77124-20-0Relevant academic research and scientific papers
Design and optimisation of a small-molecule TLR2/4 antagonist for anti-tumour therapy
Chen, Hekai,Kong, Jun,Li, Tian,Xu, Qun,Yin, Hang,Zhang, Liwei
supporting information, p. 1771 - 1779 (2021/11/19)
In anti-tumour therapy, the toll-like receptor 2/4 (TLR2/4) signalling pathway has been a double-edged sword. TLR2/4 agonists are commonly considered adjuvants for immune stimulation, whereas TLR2/4 antagonists demonstrate more feasibility for anti-tumour therapy under specific chronic inflammatory situations. In individuals with cancer retaliatory proliferation and metastasis after surgery, blocking the TLR2/4 signalling pathway may produce favourable prognosis for patients. Therefore, here, we developed a small-molecule co-inhibitor that targets the TLR2/4 signalling pathway. After high-throughput screening of a compound library containing 14 400 small molecules, followed by hit-to-lead structural optimisation, we finally obtained the compound TX-33, which has effective inhibitory properties against the TLR2/4 signalling pathways. This compound was found to significantly inhibit multiple pro-inflammatory cytokines released by RAW264.7 cells. This was followed by TX-33 demonstrating promising efficacy in subsequent anti-tumour experiments. The current results provide a novel understanding of the role of TLR2/4 in cancer and a novel strategy for anti-tumour therapy.
Structural isomers of cinnamic hydroxamic acids block HCV replication via different mechanisms
Kozlov, Maxim V.,Konduktorov, Konstantin A.,Malikova, Alsu Z.,Kamarova, Kamila A.,Shcherbakova, Anastasia S.,Solyev, Pavel N.,Kochetkov, Sergey N.
, (2019/09/30)
A set of ortho-, meta- and para-substituted cinnamic hydroxamic acids (CHAs) was synthesized. In each series of structural isomers, a phenyl substituent was linked to an aromatic ring of the parent cinnamic acid via a linker of one to four atoms in length
Multifunctional cinnamic acid derivatives
Peperidou, Aikaterini,Pontiki, Eleni,Hadjipavlou-Litina, Dimitra,Voulgari, Efstathia,Avgoustakis, Konstantinos
, (2017/09/01)
Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX) inhibition (IC50 = 6 uM) and antiproteolytic activity (IC50 = 0.425 uM). The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 uM) and good LOX inhibitory activity (IC50 = 66 uM). Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.
Synthesis of key intermediate of phosphonosulfonates (BPH-652), 1-(3-iodopropyl)-3-phenoxy benzene
Lu, Min,Zhou, Shuwen,Guan, Jing,Xu, Xing,Fan,Xu, Defeng
, p. 7619 - 7621 (2015/02/02)
A convenient and efficient four-step synthesis of 1-(3-iodopropyl)-3-phenoxy benzene can be achieved by 3-phenoxybenzaldehyde and malonic acid in the presence of piperidine and pyridine to yield (E)-3-(3-phenoxyphenyl)-2-propenoic acid, esterification with methanol in the present of p -toluene sulfonic acid, reduction with sodium borohydride to give 3-(3-phenoxyphenyl)propan-1-ol and iodination of 3-(3-phenoxy phenyl) propan-1-ol using iodine and triphenylphosphine in the present of potassium iodide and imidazole and to afford the title compound in an overall yield of 55.6 %.
Synthesis of substituted nitroolefins: A copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids
Rokade, Balaji V.,Prabhu, Kandikere Ramaiah
supporting information, p. 6713 - 6716 (2013/10/01)
A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tert-butyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.
PHENYLALKYLCARBOXYLIC ACID DELIVERY AGENTS
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Page/Page column 34, (2008/12/07)
The present invention provides phenylalkylcarboxylic acid compounds and compositions containing such compounds which facilitate the delivery of biologically active agents.
Design and synthesis of low molecular weight compounds with complement inhibition activity
Master, Hoshang E.,Khan, Shabana I.,Poojari, Krishna A.
, p. 4891 - 4899 (2007/10/03)
An attempt was made to synthesize a series of non-cytotoxic low molecular weight compounds of varying substitutions and functionalities having pharmacophore activity like carbonyl compounds, carboxylic acid and bioisosteres like tetrazole and phenyl acrylic acid. The in vitro assay of these analogues for the inhibition of complement activity revealed significant inhibitory activity for varying substituents and, particularly, for bioisosteres, that is, tetrazole and phenyl acrylic acid derivatives.
Competitive formation of β-amino acids, propenoic, and ylidenemalonic acids by the Rodionov reaction from malonic acid, aldehydes, and ammonium acetate in alcoholic medium
Lebedev,Lebedeva,Sheludyakov,Kovaleva,Ustinova,Kozhevnikov
, p. 1113 - 1124 (2007/10/03)
The Rodionov reaction of 49 available aliphatic and aromatic aldehydes with malonic acid and ammonium acetate in alcoholic medium, resulting in formation of β-amino acids, propenoic, and ylidenemalonic acids, was studied. Certain regioselectivity regularities of the reaction were revealed. Among the variety of ketones studied, cyclohexanone is the only whose reaction yields a β-amino acid. Unusual dehydrofluorination of 6-chloro-2-fluorocinnamic acid under the Rodionov reaction was discovered. 2005 Pleiades Publishing, Inc.
KOH-promoted reaction of C,O,O-tris(trimethylsilyl) ketene acetal with aldehydes: Practical and easy access to (E)-α,β-ethylenic carboxylic acids
Lensen,Mouelhi,Bellassoued
, p. 1007 - 1011 (2007/10/03)
The use of a catalytic amount of KOH has been found to be very efficient in promoting reaction of silylketene acetal 1 with aldehydes 2 to afford the corresponding (E)-α,β-ethylenic carboxylic acids 3 under very mild conditions.
Inhibition of uridine phosphorylase. Synthesis and structure-Activity relationships of aryl-substituted 1-((2-hydroxyethoxy)methyl)-5-(3- phenoxybenzyl)uracil
Orr, G. Faye,Musso, David L.,Kelley, James L.,Joyner, Suzanne S.,Davis, Stephen T.,Baccanari, David P.
, p. 1179 - 1185 (2007/10/03)
Structure-activity relationship studies on a series of 1-((2- hydroxyethoxy)methyl)-5-(3-(substituted-phenoxy)benzyl)uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC50s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vive for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.
