Article
Chemistry, Multidisciplinary
Yingying Shan, Lei Su, Dianpeng Chen, Min Yang, Wenlin Xie, Guanyinsheng Qiu
Summary: In this study, a palladium-catalyzed [4+1] cycloaddition reaction was developed for the synthesis of a series of 2-amino-4-cyanofurans and 2-amino-4-amidylpyrroles with high efficiency and broad reaction scope. Mechanism studies suggest that the palladium-catalyzed [4 + 1] imidoylative cycloaddition of prop-2-yn-1-ones was concerted. This work provides a potential strategy for the synthesis of valuable heterocyclic compounds.
CHINESE CHEMICAL LETTERS
(2021)
Article
Chemistry, Organic
Yan Chen, Andrey Shatskiy, Jian-Quan Liu, Markus D. Karkas, Xiang-Shan Wang
Summary: An unprecedented silver-promoted regioselective (4 + 1) annulation of isocyanoacetates with pyridinium salts is reported in this study, providing access to various synthetically useful N-fused heterocyclic scaffolds. The mechanism involves nucleophilic addition/protonation/elimination/cydoisomerization pathways. The protocol established in this research is controlled, facile, and modular.
Article
Chemistry, Multidisciplinary
Forough Nasuhipur, Zarrin Ghasemi, Morgane Poupon, Michal Dusek
Summary: A class of indenopyrroles was synthesized by the treatment of dihydroxy-2-methyl-4-oxoindeno[1,2-b]pyrroles with phosphorus oxychloride. The elimination of vicinal hydroxyl groups, formation of a p bond, and electrophilic chlorination produced fused aromatic pyrrole structures. Benzylic substitution of nucleophiles resulted in diverse 4-oxoindeno[1,2-b]pyrrole derivatives with yields of 58-93%. The reaction showed the highest yield when conducted in DMF. The structures of the products were confirmed using spectroscopic methods, elemental analysis, and X-ray crystallography.
Article
Chemistry, Applied
Hui-Shu Lin, Yong-Zhou Pan, Yu-Hong Tian, Ying-Ming Pan, Xu Wang
Summary: A Pd-catalyzed tandem cyclization reaction has been developed, allowing the efficient construction of new C-C and C-N bonds via the orderly insertion of isocyanides. Various indeno[2,1-b]pyrroles were prepared in moderate to high yields under air atmosphere at 100°C.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Shangfeng Ren, Keke Huang, Jin-Biao Liu, Lianpeng Zhang, Min Hou, Guanyinsheng Qiu
Summary: A palladium-catalyzed formal [2 + 2 + 1] cyclization of 1-alkynyl-8-iodonaphthalene with double isocyanides is developed, resulting in a series of 7H-acenaphtho[1,2-b]pyrrole compounds.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Athukuri Edukondalu, Sandip Sambhaji Vagh, Ting-Han Lin, Wenwei Lin
Summary: An efficient protocol for the chemoselective construction of indeno[1,2-b]pyrroles and rearranged derivatives has been reported via an N-acylation/cyclization/Wittig reaction. Mechanistic investigations revealed the crucial role of a spiro-indene-1,2'-[1,3,4]oxadiazol intermediate and its further reaction with phosphine to generate betaine, leading to the formation of the targeted heteroarenes predominantly through a Wittig reaction.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Jiangjie Zhang, Jun Ying, Xiao-Feng Wu
Summary: A novel palladium-catalyzed tandem cyclization and carbonylation reaction was developed for the synthesis of indeno[1,2-b]indol-10(5H)-one derivatives. The reaction proceeded smoothly with high yields using formic acid as the CO source. This method can also be applied for the modification of various bioactive molecules.
