregiver support, and education from the diagnosis to the intermediate stage, with a decrease in the late to end of life stage. Utilization was low, although there was a small increase in the intermediate stage. Day care and respite care were highly available in the diagnosis to the intermediate stage, with a decrease in the late to end of life stage, but both types of care were utilized by few or no caregivers through any of the disease stages. Professionals specialized in dementia (Bachelor to Master's degree) provided counselling and education, whereas caregiver support for informal caregivers and day care, respite care, and respite care at home were provided by professionals with education ranging from upper secondary schooling to a Master's degree. CONCLUSIONS: Counselling, caregiver support, and education were highly available in European countries from diagnosis to the intermediate stage of the dementia disease, decreasing in the late/end of life stages but were rarely utilized. Countries with care systems based on national guidelines for dementia care seem to be more aware of the importance of professionals specialized in dementia care when providing support to informal caregivers. Mapping the systems of support for informal caregivers of PwD is a valuable tool for evaluating existing systems, internationally, nationally and locally for policy making.

Family caregivers experiences of formal care when caring for persons with dementia through the process of the disease.

BACKGROUND: Family caregivers' experiences of formal care when caring for persons with dementia through the process of the disease is sparsely investigated. AIMS: To investigate family caregivers' experiences of formal care when caring for a person with dementia, through the stages of the disease. DESIGN: A qualitative approach with focus group interviews. METHODS: Four focus group interviews were conducted in October 2011 with 23 spouses and adult children of persons with dementia and analysed with content analysis. RESULTS: The participants' experiences of formal care when caring for a person with dementia were captured in the theme 'Family caregiving requires collaboration with formal care to get support adjusted to needs specific to the stages of dementia'. This can be broken down into the categories 'The dementia diagnosis - entry into formal care as a novice family caregiver', 'Needing expanded collaboration with formal care to continue care at home' and 'Being dependent on a nursing home and trying to maintain involvement'. CONCLUSION: Family caregiving requires collaboration with formal care to get support adjusted to the individual's needs, specific to the stages of dementia. Caregivers experience a transition process with three main turning points: the dementia diagnosis; when they realise increased need for formal care to continue caring at home; and when the person with dementia is moved into a nursing home. The interviewed caregivers experience formal care reactive to their needs and this often promoted unhealthy transitions. Formal care needs to be proactive and deliver available care and support early on in the dementia trajectory. Interventions should focus on facilitating a healthy transition for family caregivers through the trajectory of the dementia disease to ensure their well-being.

Care and Service at Home for Persons With Dementia in Europe.

PURPOSE: To describe available and utilized formal care and service at home for persons with dementia, from diagnosis to end-of-life stage, in eight European countries. DESIGN: A descriptive cross-country design concerning eight European countries as a part of the European research project RightTimePlaceCare. METHODS: The research team in each country used a mapping system to collect country-specific information concerning dementia care and service system. The mapping system consists of 50 types of care and service activities. Sixteen of the 50 predefined activities concerning care and service at home were selected for this study and subdivided into three categories, following the stages of dementia. FINDINGS: Availability was reported to be higher than utilization, and the findings indicated more similarities than differences among the eight countries involved. Even though there were several available activities of "basic care and services" and "healthcare interventions," they were utilized by few in most countries. Furthermore, "specialized dementia care and services" were sparsely available and even more sparsely utilized in the participating countries. CONCLUSIONS: The findings indicated that persons with dementia in Europe received formal care and service on a general, basic level but seldom adjusted to their specific needs. CLINICAL RELEVANCE: This study describes the gap between service provision and utilization enabling nurses to develop individually adjusted care plans for persons with dementia during the progress of the disease. The findings do not include matters of quality of care or how to best organize effective care and services. However, the activities of care and services presented here should shed light on what room there is for improvement when it comes to enabling persons with dementia to go on living at home.

Inter-country exploration of factors associated with admission to long-term institutional dementia care: evidence from the RightTimePlaceCare study.

