60479-65-4Relevant academic research and scientific papers
PREFERRED GAUCHE CONFORMATION IN N-(2-AMINOETHYL)PYRIDINIUM IONS
Razenberg, Johannes A. S. J.,Nolte, Roeland J. M.,Drenth, Wiendelt,Kanters, Jan A.,Duijneveldt, Frans B. van
, p. 111 - 118 (1984)
X-ray analysis of 1-pyridinium p-toluenesulphonate and 1-pyridinium p-toluenesulphonate reveals that in both compounds the central N-C-C-N moiety is in the syn-clinal confor
Hydrogen-Borrowing Alkylation of 1,2-Amino Alcohols in the Synthesis of Enantioenriched γ-Aminobutyric Acids
Hall, Christopher J. J.,Goundry, William R. F.,Donohoe, Timothy J.
supporting information, p. 6981 - 6985 (2021/03/01)
For the first time we have been able to employ enantiopure 1,2-amino alcohols derived from abundant amino acids in C?C bond-forming hydrogen-borrowing alkylation reactions. These reactions are facilitated by the use of the aryl ketone Ph*COMe. Racemisation of the amine stereocentre during alkylation can be prevented by the use of sub-stoichiometric base and protection of the nitrogen with a sterically hindered triphenylmethane (trityl) or benzyl group. The Ph* and trityl groups are readily cleaved in one pot to give γ-aminobutyric acid (GABA) products as their HCl salts without further purification. Both steps may be performed in sequence without isolation of the hydrogen-borrowing intermediate, removing the need for column chromatography.
Self-assembling nanoparticles of dually hydrophobic prodrugs constructed from camptothecin analogue for cancer therapy
Guan, Huashi,Jiang, Tao,Liu, Jiannan,Liu, Xuemeng,Wang, Xueting,Wu, Guanzhao,Yin, Ruijuan,Yu, Mingming,Yu, Rilei,Zhang, Yixuan
supporting information, (2020/05/25)
Nanomedicines have shown success in cancer therapy in recent years because of their excellent solubility in aqueous solution and drug accumulation through controlled release in tumor tissues, but the preparation of most nanomedicines still requires ionic materials, surfactants or the amphiphilic structure to maintain nanoparticle stability and function. In this study, we developed a couple of novel dually hydrophobic prodrugs (DHPs) by combining two hydrophobic compounds through different linkers and elaborated their self-assembly mechanisms by virtue of computational simulation. Importantly, without using any excipients, FL-2 NPs exhibited significantly prolonged retention in blood circulation and displayed a remarkable anti-tumor effect at very low concentration in vivo. Both DHPs consisted of camptothecin structural analogue(FL118) and a marine natural product (ES-285). Comparative experiments proved that these compounds could quickly form nanoparticles by way of simple preparation and remained relatively stable for long periods in PBS. FL-2 NPs linked with a disulphide bond could rapidly release bioactive FL118 after being triggered by endogenous reductive stimulus to exert anti-cancer effects. Overall, this study provides a new strategy for design of therapeutic nanomedicines consisting of dually hydrophobic molecules for cancer therapy.
Design, synthesis and evaluation of the antibacterial activity of new Linezolid dipeptide-type analogues
García-Olaiz,Alcántar-Zavala, Eleazar,Ochoa-Terán, Adrián,Cabrera, Alberto,Mu?iz-Salazar, Raquel,Montes-ávila, Julio,Salazar-Medina, Alex J.,Alday, Efrain,Velazquez, Carlos,Medina-Franco, José L.,Laniado-Laborín, Rafael
supporting information, (2019/12/23)
Worldwide studies towards development of new drugs with a lower rate in emergence of bacterial resistance have been conducted. The molecular docking analysis gives a possibility to predict the activity of new compounds before to perform their synthesis. In this work, the molecular docking analysis of 64 Linezolid dipeptide-type analogues was performed to predict their activity. The most negative scores correspond to six Fmoc-protected analogues (9as, 9bs, 9bu, 10as, 10ax and 10ay) where Fmoc group interacts in PTC for Linezolid. Twenty-six different Fmoc-protected Linezolid dipeptide-type analogues 9(as-bz) and 10(as-bz) were synthesized and tested in antimicrobial experiments. Compounds 9as, 9ay, 9ax, 10as, 10ay and 9bu show significant activity against group A Streptococcus clinical isolated. Analogue 10ay also display high activity against ATCC 25923 Staphylococcus aureus strain and MRSA-3, MRSA-4 and MRSA-5 clinical isolates, with MIC values lower than Linezolid. The highest activity against multidrug-resistant clinical isolates of Mycobacterium tuberculosis was exhibited by 9bu. Finally, a cytotoxicity assay with ARPE-19 human cells revealed a non-cytotoxic effect of 9bu and 10ay at 50 and 25 μM, respectively.
