In 2022,Huber, Imre; Pandur, Edina; Sipos, Katalin; Barna, Lilla; Harazin, Andras; Deli, Maria A.; Tyukodi, Levente; Gulyas-Fekete, Gergely; Kulcsar, Gyozo; Rozmer, Zsuzsanna published an article in European Journal of Pharmaceutical Sciences. The title of the article was 《Novel cyclic C5-curcuminoids penetrating the blood-brain barrier: Design, synthesis and antiproliferative activity against astrocytoma and neuroblastoma cells》.Synthetic Route of C4H5ClO3 The author mentioned the following in the article:
Novel series of cyclic C5-curcuminoids 17a-j and 19-22 were prepared as cytotoxic agents and evaluated against human neuroblastoma (SH-SY5Y) or human grade IV astrocytoma (CCF-STTG1) cell lines in low (∼0.1 nM – 10 nM) concentrations Among the tested 21 derivatives, 16 displayed potent antiproliferative activity with IC50 values in the low nanomolar to picomolar range (IC50 = 7.483-0.139 nM). Highly active compounds like N-monocarboxylic derivative 4-[(3′E,5′E)-3′5′-bis(p-trifluormethyl-benzylidene)-piperid-4′- one-1′-yl]-4-oxobutane-1-carboxylic acid with IC50 = 0.139 nM value against neuroblastoma and N-alkyl substituted N-(γ-oxobutyl)-3,5-bis(benzylidene)-4-piperidone with IC50 = 0.257 nM against astrocytoma proved some degree of selectivity toward non-cancerous astrocytes and kidney cells. This potent anticancer activity did not show a strong correlation with exptl. logPTLC values, but the most potent antiproliferative mols. 11-13 and 19-22 are belonging to discrete subgroups of the cyclic C5-curcuminoids. Compounds N-(γ-oxobutyl)-3,5-bis(4′-chlorobenzylidene)-4-piperidone , α-[(2E,6E)-2,6-bis(p-chlorobenzylidene)-piperid-4-one-1-yl]-N- phenyl-acetamide were subjected to blood-brain barrier (BBB) penetration studies, too. The BBB was revealed to be permeable for all of them but, as the apparent permeability coefficient (Papp) values mirrored, in different ratios. Lower toxicity of N-(γ-oxobutyl)-3,5-bis(4′-chlorobenzylidene)-4-piperidone, α-[(2E,6E)-2,6-bis(p-chlorobenzylidene)-piperid-4-one-1-yl]-N- phenyl-acetamide and 4-[(3′E,5′E)-3′,5′-bis(p-trifluormethyl-benzylidene)-piperid-4′- one-1′-yl]-4-oxobutane-1-carboxylic acid was observed toward primary rat brain endothelial cells of the BBB model, which means they remained undamaged under 10 μM concentrations Penetration depends, at least in part, on albumin binding of N-(γ-oxobutyl)-3,5-bis(4′-chlorobenzylidene)-4-piperidone, α-[(2E,6E)-2,6-bis(p-chlorobenzylidene)-piperid-4-one-1-yl]-N- phenyl-acetamide and 4-[(3′E,5′E)-3′,5′-bis(p-trifluormethyl-benzylidene)-piperid-4′- one-1′-yl]-4-oxobutane-1-carboxylic acid and the presence of monocarboxylic acid transporters in the case of 4-[(3′E,5′E)-3′,5′-bis(p-trifluormethyl-benzylidene)-piperid-4′- one-1′-yl]-4-oxobutane-1-carboxylic acid. Permeation through the BBB and albumin binding, we described here, is the first example of cyclic C5-curcuminoids as to our knowledge. The experimental part of the paper was very detailed, including the reaction process of Ethyl oxalyl monochloride(cas: 4755-77-5Synthetic Route of C4H5ClO3)
Ethyl oxalyl monochloride(cas: 4755-77-5) belongs to acyl chlorides. In the laboratory, acyl chlorides are generally prepared by treating carboxylic acids with thionyl chloride (SOCl2). The reaction is catalyzed by dimethylformamide and other additives.Synthetic Route of C4H5ClO3
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics