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Design, Synthesis, and Biological Evaluations of Pyridyl 4,5,6,7-Tetrahydro-4,7-Methanobenzo[d]isoxazoles as Potent and Selective Inhibitors of 11β-Hydroxylase J. Med. Chem. (IF 8.039) Pub Date : 2022-08-17 Lina Yin, Youtian Pan, Yuanyuan Xue, Xiaoli Chen, Taiyun You, Jiahui Huang, Qihao Xu, Qingzhong Hu
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Discovery of Novel cccDNA Reducers toward the Cure of Hepatitis B Virus Infection J. Med. Chem. (IF 8.039) Pub Date : 2022-08-16 Dongdong Chen, Xuefei Tan, Wenming Chen, Yongfu Liu, Chao Li, Jun Wu, Jiamin Zheng, Hong C. Shen, Meifang Zhang, Waikwong Wu, Lin Wang, Jing Xiong, Jieyu Dai, Kai Sun, Jitao David Zhang, Kunlun Xiang, Baocun Li, XiaoJu Ni, Qihui Zhu, Lu Gao, Li Wang, Song Feng
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Beyond Retigabine: Design, Synthesis, and Pharmacological Characterization of a Potent and Chemically Stable Neuronal Kv7 Channel Activator with Anticonvulsant Activity J. Med. Chem. (IF 8.039) Pub Date : 2022-08-16 Simona Musella, Lidia Carotenuto, Nunzio Iraci, Giulia Baroli, Tania Ciaglia, Piera Nappi, Manuela Giovanna Basilicata, Emanuela Salviati, Vincenzo Barrese, Vincenzo Vestuto, Giuseppe Pignataro, Giacomo Pepe, Eduardo Sommella, Veronica Di Sarno, Michele Manfra, Pietro Campiglia, Isabel Gomez-Monterrey, Alessia Bertamino, Maurizio Taglialatela, Carmine Ostacolo, Francesco Miceli
Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype Kv7 activator clinically approved for seizure treatment; however, severe side effects associated with long-term use have led to its market discontinuation. Building upon the recently described cryoEM structure of Kv7.2 complexed with retigabine and on previous
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Discovery of Substituted Di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines as Novel Macrofilaricidal Compounds for the Treatment of Human Filarial Infections J. Med. Chem. (IF 8.039) Pub Date : 2022-08-16 Natalie Hawryluk, Dale Robinson, Yixing Shen, Graham Kyne, Matthew Bedore, Sanjay Menon, Stacie Canan, Thomas von Geldern, Simon Townson, Suzanne Gokool, Alexandra Ehrens, Marianne Koschel, Nathaly Lhermitte-Vallarino, Coralie Martin, Achim Hoerauf, Geraldine Hernandez, Deepak Dalvie, Sabine Specht, Marc Peter Hübner, Ivan Scandale
Filarial diseases, including lymphatic filariasis and onchocerciasis, are considered among the most devastating of all tropical diseases, affecting about 145 million people worldwide. Efforts to control and eliminate onchocerciasis are impeded by a lack of effective treatments that target the adult filarial stage. Herein, we describe the discovery of a series of substituted di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines
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Identification of Monosaccharide Derivatives as Potent, Selective, and Orally Bioavailable Inhibitors of Human and Mouse Galectin-3 J. Med. Chem. (IF 8.039) Pub Date : 2022-08-15 Chunjian Liu, Prasada Rao Jalagam, Jianxin Feng, Wei Wang, Thiruvenkadam Raja, Mallikarjuna Reddy Sura, Raju K. V. L. P. Manepalli, Bheema Reddy Aliphedi, Santosh Medavarapu, Satheesh K. Nair, Vetrichelvan Muthalagu, Ramesh Natesan, Anuradha Gupta, Brett Beno, Manoranjan Panda, Kaushik Ghosh, Jinal Kaushikkumar Shukla, Harinath Sale, Priyanka Haldar, Narasimharaju Kalidindi, Devang Shah, Dipal Patel
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Therapeutic Potential of a Water-Soluble Silver-Diclofenac Coordination Polymer on 3D Pancreatic Cancer Spheroids J. Med. Chem. (IF 8.039) Pub Date : 2022-08-15 Sabina W. Jaros, Urszula K. Komarnicka, Agnieszka Kyzioł, Barbara Pucelik, Dmytro S. Nesterov, Alexander M. Kirillov, Piotr Smoleński