Regioselective Fluorination of α-Hydroxy-β-aminophosphonates by Using PyFluor
Ka?mierczak, Marcin,Kubicki, Maciej,Koroniak, Henryk
, p. 3844 - 3852 (2018/07/31)
We report a simple protocol for the synthesis of α-fluoro-β-aminophosphonates by the regioselective fluorination of α-hydroxy-β-aminophosphonates under mild conditions. The fluorination reactions were mediated by the PyFluor reagent and occurred with the retention of configuration. The main products of this reaction were a series of α-fluoro-β-aminophosphonates, which can be used as precursors in the preparation of medicinally important compounds (e.g., dipeptide analogues).
Synthetic and theoretical investigation on the one-pot halogenation of β-amino alcohols and nucleophilic ring opening of aziridinium ions
Chen, Yunwei,Sun, Xiang,Wu, Ningjie,Li, Jingbai,Jin, Shengnan,Zhong, Yongliang,Liu, Zirui,Rogachev, Andrey,Chong, Hyun-Soon
, p. 920 - 939 (2016/01/15)
Aziridinium ions are useful reactive intermediates for the synthesis of enantiomerically enriched building blocks. However, N,N-dialkyl aziridinium ions are relatively underutilized in the synthesis of optically active molecules as compared to other three
Discovery of a Fluorinated Enigmol Analog with Enhanced in Vivo Pharmacokinetic and Anti-Tumor Properties
Miller, Eric J.,Mays, Suzanne G.,Baillie, Mark T.,Howard, Randy B.,Culver, Deborah G.,Saindane, Manohar,Pruett, Sarah T.,Holt, Jason J.,Menaldino, David S.,Evers, Taylor J.,Reddy, G. Prabhakar,Arrendale, Richard F.,Natchus, Michael G.,Petros, John A.,Liotta, Dennis C.
supporting information, p. 537 - 542 (2016/06/01)
The orally bioavailable 1-deoxy-sphingosine analog, Enigmol, has demonstrated anticancer activity in numerous in vivo settings. However, as no Enigmol analog with enhanced potency in vitro has been identified, a new strategy to improve efficacy in vivo by increasing tumor uptake was adopted. Herein, synthesis and biological evaluation of two novel fluorinated Enigmol analogs, CF3-Enigmol and CF2-Enigmol, are reported. Each analog was equipotent to Enigmol in vitro, but achieved higher plasma and tissue levels than Enigmol in vivo. Although plasma and tissue exposures were anticipated to trend with fluorine content, CF2-Enigmol absorbed into tissue at strikingly higher concentrations than CF3-Enigmol. Using mouse xenograft models of prostate cancer, we also show that CF3-Enigmol underperformed Enigmol-mediated inhibition of tumor growth and elicited systemic toxicity. By contrast, CF2-Enigmol was not systemically toxic and demonstrated significantly enhanced antitumor activity as compared to Enigmol.
A - And B -fluorinated aminophosphonates-Synthesis and properties
Ka?mierczak, Marcin,Kubicki, Maciej,Koroniak, Henryk
, p. 459 - 468 (2016/04/09)
Interest in synthesis of fluorinated aminophosphonates has grown significantly in recent years due to their promising applications in medicinal and bioorganic chemistry. We report herein efficient and general methods for the synthesis of α- and β-monofluo
Synthesis of enantiomerically enriched indolines and tetrahydroisoquinolines from (S)-amino acid-derived chiral carbocations: An easy access to (3S,4R)-demethoxy-3-isopropyl diclofensine
Manna, Sudipta Kumar,Panda, Gautam
, p. 8318 - 8324 (2015/01/09)
Enantiomerically enriched indolines and tetrahydroisoquinolines were synthesized within 5 min to 2 h in high yields from easily accessible (S)-amino acid derived chiral carbocations. The diastereoselective Friedel-Crafts reaction is promoted by a Lewis acid (AlCl3) offering trans-diastereoselectivity. The rate of the reaction and diastereoselectivity of the product are significantly influenced by steric hindrance of the amino acids substituents and aryl groups. The methodology can be applied for the synthesis of the enantiomerically enriched bioactive scaffold (3S,4R)-demethoxy-3-isopropyl diclofensine. This journal is
A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-Γ-aminated nitroalkenes derived from L-α-amino acids
Pereira, Vera Lucia Patrocinio,Da Silva Moura, Andre Luiz,Vieira, Daniel Pais Pires,De Carvalho, Leandro Lara,Torres, Eliz Regina Bueno,Da Silva Costa, Jeronimo
, p. 832 - 837 (2013/06/05)
New chiral (S,E)-γ-N,N-dibenzylated nitroalkenes 2a-c were synthesized from natural L-(α)-amino acids in five steps with overall yields of 68-88%. The conjugate addition of hydride, methoxide, nitronate and azide nucleophiles to 2a-c led to the corresponding chiral 1,3-nitroamines in 74-90% yield. The conjugate addition of cyanide anion to 2a,b was followed by HNO2 elimination affording chiral aminated acrylonitriles (73-98%). On the other hand, the azide anion reacted with 2a, in acetonitrile, via a [3 + 2]-cycloaddition in which HNO2 was lost, providing the corresponding 1,2,3-triazole derivative. Direct reduction of 1,3- nitroamine derivatives 9a,b produced the corresponding 1,3-diamines in good yields.