JOURNAL OF CATALYSIS
(2023)
Article
Chemistry, Organic
Dattatri, Maneesh Kumar Reddy Singam, Jagadeesh Babu Nanubolu, Maddi Sridhar Reddy
Summary: A cascade reaction of enynones with enaminones via carbene insertion and aryl migration is reported in this study, which efficiently constructs distinctive multisubstituted furans with an all-carbon quaternary center. The protocol can be extended to synthesize furano-pyrrole bis-heterocycles in the same pot. The heterogeneity of this reaction was demonstrated by generating divergent chemical space under relatively mild reaction conditions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Zhi-Wei Xi, Yan He, Li-Qiu Liu, Ying-Chun Wang, Hui-Ying Zeng
Summary: Under the catalysis of both Pd(dppf)Cl2 and Cu(OAc)2, a three-component domino reaction of thioamides, benzyl isocyanide, and water resulted in novel 1,2,4-thiadiazolidin-3-one cyclic compounds. In contrast, the same reaction with tertiary alkylisonitriles in the presence of rare earth metal salt [La(OTf)3] produced (E)-N-(1,2-diamino-2-thioxoethylidene)benzamide open chain products. This divergent reaction enabled the formation of five (N-S, C-S, C-O, and two C-N) or four (C-S, C-N, C-O, and C-C) new chemical bonds. Mechanism studies revealed that the oxygen atom in the product was derived from water.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mingming Zhao, Yiming Guo, Qi Wang, Lanqi Liu, Shujie Zhang, Wei Guo, Lin-Ping Wu, Fayang G. Qiu
Summary: This paper presents an efficient synthesis of 2-iminothiazolidin-4-ones through a copper-catalyzed tandem annulation reaction involving alkyl amines, isothiocyanates, and diazo acetates. The [2 + 1 + 2] cyclization method offers advantages such as readily accessible starting materials, simplicity of operation, mild reaction conditions, high yields, step-economy, and tolerance towards diverse functional groups. Furthermore, the reaction is applicable to gram-scale synthesis and the preparation of bioactive molecules.
Article
Chemistry, Organic
Yifan Ouyang, Kaifu Wu, Wei Zhou, Qian Cai
Summary: An efficient and convenient method for the synthesis of pyrrole-fused tetracyclic skeletons is described in this study, utilizing CuI as a catalyst. The reaction involves tandem [3 + 2] cycloaddition and C-C coupling processes to form 7-membered cyclic ketones fused with pyrrole and biphenyl rings.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Subba Rao Polimera, Murugaiah A. M. Subbaiah, Andivelu Ilangovan
Summary: A regioselective 1,2-addition of silyl enol ethers to quinones can now be achieved via a palladium(II) enolate pathway, providing access to cyclohexadienone derivatives. This protocol proceeds under mild reaction conditions without the need for an external ligand or base, and the products have been used as synthetic precursors for fused heteroaryl systems.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ritiele Heck, Thiago Anjos, Maira R. Giehl, Ricardo F. Schumacher, Benhur Godoi
Summary: Flavone and its analogues are important biologically active substances commonly found in diverse plants. This study demonstrates an efficient synthetic strategy for preparing functionalized flavones using catalytic amounts of base and a thiol. The reactions proceed smoothly under transition-metal-free and open to air conditions, yielding the desired compounds in short reaction time.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Multidisciplinary
Vinu V. Panikkattu, Abhijeet S. Sinha, Christer B. Aakeroy
Summary: Strong halogen bonds serve as a foundation for reliable supramolecular strategies in self-assembly and material design. A new class of halogen-bond donors, such as the 3-iodo-1-phenylprop-2-yn-1-ones, show promising features for crystal engineering.
