RESUMEN
An efficient enantioselective synthesis of the chiral polycyclic cholesteryl ester transfer protein (CETP) inhibitor 1 has been developed. The synthesis was rendered practical for large scale via the development of a modified Hantzsch-type reaction to prepare the sterically hindered pyridine ring, enantioselective hydrogenation of hindered ketone 6 utilizing novel BIBOP-amino-pyridine derived Ru complex, efficient ICl promoted lactone formation, and a BF3 mediated hydrogenation process for diastereoselective lactol reduction. This efficient route was successfully scaled to produce multikilogram quantities of challenging CETP drug candidate 1.
Asunto(s)
Proteínas de Transferencia de Ésteres de Colesterol/antagonistas & inhibidores , Piridinas/síntesis química , Piridinas/farmacología , Cristalografía por Rayos X , Hidrogenación , Conformación Molecular , Estructura Molecular , Piridinas/química , EstereoisomerismoRESUMEN
OBJECTIVE: Although patient education may enhance knowledge, coping with illness, and quality of life among cancer patients, it is uncertain which didactic method is most effective. We compared the impact of an interactive, patient-oriented group program to a lecture-based, information-only program in gastric cancer patients. METHODS: In this prospective, controlled trial, 121 gastric cancer patients attending inpatient rehabilitation after surgical treatment received either the interactive intervention or lectures providing information. The outcomes were patients' disease-related knowledge, active coping with illness, and quality of life (QoL) at the end of their stay and 6 and 12 months thereafter. RESULTS: Both groups improved their knowledge and QoL during rehabilitation; however, knowledge was significantly higher in the interactive group compared to the lecture group. This difference was maintained at the 6- and 12-months follow-ups. In addition, the interactive group proved superior to the lecture group regarding active coping with illness and QoL at the end of rehabilitation, but not during follow-up. CONCLUSIONS: A structured, interactive patient education program proved superior to lecture-based provision of information in regards to short-term and long-term knowledge as well as short-term coping and QoL. PRACTICE IMPLICATIONS: In gastric cancer patients, interactive patient education seems preferable over lectures.
