127172-22-9Relevant academic research and scientific papers
Novel sulfonamide derivatives carrying a biologically active 3,4-dimethoxyphenyl moiety as VEGFR-2 inhibitors
Ghorab, Mostafa Mohammed,Alsaid, Mansour Sulaiman,Nissan, Yassin Mohammed,Ashour, Abdelkader Elbadawy,Al-Mishari, Abdullah Abdulalrahman,Kumar, Ashok,Ahmed, Sheikh Fayaz
, p. 1747 - 1754 (2016)
Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR, 1H-NMR, 13C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug. Among the tested derivatives, compounds 4, 10, 16, and 19 showed good activity as cytotoxic agents. The most active derivatives were evaluated for their ability to inhibit vascular endothelial growth factor receptor (VEGFR)-2. Compounds Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(5-methyl-1,3,4-thiadiazol-2-yl)-benzenesulfonamide 10 and Z-4-(3-(3,4-dimethoxyphenyl)-3-oxoprop-1-enylamino)-N-(1H-indazol-6-yl)-benzenesulfonamide 19 were more active as VEGFR-2 inhibitors than dasatinib. Molecular docking of the most active derivatives on the active site of VEGFR-2 revealed that compound 19 exhibited favorable and promising results.
Pyridine-ureas as potential anticancer agents: Synthesis and in vitro biological evaluation
El-Naggar, Mohamed,Almahli, Hadia,Ibrahim, Hany S.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.
, (2018)
In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a-n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC50 = 0.22 and 1.88 μM after 48 h treatment; 0.11 and 0.80 μM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC50 = 1.93 μM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l-n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12-78%, GI for 8e; 15-91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC50 values 5.0 ± 1.91 and 3.93 ± 0.73 μM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.
DDQ-mediated oxidative coupling reaction of N,N-dimethyl enaminones with cycloheptatriene
Cheng, Dongping,Yu, Chenze,Pu, Yueqi,Xu, Xiaoliang
supporting information, (2022/01/23)
An efficient 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated oxidative coupling reaction of N,N-dimethyl enaminones with cycloheptatriene is developed. It provides a variety of α-alkenylated 1,3-dicarbonyl compounds in moderate to good yields under mild conditions.
Design, synthesis, in silico, and in vitro evaluation of 3-phenylpyrazole acetamide derivatives as antimycobacterial agents
Gaikwad, Nikhil B.,Nirmale, Krishna,Sahoo, Santosh K.,Ahmad, Mohammad N.,Kaul, Grace,Shukla, Manjulika,Nanduri, Srinivas,Das Gupta, Arunava,Chopra, Sidharth,Yaddanapudi, Madhavi V.
, (2020/12/23)
Mycobacterium tuberculosis (Mtb) is one of the most dangerous pathogens affecting immunocompetent and immunocompromised patients worldwide. Novel molecules, which are efficient and can reduce the duration of therapy against drug-resistant strains, are an
Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
supporting information, p. 3672 - 3690 (2021/08/07)
Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines
Huo, Xian-Sen,Jian, Xie-Er,Ou-Yang, Jie,Chen, Lin,Yang, Fang,Lv, Dong-Xin,You, Wen-Wei,Rao, Jin-Jun,Zhao, Pei-Liang
, (2021/05/10)
By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.
Harnessing Stereospecific Z-Enamides through Silver-Free Cp?Rh(III) Catalysis by Using Isoxazoles as Masked Electrophiles
Debbarma, Suvankar,Bera, Sourav Sekhar,Maji, Modhu Sudan
supporting information, p. 835 - 839 (2019/01/26)
The stereospecific synthesis of Z-enamides is described in this paper. For the first time, isoxazoles have been employed as electrophiles in C-H functionalization to afford thermodynamically less stable Z-enamides utilizing salicylaldehydes in an atom- and step-economic fashion. The stereochemistry of enamides might originate from the relative disposition of atoms present in isoxazole and the intramolecular hydrogen bonding. The reaction showed excellent scope as several structurally and electronically diverse salicylaldehydes and isoxazoles reacted efficiently.
The use of enaminones and enamines as effective synthons for MSA-catalyzed regioselective synthesis of 1,3,4-tri- And 1,3,4,5-tetrasubstituted pyrazoles
Duan, Liancheng,Zhou, Hui,Gu, Yucheng,Gong, Ping,Qin, Mingze
supporting information, p. 16131 - 16137 (2019/11/03)
In the present work, an efficient regioselective synthesis of 1,3,4-tri- and 1,3,4,5-tetrasubstituted pyrazoles via a methanesulfonic acid (MSA)-catalyzed reaction of hydrazones with enaminones or enamines is reported. Mechanistically, the formation of the title compounds involves the [2+3] cycloaddition of hydrazones with enaminones or enamines followed by aromatization with acid and oxygen. This convenient method under mild conditions with various hydrazones, enaminones, and enamines was well-tolerated to afford products in good to excellent yields. Compared with the literature methods, this strategy has advantages such as materials that are available economically, metal-free catalysis, excellent regioselectivity, and high efficiency.
[3+2] Anionic Cycloaddition of Isocyanides to Acyclic Enamines and Enaminones: A New, Simple, and Convenient Method for the Synthesis of 2,4-Disubstituted Pyrroles
Bakulev, Vasiliy A.,Efimov, Ilya V.,Luque, Rafael,Matveeva, Maria D.,Voskressensky, Leonid G.
supporting information, (2020/02/27)
We herein demonstrate a new approach for the synthesis of 2,4-disubstituted pyrroles by [3+2] cycloaddition reaction of isocyanides to the activated double bond of various enamines and enaminones. This process paved the way for the synthesis a series of 2,4-disubstituted pyrroles, which are known to be intermediates in the synthesis of biologically active compounds, in good to excellent yields from simple and commercially available starting materials. The process is carried out efficiently using a strong base, tBuOK, at low temperatures (0 °C). The described method is simple, proceeds in one step, does not require additional catalysts and hence, has a wide scope.
Synthesis and in vitro evaluation of piperazinyl-ureido sulfamates as steroid sulfatase inhibitors
Moi, Davide,Foster, Paul A.,Rimmer, Lucy G.,Jaffri, Alisha,Deplano, Alessandro,Balboni, Gianfranco,Onnis, Valentina,Potter, Barry V.L.
, (2019/08/20)
Two new piperazinyl-ureido single ring aryl sulfamate-based inhibitor series were designed against the emerging oncology drug target steroid sulfatase (STS), for which there are existing potent steroidal and non-steroidal agents in clinical trials. 4-(Pip