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Insight into Thermodynamic and Kinetic Profiles in Small-Molecule Optimization J. Med. Chem. (IF 8.039) Pub Date : 2022-08-15 Wei Liu, Jingsheng Jiang, Yating Lin, Qidong You, Lei Wang
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Large-Scale Ligand Perturbations of the Protein Conformational Landscape Reveal State-Specific Interaction Hotspots J. Med. Chem. (IF 8.039) Pub Date : 2022-08-15 Timothy R. Stachowski, Marcus Fischer
Protein flexibility is important for ligand binding but often ignored in drug design. Considering proteins as ensembles rather than static snapshots creates opportunities to target dynamic proteins that lack FDA-approved drugs, such as the human chaperone, heat shock protein 90 (Hsp90). Hsp90α accommodates ligands with a dynamic lid domain, yet no comprehensive analysis relating lid conformations to
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Selective Inhibitors of Medium-Size S1′ Pocket Matrix Metalloproteinases: A Stepping Stone of Future Drug Discovery J. Med. Chem. (IF 8.039) Pub Date : 2022-08-15 Sandip Kumar Baidya, Suvankar Banerjee, Nilanjan Adhikari, Tarun Jha
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Design, Synthesis, and Pharmacological Evaluation of Benzimidazolo-thiazoles as Potent CXCR3 Antagonists with Therapeutic Potential in Autoimmune Diseases: Discovery of ACT-672125 J. Med. Chem. (IF 8.039) Pub Date : 2022-08-15 Eva Caroff, Emmanuel A. Meyer, Päivi Äänismaa, Sylvie Froidevaux, Marcel Keller, Luca Piali
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N-Benzyl Benzamide Derivatives as Selective Sub-Nanomolar Butyrylcholinesterase Inhibitors for Possible Treatment in Advanced Alzheimer’s Disease J. Med. Chem. (IF 8.039) Pub Date : 2022-08-15 Chenxi Du, Lei Wang, Qianwen Guan, Hongyu Yang, Tingkai Chen, Yijun Liu, Qihang Li, Weiping Lyu, Xin Lu, Ying Chen, Yang Liu, Hui Liu, Feng Feng, Wenyuan Liu, Zongliang Liu, Wei Li, Yao Chen, Haopeng Sun
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Construction of Covalent Bisubstrate Inhibitor of Protein Kinase Reacting with Cysteine Residue at Substrate-Binding Site J. Med. Chem. (IF 8.039) Pub Date : 2022-08-12 Tanel Sõrmus, Darja Lavogina, Anu Teearu, Erki Enkvist, Asko Uri, Kaido Viht
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Development of an Orally Active Small-Molecule Inhibitor of Receptor Activator of Nuclear Factor-κB Ligand J. Med. Chem. (IF 8.039) Pub Date : 2022-08-12 Kai Yang, Shunyao Li, Tianqi Wang, Xueming Yan, Qian He, Ruonan Ning, Xing Xu, Wei Yao, Xiaofei Zhang, Chunhao Yang, Min Jiang, Lianfu Deng
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Fragment Libraries Designed to Be Functionally Diverse Recover Protein Binding Information More Efficiently Than Standard Structurally Diverse Libraries J. Med. Chem. (IF 8.039) Pub Date : 2022-08-12 Anna Carbery, Rachael Skyner, Frank von Delft, Charlotte M. Deane
Current fragment-based drug design relies on the efficient exploration of chemical space by using structurally diverse libraries of small fragments. However, structurally dissimilar compounds can exploit the same interactions and thus be functionally similar. Using three-dimensional structures of many fragments bound to multiple targets, we examined if a better strategy for selecting fragments for
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Non-Covalent Albumin Ligands in FDA-Approved Therapeutic Peptides and Proteins J. Med. Chem. (IF 8.039) Pub Date : 2022-08-12 Florencio Zaragoza
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Development, Optimization, and In Vivo Validation of New Imidazopyridine Chemotypes as Dual TLR7/TLR9 Antagonists through Activity-Directed Sequential Incorporation of Relevant Structural Subunits J. Med. Chem. (IF 8.039) Pub Date : 2022-08-12 Nirmal Das, Purbita Bandopadhyay, Swarnali Roy, Bishnu Prasad Sinha, Uddipta Ghosh Dastidar, Oindrila Rahaman, Sourav Pal, Dipyaman Ganguly, Arindam Talukdar
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Discovery of the First Selective IDO2 Inhibitor As Novel Immunotherapeutic Avenues for Rheumatoid Arthritis J. Med. Chem. (IF 8.039) Pub Date : 2022-08-11 Guangchao He, Sheng Wan, Yunze Wu, Zhaoxing Chu, Hui Shen, Shan Zhang, Linya Chen, Zijing Bao, Shuhui Gu, Junzhang Huang, Lei Huang, Guoqing Gong, Yi Zou, Qihua Zhu, Yungen Xu
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Improving Drug Delivery While Tailoring Prodrug Activation to Modulate Cmax and Cmin by Optimization of (Carbonyl)oxyalkyl Linker-Based Prodrugs of Atazanavir J. Med. Chem. (IF 8.039) Pub Date : 2022-08-11 Murugaiah A. M. Subbaiah, Lakshumanan Subramani, Thangeswaran Ramar, Salil Desai, Sarmistha Sinha, Sandhya Mandlekar, John F. Kadow, Susan Jenkins, Mark Krystal, Murali Subramanian, Srikanth Sridhar, Shweta Padmanabhan, Priyadeep Bhutani, Rambabu Arla, Nicholas A. Meanwell
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Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA2), UCM-14216, Ameliorates Spinal Cord Injury in Mice J. Med. Chem. (IF 8.039) Pub Date : 2022-08-10 Nora Khiar-Fernández, Debora Zian, Henar Vázquez-Villa, R. Fernando Martínez, Andrea Escobar-Peña, Román Foronda-Sainz, Manisha Ray, Maria Puigdomenech-Poch, Giovanni Cincilla, Melchor Sánchez-Martínez, Yasuyuki Kihara, Jerold Chun, Rubèn López-Vales, María L. López-Rodríguez, Silvia Ortega-Gutiérrez
Spinal cord injuries (SCIs) irreversibly disrupt spinal connectivity, leading to permanent neurological disabilities. Current medical treatments for reducing the secondary damage that follows the initial injury are limited to surgical decompression and anti-inflammatory drugs, so there is a pressing need for new therapeutic strategies. Inhibition of the type 2 lysophosphatidic acid receptor (LPA2)
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Discovery and In Vivo Evaluation of ACT-660602: A Potent and Selective Antagonist of the Chemokine Receptor CXCR3 for Autoimmune Diseases J. Med. Chem. (IF 8.039) Pub Date : 2022-08-10 Emmanuel A. Meyer, Päivi Äänismaa, Sylvie Froidevaux, Marcel Keller, Luca Piali, Eva Caroff
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Investigating the Structure–Activity Relationship of 1,2,4-Triazine G-Protein-Coupled Receptor 84 (GPR84) Antagonists J. Med. Chem. (IF 8.039) Pub Date : 2022-08-10 Amit Mahindra, Laura Jenkins, Sara Marsango, Mark Huggett, Margaret Huggett, Lindsay Robinson, Jonathan Gillespie, Muralikrishnan Rajamanickam, Angus Morrison, Stuart McElroy, Irina G. Tikhonova, Graeme Milligan, Andrew G. Jamieson
G-protein-coupled receptor 84 (GPR84) is a proinflammatory orphan G-protein-coupled receptor implicated in several inflammatory and fibrotic diseases. Several agonist and antagonist ligands have been developed that target GPR84; however, a noncompetitive receptor blocker that was progressed to phase II clinical trials failed to demonstrate efficacy. New high-quality antagonists are required to investigate
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Correction to “Nitric Oxide Photo-Donor Hybrids of Ciprofloxacin and Norfloxacin: A Shift in Activity from Antimicrobial to Anticancer Agents” J. Med. Chem. (IF 8.039) Pub Date : 2022-08-10 Antonino Nicolò Fallica, Carla Barbaraci, Emanuele Amata, Lorella Pasquinucci, Rita Turnaturi, Maria Dichiara, Sebastiano Intagliata, Marzia Bruna Gariboldi, Emanuela Marras, Viviana Teresa Orlandi, Claudia Ferroni, Cecilia Martini, Antonio Rescifina, Davide Gentile, Greta Varchi, Agostino Marrazzo
Pages 11611 and 11612, references 18 and 42 should be switched, such that ref 18, cited on page 11598, refers to the work by Sorrenti et al., and ref 42, cited on page 11599, refers to the work by Amata et al. Page 11599. A new reference (cited here as ref (1)) should be added at the end of the first sentence of the last paragraph of the Introduction: “...endowed with a 4-nitro-3-trifluoromethylaniline
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Designing Novel BCR-ABL Inhibitors for Chronic Myeloid Leukemia with Improved Cardiac Safety J. Med. Chem. (IF 8.039) Pub Date : 2022-08-09 Mallesh Pandrala, Arne Antoon N. Bruyneel, Anna P. Hnatiuk, Mark Mercola, Sanjay V. Malhotra
Development of tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL oncogene constitutes an effective approach for the treatment of chronic myeloid leukemia (CML) and/or acute lymphoblastic leukemia. However, currently available inhibitors are limited by drug resistance and toxicity. Ponatinib, a third-generation inhibitor, has demonstrated excellent efficacy against both wild type and mutant BCR-ABL
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Build–Couple–Transform: A Paradigm for Lead-like Library Synthesis with Scaffold Diversity J. Med. Chem. (IF 8.039) Pub Date : 2022-08-09 Mélanie Uguen, Gemma Davison, Lukas J. Sprenger, James H. Hunter, Mathew P. Martin, Shannon Turberville, Jessica E. Watt, Bernard T. Golding, Martin E. M. Noble, Hannah L. Stewart, Michael J. Waring
High-throughput screening provides one of the most common ways of finding hit compounds. Lead-like libraries, in particular, provide hits with compatible functional groups and vectors for structural elaboration and physical properties suitable for optimization. Library synthesis approaches can lead to a lack of chemical diversity because they employ parallel derivatization of common building blocks
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Iterative Optimization and Structure–Activity Relationship Studies of Oseltamivir Amino Derivatives as Potent and Selective Neuraminidase Inhibitors via Targeting 150-Cavity J. Med. Chem. (IF 8.039) Pub Date : 2022-08-08 Han Ju, Lingxin Hou, Fabao Zhao, Ying Zhang, Ruifang Jia, Laura Guizzo, Anna Bonomini, Jiwei Zhang, Zhen Gao, Ruipeng Liang, Chiara Bertagnin, Xiujie Kong, Xiuli Ma, Dongwei Kang, Arianna Loregian, Bing Huang, Xinyong Liu, Peng Zhan
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Rational Design and Optimization of m6A-RNA Demethylase FTO Inhibitors as Anticancer Agents J. Med. Chem. (IF 8.039) Pub Date : 2022-08-08 Sarah Huff, Indrasena Reddy Kummetha, Lingzhi Zhang, Lingling Wang, William Bray, Jiekai Yin, Vanessa Kelley, Yinsheng Wang, Tariq M. Rana
Aberrant regulation of N6-methyladenosine (m6A) RNA modification has been implicated in the progression of multiple diseases, including cancer. Previously, we identified a small molecule inhibitor of the m6A demethylase fat mass- and obesity-associated protein (FTO), which removes both m6A and N6,2′-O-dimethyladenosine (m6Am) RNA modifications. In this work, we describe the rational design and optimization
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Positron Emission Tomography (PET) Imaging Tracers for Serotonin Receptors J. Med. Chem. (IF 8.039) Pub Date : 2022-08-08 Hualong Fu, Jian Rong, Zhen Chen, Jingyin Zhou, Thomas Collier, Steven H. Liang
