Further insights into the SAR of α-substituted cyclopropylamine derivatives as inhibitors of histone demethylase KDM1A

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

“…Reacting benzyl cyanide and epichlorohydrin in the presence of sodium amide, at 90 C in benzene, the corresponding cyclopropyl alcohol was obtained, that on turn underwent basic hydrolysis to give the title compound 28 in 44% overall yields (Scheme 3). Attempts to synthesize the ethyl ester of 28 according to other reported procedures 27,30 failed to give the desired compound.…”

“…These structures were rationally designed based on the Haemophilus influenzae (H. influenzae) SAT (HiSAT) native Cterminal pentapeptide MNLNI, which is the natural inhibitor of OASS, and the substituent at position C-2 was represented by a small alkenyl chain, as in the case of compound 29 ( Figure 1) 25 . In a second round of optimization, the alkenyl chain was embodied into a phenyl ring 30 , maintaining the trans stereorelationship with the carboxylic moiety. This modification led to improved synthetic feasibility and stability, and the insertion of a phenyl ring expanded the scope for further manipulation to modulate activity and drug-likeness.…”

“…To obtain the trans-cyclopropane-1,2-carboxylic acid derivatives, diethyl (1R,2R)-cyclopropane-1,2-dicarboxylate was hydrolyzed in the presence of stoichiometric amount of potassium hydroxide, to give derivatives 5 and 6 in quantitative yields. For the synthesis of substituted cyclopropane-1,2-dicarboxylic acids (Scheme 2), key intermediates 13-18 were prepared according to a protocol described by McCoy 28,29 , since the procedures already set by us proved to be not efficient 30,31 . Therefore, the suitable acrylates and a-halo esters were reacted in the presence of NaH, and the diethyl ciscyclopropane-1,2-dicarboxylates were obtained.…”

Discovery and preliminary evaluation of 2-aminobenzamide and hydroxamate derivatives containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors

“…The reversible acetylation and deacetylation of lysine residues of histone are crucial post-translational modifications in the epigenetic control [1][2][3][4]. The opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs) tightly regulate the gene expression through chromatin modifications [5,6].…”

Cyclopropane derivatives as potential human serine racemase inhibitors: unveiling novel insights into a difficult target

“…Moreover, given the apparent difficulty to identify potent inhibitors, we reasoned that low molecular weight compounds may increase the probability to find reasonable hits, which can then be further optimized without stepping away from developability metrics such as the Lipinski rule of five 27 . In the present study, also on the basis of our expertise in the synthesis of cyclopropane derivatives 28,29 , we present our efforts to develop a new series of non-covalent competitive SR inhibitors based on the cyclopropane scaffold (Table 1), together with synthetic routes, chemical characterization, experimental tests, and a rational explanation for the observed results.…”