| Reference | 1. Eur J Med Chem. 2017 Jun 16;133:121-138. doi: 10.1016/j.ejmech.2017.03.049. Epub 2017 Mar 27.<br />
Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages.<br />
Shrestha A(1), Jin Oh H(1), Kim MJ(1), Pun NT(1), Magar TBT(1), Bist G(1), Choi H(1), Park PH(2), Lee ES(3).<br />
Author information: (1)College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. (2)College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: [email protected]. (3)College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. Electronic address: [email protected].<br />
As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents.<br />
DOI: 10.1016/j.ejmech.2017.03.049 PMID: 28384544 [Indexed for MEDLINE]<br />
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2. Front Chem. 2020 Apr 17;8:234. doi: 10.3389/fchem.2020.00234. eCollection 2020.<br />
Copper-Catalyzed Annulation-Cyanotrifluoromethylation of 1,6-Enynes Toward 1-Indanones via a Radical Process.<br />
Zhang TS(1), Hao WJ(2), Cai PJ(1), Li G(3)(4), Tu SJ(2), Jiang B(2).<br />
Author information: (1)School of Chemical Engineering & Technology, China University of Mining and Technology, Xuzhou, China. (2)Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou, China. (3)Collaborative Innovation Center of Chemistry for Life Sciences, Institute of Chemistry and BioMedical Sciences, Nanjing University, Nanjing, China. (4)Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, United States.<br />
A new Cu(II)-catalyzed annulation-cyanotrifluoromethylation of 1,6-enynes with Togni's reagent and trimethylsilyl cyanide (TMSCN) has been established, enabling the direct construction of trifluoromethylated 1-indanones with an all-carbon quaternary center in good yields. This reaction was performed by using low-cost Cu(OTf)2 as the catalyst and Togni's reagent as both the radical initiator and a CF3 source, providing an efficient protocol for building up an 1-indanone framework with wide functional group compatibility. The reaction mechanism was proposed through a radical triggered addition/5-exo-dig cyclization/oxidation/nucleophilic cascade.<br />
DOI: 10.3389/fchem.2020.00234 PMCID: PMC7180230 PMID: 32363174<br />
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3. ACS Chem Neurosci. 2020 Sep 16;11(18):2849-2860. doi: 10.1021/acschemneuro.0c00403. Epub 2020 Sep 3.<br />
Novel Benzylated (Pyrrolidin-2-one)/(Imidazolidin-2-one) Derivatives as Potential Anti-Alzheimer's Agents: Synthesis and Pharmacological Investigations.<br />
Gupta M(1), Ojha M(1), Yadav D(1), Pant S(1), Yadav R(1).<br />
Author information: (1)Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan 304022, India.<br />
A series of N-benzylated (pyrrolidin-2-one)/(imidazolidin-2-one) derivatives were synthesized and evaluated for anti-Alzheimer's activity. The analogs were designed and synthesized on the basis of lead compound donepezil, which is currently prescribed as a major drug for the management of mild to severe Alzheimer's disease. Considering the structure activity relationship (SAR) of the lead compound, we first replaced the 5,6-dimethoxy-1-indanone moiety with N-benzylated (pyrrolidin-2-one)/(imidazolidin-2-one) (head) without depriving the key functionality interactions like carbonyl and dimethoxyphenyl and second substituted the spacer linkage (tail) in donepezil. The newly synthesized compounds were characterized by structural conformity and purity using various techniques. The compounds were then subjected to in vivo (behavioral studies) and in vitro (biochemical assays) evaluation using appropriate animal models against the standard drug. Compounds 3-(4-(4-fluorobenzoyl)-piperidin-1-yl)-1-(4-methoxybenzyl)-pyrrolidin-2-one (10b) and 1-(3,4-dimethoxybenzyl)-3-((1-(2-(trifluoromethyl)-benzyl)-piperidin-4-yl)-methyl)-imidazolidin-2-one (18c) displayed an excellent anti-Alzheimer's profile, while the rest of the compounds showed satisfactory results in comparison to donepezil.<br />
DOI: 10.1021/acschemneuro.0c00403 PMID: 32816447 [Indexed for MEDLINE]
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