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Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13 J. Med. Chem. (IF 8.039) Pub Date : 2022-08-08 Jianzhang Yang, Yu Chang, Jean Ching-Yi Tien, Zhen Wang, Yang Zhou, Pujuan Zhang, Weixue Huang, Josh Vo, Ingrid J. Apel, Cynthia Wang, Victoria Zhixuan Zeng, Yunhui Cheng, Shuqin Li, George Xiaoju Wang, Arul M. Chinnaiyan, Ke Ding
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Discovery of SPH3127: A Novel, Highly Potent, and Orally Active Direct Renin Inhibitor J. Med. Chem. (IF 8.039) Pub Date : 2022-08-08 Daisuke Iijima, Hiroshi Sugama, Yoichi Takahashi, Miki Hirai, Yuko Togashi, Jianshu Xie, Jingkang Shen, Ying Ke, Hidenori Akatsuka, Takayuki Kawaguchi, Kei Takedomi, Akiko Kashima, Masashi Nishio, Yosuke Inui, Hikaru Yoneda, Guangxin Xia, Toru Iijima
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Discovery of 1-(Hetero)aryl-β-carboline Derivatives as IDO1/TDO Dual Inhibitors with Antidepressant Activity J. Med. Chem. (IF 8.039) Pub Date : 2022-08-07 Yu Zhang, Yingchun Li, Xiang Chen, Xuan Chen, Chao Chen, Li Wang, Xu Dong, Guoli Wang, Ruxin Gu, Fei Li, Feng Han, Dongyin Chen
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Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP J. Med. Chem. (IF 8.039) Pub Date : 2022-08-05 Arindom Pal, Sadakatali Gori, Seung-wan Yoo, Ajit G. Thomas, Ying Wu, Jacob Friedman, Lukáš Tenora, Harshit Bhasin, Jesse Alt, Norman Haughey, Barbara S. Slusher, Rana Rais
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GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1 J. Med. Chem. (IF 8.039) Pub Date : 2022-08-05 Alexander M. Taylor, Chris Bailey, Lisa D. Belmont, Robert Campbell, Nico Cantone, Alexandre Côté, Terry D. Crawford, Richard Cummings, Kevin DeMent, Martin Duplessis, Megan Flynn, Andrew C. Good, Hon-Ren Huang, Shivangi Joshi, Yves Leblanc, Jeremy Murray, Christopher G. Nasveschuk, Adrianne Neiss, Florence Poy, F. Anthony Romero, Peter Sandy, Yong Tang, Vickie Tsui, Laura Zawadzke, Robert J. Sims
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Unveiling the Structure–Activity Relationships at the Orthosteric Binding Site of P2X Ion Channels: The Route to Selectivity J. Med. Chem. (IF 8.039) Pub Date : 2022-08-05 Andreas Isaak, Clemens Dobelmann, Friederike Theresa Füsser, Katharina Sophie Erlitz, Oliver Koch, Anna Junker
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N-Arylimidazoliums as Highly Selective Biomimetic Antimicrobial Agents J. Med. Chem. (IF 8.039) Pub Date : 2022-08-05 Qunshou Kong, Gaocan Li, Fanjun Zhang, Tao Yu, Xiaotong Chen, Qing Jiang, Yunbing Wang
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Design and Validation of the First Family of Photo-Activatable Ligands for Melatonin Receptors J. Med. Chem. (IF 8.039) Pub Date : 2022-08-05 Gloria Somalo-Barranco, Carme Serra, David Lyons, Hugh D. Piggins, Ralf Jockers, Amadeu Llebaria
Melatonin is a neurohormone released in a circadian manner with peak levels at night. Melatonin mediates its effects mainly through G protein-coupled MT1 and MT2 receptors. Drugs acting on melatonin receptors are indicated for circadian rhythm- and sleep-related disorders. Tools to study the activation of these receptors with high temporal resolution are lacking. Here, we synthesized a family of light-activatable
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Discovery of Small-Molecule Degraders of the CDK9-Cyclin T1 Complex for Targeting Transcriptional Addiction in Prostate Cancer J. Med. Chem. (IF 8.039) Pub Date : 2022-08-04 Jiacheng Li, Ting Liu, Yuanli Song, Mingyu Wang, Liping Liu, Hongwen Zhu, Qi Li, Jin Lin, Hualiang Jiang, Kaixian Chen, Kehao Zhao, Mingliang Wang, Hu Zhou, Hua Lin, Cheng Luo