Article
Chemistry, Physical
Satbir Mor, Mohini Khatri
Summary: A series of thiazole tethered indenopyrazoles exhibit potent antimicrobial and alpha-amylase inhibitory activities, with compound 3d showing the highest potency. The compounds show better inhibitory activity against the fungus Candida albicans compared to the standard drug Fluconazole, and compounds 3j and 3k are recognized as good alpha-amylase inhibitors.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Xiaoyun Lu, Jeff B. Smaill, Adam Patterson, Ke Ding
Summary: Small molecule covalent kinase inhibitors (CKIs) have advantages for sustained target inhibition and high selectivity, with major medicinal chemistry strategies involving the addition of a warhead to a reversible lead/inhibitor scaffold to generate CKIs, while also facing challenges in drug discovery in this area.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhen Zhang, Jie Li, Hao Chen, Jing Huang, Xiaojuan Song, Zheng-Chao Tu, Zhang Zhang, Lijie Peng, Yang Zhou, Ke Ding
Summary: Aberrant FGF19/FGFR4 signaling has been identified as an oncogenic driver for human hepatocellular carcinoma (HCC). A new series of inhibitors targeting FGFR4 have been synthesized, and the representative compound 9ka showed potent activity against FGFR4 with excellent kinome selectivity. Compound 9ka also demonstrated favorable pharmacokinetic properties and induced significant tumor regression in a mouse model without apparent toxicity. Compound 9ka may serve as a promising lead compound for further development of anticancer drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jibu Lu, Yongjun Huang, Jing Huang, Rui He, Minhao Huang, Xiaoyun Lu, Yong Xu, Fengtao Zhou, Zhang Zhang, Ke Ding
Summary: The first examples of threonine tyrosine kinase (TTK) PROTACs were successfully designed and synthesized, showing strong degradation effects in human colorectal cancer cells and potential anticancer activities.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhen Wang, Weixue Huang, Kaijie Zhou, Xiaomei Ren, Ke Ding
Summary: Protein kinases have been proven to be effective targets for cancer drug discovery, but most drugs inhibit kinase catalytic activity by binding to ATP-site. Recent studies have shown that kinases also have noncatalytic functions, which play important roles in cellular signaling and cell fate controls. Small-molecule modulators targeting the noncatalytic functions of kinases have emerged as promising therapeutic strategies. This article summarizes the noncatalytic functions of kinases and discusses the progress in developing small-molecule modulators. It is speculated that targeting the noncatalytic functions could open a new direction for kinase-based drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hualin Zhang, Ruliang Xie, Hawaa AI-furas, Yupeng Li, Qingxia Wu, Jian Li, Fang Xu, Tianfeng Xu
Summary: A series of EGFR proteolysis-targeting chimeras (PROTACs) were designed and synthesized to induce degradation of EGFR C797S mutant in resistant non-small cell lung cancer patients, with compound 6h showing promising degradation and antiproliferation activity.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Peng Lyu, Kaili Jiang, Yuee Zhou, Jun Hu, Yu Chang, Zhang Zhang, Minhao Huang, Zhi-Min Zhang, Ke Ding, Piliang Hao, Ligen Lin, Zhengqiu Li
Summary: This study successfully identified the cellular off-target NT5DC1 of HP-1, a potential drug candidate for non-small cell lung cancer, through chemical proteomics and bioimaging studies.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Wenhong Su, Zhiwen Chen, Meiying Liu, Rui He, Chaoyi Liu, Rui Li, Mingshan Gao, Mingyue Zheng, Zhengchao Tu, Zhang Zhang, Tianfeng Xu
Summary: This study presents a new series of JAK3 covalent inhibitors and identifies compound 10f as the most potent inhibitor with high selectivity and inhibitory activity against JAK3. It may serve as a promising tool molecule for treating cancers with aberrantly activated JAK3.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Chuan Zhou, Zisheng Fan, Zehui Zhou, Yupeng Li, Rongrong Cui, Chaoyi Liu, Guizhen Zhou, Xingxing Diao, Hualiang Jiang, Mingyue Zheng, Sulin Zhang, Tianfeng Xu
