- O -Phenylenediamine: A privileged pharmacophore of ferrostatins for radical-trapping reactivity in blocking ferroptosis
-
Ferroptosis is a non-apoptotic, iron dependent form of regulated cell death that is characterized by the accumulation of lipid hydroperoxides. It has drawn considerable attention owing to its putative involvement in diverse neurodegenerative diseases. Ferrostatins are the first identified inhibitors of ferroptosis and they inhibit ferroptosis by efficiently scavenging free radicals in lipid bilayers. However, their further medicinal application has been limited due to the deficient knowledge of the lipid peroxyl radical-trapping mechanism. In this study, experimental and theoretical methods were performed to illustrate the possible lipid hydroperoxide inhibition mechanism of ferrostatins. The results show that an ortho-amine (-NH) moiety from ferrostatins can simultaneously interact with lipid radicals, and then form a planar seven-membered ring in the transition state, and finally present greater reactivity. NBO analysis shows that the formed planar seven-membered ring forces ortho-amines into better alignment with the aromatic π-system. It significantly increases the magnitudes of amine conjugation and improves spin delocalization in the transition state. Additionally, a classical H-bond type interaction was discovered between a radical and an o-NH group as another transition state stabilizing effect. This type of radical-trapping mechanism is novel and has not been found in diphenylamine or traditional polyphenol antioxidants. It can be said that o-phenylenediamine is a privileged pharmacophore for the design and development of ferroptosis inhibitors.
- Sheng, Xie-Huang,Cui, Cheng-Cheng,Shan, Chao,Li, Yu-Zhen,Sheng, Duo-Hong,Sun, Bin,Chen, De-Zhan
-
p. 3952 - 3960
(2018/06/11)
-
- Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF
-
A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubbe
- Blacker, A. John,Moran-Malagon, Gabriel,Powell, Lyn,Reynolds, William,Stones, Rebecca,Chapman, Michael R.
-
-
- Development of an SNAr Reaction: A Practical and Scalable Strategy to Sequester and Remove HF
-
A simple and operationally practical method to sequester and remove fluoride generated through the SNAr reaction between amines and aryl fluorides is reported. Calcium propionate acts as an inexpensive and environmentally benign in situ scrubbe
- Blacker, A. John,Moran-Malagon, Gabriel,Powell, Lyn,Reynolds, William,Stones, Rebecca,Chapman, Michael R.
-
p. 1086 - 1091
(2018/09/29)
-
- Direct palladium-catalyzed selective monoallylation of anilines using allylic alcohols
-
N-Allylation of anilines using allylic alcohols directly to give monoallylic anilines selectively in high yields has been realized by employing palladium acetate-triphenylphosphine as the catalyst. Palladium-catalyzed one-pot cyclization of 2-aminophenols with 2-butene-1,4-diol leads to 3,4-dihydro-2-vinyl-2H-1,4-benzoxazines. (C) 2000 Elsevier Science Ltd.
- Yang,Yu,Tsai
-
p. 7097 - 7100
(2007/10/03)
-
- An efficient palladium-catalyzed route to N-allylanilines by the direct use of allyl alcohols
-
The direct activation of C-O bonds in allyl alcohols by palladium complexes has been accelerated by carrying out the reactions in the presence of titanium(IV) isopropoxide and molecular sieves (4A). N-Allylation of anilines to give mono- and diallylanilines directly using allyl alcohols has been realized by employing palladium catalysts.
- Yang, Shyh-Chyun,Hung, Chung-Wei
-
p. 1747 - 1752
(2007/10/03)
-
- N-Alkylation of Aniline Derivatives by Use of Potassium Cation-exchanged Y-Type Zeolite
-
Zeolite K-Y is effective as a promoter in the N-alkylation of aniline derivatives in comparison with γ-alumina.
- Onaka, Makoto,Umezono, Akihiro,Kawai, Motomitsu,Izumi, Yusuke
-
p. 1202 - 1203
(2007/10/02)
-