112655-56-8Relevant academic research and scientific papers
Amine exchange and unexpected ring-opening reactions of pyranone derivatives: Synthesis of 3-amino-substituted oxonaphthopyran-carbaldehydes and tetrahydropyrimidinethanones as new potential oligonucleotide stabilization agents
Sottofattori, Enzo,Anzaldi, Maria,Balbi, Alessandro,Artali, Roberto,Bombieri, Gabriella
, p. 1698 - 1705 (2002)
3-[(3-Aminopropyl)amino]-1-oxo-1H-naphtho[2,1-b]pyran-2-carbaldehyde (10) was synthesized by nucleophilic substitution reaction of 2-(3-dimethylamino)-1-oxo-1H-naphtho[2,1-b]pyran-2-carbaldehyde (9) and the monoprotected propane-1,3-diamine. The reaction
General Approach for the Liquid-Phase Fragment Synthesis of Orthogonally Protected Naturally Occurring Polyamines and Applications Thereof
Kalantzi, Stefania,Athanassopoulos, Constantinos M.,Ruonala, Raili,Helariutta, Yrjo,Papaioannou, Dionissios
, p. 15118 - 15130 (2019/11/19)
Orthogonally protected polyamines (PAs) have been synthesized using α,ω-diamines and ω-aminoalcohols as N-Cx-N and N-Cy synthons, respectively, and the Mitsunobu reaction as the key reaction for the assembly of the PA skeleta. The Trt, Dde, and Phth groups have been employed for protecting the primary amino functions and the Ns group for activating the primary amino functions toward alkylation and secondary amino function protection. The approach has been readily extended to accommodate the total synthesis of the spider toxins Agel 416 and HO-416b, incorporating the 3-4-3-3 and the 3-3-3-4 PA skeleton, respectively.
Triphenylbutanamines: Kinesin spindle protein inhibitors with in vivo antitumor activity
Wang, Fang,Good, James A. D.,Rath, Oliver,Kaan, Hung Yi Kristal,Sutcliffe, Oliver B.,MacKay, Simon P.,Kozielski, Frank
supporting information; experimental part, p. 1511 - 1525 (2012/04/10)
The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-l-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit Kiapp ≥ 10 nM and GI50 ≈ 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.
Design, synthesis and evaluation of novel uracil acetamide derivatives as potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase
McCarthy, Orla,Musso-Buendia, Alex,Kaiser, Marcel,Brun, Reto,Ruiz-Perez, Luis M.,Johansson, Nils Gunnar,Pacanowska, Dolores Gonzalez,Gilbert, Ian H.
experimental part, p. 678 - 688 (2009/09/27)
The ubiquitous enzyme dUTP nucleotidohydrolase (dUTPase) catalyses the hydrolysis of dUTP to dUMP and can be considered as the first line of defence against incorporation of uracil into DNA. Inhibition of this enzyme results in over-incorporation of uraci
A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics
Bergeron, Raymond J.,Feng, Yang,Weimar, William R.,McManis, James S.,Dimova, Hristina,Porter, Carl,Raisler, Brian,Phanstiel, Otto
, p. 1475 - 1494 (2007/10/03)
A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S- adenosyl-L-methionine decarboxylase, spermidine/spermine N1- acetyltransferase, the maintenance of cellular charge, i.e., cationic equivalence associated with the polyamines and their analogues, and compares their ability to compete with spermidine for transport. The findings clearly demonstrate that the activity of the linear polyamine analogues is highly dependent on the length of the triamines and the size of the N(α),N(ω)- substituents. It appears that there is an optimum chain length for various activities and that the larger the N(α)N(ω)-alkyls, the less active the compound. Metabolic transformation including N-dealkylation of these compounds is also evaluated. While there is no monotonic relationship between chain length and the ability of the analogue to be metabolized, the dipropyl triamines are clearly more actively catabolized than the corresponding methyl and ethyl systems. A comparison of the triamines with the corresponding tetraamines is made throughout the text regarding both in vitro activity against L1210 cells and in vivo toxicity measurements, suggesting that several triamine analogues may offer therapeutic advantages over the corresponding tetraamines.
