CAS: 68489-09-8; (1R,2S,5R)-2-Isopropyl-N-(4-Methoxyphenyl)-5-Methylcyclohexane-1-Carboxamide

📜氯代薄荷脑置于benzotriazol-1-Yloxyl-Tris-(Pyrrolidino)-Phosphonium Hexafluorophosphate,Magnesium,N,N-二异丙基乙胺体系中,用 乙醚,N,N-二甲基乙酰胺 作为反应溶剂,化学反应生成 (1R,2S,5R)-2-异丙基-N-(4-甲氧基苯基)-5-甲基环己烷-1-甲酰胺
参考文献:临床候选药物 Ar-15512 的 (1S,2S,5R)-非对映体和对映体的合成,表征和 HPLC 分析
标题:临床候选药物 Ar-15512 的 (1S,2S,5R)-非对映体和对映体的合成,表征和 HPLC 分析
摘要:Ar-15512(以前称为 Avx-012 和 Ws-12)是一种 Trpm8 受体激动剂,目前处于治疗干眼症的 2B 期临床试验中.这种具有类似薄荷醇清凉活性的生物活性化合物具有三个立体中心,其最终结构和绝对构型(1 R,2 S,5 R)先前已通过冷冻电子显微镜解析. Ar-15512 的合成路线也已被报道,揭示了 C-1 的差向异构过程可能发生在合成的特定阶段.为了确认 Ar-15512 的所需构型在整个过程中不会发生变化,并排除由于初始起始原料可能受到污染而导致最终产品中存在的对映异构体,Ar-15512 的对映异构体和非对映异构体在c-1处进行了合成并充分表征.此外,通过x射线晶体学分析确定了(1S,2S,5R)-非对映异构体的绝对构型,并设计和开发了新的HPLC方法来鉴定这两种立体异构体并与临床进行比较.候选者 Ar-15512.
DOI:10.3390/molecules26040906

专利信息

专利号:US-11389397-B2
优先权日:2020-05-21
标 题 :Method to reduce face mask and respirator discomfort
发明人：WEI EDWARD TAK
权利人:WEI EDWARD TAK
摘要:Wearing a face mask or a filtering facepiece respirator, especially in hot weather for more than one hour, causes discomfort. But, in a viral pandemic, a barrier to filter inhaled and exhaled air is necessary to protect against airborne pathogens. The sensations of heat abstraction, that is, coolness and cold, can be captured by the rational design of optimized molecules called TRPM8 receptor agonists. The topical application of these molecules alleviates the discomfort of wearing a face mask covering. Several entities were identified by synthesis and experiment as having the ideal properties for achieving this purpose. The preferred embodiments are certain 1-diisopropyl-phosphinoyl-alkanes described as DIPA-1-5, DIPA-1-6, DIPA-1-7, DIPA-1-8, and DIPA-1-9, collectively referred to herein as “DIPA compounds.â€? The applicant found that topical delivery of DIPA compounds to the facial skin, especially to the surface of the nares (nostrils), alleviates face mask discomfort. From these studies, it is hypothesized that it is the absence of cool air dynamics about the nostrils that causes face mask discomfort. The present discovery pertains to pharmaceutical compositions that relieve face mask discmfort.

专利号:CN-117945886-A
优先权日:2023-12-07
标题 :Synthesis method of WS series cooling agent key intermediate menthyl formic acid

专利号:CN-117945886-B
优先权日:2023-12-07
标 题:Synthesis method of WS series cooling agent key intermediate menthyl formic acid