AIM: To explore inter-country variation of factors associated with institutionalization of people with dementia. BACKGROUND: There is an urgent need for evidence on whether factors associated with admission to institutional dementia care are applicable across healthcare systems, as increasing evidence suggests that these factors could be country-specific. DESIGN: A prospective cohort study. METHOD: Primary data were collected in eight European countries, at baseline and after 3 months follow-up (November 2010-April 2012). The sample included 2014 dyads of people with dementia and their informal caregivers; 791 patients were recently institutionalized, 1223 patients lived at home and were at risk of institutionalization. Associations between care setting (institution vs. home) and factors shown to influence institutionalization (e.g. cognition, independence in activities of daily life, behaviour) were studied. RESULTS: Considerable differences were found between the eight countries in characteristics of people with dementia who had been recently admitted to ILTC. However, caregiver burden appeared the most consistent factor associated with institutionalization in all analyses. Indications for the importance of independence in activities of daily life were found as well, although country differences may be more prominent for this factor. CONCLUSION: Evidence was found for two common factors, crucial in the process of institutionalization across countries: caregiver burden and independency in activities of daily life. However, this study also suggests that admission to institutional dementia care is context-specific, as wide variation exists in factors associated with institutionalization across countries. Tailored best-practice strategies are needed to reflect variations in response to these needs.

Most appropriate placement for people with dementia: individual experts' vs. expert groups' decisions in eight European countries.

AIMS: To investigate the extent of variability in individuals' and multidisciplinary groups' decisions about the most appropriate setting in which to support people with dementia in different European countries. BACKGROUND: Professionals' views of appropriate care depend on care systems, cultural background and professional discipline. It is not known to what extent decisions made by individual experts and multidisciplinary groups coincide. DESIGN: A modified nominal group approach was employed in eight countries (Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden and the UK) as part of the RightTimePlaceCare Project. METHODS: Detailed vignettes about 14 typical case types of people with dementia were presented to experts in dementia care (n = 161) during November and December 2012. First, experts recorded their personal judgements about the most appropriate settings (home care, assisted living, care home, nursing home) in which to support each of the depicted individuals. Second, participants worked in small groups to reach joint decisions for the same vignettes. RESULTS: Considerable variation was seen in individuals' recommendations for more than half the case types. Cognitive impairment, functional dependency, living situation and caregiver burden did not differentiate between case types generating high and low degrees of consensus. Group-based decisions were more consistent, but country-specific patterns remained. CONCLUSIONS: A multidisciplinary approach would standardize the decisions made about the care needed by people with dementia on the cusp of care home admission. The results suggest that certain individuals could be appropriately diverted from care home entry if suitable community services were available.

Dementia care in European countries, from the perspective of people with dementia and their caregivers.

AIM: To investigate persons with dementia and their informal caregivers' views of inter-sectoral information, communication and collaboration throughout the trajectory of dementia care, in eight European countries. BACKGROUND: Living with dementia and being next of kin to a person with dementia means having to live through stages that have different characteristics, needs, challenges and requirements. DESIGN: Qualitative research. Focus groups were conducted in England, Estonia, Finland, France, Germany, The Netherlands, Spain and Sweden. METHODS: Persons with dementia and their informal caregivers (N = 137) participated in focus group interviews during 2011. Content analysis generated a tentative model of information, communication and collaboration for people with dementia and their caregivers, which was then tested. RESULTS: The core finding was that information, communication and collaboration were to be focused on the persons with dementia and the informal caregivers. Entering into the trajectory of the disease and its consequences was addressed as an important point of departure. The relation to professional care required establishing a trusting relationship, tailor-made intervention and a single person or organization to contact. Professional knowledge and commitment, variation in service and care adapted to needs were important. CONCLUSION: As focus of care is on the person with dementia and their informal caregivers, a dyadic approach seems most suitable for dementia care. A trusting relationship and a specific person or organization to contact seem to be indicators of best practice, as does adaptation to the needs of the person with dementia and their informal caregiver.

