83-15-8Relevant articles and documents
Ru-Catalyzed C(sp2)?H Bond Arylation of Benzamides Bearing a Novel 4-Aminoantipyrine as a Directing Group
Al Mamari, Hamad H.,Al Kiumi, Diana,Al Rashdi, Tamadher,Al Quraini, Huda,Al Rashdi, Malak,Al Sheraiqi, Sumayya,Al Harmali, Sara,Al Lamki, Mohammed,Al Sheidi, Ahmed,Al Zadjali, Asma
supporting information, p. 3598 - 3603 (2021/07/22)
A novel design-based removable N,O-bidentate directing group based on cheap and commercially available 4-aminoantipyrine (AAP) is reported. Aromatic AP amides bearing 4-aminoantipyrine underwent efficient Ru-catalyzed C(sp2)?H arylation using [RuCl2(PPh3)3] as a catalyst and aryl bromides as electrophiles. The novel bidentate directing group enabled the C?H functionalization reaction with good scope, good functional group tolerance and in decent yields.
Detailed investigation of anticancer activity of sulfamoyl benz(sulfon)amides and 1H–pyrazol–4–yl benzamides: An experimental and computational study
Iqbal, Jamshed,Ejaz, Syeda Abida,Saeed, Aamer,al-Rashida, Mariya
, p. 11 - 24 (2018/05/28)
Cancer is the second leading cause of mortality worldwide. Therapeutic approach to cancer is a multi-faceted one, whereby many cellular/enzymatic pathways have been discovered as important drug targets for the treatment of cancer. A major disadvantage of most of the currently available anticancer drugs is their non-selective cytotoxicity towards cancerous as well as healthy cells. Another major hurdle in cancer therapy is the development of resistance to anticancer drugs. This necessitates the discovery of new molecules with potent and selective cytotoxic activity towards only cancerous cells, with minimum or no damage to the normal/healthy cells. Herein we report detailed investigation into the anticancer activity of sulfamoyl benz(sulfon)amides (1a-1g, 2a-2k) and 1H–pyrazol–4–yl benzamides (3a-3j) against three cancer cell lines, breast cancer cells (MCF–7), bone-marrow cancer cells (K–562) and cervical cancer cells (HeLa). For comparison, screening against healthy baby hamster kidney cells (BHK-21) was carried out. All compounds exhibited selective cytotoxicity towards cancerous cells. Cell cycle analysis was carried out using flow cytometry, followed by fluorescence microscopic analysis. DNA interaction and docking studies were also carried out.
NMR-derived models of amidopyrine and its metabolites in complexes with rabbit cytochrome P450 2B4 reveal a structural mechanism of sequential N-dealkylation
Roberts, Arthur G.,Sjoegren, Sara E. A.,Fomina, Nadezda,Vu, Kathy T.,Almutairi, Adah,Halpert, James R.
experimental part, p. 2123 - 2134 (2012/03/10)
To understand the molecular basis of sequential N-dealkylation by cytochrome P450 2B enzymes, we studied the binding of amidopyrine (AP) as well as the metabolites of this reaction, desmethylamidopyrine (DMAP) and aminoantipyrine (AAP), using the X-ray crystal structure of rabbit P450 2B4 and two nuclear magnetic resonance (NMR) techniques: saturation transfer difference (STD) spectroscopy and longitudinal (T1) relaxation NMR. Results of STD NMR of AP and its metabolites bound to P450 2B4 were similar, suggesting that they occupy similar niches within the enzyme's active site. The model-dependent relaxation rates (RM) determined from T1 relaxation NMR of AP and DMAP suggest that the N-linked methyl is closest to the heme. To determine the orientation(s) of AP and its metabolites within the P450 2B4 active site, we used distances calculated from the relaxation rates to constrain the metabolites to the X-ray crystal structure of P450 2B4. Simulated annealing of the complex revealed that the metabolites do indeed occupy similar hydrophobic pockets within the active site, while the N-linked methyls are free to rotate between two binding modes. From these bound structures, a model of N-demethylation in which the N-linked methyl functional groups rotate between catalytic and noncatalytic positions was developed. This study is the first to provide a structural model of a drug and its metabolites complexed to a cytochrome P450 based on NMR and to provide a structural mechanism for how a drug can undergo sequential oxidations without unbinding. The rotation of the amide functional group might represent a common structural mechanism for N-dealkylation reactions for other drugs such as the local anesthetic lidocaine.
