10541-83-0Relevant academic research and scientific papers
PABA/NO lead optimization: Improved targeting of cytotoxicity to glutathione S-transferase P1-overexpressing cancer cells
Kim, Youseung,Maciag, Anna E.,Cao, Zhao,Deschamps, Jeffrey R.,Saavedra, Joseph E.,Keefer, Larry K.,Holland, Ryan J.
, p. 4980 - 4988 (2015)
PABA/NO [O2-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino) diazen-1-ium-1,2-diolate] is a nitric oxide (NO)-releasing arylating agent designed to be selectively activated by reaction with glutathione (GSH) on catalysis by glutathione S-transferase P1 (GSTP1), an enzyme frequently overexpressed in cancer cells. PABA/NO has proven active in several cancer models in vitro and in vivo, but its tendency to be metabolized via a variety of pathways, some that generate inactive metabolites and hydrolysis products, limits its potential as a drug. Here we show that a simple replacement of cyano for nitro at the 4 position to give compound 4b ('p-cyano-PABA/NO') has the dual effect of slowing the undesired side reactions while enhancing the proportion of NO release and arylating activity on catalysis by GSTP1. Compound 4b showed increased resistance to hydrolysis and uncatalyzed reaction with GSH, along with a more favorable product distribution in the presence of GSTP1. It also showed significant proapoptotic activity. The data suggest p-cyano-PABA/NO to be a more promising prodrug than PABA/NO, with better selectivity toward cancer cells.
Acetic Acid Accelerated Visible-Light Photoredox Catalyzed N-Demethylation of N,N-Dimethylaminophenyl Derivatives
Wu, Guolin,Li, Yazhen,Yu, Xuemei,Gao, Yu,Chen, Haijun
supporting information, p. 687 - 692 (2017/02/23)
N,N-Dimethylaminophenyl moiety is a common fragment in medicinal chemistry as several pharmaceuticals bearing this privileged motif are on the market and under clinical evaluation. Oxidative N-demethylation is generally regarded as the major metabolic pathway. However, pharmacokinetics, metabolites studies as well as the further structural modification are precluded by the impracticality of chemical synthesis. Here we report that acetic acid can significantly accelerate visible-light photoredox catalyzed N-demethylation of N,N-dimethylaminophenyl derivatives. This approach is easy for large scale reaction and even for potential industrial manufacture. (Figure presented.).
A facile and practical copper powder-catalyzed, organic solvent-and ligand-free ullmann amination of aryl halides
Jiao, Jiao,Zhang, Xi-Ru,Chang, Ning-Hui,Wang, Jie,Wei, Jun-Fa,Shi, Xian-Ying,Chen, Zhan-Guo
supporting information; experimental part, p. 1180 - 1183 (2011/04/24)
A facile and practical method that the copper powder-catalyzed Ullmann amination of aryl halides with aqueous methylamine under organic solvent-and ligand-free condition at 100 °C and in air gave N-arylamines as sole products in good to excellent yields. The presence of a small amount of air is essential. Other aliphatic primary amines show good to very high reactivity. Secondary amines and aniline are not reactive. Sensitive substituents (i.e., CHO, MeCO, CN and Cl) are tolerable in the reaction.