Predicting institutional long-term care admission in dementia: a mixed-methods study of informal caregivers' reports.

AIM: To investigate agreement between: (1) expected reasons and actual reasons for admission of people with dementia according to informal caregivers; (2) scores on measurement instruments prior to admission and the actual reasons for admission according to informal caregivers. BACKGROUND: Timely admission of people with dementia is a crucial issue. Information is highly warranted on whether informal caregivers are capable of prior identification of causes of admission and, can thus be considered a reliable prospective source on causes of admission. DESIGN: A cohort study among informal caregivers of people with dementia who made a transition to institutional long-term care. METHODS: Qualitative data on the expected and actual reasons for admission were collected via open-ended questions at baseline and follow-up. Furthermore, at baseline, data were collected using measurement instruments to measure pre-admission characteristics. Interviews took place between November 2010-April 2012. After categorizing the answers, the agreement between the expected and actual reasons was calculated. Furthermore, bivariate associations were calculated between the actual reasons for admission and scores on corresponding measurement instruments. RESULTS/FINDINGS: For most informal caregivers, there was agreement between their statements on the expected reason and the actual reason for admission. A third of the caregivers showed no conformity. Bivariate associations showed that there is also agreement between the actual reasons for admission and scores on corresponding measurement instruments. CONCLUSION: Informal caregivers can be considered reliable sources of information regarding what causes the admission of a person with dementia. Professional care should anticipate informal caregivers' statements and collaborate with them to strive for timely and appropriate admission.

Deterioration of basic activities of daily living and their impact on quality of life across different cognitive stages of dementia: a European study.

BACKGROUND: Performing basic activities of daily living (ADLs) is one of the major difficulties encountered in dementia, which can have considerable negative impacts on the quality of life (QoL) of people with dementia (PwD). However, the extent to which basic ADL performance deteriorates across mild, moderate, and severe dementia is little examined and its impact, together with depression and neuropsychiatric behavior, upon QoL, is of considerable relevance across European countries. METHODS: Data were drawn from people living in the community who were participants in a large-scale European study on transition from community living to care homes of PwD. PwD completed measures on cognitive functioning and QoL, and informal carers reported upon QoL, depressive symptomatology, psychopathology, and functional ability of the PwD. RESULTS: ADL performance deteriorated differently for each activity. In particular, toileting, transfer, and feeding remained relatively intact throughout, whereas performance on bathing and dressing deteriorated to a greater extent from mild to severe dementia. It appears that continence was not affected by the stage of dementia with similar levels of impairment. Basic ADL performance impacted to different degrees on QoL across dementia stages and countries. CONCLUSIONS: Interventions aimed at maintaining independence or QoL need to target different ADLs across different dementia stages and perhaps also tailor interventions to the context of different countries. Findings contribute to the development of non-pharmaceutical interventions and governmental pledges to promote independence in dementia.

Best practice and needs for improvement in the chain of care for persons with dementia in Sweden: a qualitative study based on focus group interviews.

BACKGROUND: Persons with dementia receive health care and social services from a wide range of professional care providers during the disease trajectory, presenting risks of miscommunication, duplication and/or missed nursing interventions. Accordingly, the aim of this study was to investigate professional care providers' views on conditions for best practice in terms of collaboration and improvement needs in the chain of care from early to end-of-life stage for persons with dementia in Sweden. METHODS: The study had a qualitative design based on three focus group interviews. A strategic sample of 23 professional care providers was included. Data were subjected to content analysis based on the three stages of dementia (early, moderate, end-of-life). RESULTS: The results were divided into five categories: Diagnosis is a prerequisite for specialized dementia care, Creating routines in the chain of care, Competent staff a prerequisite for high-quality care, Day care facilitates transition in the chain of care and Next-of-kin participation is a prerequisite for continuity in the chain of care. It was clear that, according to the participants, best practice in dementia care in Sweden is not achieved in every respect. It appeared that transitions of care between different organizations are critical events which need to be improved. The further the disease progresses, the less collaboration there seems to be among professional care providers, which is when the next of kin are usually called upon to maintain continuity in the chain of care. CONCLUSIONS: The results indicate that, according to the care providers, best practice in terms of collaboration is achieved to a higher degree during the early stage of dementia compared with the moderate and end-of-life stages. Lack of best practice strategies during these stages makes it difficult to meet the needs of persons with dementia and reduce the burden for next of kin. These are experiences to be taken into account to improve the quality of dementia care. Implementation research is needed to develop strategies for best practice on the basis of national knowledge-based guidelines and to apply these strategies in the moderate and end-of-life stages.

