5428-43-3Relevant academic research and scientific papers
Sequence-Defined Dithiocarbamate Oligomers via a Scalable, Support-free, Iterative Strategy
Nanjan, Pandurangan,Jose, Anna,Thurakkal, Liya,Porel, Mintu
, p. 11019 - 11026 (2020/12/22)
Precise control over the monomeric sequence on natural sequence-defined polymers (SDPs) leads to their structural diversity and functions. However, absolute control over the monomeric sequence on a synthetic polymer remains a challenging process. Herein, we describe a support-free, protection-deprotection-free, cost-effective, and fast iterative strategy for multigram production of a new class of SDP with a unique functional group, dithiocarbamate, a potential group for material and biomedical applications. The strategy is based on a unique monomer, named as amine-hydroxyl monomer, and a three-component reaction between the monomer, CS2, and terminal chloro group of the growing chain. The fast strategy allows us to synthesize a 5-mer sequence-defined oligomer in 6 h. For a proof of concept, a range of aliphatic and aromatic groups have been incorporated at different sequences in the sequence-defined oligomer. This SDP platform has further been advanced by two ways: (i) multiple approaches for postsynthetic modification of SDP and (ii) increasing the chain length in a single step.
Design, Synthesis, and Structure-Activity Relationship Studies of Novel Indolyalkylpiperazine Derivatives as Selective 5-HT1A Receptor Agonists
Wang, Wenli,Zheng, Lan,Li, Wei,Zhu, Chen,Peng, Weiqing,Han, Bing,Fu, Wei
, p. 235 - 248 (2020/02/18)
5-HT1A receptor (5-HT1AR) agonists have been implicated in the treatment of a variety of central nervous system (CNS) diseases such as depression and anxiety, et al. Based on our previously found compound FW01 (Ki = 51 ± 16 nM) obtained by virtual screening, a series of FW01 derivatives were designed and synthesized by the modification of the amide tail group as well as indole headgroup of FW01. SAR exploration found that amide tail group and indole headgroup play pivotal roles in determining the binding affinity and selectivity on dopamine and serotonin receptor subtypes. Among all tested compounds, 9_24 has a Ki value of 5 ± 0.6 nM with a good selectivity toward 5-HT1AR. The [35S] GTPγS assay showed that 9_24 is a full agonist toward 5-HT1AR with an EC50 value of 0.059 nM, which shows 266.2 and 146.4-fold selectivity to 5-HT2A and D3 respectively. Molecular dynamics simulations and molecular docking studies with 5-HT1AR-9_24 were performed to disclose the mechanism of its high activity and selectivity. Finally, a detailed stepwise 9_24 induced signal transduction mechanism of 5-HT1AR is proposed.
Design, synthesis, biological evaluation and molecular modeling study of new thieno[2,3-d]pyrimidines with anti-proliferative activity on pancreatic cancer cell lines
Salem, Mohamed S.H.,Abdel Aziz, Yasmine M.,Elgawish, Mohamed S.,Said, Mohamed M.,Abouzid, Khaled A.M.
, (2019/12/24)
Pancreatic cancer is one of the most challenging diseases with seven months only as median survival time due to its poor prognosis. Several enzymes are blamed for the progress of pancreatic cancer especially, platelet-derived growth factor receptors (PDGFRs), this in turn makes them promising targets for its treatment. In this study, twenty eight new compounds based on thieno[2,3-d]pyrimidine scaffold were synthesized as anti-pancreatic cancer agents mimicking the benzofuro[3,2-d]pyrimidine derivative, amuvatinib. Various linkers including amides, esters, ketones, urea and thiourea derivatives were utilized to study their effect on the anti-proliferative activity of these compounds. Most of the tested compounds revealed good cytotoxic activities against pancreatic carcinoma cell line PANC-1. Compound 9d showed the highest cytotoxicity with an IC50 value of 5.4 μM. Furthermore, 9d showed excellent platelet derived growth factor receptor (PDGFR-α) inhibitory activity, with IC50 value 0.155 μM. Docking study was carried out into PDGFR-α active site which showed comparable binding mode to that of FDA approved PDGFR-α inhibitor, imatinib. 3D-Quantitative structure activity relationship (QSAR) model was built up with five-featured pharmacophore which could be implemented for emerging effective lead structures. These compounds could serve as a new chemotype for discovering new agents for pancreatic cancer therapy.
Intramolecular carbene C-H insertion reactions of 2-diazo-2-sulfamoylacetamides
Que, Chuqiang,Huang, Peipei,Yang, Zhanhui,Chen, Ning,Xu, Jiaxi
, (2019/08/01)
The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo-N,N-dimethyl-2-(N,N-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its N-phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[c]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(N,N-dialkylsulfamoyl)acetamides; and (3) for 2-diazo-N-phenyl-2-(N-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the N-phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the N-aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group.
