61240-27-5Relevant academic research and scientific papers
Synthesis and Evaluation of PPARδAgonists That Promote Osteogenesis in a Human Mesenchymal Stem Cell Culture and in a Mouse Model of Human Osteoporosis
Kress, Brian J.,Kim, Dong Hyun,Mayo, Jared R.,Farris, Jeffery T.,Heck, Benjamin,Sarver, Jeffrey G.,Andy, Divya,Trendel, Jill A.,Heck, Bruce E.,Erhardt, Paul W.
, p. 6996 - 7032 (2021/05/29)
We synthesized a directed library of compounds to explore the structure-activity relationships of peroxisome proliferator-activated receptor δ(PPARδ) activation relative to mesenchymal stem cell (MSC) osteogenesis. Our scaffold used para-substituted cinnamic acids as a polar headgroup, a heteroatom and heterocycle core connecting units, and substituted phenyl groups for the lipophilic tail. Compounds were screened for their ability to increase osteogenesis in MSCs, and the most promising were examined for subunit specificity using a quantitative PPAR transactivation assay. Six compounds were selected for in vivo studies in an ovariectomized mouse model of human postmenopausal osteoporosis. Four compounds improved bone density in vivo, with two (12d and 31a) having activity comparable to that of GW0742, a well-studied PPARδ-selective agonist. 31a (2-methyl-4-[N-methyl-N-[5-methylene-4-methyl-2-[4-(trifluoromethyl)phenyl]thiazole]]aminocinnamic acid) had the highest selectivity for PPARδcompared to other subtypes, its selectivity far exceeding that of GW0742. Our results confirm that PPARδis a new drug target for possible treatment of osteoporosis via in situ manipulation of MSCs.
BIVALENT LECA INHIBITORS TARGETING BIOFILM FORMATION OF PSEUDOMONAS AERUGINOSA
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Page/Page column 48; 50-51, (2021/05/15)
The present invention relates to divalent compounds binding to LecA. The compounds are useful to block biofilm formation of Pseudomonas aeruginosa. The invention further relates to pharmaceutical compositions comprising these compounds and to therapeutic methods and uses of these compounds, in particular to therapeutic methods and uses for the treatment of Pseudomonas aeruginosa infections in a subject. The invention also relates to imaging of infections, such as biofilms produced by Pseudomonas aeruginosa, by using these divalent compounds.
Optimization of the reaction conditions for the synthesis of dihydrobenzofuran neolignans
Crotti, Ant?nio E. M.,Dias, Herbert J.,Rodrigues, Matheus L.
, p. 20 - 28 (2020/12/28)
We have optimized the experimental conditions for the silver(I)-promoted oxidative coupling of methyl p-coumarate (I) and methyl ferulate (II), which is the most frequently used methodology to synthesize the bioactive dihydrobenzofuran neolignans 1 ((±)-trans-dehydrodicoumarate dimethyl ester) and 2 ((±)-trans-dehydrodiferulate dimethyl ester). Most of the tested conditions affected the conversion (i.e., the consumption of I and II) and the selectivity (i.e., the percentage of I and II that was converted into 1 and 2, respectively), so the optimized conditions were the ones that afforded the best balance between conversion and selectivity. Silver(I) oxide (0.5 equiv.) is the most efficient oxidant agent amongst the silver(I) reagents that were tested to convert methyl esters I and II into compounds 1 and 2, respectively. Acetonitrile, which has not yet been reported as a solvent for this reaction, provided the best balance between conversion and selectivity, besides being "greener" than other solvents that are more often employed (e.g., dichloromethane and benzene). Under the optimized conditions, the reaction time decreased from 20 to 4 h without significantly impacting the conversion and selectivity.
Pd salen complex@CPGO as a convenient, effective heterogeneous catalyst for Suzuki–Miyaura and Heck–Mizoroki cross-coupling reactions
Ghabdian, Mahdieh,Nasseri, Mohammad Ali,Allahresani, Ali,Motavallizadehkakhky, Alireza
, p. 1713 - 1728 (2018/05/25)
A Pd(II) Schiff base complex supported on graphene oxide nanosheets (Pd(II) salen@CPGO) has been synthesized and characterized by FT-IR, ICP-AES, XRD, SEM/EDX and TEM. The synthesized nanocatalyst has been found to be an efficient heterogeneous catalyst for Suzuki–Miyaura and Heck–Mizoroki coupling reactions. Pd(II) salen@CPGO could be separated and recovered easily from the reaction mixture and recycled several times without a discernible decrease in its catalytic activity. The construction of a solid sheet-supported Pd catalyst would be expected to be a promising system to perform heterogeneous catalytic reactions.
Structure?Activity Relationships of Cinnamate Ester Analogues as Potent Antiprotozoal Agents
Bernal, Freddy A.,Kaiser, Marcel,Wünsch, Bernhard,Schmidt, Thomas J.
, p. 68 - 78 (2019/11/22)
Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model.
Preparation method of esmolol hydrochloride intermediate
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Paragraph 0041-0043; 0046-0048, (2020/09/16)
The invention belongs to the field of organic synthesis of medicines, and particularly relates to a preparation method of a medicine esmolol hydrochloride intermediate for treating hypertension. The synthesis route provided by the invention comprises the following steps: reacting p-bromophenol with methyl acrylate in the presence of a palladium catalyst and a phosphine ligand to generate 3-(4-hydroxyphenyl) methyl acrylate; and hydrogenating the generated 3-(4-hydroxyphenyl) methyl acrylate in the presence of a palladium-carbon catalyst to obtain a target product methyl 4-hydroxyphenylpropionate. The method has the advantages of short reaction steps, cheap and accessible raw materials, simple technique and convenience of operation, and does not need special reaction conditions, thereby being more suitable for industrial production.