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Discovery and Mechanistic Study of Mycobacterium tuberculosis PafA Inhibitors J. Med. Chem. (IF 8.039) Pub Date : 2022-08-04 Cong Li, Song Liu, Baoyu Dong, Chungen Li, Lunan Jian, Juan He, Jumei Zeng, Qiao Zhou, Da Jia, Youfu Luo, Qingxiang Sun
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Discovery of a Novel Vascular Disrupting Agent Inhibiting Tubulin Polymerization and HDACs with Potent Antitumor Effects J. Med. Chem. (IF 8.039) Pub Date : 2022-08-04 Huajian Zhu, Yuchen Tan, Chen He, Yang Liu, Yiping Duan, Wenjian Zhu, Tiandong Zheng, Dahong Li, Jinyi Xu, Dong-Hua Yang, Zhe-Sheng Chen, Shengtao Xu
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N-Heterocyclic 3-Pyridyl Carboxamide Inhibitors of DHODH for the Treatment of Acute Myelogenous Leukemia J. Med. Chem. (IF 8.039) Pub Date : 2022-08-04 Justin S. Cisar, Christine Pietsch, Lindsey G. DeRatt, Edgar Jacoby, Faraz Kazmi, Colleen Keohane, Katie Legenski, Rosalie Matico, Paul Shaffer, Yvan Simonnet, Alexandra Tanner, Chao-Yuan Wang, Weixue Wang, Ricardo Attar, James P. Edwards, Scott D. Kuduk
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Sodium-Glucose Cotransporter Inhibitors as Antidiabetic Drugs: Current Development and Future Perspectives J. Med. Chem. (IF 8.039) Pub Date : 2022-08-04 Rosanna Maccari, Rosaria Ottanà
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Discovery of Novel 7-Hydroxy-5-oxo-4,5-dihydrothieno[3,2-b]pyridine-6-carboxamide Derivatives with Potent and Selective Antifungal Activity against Cryptococcus Species J. Med. Chem. (IF 8.039) Pub Date : 2022-08-03 Liping Li, Hao Wu, Shuo Zhu, Zhe Ji, Xiaochen Chi, Fei Xie, Yumeng Hao, Hui Lu, Feng Yang, Lan Yan, Dazhi Zhang, Yuanying Jiang, Tingjunhong Ni
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Structure-Based Design of Xanthine-Benzimidazole Derivatives as Novel and Potent Tryptophan Hydroxylase Inhibitors J. Med. Chem. (IF 8.039) Pub Date : 2022-08-03 Edgar Specker, Susann Matthes, Radoslaw Wesolowski, Anja Schütz, Maik Grohmann, Natalia Alenina, Dirk Pleimes, Keven Mallow, Martin Neuenschwander, Angelina Gogolin, Marie Weise, Jochen Pfeifer, Nandor Ziebart, Udo Heinemann, Jens Peter von Kries, Marc Nazaré, Michael Bader
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Lysine-Tethered Stable Bicyclic Cationic Antimicrobial Peptide Combats Bacterial Infection in Vivo J. Med. Chem. (IF 8.039) Pub Date : 2022-08-03 Tong He, Lei Xu, Yuchen Hu, Xiaomin Tang, Rui Qu, Xuejun Zhao, Hao Bai, Lixian Li, Wanyi Chen, Guangli Luo, Gang Fu, Wei Wang, Xuefeng Xia, Jinqiang Zhang
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Boosting Protein–Ligand Binding Pose Prediction and Virtual Screening Based on Residue–Atom Distance Likelihood Potential and Graph Transformer J. Med. Chem. (IF 8.039) Pub Date : 2022-08-02 Chao Shen, Xujun Zhang, Yafeng Deng, Junbo Gao, Dong Wang, Lei Xu, Peichen Pan, Tingjun Hou, Yu Kang
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Nucleic-Acid-Based Targeted Degradation in Drug Discovery J. Med. Chem. (IF 8.039) Pub Date : 2022-08-02 Wei Wang, Shipeng He, Guoqiang Dong, Chunquan Sheng
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Design, Synthesis, and Biological Evaluation of Pyrrole-2-carboxamide Derivatives as Mycobacterial Membrane Protein Large 3 Inhibitors for Treating Drug-Resistant Tuberculosis J. Med. Chem. (IF 8.039) Pub Date : 2022-08-01 Hongyi Zhao, Yongxin Gao, Wei Li, Li Sheng, Keli Cui, Bin Wang, Lei Fu, Meng Gao, Ziyun Lin, Xiaowen Zou, Mary Jackson, Haihong Huang, Yu Lu, Dongfeng Zhang