Mono-N-methylation of functionalized anilines with alkyl methyl carbonates over NaY faujasites. 4. Kinetics and selectivity
Selva, Maurizio,Tundo, Pietro,Foccardi, Tommaso
, p. 2476 - 2485 (2007/10/03)
(Chemical Equation Presented) In the presence of NaY faujasite as the catalyst, the reaction of bifunctional anilines (1-4: XC6H 4-NH2; X = OH, CO2H, CH2OH, and CONH2) with methyl alkyl carbonates [MeOCO2R′: R′ = Me or MeO(CH2)2O(CH2)2] proceeds with a very high mono-N-methyl selectivity (XC6H 4NHMe up to 99%), and chemoselectivity as well, with other nucleophilic functions (OH, CO2H, CH2OH, CONH2) fully preserved from alkylation and/or transesterification reactions. Aromatic substituents, however, modify the relative reactivity of amines 1-4: good evidence suggests that, not only steric and electronic effects, but, importantly, direct acid-base interactions between substituents and the catalyst are involved. Weakly acidic groups (OH, CH2OH, CONH2, pKa ≥ 10) may help the reaction, while aminobenzoic acids (pK a of 4-5) are the least reactive substrates. The solvent polarity also affects the reaction, which is faster in xylene than in the more polar diglyme. The mono-N-methyl selectivity is explained by the adsorption pattern of reagents within the zeolite pores: a BAl2 displacement of the amine on methyl alkyl carbonate should occur aided by the geometric features of the NaY supercavities. Different factors account for the reaction chemoselectivity. Evidence proves that the polarizability of the two nucleophilic terms (NH 2 and X groups) of anilines is relevant, although adsorption and confinement phenomena of reagents promoted by the zeolite should also be considered.
N-THIAZOL-2-YL-BENZAMIDE DERIVATIVES
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Page/Page column 23, (2008/06/13)
The invention relates to N-thiazol-2-yl-benzamide derivatives of the formula I in the description wherein the variables are as defined in the claims. The compounds are A2A-receptor ligands, such as antagonists, agonists, reverse agonists or partial agonists, and are useful in the treatment of neurological and psychiatric disorders where an A2A-receptor is implicated.
Synthesis of mono-N-substituted functionalized anilines
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Page 4, (2008/06/13)
The present invention relates to a process for direct and selective synthesis of mono-N-substituted functionalized anilines by using alkylating agents selected from the class of organic carbonates, preferably of the dialkyl, dibenzyl and diallyl types, in the presence of suitable catalysts that are chemically related to the class of aluminosilicates.
Synthesis of mono-N-substituted functionalized anilines
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Page 6, (2008/06/13)
The present invention relates to a process for direct and selective synthesis of mono-N-substituted functionalized anilines by using alkylating agents selected from the class of organic carbonates, preferably of the dialkyl, dibenzyl and diallyl types, in the presence of suitable catalysts that are chemically related to the class of aluminosilicates.
Reaction of functionalized anilines with dimethyl carbonate over NaY faujasite. 3. Chemoselectivity toward mono-N-methylation
Selva, Maurizio,Tundo, Pietro,Perosa, Alvise
, p. 7374 - 7378 (2007/10/03)
In the presence of NaY faujasite, dimethyl carbonate (MeOCO2Me, DMC) is a highly chemoselective methylating agent of functionalized anilines such as aminophenols (1), aminobenzyl alcohols (2), aminobenzoic acids (3), and aminobenzamides (4). The reaction proceeds with the exclusive formation of N-methylanilines without any concurrent O-methylation or N-/O-methoxy carbonylation side processes. Particularly, only mono-N-methyl derivatives [XC6H4NHMe, X = o-, m-, and p-OH; o- and p-CH 2OH; o- and P-CO2H; o- and p-CONH2] are obtained with selectivity up to 99% and isolated yields of 74-99%. DMC, which usually promotes methylations only at T > 120 °C, is activated by the zeolite catalyst and it reacts with compounds 1, 2, and 4, at 90 °C. Aminobenzoic acids (3) require a higher reaction temperature (≥130 °C).
Supramolecular catalysis of ester and amide cleavage by a dinuclear barium(II) complex
Cacciapaglia, Roberta,Di Stefano, Stefano,Kelderman, Erik,Mandolini, Luigi
, p. 348 - 351 (2007/10/03)
Five components spontaneously self-assemble to yield the productive complex 1, where one barium ion delivers and ethoxide to the carbonyl group of an amide substrate anchored by means of a distal carboxylate moiety to the other barium ion. High substrate specificity, fairly high reaction rates with catalytic turnover, and competitive inhibition by inert substrates are observed.
