67848-59-3Relevant articles and documents
Optimization and evaluation of novel tetrahydropyrido[4,3-d]pyrimidine derivatives as ATX inhibitors for cardiac and hepatic fibrosis
Cao, Meng,Gong, Ping,Guo, Ming,Jiang, Nan,Lei, Hongrui,Su, Guangyue,Zhai, Xin,Zhang, Junlong,Zhou, Yuhong,Zhu, Minglin
, (2019)
Aiming to develop potent autotaxin (ATX) inhibitors for fibrosis diseases, a novel series of tetrahydropyrido[4,3-d]pyrimidine derivatives was designed and synthesized based on our previous study. The enzymatic assay combined with anti-proliferative activities against cardiac fibroblasts (CFs) and hepatic stellate cell (HSC) in vitro were applied for preliminary evaluation of anti-fibrosis potency of target compounds, resulting in two outstanding ATX inhibitors 8b and 10g with the IC50 values in a nanomolar range (24.6 and 15.3 nM). Differently, 8b was the most prominent compound against CFs with inhibition ratio of 81.5%, while 10g exhibited the maximum inhibition ratio of 83.7% against t-HSC/Cl-6 cells. In the further pharmacological evaluations in vivo, collagen deposition assay demonstrated the conspicuous capacity of 8b to suppress TGF-β-mediated cardiac fibrosis. Simultaneously, H&E and Masson stains assays of mice liver validated 10g as an excellent anti-hepatofibrosis candidate, which reduced CCl4-induced hepatic fibrosis level prominently. Besides, the molecular binding models identified the essential interactions between 8b and ATX which was coincided with the SARs.
Preparation method of nicotinic acid derivative
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Paragraph 0062-0063, (2019/12/02)
The invention relates to a preparation method of a nicotinic acid derivative. The method comprises the following steps: with N-benzylpiperidine-4-keto-3-formate as a raw material, carrying out a hydrogenolysis reaction to obtain piperidine-4-keto-3-formate; performing halogenation reaction with a certain amount of a halogenation reagent to obtain 3,5-dihalogenated piperidine-4-one-3-formate or 3,5,5-trihalogenated piperidine-4-one-3-formateperforming one-pot process with different alkaline reagent for removing halogen hydride through elimination, and performing hydrolysis and performing acidification with hydrochloric to generate corresponding nicotinic acid derivatives: 4-hydroxynicotinic acid, 4-aminonicotinic acid, 4-hydroxy-5-chloronicotinic acid, 4-amino-5-chloronicotinic acid and 4-amino-5-bromonicotinic acid. The method is simple and convenient to operate, mild in condition, short in technological process, low in wastewater amount, environmentally friendly and low in cost, and green industrial production of the nicotinic acid derivative is facilitated.
Substituted 1,2,3,4-tetrahydrobenzo[C][2,7] naphthyridines and derivatives thereof as kinase inhibitors
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Page/Page column 46, (2016/03/06)
The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.
Synthesis and antiproliferative activity of cyclic arylidene ketones: a direct comparison of monobenzylidene and dibenzylidene derivatives
Huber, Imre,Zupk, Istvn,Kovcs, Ida J.,Minorics, Renta,Gulys-Fekete, Gergely,Masz, Gbor,Perjsi, Pl
, p. 973 - 981 (2015/02/19)
Abstract To give further insight into the influence of the structural modifications of enones and dienones on their antiproliferative properties, 25 derivatives of enones: (E)-2-benzylidene-1-cyclohexanones, (E)-2-benzylidene-1-tetralones, (E)-2-benzylidene-1-indanone, and dienones: (E,E)-2,5- or 2,6-dibenzylidene-1-cyclanones, (E,E)-3,5-dibenzylidene-4-piperidones were synthesized using a newly developed "one-pot" synthetic method. Due to the fact that all of them have the same aryl substituents (phenyl or 4-chlorophenyl) in the arylidene moiety, it is possible to compare the relevant contribution of the single-point structural modifications (type of ring or N-substitution) on their potency on the basis of their IC 50 values. Their antiproliferative activity was evaluated against the following four human adherent cancer cell lines: HeLa, A431, A2780, and MCF7. The cytotoxicity screen has revealed that the dibenzylidene dienones in general dominate the monobenzylidene enones in this respect. The nitrogen-containing heterocyclic dienones at the same time displayed higher inhibitory properties toward these human carcinoma cell lines compared with their homocyclic dienone analogs. One of the eight newly prepared 4-piperidone derivatives, N-(γ-oxobutyl)-(E,E)-3,5-bis(p-chlorobenzylidene)-4-piperidone is as potent a cell growth inhibitor (IC 50 of 0.438-1.409 μM) as the N-methyl-(E,E)-3,5-bis(p-chlorobenzylidene)-4-piperidone (IC 50 of 0.447-1.048 μM), one of the most active among the previously described compounds in this series. Catalytic hydrogen-transfer isomerization of compounds with two exocyclic benzylidene double bonds to derivatives with endocyclic double bonds results in the complete loss of antiproliferative activity. The structural modifications and 50 % inhibitory concentration (IC 50) values resulted in correlations which can promote the design of more potent derivatives of the 4-piperidone dienones.
Design and syntheses of melanocortin subtype-4 receptor agonists. Part 2: Discovery of the dihydropyridazinone motif
Ujjainwalla, Feroze,Warner, Daniel,Snedden, Christine,Grisson, Ricky D.,Walsh, Thomas F.,Wyvratt, Matthew J.,Kalyani, Rubana N.,MacNeil, Tanya,Tang, Rui,Weinberg, David H.,Van Der Ploeg, Lex,Goulet, Mark T.
, p. 4023 - 4028 (2007/10/03)
Optimization of the biological activity of a new class of non-peptidyl, pyridazinone derived human melanocortin subtype-4 receptor agonists is disclosed.