Living with a person with young onset dementia - spousal experience.

PURPOSE: Being of working age while at the same time needing to help a partner with young onset dementia has specific consequences for spouses. Research to date has been sparse concerning this particular group of spouses. The aim of the study was to explore spouses' everyday experiences when living with a person with young onset dementia. METHOD: The study had a descriptive qualitative design with semi-structured interviews with nine spouses. The interviews were analysed using content analysis. RESULT: The interviewed spouses experienced emotions that varied from feelings of loneliness, frustration, and worry to peace of mind. They said that they used coping strategies, which included adopting a positive mindset, adapting to inabilities, adopting an avoidant approach, and finding ways to recharge. Spouses also felt that they could use more support, both formal and informal. CONCLUSION: The spouse of a person with young onset dementia has a range of emotional experiences and has resourceful ways of handling everyday life. Various types of support are offered to spouses, however, they seemed to desire more from health care services.

Mild Strategy for the Preparation of Alkyl Sulfonyl Fluorides from Alkyl Bromides and Alcohols Using Photoredox Catalysis and Flow Chemistry.

Facile access to sp3-rich scaffolds containing a sulfonyl fluoride group is still limited. Herein, we describe a mild and scalable strategy for the preparation of alkyl sulfonyl fluorides from readily available alkyl bromides and alcohols using photoredox catalysis. This approach is based on halogen atom transfer (XAT), followed by SO2 capture and fluorination. The method features mild conditions enabling fast access to high-value derivatives and has been scaled up to 5 g using a continuous stirred tank reactor cascade.

Organic Solvent Nanofiltration in Pharmaceutical Applications.

Separation and purification in organic solvents are indispensable procedures in pharmaceutical manufacturing. However, they still heavily rely on the conventional separation technologies of distillation and chromatography, resulting in high energy and massive solvent consumption. As an alternative, organic solvent nanofiltration (OSN) offers the benefits of low energy consumption, low solid waste generation, and easy scale-up and incorporation into continuous processes. Thus, there is a growing interest in employing membrane technology in the pharmaceutical area to improve process sustainability and energy efficiency. This Review comprehensively summarizes the recent progress (especially the last 10 years) of organic solvent nanofiltration and its applications in the pharmaceutical industry, including the concentration and purification of active pharmaceutical ingredients, homogeneous catalyst recovery, solvent exchange and recovery, and OSN-assisted peptide/oligonucleotide synthesis. Furthermore, the challenges and future perspectives of membrane technology in pharmaceutical applications are discussed in detail.

Discovery of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide as a selective T-type calcium channel (Cav3.2) inhibitor.

The T-type calcium channel inhibitor Mibefradil was reported to protect the heart from atrial remodeling, a key process involved in the development of atrial fibrillation and arrhythmias. Mibefradil is not a selective T-type calcium channel inhibitor and also affects the function of different ion channels. Our aim was to develop a selective T-type calcium channel inhibitor to validate the importance of T-type-related pharmacology in atrial fibrillation. Structural optimisation of a previously disclosed hit series focussed on minimising exposure to the central nervous system and improving pharmacokinetic properties, while maintain adequate potency and selectivity. This resulted in the design of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide, a novel, selective, peripherally restricted chemical probe to verify the role of T-type calcium channel inhibition on atrial fibrillation protection.