Synthesis

合成核心(核心C)提供对加州大学旧金山分校囊性纤维化研究和 翻译核心中心。该中心的目标是发现和评估新的小分子 囊性纤维化(CF)的治疗方法和合成核心将在这一努力中发挥突出作用 靶向和小分子文库合成。综合中心与研究人员的核心互动是 按三个服务级别进行分类。第一个层面涉及结构的领先优化和探索-- 通过穷举合成的活度关系(SAR)，就像ΔF508-CFTR奖中所做的那样 校正器和增强器。预计ΔF508-cftr校正器和 增强剂，以及TMEM16A激活剂、CACC激活剂和铜绿假单胞菌C12抑制剂。 取决于高通量筛选(HTS)核心发现进度，以及 专注于会议中心的化学目标，这种程度的参与可能还需要额外的 项目。先导化合物的重新合成，提供药物化学建议，以及SAR分析是 中心的第二级核心C参与，许多项目将从这一级别的服务中受益。这个 最后一级服务包括提供已经合成的化合物(包括抑制剂 以及CFTR和TMEM16A的激活剂)，并提供关于活性物质的药物化学的建议 化合物。合成核心还将与HTS核心密切合作，以核实HITS和 通过HIT重新合成和光谱表征验证HIT活性。所有的先导化合物由 项目和核心活动的合成核心将得到高度提纯(一般为~95%)。

The Synthesis Core (Core C) provides enabling technology vital to the UCSF Cystic Fibrosis Research and Translation Core Center. The objective of this Center is to discover and evaluate novel small-molecule therapies for cystic fibrosis (CF), and the Synthesis Core will figure prominently in this effort by performing targeted and small molecule library synthesis. Synthesis Core interactions with investigators in the Center are categorized by three levels of service. The first level involves lead optimization and exploration of structure– activity relationships (SAR) by exhaustive synthesis, as has been done in the current award for ΔF508-CFTR correctors and potentiators. This level of participation is anticipated for ΔF508-CFTR correctors and potentiators, as well as for TMEM16A activators, CaCC activators, and P. aeruginosa C12-inhibitors. Depending on High-Throughput Screening (HTS) Core discovery progress, as well as the importance of focused chemistry in meeting Center goals, this level of involvement may also be warranted for additional projects. Re-synthesis of lead compounds, provision of medicinal chemistry advice, and SAR analysis is the second level of Core C involvement in the Center, and many projects will benefit from this level of service. The last level of service consists of providing compounds that have already been synthesized (including inhibitiors and activators of CFTR and TMEM16A) as well as providing advice on the medicinal chemistry of active compounds. The Synthesis Core will also work closely with the HTS Core to verify the identity of hits and validate hit activity by hit re-synthesis and spectroscopic characterization. All lead compounds supplied by the Synthesis Core for project and Core activities will be highly purified (generally at ~95%).