83528-16-9Relevant articles and documents
Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitors
Kildahl-Andersen, Geir,Schnaars, Christian,Prandina, Anthony,Radix, Sylvie,Le Borgne, Marc,Jordheim, Lars Petter,Gj?en, Tor,Andresen, Adriana Magalh?es Santos,Lauksund, Silje,Fr?hlich, Christopher,Samuelsen, ?rjan,Rongved, P?l,?strand, Ove Alexander H?gmoen
, p. 528 - 537 (2019)
The syntheses of metallo-β-lactamase inhibitors comprising chelating moieties, with varying zinc affinities, and peptides partly inspired from bacterial peptide sequences, have been undertaken. The zinc chelator strength was varied using the following chelators, arranged in order of ascending binding affinity: dipicolylamine (DPA, tridentate), dipicolyl-1,2,3-triazolylmethylamine (DPTA, tetradentate) dipicolyl ethylenediamine (DPED, tetradentate) and trispicolyl ethylenediamine (TPED, pentadentate). The chosen peptides were mainly based on the known sequence of the C-terminus of the bacterial peptidoglycan precursors. Biological evaluation on clinical bacterial isolates, harbouring either the NDM-1 or VIM-2 metallo-β-lactamase, showed a clear relationship between the zinc chelator strength and restoration of meropenem activity. However, evaluation of toxicity on different cancer cell lines demonstrated a similar trend, and thus inclusion of the bacterial peptides did possess rather high toxicity towards eukaryotic cells.
Perfluorinated HDAC inhibitors as selective anticancer agents
Walton, James W.,Cross, Jasmine M.,Riedel, Tina,Dyson, Paul J.
supporting information, p. 9186 - 9190 (2017/11/14)
A series of potent histone deacetylase inhibitors is presented that incorporate alkyl or perfluorinated alkyl chains. Several new compounds show greater in vitro antiproliferative activity than the clinically approved inhibitor, SAHA. Furthermore, the new
Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from plasmodium falciparum
Kannan Sivaraman, Komagal,Paiardini, Alessandro,Sieńczyk, Marcin,Ruggeri, Chiara,Oellig, Christine A.,Dalton, John P.,Scammells, Peter J.,Drag, Marcin,McGowan, Sheena
supporting information, p. 5213 - 5217 (2013/07/26)
The malaria parasite Plasmodium falciparum employs two metallo- aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.
Chemical process
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, (2008/06/13)
A process for the preparation of a salt of 5-phenylpentanoyl-(S)-arginyl-(S)-alanyl-{(S)-2-[(R)-3-amino-2-oxopyrrolidin-1-yl]propionyl}-(S)-alanyl-(S)-arginyl-(S)-alanyl-4-aminophenylacetamide (SEQ ID NO: 1) which comprises deprotection of a compound of t
Synthesis of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas and evaluation as modulators of the isoforms of nitric oxide synthase
Goodyer, Claire L. M.,Chinje, Edwin C.,Jaffar, Mohammed,Stratford, Ian J.,Threadgill, Michael D.
, p. 4189 - 4206 (2007/10/03)
Inhibition of the isoforms of nitric oxide synthase (NOS) has important applications in therapy of several diseases, including cancer. Using 1400W [N-(3-aminomethylbenzyl)acetamidine], thiocitrulline and N δ-(4,5-dihydrothiazol-2-yl)ornithine as lead compounds, series of N-benzyl- and N-phenyl-2-amino-4,5-dihydrothiazoles and thioureas were designed as inhibitors of NOS. Ring-substituted benzyl and phenyl isothiocyanates were synthesised by condensation of the corresponding amines with thiophosgene and addition of ammonia gave the corresponding thioureas in high yields. The substituted 2-amino-4,5-dihydrothiazoles were approached by two routes. Treatment of simple benzylamines with 2-methylthio-4,5-dihydrothiazole at 180 °C afforded the corresponding 2-benzylamino-4,5-dihydrothiazoles. For less nucleophilic amines and those carrying more thermally labile substituents, the 4,5-dihydrothiazoles were approached by acid-catalysed cyclisation of N-(2-hydroxyethyl)thioureas. This cyclisation was shown to proceed by an SN2-like process. Modest inhibitory activity was shown by most of the thioureas and 4,5-dihydrothiazoles, with N-(3-aminomethylphenyl)thiourea (IC50=13 μM vs rat neuronal NOS and IC50=23 μM vs rat inducible NOS) and 2-(3-aminomethylphenylamino)-4,5-dihydrothiazole (IC50=13 μM vs rat neuronal NOS and IC50=19 μM vs human inducible NOS) being the most potent. Several thioureas and 4,5-dihydrothiazoles were found to stimulate the activity of human inducible NOS in a time-dependent manner.
Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production
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, (2008/06/13)
The present invention relates to carboxylic acid derivatives of the general formula STR1 in which Ra to Rc, A, B, D, E and X1 to X3 are as defined in claim 1, their tautomers, their stereoisomers including their mixtures, and their salts, in particular their physiologically tolerated salts with inorganic or organic acids or bases, which have useful pharmacological properties, preferably aggregation-inhibiting inhibiting actions, medicaments containing these compounds, their use and processes for their preparation.
Functionalized congeners of adenosine: Preparation of analogues with high affinity for A1-adenosine receptors
Jacobson,Kirk,Padgett,Daly
, p. 1341 - 1346 (2007/10/02)
A series of functionalized congeners of adenosine based on N6-phenyladenosine, a potent A1-adenosine receptor agonist, was synthesized. Derivatives of the various congeners should be useful as receptor and histochemical probes and for the preparation of radioligands and affinity columns or as targeted drugs. N6-[4-(Carboxymethyl)phenyl]adenosine served as the starting point for synthesis of the methyl ester, the methyl amide, the ethyl glycinate, and various substituted anilides. One of the latter, N6-[4-[[[4-(carbomethoxymethyl)anilino]carbonyl]methyl]phenyl]adenosine, served as the starting point for the synthesis of another series of congeners including the methyl amide, the hydrazide, and the aminoethyl amide. The terminal amino function of the last congener was acylated to provide further analogues. The various congeners were potent competitive antagonists of binding of N6-[3H]cyclohexyladenosine to A1-adenosine receptors in rat cerebral cortical membranes. The affinity of the congener for the A1 receptor was highly dependent on the nature of the spacer group and the terminal moiety with K(i) values ranging 1-100 nM. A biotinylated analogue had a K(i) value of 11 nM. A conjugate derived from the Bolton-Hunter reagent had a K(i) value of 4.5 nM. The most potent congener contained a terminal [(aminoethyl)amino]carbonyl function and had a K(i) value of less than 1 nM.