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Protein Lysine Methyltransferase SMYD2: A Promising Small Molecule Target for Cancer Therapy J. Med. Chem. (IF 8.039) Pub Date : 2022-08-01 Quan Zheng, Wen Zhang, Guo-Wu Rao
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Ruthenium(II)–Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis J. Med. Chem. (IF 8.039) Pub Date : 2022-08-01 Jakub Cervinka, Alberto Gobbo, Lorenzo Biancalana, Lenka Markova, Vojtech Novohradsky, Massimo Guelfi, Stefano Zacchini, Jana Kasparkova, Viktor Brabec, Fabio Marchetti
While ruthenium arene complexes have been widely investigated for their medicinal potential, studies on homologous compounds containing a tridentate tris(1-pyrazolyl)methane ligand are almost absent in the literature. Ruthenium(II) complex 1 was obtained by a modified reported procedure; then, the reactions with a series of organic molecules (L) in boiling alcohol afforded novel complexes 2–9 in 77–99%
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Optimization of Covalent MKK7 Inhibitors via Crude Nanomole-Scale Libraries J. Med. Chem. (IF 8.039) Pub Date : 2022-07-30 Paul Gehrtz, Shir Marom, Mike Bührmann, Julia Hardick, Silke Kleinbölting, Amit Shraga, Christian Dubiella, Ronen Gabizon, Jan N. Wiese, Matthias P. Müller, Galit Cohen, Ilana Babaev, Khriesto Shurrush, Liat Avram, Efrat Resnick, Haim Barr, Daniel Rauh, Nir London
High-throughput nanomole-scale synthesis allows for late-stage functionalization (LSF) of compounds in an efficient and economical manner. Here, we demonstrated that copper-catalyzed azide–alkyne cycloaddition could be used for the LSF of covalent kinase inhibitors at the nanoscale, enabling the synthesis of hundreds of compounds that did not require purification for biological assay screening, thus
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Peptide-to-Small Molecule: A Pharmacophore-Guided Small Molecule Lead Generation Strategy from High-Affinity Macrocyclic Peptides J. Med. Chem. (IF 8.039) Pub Date : 2022-07-29 Shuhei Yoshida, Shota Uehara, Noriyasu Kondo, Yu Takahashi, Shiho Yamamoto, Atsushi Kameda, Soichiro Kawagoe, Naoko Inoue, Masami Yamada, Norito Yoshimura, Yuki Tachibana
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Discovery of Clinical Candidate CHF-6366: A Novel Super-soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases J. Med. Chem. (IF 8.039) Pub Date : 2022-07-28 Laura Carzaniga, Ian D. Linney, Andrea Rizzi, Maurizio Delcanale, Wolfgang Schmidt, Christopher K. Knight, Fiorella Pastore, Daniela Miglietta, Chiara Carnini, Nicola Cesari, Benedetta Riccardi, Valentina Mileo, Luca Venturi, Elisa Moretti, Wesley P. Blackaby, Riccardo Patacchini, Alessandro Accetta, Matteo Biagetti, Franco Bassani, Marina Tondelli, Annalisa Murgo, Loredana Battipaglia, Gino Villetti
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SLL-627 Is a Highly Selective and Potent κ Opioid Receptor (KOR) Agonist with an Unexpected Nonreduction in Locomotor Activity J. Med. Chem. (IF 8.039) Pub Date : 2022-07-28 Linghui Kong, Xuelian Shu, Siyuan Tang, Rongrong Ye, Huijiao Sun, Shuang Jiang, Zixiang Li, Jingrui Chai, Yun Fang, Yinjie Lan, Linqian Yu, Qiong Xie, Wei Fu, Yujun Wang, Wei Li, Zhuibai Qiu, Jinggen Liu, Liming Shao
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DEAD-Box Helicase DDX3X as a Host Target against Emerging Viruses: New Insights for Medicinal Chemical Approaches J. Med. Chem. (IF 8.039) Pub Date : 2022-07-28 Annalaura Brai, Claudia Immacolata Trivisani, Federica Poggialini, Claudia Pasqualini, Chiara Vagaggini, Elena Dreassi
