Statistical Modeling of Antiemetic Activity of Chemical Compounds

A model has been built linking the molecular structure of drugs with their antiemetic activity. It is shown that the bioactivity of drugs depends on the pseudopotential of the molecule, the information function of the molecule, and the geometric size of the substituents. The critical conditions for the emergence of effective antiemetic activity of molecules have been established. The optimal sizes of the substituents were determined, which correspond to the maximum bioactivity of the drugs. The mechanism of the threshold action of substituted benzamides was revealed.

Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and N-Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a–8i and 9a–9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC50 = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 μM) and A431 cells (IC50 = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.

A Catalytic Highly Enantioselective Synthesis of Spirooxazolines

A catalytic highly enantioselective synthesis of spirooxazolines is presented. Starting from readily available 2-naphthol-substituted benzamides and using catalytic amounts of a chiral triazole-substituted iodoarene catalyst, a variety of spirooxazolines can be isolated through an enantioselective oxidative dearomatization in up to 92% yield and 97% ee. The further synthetic utility of the optically enriched spirooxazolines was examined providing a corresponding 2-naphthalenole and an oxepin.<br>

A Catalytic Highly Enantioselective Synthesis of Spirooxazolines

A catalytic highly enantioselective synthesis of spirooxazolines is presented. Starting from readily available 2-naphthol-substituted benzamides and using catalytic amounts of a chiral triazole-substituted iodoarene catalyst, a variety of spirooxazolines can be isolated through an enantioselective oxidative dearomatization in up to 92% yield and 97% ee. The further synthetic utility of the optically enriched spirooxazolines was examined providing a corresponding 2-naphthalenole and an oxepin.<br>

Synthesis and Single Crystal Structures of N-Substituted Benzamides and Their Chemoselective Selenation/Reduction Derivatives

A series of N-aryl-N-(2-oxo-2-arylethyl) benzamides and cinnamides has been prepared. The reaction of the benzamides with Woollins’ reagent, a highly efficient chemoselective selenation/reduction reagent, gave the corresponding N-aryl-N-(arylenethyl) benzoselenoamides in good yields. Five representative single crystal X-ray structures are discussed.

Application of Chiral Triazole-Substituted Iodoarenes in the Enantioselective Construction of Spirooxazolines

A catalytic highly enantioselective synthesis of spirooxazolines is presented. Starting from readily available 2-naphthol-substituted benzamides and using catalytic amounts of a chiral triazole-substituted iodoarene catalyst, a variety of spirooxazolines can...

Discovery of 3-Cinnamamido-N-Substituted Benzamides as Potential Antimalarial Agents

Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3-cinnamamido-N-substituted benzamides. Method: In this study, a screening of our compound library was carried out against the multidrug-sensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 µM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 µM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, phenotypic screen of our compound library resulted in the first report of 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against P. falciparum 3D7 strain with IC50 values around 0.1 µM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.