103324-20-5Relevant articles and documents
Synthesis of pharmaceutical drugs from cardanol derived from cashew nut shell liquid
Shi, Yiping,Kamer, Paul C. J.,Cole-Hamilton, David J.
, p. 1043 - 1053 (2019/03/12)
Cardanol from cashew nut shell liquid extracted from cashew nut shells was successfully converted into various useful pharmaceutical drugs, such as norfenefrine, rac-phenylephrine, etilefrine and fenoprofene. 3-Vinylphenol, the key intermediate for the synthesis of these drugs, was synthesised from cardanol by ethenolysis to 3-non-8-enylphenol followed by isomerising ethenolysis. The metathesis reaction worked very well using DCM, but the greener solvent, 2-methyl tetrahydrofuran, also gave very similar results. Hydroxyamination of 3-vinylphenol with an iron porphyrin catalyst afforded norfenefrine in over 70% yield. Methylation and ethylation of norfenefrine afforded rac-phenylephrine and etilefrine respectively. A sequence of C-O coupling, isomerising metathesis and selective methoxycarbonylation afforded fenoprofene in good yield. A comparison of the routes described in this paper with some standard literature syntheses of 3-vinylphenol and of the drug molecules shows significant environmental advantages in terms of precursors, yields, number of steps, conditions and the use of catalysts. The Atom Economy of our processes is generally similar or significantly superior to those of the literature processes mainly because the side products produced during synthesis of 3-vinylphenol (1-octeme, 1,4-cyclohexadiene and propene) are easily separable and of commercial value, especially as they are bio-derived. The E Factor for the production of 2-vinylphenol by our process is also very low compared with those of previously reported syntheses.
Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach
Xin, Zhili,Peng, Hairuo,Zhang, Andrew,Talreja, Tina,Kumaravel, Gnanasambandam,Xu, Lin,Rohde, Ellen,Jung, Mi-Yong,Shackett, Melanie N.,Kocisko, David,Chollate, Sowmya,Dunah, Anthone W.,Snodgrass-Belt, Pamela A.,Moore Arnold,Taveras, Arthur G.,Rhodes, Kenneth J.,Scannevin, Robert H.
, p. 7277 - 7280 (2012/02/04)
Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid γ-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable γ-secretase modulation profile. Scaffold optimization led to the discovery of a novel chemical series, represented by 6b, having improved brain penetration. Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain Aβ42 levels in mice and rats.
CARBOXYLIC ACID-CONTAINING COMPOUNDS, DERIVATIVES THEREOF, AND RELATED METHODS OF USE
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Page/Page column 110-111, (2010/12/26)
Compounds that modulate gamma secretase (e.g., alter the cleavage pattern of gamma secretase) are described herein. Also disclosed are pharmaceutical compositions, methods of modulating the activity of gamma secretase, and methods of treating Alzheimer's Disease using the compounds described herein.
