57177-83-0Relevant academic research and scientific papers
Synthesis, docking study and inhibitory activity of 2,6-diketopiperazines derived from α-amino acids on HDAC8
Garrido González, Flor Paulina,Mancilla Percino, Teresa
supporting information, (2020/07/21)
Diketopiperazines (DKPs) have been regarded as an important scaffold from the viewpoint of synthesis due to their biological properties for the treatment of several diseases, including cancer. In this work, two novel series of enantiomeric 2,6-DKPs derived from α-amino acids were synthesized through nucleophilic substitution and intramolecular cyclization reactions. All the compounds were docked against histone deacetylase 8 (HDAC8), which is a promising target for the development of anticancer drugs. These compounds bound into the active site of HDAC8 in a similar way to Trichostatin A (TSA), which is an HDAC8 inhibitor. This study showed that the conformation of the 2,6-DKP ring, stereochemistry, and the type of substituent on the chiral center had an important role in the binding modes. The Gibbs free energies and dissociation constants values of HDAC8-ligand complexes showed that compounds (S)-4hBn, (S)-4m, (R)-4h, and (R)-4m were more stable and affine towards HDAC8 than TSA. The inhibitory activities of 4a, (S)-4h, (S)- and (R)-4(g, l, m) were evaluated in vitro on HDAC8. It was found that compounds (R)-4g (IC50 = 21.54 nM) and (R)-4m (IC50 = 10.81 nM) exhibited better inhibitory activities than TSA (IC50 = 28.32 nM). These results suggested that 2,6-DKPs derivatives may be promising anticancer agents for further biological studies.
Deprotection/reprotection of the amino group in α-amino acids and peptides. A one-pot procedure in [Bmim][BF4] ionic liquid
Di Gioia,Barattucci,Bonaccorsi,Leggio,Minuti,Romio,Temperini,Siciliano
, p. 2678 - 2686 (2014/01/06)
This paper presents an efficient one-pot protocol for the sequential deprotection/reprotection of the α-amino group in α-amino acid and dipeptide methyl esters. [Bmim][BF4] is used as the solvent in the entire process. In particular, the use of the ionic liquid allows for rapid and clean removal of the 4-nitrobenzenesulfonyl (nosyl) group and for facile subsequent tert-butyloxycarbonylation of the free α-amino function under very mild conditions. N-Boc-α-amino acid as well as peptide derivatives are isolated in excellent yields, and do not require any further purification. Absolute configurations of the precursors are totally preserved during the process.
Design, synthesis and evaluation of novel metalloproteinase inhibitors based on l-tyrosine scaffold
Cheng, Xian-Chao,Wang, Run-Ling,Dong, Zhen-Ke,Li, Jing,Li, Yao-Yuan,Li, Rong-Rong
, p. 5738 - 5744 (2012/11/06)
A series of novel l-tyrosine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and histone deacetylase 8 (HDAC-8). The results showed that these l-tyrosine derivatives exhibited inhibitory profiles against MMP-2 and HDAC-8. The compounds 6h (IC50 = 0.013 ± 0.001 μM) and 6j (IC 50 = 0.017 ± 0.001 μM) were equal potent MMP-2 inhibitors to the positive control NNGH (IC50 = 0.014 ± 0.001 μM). As for HDAC-8 inhibition, some of the hydroxamate compounds, such as 6d (IC 50 = 3.6 ± 0.2 μM) and 6c (IC50 = 5.8 ± 0.5 μM), were equal potent to the positive control SAHA (IC50 = 1.6 ± 0.1 μM). Structure-activity relationships were also briefly discussed.
A novel naphthylmethyleneimino-type photocleavable protecting group for primary amines
Igarashi, Tetsutaro,Shimokawa, Masaru,Iwasaki, Miyuki,Nagata, Kensaku,Fujii, Masato,Sakurai, Tadamitsu
, p. 1436 - 1440 (2008/02/13)
A novel naphthylmethyleneimino-type protecting group for aliphatic and aromatic primary amines including α-amino acids was devised and its introduction was accomplished in good to excellent yields. This type of protecting group was found to be cleanly removed photochemically to regenerate the primary amines in good to high yields, regardless of steric and electronic properties. Georg Thieme Verlag Stuttgart.