Design, synthesis and antitumor evaluation of novel celastrol derivatives
Xu, Manyi,Li, Na,Zhao, Zihao,Shi, Zhixian,Sun, Jianbo,Chen, Li
, p. 265 - 276 (2019/05/04)
On the basis of the hybridization strategy of natural products, a total of 32 novel celastrol hybrids were designed, synthesized and evaluated for their antitumor activities. Most of these derivatives exihibited significant antiproliferative activities compared to celastrol, among which compound 29 displayed the strongest inhibitory capability [IC50 = 0.15 ± 0.03 μM (A549),0.17 ± 0.03 μM (MCF-7), 0.26 ± 0.02 μM (HepG2)], which exhibited equal or superior anti-cancer activities in comparison to 2-cyano-3,12-dioxoolean-1,9 (11)-dien-28-oic acid methyl ester (CDDO-Me). The mechanism of pharmacological research indicated that 29 possessed the ability to disrupt Hsp90-Cdc37 complex which was stronger than celastrol. Meanwhile, compound 29 could induce abnormal regulation of clients (p-Akt and Cdk4) of Hsp90 and cell cycle arrest at G0/G1 phase in a concentration-dependent manner. In addition, compound 29 could also induce cell apoptosis through the death receptor pathway on A549 cells. Taken together, our results demonstrated that 29 might be a promising novel candidate for further druggability research.
Hydroxamic Acid Derivatives of β-Carboline/Hydroxycinnamic Acid Hybrids Inducing Apoptosis and Autophagy through the PI3K/Akt/mTOR Pathways
Ling, Yong,Li, Yangyang,Zhu, Rui,Qian, Jianqiang,Liu, Ji,Gao, Weijie,Meng, Chi,Miao, Jiefei,Xiong, Biao,Qiu, Xiaodong,Ling, Changchun,Dai, Hong,Zhang, Yanan
, p. 1442 - 1450 (2019/07/05)
Naturally occurring β-carbolines are known to have antitumor activities but with limited effectiveness. In order to improve their efficacy, a series of new hydroxamic-acid-containing β-carbolines connected via a hydroxycinnamic acid moitey (12a-f) were developed to incorporate histone deacetylase (HDAC) inhibition for possible synergistic effects. When evaluated in in vitro assays, most of the analogues showed significant antitumor activities against four human cancer cells. In particular, 12b showed the highest cytotoxic potency of the series, including drug-resistant Bel7402 cells, but had minimal effect on normal hepatic LO2 cells. These compounds also showed excellent inhibitory effects against HDAC1/6, which appear to contribute greatly to their antiproliferative properties. Compound 12b enhanced the acetylation levels of histone H3 and α-tubulin and induced greater cancer cell apoptosis than the FDA-approved HDAC inhibitor SAHA by regulating expression of apoptotic proteins Bax, Bcl-2, and caspase 3. Importantly, 12b also induced a significant amount of autophagic flux activity in Bel7402 cells by increasing the expression of Beclin-1 and LC3-II proteins and decreasing that of LC3-I and p62. Finally, 12b significantly inhibited PI3K/Akt/mTOR signaling, an important cell-growth-promoting pathway aberrantly activated in many cancers. Together, the results suggest that these hydroxamic-acid-containing β-carboline derivatives may be new leads for the discovery of agents for the treatment of human carcinoma cancers.
Synthesis of Phenols: Organophotoredox/Nickel Dual Catalytic Hydroxylation of Aryl Halides with Water
Yang, Liu,Huang, Zhiyan,Li, Gang,Zhang, Wei,Cao, Rui,Wang, Chao,Xiao, Jianliang,Xue, Dong
supporting information, p. 1968 - 1972 (2018/02/06)
A highly effective hydroxylation reaction of aryl halides with water under synergistic organophotoredox and nickel catalysis is reported. The OH group of the resulting phenols originates from water, following deprotonation facilitated by an intramolecular base group on the ligand. Significantly, aryl bromides as well as less reactive aryl chlorides served as effective substrates to afford phenols with a wide range of functional groups. Without the need for a strong inorganic base or an expensive noble-metal catalyst, this process can be applied to the efficient preparation of diverse phenols and enables the hydroxylation of multifunctional pharmaceutically relevant aryl halides.
Synthesis and Mesogenic Properties of Liquid Crystals Based on Cholesterol and Cinnamic Acid Derivatives
Zong, Xuenan,Wu, Changcheng
, p. 60 - 73 (2019/03/05)
A group of new mesomorphic compounds with cholesterol-based, which have derivative of the cinnamic acid, with different lengths of terminal alkoxy chains, are synthesized and characterized. The mesomorphic properties were investigated by DSC and POM. All target compounds showed a cholesteric phase. For 12-TC and 14-TC besides a cholesteric phase, also revealed a SmA* phase. The experimental results demonstrated that with the increase in the terminal chain lengths, the thermal stability of the smectic mesophases of these liquid crystals was increased, and these compounds shows brilliant color changes in the temperature ranges of cholesteric phase.