Summary: Regulating SOS1 functions may lead to targeted therapy for pan-KRAS. Small-molecule SOS1 inhibitors have shown promise as anticancer agents, and the most advanced one, BI 1701963, is currently in phase I clinical studies. SOS1 agonists offer new opportunities for cancer treatment, but the underlying mechanisms still need further investigation. This study reports the discovery of the first SOS1 PROTACs, designed by connecting a VHL ligand to a known SOS1 agonist, ensuring that the observed inhibitory activity is due to degraders. The best compound, 9d, induced SOS1 degradation in various KRAS-driven cancer cells and exhibited superior antiproliferation activity compared to the agonist itself. Tumor xenograft study demonstrated the promising antitumor potency of 9d against human lung cancer. The study provides strong evidence for using agonists to design SOS1 PROTACs and demonstrates that targeted SOS1 degradation is an effective therapeutic strategy for overcoming KRAS-driven cancers.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yue Liu, Jiacong Liu, Xianfang Zhang, Cuiping Guo, Zhi-Min Zhang, Xiwen Xing, Ke Ding, Zhengqiu Li
Summary: Chemical proteomics is a powerful technology for studying uncharacterized proteins in the human proteome. A new protein-labeling strategy using nitrile oxide has been developed, which can efficiently react with target proteins. This method has shown excellent chemoselectivity and successfully characterized over 4000 cysteine residues, including KRAS G12C, demonstrating its complementary utility.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Rui He, Zhiqiang Song, Yu Bai, Sheng He, Jing Huang, Yongxing Wang, Fengtao Zhou, Weixue Huang, Jing Guo, Zhen Wang, Zheng-Chao Tu, Xiaomei Ren, Zhang Zhang, Jian Xu, Ke Ding
Summary: AXL kinase is crucially involved in cancer tumorigenesis, metastasis, and drug resistance, and multiple AXL inhibitors are currently being investigated in clinical trials. Recent research has highlighted the importance of the N-terminal region of AXL in cell invasiveness, suggesting that targeting AXL degradation could be a more effective therapeutic approach compared to kinase inhibitors. In this study, a series of new AXL PROTAC degraders were discovered, with compound 6n emerging as a potent AXL depletor in TNBC cells. It exhibited superior inhibitory effects on AXL signaling activation, cell proliferation, migration, and invasion compared to the corresponding kinase inhibitor. Additionally, compound 6n showed promising therapeutic potential in patient-derived organoids and a mouse model of MDA-MB-231 cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yiying Wei, Xinxin Xu, Minchuan Jiang, Yongxing Wang, Yang Zhou, Zhen Wang, Zhang Zhang, Fengtao Zhou, Ke Ding
Summary: A new selective GSPT1 degrader was developed, which could effectively degrade GSPT1 and showed good selectivity in the global proteomic profiling study. The compound also displayed good antiproliferative activities and induced cell cycle arrest and apoptosis in U937 cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shumin Lv, Fang Xu, Youlong Fan, Ke Ding, Zhengqiu Li
Summary: Due to the limited targets for drug development, triple-negative breast cancer (TNBC) is considered a challenging disease for chemotherapy. In this study, a set of novel electrophilic warheads was used to search for potential targets for TNBC in chemical proteomics studies. These warheads were found to modify not only highly nucleophilic residues but also weakly nucleophilic residues. Cys12 of Kirsten rat sarcoma (KRASG12C) was successfully labeled by cyclopropenone and cyclopropeniminium ions. Preliminary results showed moderate inhibitory activity against TNBC cells with these electrophile-based probes, and FABP5 was identified as a potential target for TNBC through further functional validation experiments.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zuqin Wang, Jie Wang, Yongjin Wang, Shuang Xiang, Hengliang Zhou, Shukai Song, Xiaojuan Song, Zhengchao Tu, Yang Zhou, Ke Ding, Zhi-Min Zhang, Zhang Zhang, Xiaoyun Lu
Summary: This study focuses on the development of new type II TRK inhibitors to combat acquired resistance mutations. Compound 10g displayed excellent potency against TRK mutants and demonstrated strong inhibition of cell proliferation. The results provide a promising lead compound for pan-anticancer drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Chungen Li, Yuanyuan Qiao, Xia Jiang, Lianchao Liu, Yang Zheng, Yudi Qiu, Caleb Cheng, Fengtao Zhou, Yang Zhou, Weixue Huang, Xiaomei Ren, Yuzhuo Wang, Zhen Wang, Arul M. Chinnaiyan, Ke Ding
Summary: Researchers have discovered a first-in-class PIKfyve degrader, PIK5-12d, which can effectively degrade PIKfyve protein and inhibit the growth of prostate cancer cells. It provides a valuable chemical tool for exploring PIKfyve-based targeted therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