Preparation method for N-phenyl indolone
-
Paragraph 0030; 0040; 0041; 0042, (2018/09/21)
The invention especially relates to a preparation method for N-phenyl indolone, belonging to the field of organic synthesis. The preparation method for N-phenyl indolone comprises the following steps:subjecting diphenylamine (a compound as shown in a formula II) and chloroacetyl chloride (a compound as shown in a formula III) to a condensation reaction to prepare 2-chloro-N,N-diphenylacetamide (acompound as shown in a formula IV); subjecting 2-chloro-N,N-diphenylacetamide and acetate to an esterification reaction so as to obtain 2-acetoxy-N,N-diphenylacetamide (a compound as shown in a formula V); and subjecting 2-acetoxy-N,N-diphenylacetamide to a ring closure reaction so as to obtain N-phenyl indolone. The preparation method provided by the invention is a clean high-efficiency synthesis method for N-phenyl indolone; in the whole preparation process, high-contamination raw materials are discarded, and reaction temperature is lowered; and the method is friendly to environment and safe and simple to operate, and has great industrial application value.
Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase
Marcu, Ana,Schurigt, Uta,Müller, Klaus,Moll, Heidrun,Krauth-Siegel, R. Luise,Prinz, Helge
supporting information, p. 436 - 443 (2015/12/24)
A number of phenothiazine-, phenoxazine- and related tricyclics-derived chloroacetamides were synthesized and evaluated in vitro for antiprotozoal activities against Leishmania major (L. major) promastigotes. Several analogs were remarkably potent inhibitors, with antileishmanial activities being comparable or superior to those of the reference antiprotozoal drugs. Furthermore, we explored the structure-activity relationships of N-10 haloacetamides that influence the potency of such analogs toward inhibition of L. major promastigote growth in vitro. With respect to the mechanism of action, selected compounds were evaluated for time-dependent inactivation of Trypanosoma brucei trypanothione reductase. Our results are indicative of a covalent interaction which could account for potent antiprotozoal activities.
Efficiently functionalized oxacalix[4]arenes: Synthesis, characterization and exploration of their biological profile as novel HDAC inhibitors
Mehta, Viren,Athar, Mohd,Jha,Panchal, Manthan,Modi, Krunal,Jain
supporting information, p. 1005 - 1010 (2016/05/24)
A series of novel substituted oxacalix[4]arene has been synthesized and explored for their biological profile by evaluating anticancer, antifungal and antibacterial properties. The derivatives have been characterized by various spectroscopic techniques su
Visible light photoredox-catalysed intermolecular radical addition of α-halo amides to olefins
Nakajima, Masaki,Lefebvre, Quentin,Rueping, Magnus
supporting information, p. 3619 - 3622 (2014/04/03)
We present α-chloro amides as a new class of α-acetyl radical precursors, which undergo a tin-free, photoredox-catalysed intermolecular α-alkylation with various olefins exclusively in an anti-Markovnikov fashion. The reaction represents a reductive atom
One-pot synthesis of indolo[2,3-c]quinolin-6-ones by sequential photocyclizations of 3-(2-azidophenyl)-N-phenylacrylamides
Li, Zhanshan,Wang, Weixia,Zhang, Xiaotian,Hu, Congcong,Zhang, Wei
supporting information, p. 73 - 78 (2013/04/24)
A one-pot synthesis of indolo[2,3-c]quinolin-6(7H)-ones was achieved by sequential photocyclizations of 3-(2-azidophenyl)-N-phenylacrylamides in moderate to high yields. The reactions proceeded via photochemical cyclization of aryl azides to form N-phenylindol-2-carbamides and subsequent 6π-electrocyclic reaction and oxidative aromatization to afford the corresponding indolo[2,3-c]quinolin-6(7H)-ones. Georg Thieme Verlag Stuttgart · New York.
Photoinduced and N-bromosuccinimide-mediated cyclization of 2-azido-N-phenylacetamides
Li, Zhan-Shan,Wang, Wei-Xia,Yang, Ji-Dong,Wu, Yue-Wei,Zhang, Wei
supporting information, p. 3820 - 3823 (2013/09/02)
An efficient synthesis of quinoxalin-2(1H)-ones or spiro[cyclohexene-1, 2′-imidazol]-4′-ones has been achieved in moderate to high yields by the visible light-induced and N-bromosuccinimide-mediated cyclization reaction of 2-azido-N-phenylacetamides at ambient temperature. Both the regioselectivity and the speed of cyclization are affected by the substituents attached to the phenyl ring. For example, quinoxalin-2-ones are produced as the main products when the substrates bear electron-withdrawing groups at the para-position of the phenyl ring; in contrast, spiro[cyclohexene-1,2′-imidazol]-4′-ones are obtained as the main products when the substrates bear electron-donating groups at the para-position.