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Correction to “Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis” J. Med. Chem. (IF 8.039) Pub Date : 2022-07-27 Abdellah Ezzanad, Ricardo Gómez-Oliva, Felipe Escobar-Montaño, Mónica Díez-Salguero, Noelia Geribaldi-Doldan, Samuel Dominguez-Garcia, José Manuel Botubol-Ares, Carolina de los Reyes, Rosa Durán-Patrón, Pedro Nunez-Abades, Antonio J. Macías-Sánchez, Carmen Castro, Rosario Hernández-Galán
The δC value for carbon 4′ of compound 10 was incorrect, and one of the funding sources (and associated grant proposal code) was omitted. Therefore, we provide here a correct value for the δC-4′ (19.4 ppm) in a corrected version of Table 1. We also provide the missing funding source and grant number. 1H NMR (600 MHz, CD3OD). 13C NMR (151 MHz, CD3OD). 1H NMR (500 MHz, CD3OD). 13C NMR (126 MHz, CD3OD)
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Discovery of a First-in-Class Degrader for Nuclear Receptor Binding SET Domain Protein 2 (NSD2) and Ikaros/Aiolos J. Med. Chem. (IF 8.039) Pub Date : 2022-07-27 Fanye Meng, Chenxi Xu, Kwang-Su Park, H. Ümit Kaniskan, Gang Greg Wang, Jian Jin
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Inhibition of Metastasis by Polypyridyl Ru(II) Complexes through Modification of Cancer Cell Adhesion – In Vitro Functional and Molecular Studies J. Med. Chem. (IF 8.039) Pub Date : 2022-07-27 Ilona Gurgul, Ewelina Janczy-Cempa, Olga Mazuryk, Małgorzata Lekka, Michał Łomzik, Franck Suzenet, Philippe C. Gros, Małgorzata Brindell
The effect of polypyridyl Ru(II) complexes on the ability of cancer cells to migrate and invade, two features important in the formation of metastases, is evaluated. In vitro studies are carried out on breast cancer cell lines, MDA-MB-231 and MCF-7, as well as melanoma cell lines A2058 and A375. Three Ru(II) complexes comprising two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and as a third ligand
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Targeting Human CD22/Siglec-2 with Dimeric Sialosides as Novel Oligosaccharide Mimetics J. Med. Chem. (IF 8.039) Pub Date : 2022-07-26 Horst Prescher, Astrid Schweizer, Martin Frank, Elena Kuhfeldt, Julia Ring, Lars Nitschke
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Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors J. Med. Chem. (IF 8.039) Pub Date : 2022-07-26 Shengrong Li, Pengwei Zhang, Fang Xu, Shengcao Hu, Jiacong Liu, Yi Tan, Zhengchao Tu, Hongyan Sun, Zhi-Min Zhang, Qing-Yu He, Pinghua Sun, Ke Ding, Zhengqiu Li
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Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306 J. Med. Chem. (IF 8.039) Pub Date : 2022-07-26 Janek Szychowski, Robert Papp, Evelyne Dietrich, Bingcan Liu, Frédéric Vallée, Marie-Eve Leclaire, Jimmy Fourtounis, Giovanni Martino, Alexander L. Perryman, Victor Pau, Shou Yun Yin, Pavel Mader, Anne Roulston, Jean-Francois Truchon, C. Gary Marshall, Mohamed Diallo, Nicole M. Duffy, Rino Stocco, Claude Godbout, Alexanne Bonneau-Fortin, Rosie Kryczka, Vivek Bhaskaran, Daniel Mao, Stephen Orlicky,
PKMYT1 is a regulator of CDK1 phosphorylation and is a compelling therapeutic target for the treatment of certain types of DNA damage response cancers due to its established synthetic lethal relationship with CCNE1 amplification. To date, no selective inhibitors have been reported for this kinase that would allow for investigation of the pharmacological role of PKMYT1. To address this need compound
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Targeting Undruggable Transcription Factors with PROTACs: Advances and Perspectives J. Med. Chem. (IF 8.039) Pub Date : 2022-07-26 Yan Li, Jian Song, Ping Zhou, Jun Zhou, Songbo Xie