Hepatoselectivity of statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors
摘要:
4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3 + 2] cycloaddition of a Munchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development. (C) 2007 Elsevier Ltd. All rights reserved.
DOI:
10.1016/j.bmcl.2007.11.124
作为产物:
描述:
甲基磺酰氯 、 3-氨基苯酚 在
氯化钠 、 乙酸乙酯 、 碳酸氢钠 、 aqueous solution 、 sodium hydroxide 、 盐酸 、 Sodium sulfate-III 作用下,
以
吡啶 为溶剂,
反应 18.0h,
以3.3 g (yield=80%) of N-(3-hydroxyphenyl)methanesulfonamide were obtained as an oil的产率得到N-(3-hydroxyphenyl)methanesulfonamide
参考文献:
名称:
IMIDAZOPYRIDINE DERIVATIVES USEFUL IN TREATING DIABETES
IMIDAZOPYRIDINE DERIVATIVES USEFUL IN TREATING DIABETES
申请人:METABRAIN RESEARCH
公开号:US20150182507A1
公开(公告)日:2015-07-02
The present invention relates to imidazopyridine derivatives of the following general formula I:
and to their use as a drug, in particular in treating and/or preventing diabetes, its complications and/or associated pathologies.
The invention is related to phosphorus substituted anti-cancer compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
Imidazopyridine derivatives useful in treating diabetes
申请人:METABRAIN RESEARCH
公开号:US09381191B2
公开(公告)日:2016-07-05
The present invention relates to imidazopyridine derivatives of the following general formula I:
and to their use as a drug, in particular in treating and/or preventing diabetes, its complications and/or associated pathologies.
The invention is related to phosphorus substituted kinase inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.