56970-25-3Relevant academic research and scientific papers
Catalyst-Controlled Regioselective Chlorination of Phenols and Anilines through a Lewis Basic Selenoether Catalyst
Dinh, Andrew N.,Maddox, Sean M.,Vaidya, Sagar D.,Saputra, Mirza A.,Nalbandian, Christopher J.,Gustafson, Jeffrey L.
, p. 13895 - 13905 (2020/11/03)
We report a highly efficient ortho-selective electrophilic chlorination of phenols utilizing a Lewis basic selenoether catalyst. The selenoether catalyst resulted in comparable selectivities to our previously reported bis-thiourea ortho-selective catalyst, with a catalyst loading as low as 1%. The new catalytic system also allowed us to extend this chemistry to obtain excellent ortho-selectivities for unprotected anilines. The selectivities of this reaction are up to >20:1 ortho/para, while the innate selectivities for phenols and anilines are approximately 1:4 ortho/para. A series of preliminary studies revealed that the substrates require a hydrogen-bonding moiety for selectivity.
Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings
Li, Wenlu,Sun, Qinsheng,Song, Lu,Gao, Chunmei,Liu, Feng,Chen, Yuzong,Jiang, Yuyang
, p. 721 - 733 (2017/11/01)
PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-negative breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231.
Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents
Suryadevara, Praveen Kumar,Racherla, Kishore Kumar,Olepu, Srinivas,Norcross, Neil R.,Tatipaka, Hari Babu,Arif, Jennifer A.,Planer, Joseph D.,Lepesheva, Galina I.,Verlinde, Christophe L.M.J.,Buckner, Frederick S.,Gelb, Michael H.
supporting information, p. 6492 - 6499 (2013/11/19)
New dialkylimidazole based sterol 14α-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 1 nM) against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate.
Structurally simple inhibitors of lanosterol 14α-demethylase are efficacious in a rodent model of acute Chagas disease
Suryadevara, Praveen Kumar,Olepu, Srinivas,Lockman, Jeffrey W.,Ohkanda, Junko,Karimi, Mandana,Verlinde, Christophe L. M. J.,Kraus, James M.,Schoepe, Jan,Van Voorhis, Wesley C.,Hamilton, Andrew D.,Buckner, Frederick S.,Gelb, Michael H.
experimental part, p. 3703 - 3715 (2010/04/24)
We report structure-activity studies of a large number of dialkyl imidazoles as inhibitors of Trypanosoma cruzi lanosterol-14α-demethylase (L14DM). The compounds have a simple structure compared to posaconazole, another L14DM inhibitor that is an anti-Chagas drug candidate. Several compounds display potency for killing T. cruzi amastigotes in vitro with values of EC 50 in the 0.4-10 nM range. Two compounds were selected for efficacy studies in a mouse model of acute Chagas disease. At oral doses of 20-50 mg/kg given after establishment of parasite infection, the compounds reduced parasitemia in the blood to undetectable levels, and analysis of remaining parasites by PCR revealed a lack of parasites in the majority of animals. These dialkyl imidazoles are substantially less expensive to produce than posaconazole and are appropriate for further development toward an anti-Chagas disease clinical candidate.