Initial structure-activity relationships of lysophosphatidic acid receptor antagonists: Discovery of a high-affinity LPA1/LPA3 receptor antagonist
Heasley, Brian H.,Jarosz, Renata,Lynch, Kevin R.,Macdonald, Timothy L.
, p. 2735 - 2740 (2007/10/03)
A recently reported dual LPA1/LPA3 receptor antagonist (VPC12249, 1) has been modified herein so as to optimize potency and selectivity at LPA receptors. Compounds containing variation in the acyl lipid chain and linker region have been synthesized and screened for activity at individual LPA receptors. LPA1-selective (14b) and LPA 3-selective (10g,m) compounds of modest potency have been discovered. Additionally, 2-pyridyl derivative 10t exhibits a Ki value of 18nM at the LPA1 receptor and is significantly more potent than 1 at the LPA3 receptor. This paper describes the synthetic methods, biological evaluation, and structure-activity relationships (SARs) of LPA receptor antagonists.
Enantioselective alkylation of aldehydes promoted by (S)-tyrosine-derived β-amino alcohols
Wolf, Christian,Francis, Christopher J.,Hawes, Pili A.,Shah, Mirage
, p. 1733 - 1741 (2007/10/03)
Two (S)-tyrosine-derived β-amino alcohols exhibiting a secondary and tertiary amino moiety, respectively, were employed in the enantioselective alkylation of aldehydes using diethylzinc. The enantioselectivity, catalytic activity and substrate specificity of these precatalysts were compared by high-throughput screening of benzaldehyde, cyclohexanecarboxaldehyde and hexanal. The homochiral catalysts were found to exhibit opposite chiral induction. The secondary amino alcohol favors the formation of (S)-alcohols, whereas the tertiary amino alcohol provides (R)-alcohols. Enantioselectivity and sense of chiral induction obtained with the secondary amino alcohol was proven to depend on the choice of solvent and experimental procedure. The mechanism of the enantioselective ethylation of benzaldehyde promoted by (S)-tyrosine-derived β-amino alcohols was studied by stoichiometric experiments and MM2 computations.
Biomimetic total syntheses of (-)-TAN1251A, (+)-TAN1251B, (+)-TAN1251C, and (+)-TAN1251D
Snider, Barry B.,Lin, Hong
, p. 643 - 646 (2007/10/03)
(equation presented) The muscarinic antagonists (-)-TAN1251A (1), (+)-TAN1251B (2), (+)-TAN1251C (3), and (+)-TAN1251D (4) have been synthesized biomimetically by enamine formation from an amino aldehyde to give TAN1251C ketal 18. Oxidation and reduction lead to TAN1251A (1), which has been hydroxylated to give TAN1251B (2). Stereospecific reduction of TAN1251C ketal 18 leads to TAN1251D (4).
Suppression effect of the Pd/C-catalyzed hydrogenolysis of a phenolic benzyl protective group by the addition of nitrogen-containing bases
Sajiki, Hironao,Kuno, Hiroko,Hirota, Kosaku
, p. 7127 - 7130 (2007/10/03)
A mild and chemoselective hydrogenation method using 5% Pd/C for olefin, N-Cbz, benzyl ester and nitro functionalities distinguishing from the benzyl protective group for the phenolic hydroxyl group has been developed by the employment of 2,2'-dipyridyl as an additive. The suppressive effect on the benzyl ether hydrogenolysis was strongly influenced by the sorts of nitrogen- containing bases employed as an additive.
A novel type of Pd/C-catalyzed hydrogenation using a catalyst poison: Chemoselective inhibition of the hydrogenolysis for O-benzyl protective group by the addition of a nitrogen-containing base
Sajiki, Hironao,Hirota, Kosaku
, p. 13981 - 13996 (2007/10/03)
A mild and chemoselective hydrogenation method for a variety of reducible functional groups distinguishing front aliphatic and aromatic' benzyl ethers was accomplished by the addition of an appropriate nitrogen- containing base to the Pd/C-catalyzed hydrogenation system.
