79148-89-3Relevant academic research and scientific papers
Synthesis, preliminarily biological evaluation and molecular docking study of new Olaparib analogues as multifunctional PARP-1 and cholinesterase inhibitors
Gao, Cheng-Zhi,Dong, Wei,Cui, Zhi-Wen,Yuan, Qiong,Hu, Xia-Min,Wu, Qing-Ming,Han, Xianlin,Xu, Yao,Min, Zhen-Li
, p. 150 - 162 (2019)
A series of new Olaparib derivatives was designed and synthesized, and their inhibitory activities against poly (ADP-ribose) polymerases-1 (PARP-1) enzyme and cancer cell line MDA-MB-436 in vitro were evaluated. The results showed that compound 5l exhibited the most potent inhibitory effects on PARP-1 enzyme (16.10 ± 1.25 nM) and MDA-MB-436 cancer cell (11.62 ± 2.15 μM), which was close to that of Olaparib. As a PARP-1 inhibitor had been reported to be viable to neuroprotection, in order to search for new multitarget-directed ligands (MTDLs) for the treatment of Alzheimer’s disease (AD), the inhibitory activities of the synthesized compounds against the enzymes AChE (from electric eel) and BChE (from equine serum) were also tested. Compound 5l displayed moderate BChE inhibitory activity (9.16 ± 0.91 μM) which was stronger than neostigmine (12.01 ± 0.45 μM) and exhibited selectivity for BChE over AChE to some degree. Molecular docking studies indicated that 5l could bind simultaneously to the catalytic active of PARP-1, but it could not interact well with huBChE. For pursuit of PARP-1 and BChE dual-targeted inhibitors against AD, small and flexible non-polar groups introduced to the compound seemed to be conducive to improving its inhibitory potency on huBChE, while keeping phthalazine-1-one moiety unchanged which was mainly responsible for PARP-1 inhibitory activity. Our research gave a clue to search for new agents based on AChE and PARP-1 dual-inhibited activities to treat Alzheimer’s disease.
Design and synthesis novel amide derivatives containing an 1,3,4-oxadiazole moiety as potential antibacterial agents
Chen, Jixiang,Chen, Yifang,Luo, Xin,Wang, Yu,Xing, Zhifu
supporting information, (2022/02/17)
To find new antibacterial agents, 25 novel amide derivatives containing an 1,3,4-oxadiazole moiety were designed and synthesized, and their antibacterial activity against Xanthomonas oryzae pv. oryzicola (Xoc) and Xanthomonas oryzae pv. oryzae (Xoo) were tested. Interestingly, all target compounds showed excellent antibacterial activities against Xoc and Xoo. The EC50 values of compounds 1–25 against Xoc and Xoo were 1.2–4.0?mg/L and 0.5–2.3?mg/L, respectively, which were significantly superior to those of the thiodiazole copper (95.1 and 89.0?mg/L) and bismerthhibol (73.8 and 68.8?mg/L). For example, the EC50 values of compound 16 against Xoc and Xoo were 1.7 and 0.5?mg/L, respectively. Meanwhile, the curative and protection activity of compound 16 against rice bacterial leaf blight were 42.4% and 42.1%, respectively, which were superior to the control of jiahuangxianjunzuo (34.1% and 32.6%) and thiodiazole copper (33.0% and 27.1%). In addition, compound 16 might suppress the cell growth of Xoo by inhibiting the production of extracellular polysaccharide, the formation of biofilm, changes the cell membrane permeability, and cell surface morphology.
Quinoline derivative containing furyl and preparation method and application thereof
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Paragraph 0098-0102, (2021/05/08)
The invention belongs to the field of anti-cancer drugs, and particularly relates to a furyl-containing quinoline derivative and a preparation method and application thereof. The invention provides a compound as shown in the formula I, and a stereoisomer or pharmaceutically acceptable salt thereof. Compared with an existing antitumor drug, the compound disclosed by the invention has excellent antitumor activity on A431, SKOV3, SK-BR-3, BT474 and the like, and has a very good application prospect. In addition, the preparation method of the compound is low in cost, simple in step, mild in reaction condition, high in yield and easy for post-treatment.
Template-Directed Photochemical Homodimerization and Heterodimerization Reactions of Cinnamic Acids
Yagci, Bilge Banu,Zorlu, Yunus,Türkmen, Yunus Emre
, p. 13118 - 13128 (2021/09/18)
We developed a general method for the selective photochemical homo- and heterodimerization of cinnamic acid derivatives with the use of commercially available 1,8-dihydroxynaphthalene as a covalent template. A variety of symmetrical and unsymmetrical β-tr
Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis
Chen, Liu Zeng,Shu, Hai Yang,Wu, Jing,Yu, Yun Long,Ma, Duo,Huang, Xin,Liu, Ming Ming,Liu, Xin Hua,Shi, Jing Bo
, (2021/02/03)
In order to discover and develop drug-like anti-inflammatory agents against arthritis, based on “Hit” we found earlier and to overcome drawbacks of toxicity, twelve series of total 89 novel pyrimidine, pyrazolo[4,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives were designed, synthesized and screened for their anti-inflammatory activity against NO and toxicity for normal liver cells (LO2). Relationships of balance toxicity and activity have been summarized through multi-steps, and title compounds 22o, 22l were found to show lower toxicity (against LO2: IC50 = 2934, 2301 μM, respectively) and potent effect against NO release (IR = 98.3, 97.67%, at 10 μM, respectively). Furthermore, compound 22o showed potent iNOS inhibitory activity with value of IC50 is 0.96 μM and could interfere stability and formation of the active dimeric iNOS. It's anti-inflammatory activity in vivo was assessed by AIA rat model. Furthermore, the results of metabolic stability, CYP, PK study in vivo, acute toxicity study and subacute toxicity assessment indicated this compound had good drug-like properties for treatment.
Multicomponent Enantioselective Synthesis of Tetrahydropyridazinones Employing Chiral α,β-Unsaturated Acylammonium Salts
Kiledal, Sigrid A.,Jourdain, Roxane,Vellalath, Sreekumar,Romo, Daniel
supporting information, p. 6622 - 6627 (2021/09/13)
An enantioselective three-component reaction was developed for the synthesis of tetrahydropyridazinones employing chiral α,β-unsaturated acylammonium salts, malonates, and azodicarboxylates. An initial α-amination of a malonate with an azodicarboxylate an
Practical access to fluorescent 2,3-naphthalimide derivatives: Via didehydro-Diels-Alder reaction
Chen, Xia,Zhong, Cheng,Lu, Yuling,Yao, Meng,Guan, Zhenhua,Chen, Chunmei,Zhu, Hucheng,Luo, Zengwei,Zhang, Yonghui
supporting information, p. 5155 - 5158 (2021/05/31)
A practical and efficient approach for the synthesis of fluorescent 2,3-naphthalimide derivatives has been developed from readily available starting materials via an intramolecular didehydro-Diels-Alder reaction, which proceeded well under room temperature, exhibiting a wide substrate scope and good functional group tolerance. The practicability of this methodology has been verified by one-step synthesis of the environmentally sensitive fluorophore 6-DMN on a gram scale with a shorter time, fewer steps and less waste disposal, and without the utilization of toxic transition metals. The present experimental and computational studies support the crucial role of the propiolimide moiety in the transformation.
Modular Cyclopentenone Synthesis through the Catalytic Molecular Shuffling of Unsaturated Acid Chlorides and Alkynes
Lee, Yong Ho,Denton, Elliott H.,Morandi, Bill
supporting information, p. 20948 - 20955 (2020/12/21)
We describe a general strategy for the intermolecular synthesis of polysubstituted cyclopentenones using palladium catalysis. Overall, this reaction is achieved via a molecular shuffling process involving an alkyne, an α,β-unsaturated acid chloride, which serves as both the alkene and carbon monoxide source, and a hydrosilane to create three new C-C bonds. This new carbon monoxide-free pathway delivers the products with excellent yields. Furthermore, the regioselectivity is complementary to conventional methods for cyclopentenone synthesis. In addition, a set of regio- and chemodivergent reactions are presented to emphasize the synthetic potential of this novel strategy.
Enantioselective Synthesis of 3,4-Dihydropyran-2-ones via Phase-Transfer-Catalyzed Addition-Cyclization of Acetylacetone to Cinnamic Thioesters
Destro, Dario,Bottinelli, Carlo,Ferrari, Ludovica,Albanese, Domenico C. M.,Bencivenni, Grazia,Gillick-Healy, Malachi W.,Kelly, Brian G.,Adamo, Mauro F. A.
supporting information, p. 5183 - 5192 (2020/04/10)
Herein, we present the first example of synthesis of 3,4-dihydropyran-2-ones from cinnamic thioesters via a stereoselective phase-transfer-catalyzed domino Michael-cyclization reaction with acetylacetone. The reaction proceeded under the catalysis of Cinchona-derived quaternary ammonium phenoxide that, in combination with inorganic bases, provided 3,4-dihydropyran-2-ones in yields of up to 93% and enantioselectivities of up to 88% enantiomeric excess.
Novel paeonol derivatives: Design, synthesis and anti-inflammatory activity in vitro and in vivo
Hu, Yang Sheng,Han, Xu,Yu, Pei Jing,Jiao, Ming Ming,Liu, Xin Hua,Shi, Jing Bo
, (2020/03/13)
Paeonol has been proved to have potential anti-inflammatory activity, but its clinical application is not extensive due to the poor anti-inflammatory activity (14.74% inhibitory activity at 20 μM). In order to discover novel lead compound with high anti-inflammatory activity, series of paeonol derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. Structure-activity relationships (SARs) have been fully concluded, and finally (E)-N-(4-(2-acetyl-5-methoxyphenoxy)phenyl)-3-(3,4,5-trimet-hoxyphenyl)acrylamide (compound 11a) was found to be the best active compound with low toxicity, which showed 96.32% inhibitory activity at 20 μM and IC50 value of 6.96 μM against LPS-induced over expression of nitric oxide (NO) in RAW 264.7 macrophages. Preliminary mechanism studies indicated that it could inhibit the expression of TLR4, resulting in inhibiting of NF-κB and MAPK pathways. Further studies have shown that compound 11a has obvious therapeutic effect against the adjuvant-induced rat arthritis model.
