Back in Person: Frontiers in Medicinal Chemistry 2023

The Frontiers in Medicinal Chemistry (FiMC) is the largest international Medicinal Chemistry conference in the German speaking area and took place from April 3rd to 5th 2023 in Vienna (Austria). Fortunately, after being cancelled in 2020 and two years (2021-2022) of entirely virtual meetings, due to the COVID-19 pandemic, the FiMC could be held in a face-to-face format again. Organized by the Division of Medicinal Chemistry of the German Chemical Society (GDCh), the Division of Pharmaceutical and Medicinal Chemistry of the German Pharmaceutical Society (DPhG), together with the Division of Medicinal Chemistry of the Austrian Chemical Society (GÖCH), the Austrian Pharmaceutical Society (ÖPhG), and a local organization committee from the University of Vienna headed by Thierry Langer, the meeting brought together 260 participants from 21 countries. The program included 38 lectures by leading scientists from industry and academia as well as early career investigators. Moreover, 102 posters were presented in two highly interactive poster sessions.

[1]  Lukas Zeisel,et al.  Cyclic Dichalcogenides Extend the Reach of Bioreductive Prodrugs to Harness Thiol/Disulfide Oxidoreductases: Applications to seco-Duocarmycins Targeting the Thioredoxin System , 2023, ACS central science.

[2]  E. Salah,et al.  Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine , 2023, Journal of medicinal chemistry.

[3]  G. Wang,et al.  Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of mTORC1, for the Treatment of mTORC1-Activated Tumors , 2022, Journal of medicinal chemistry.

[4]  P. Bogner,et al.  BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor , 2022, Journal of medicinal chemistry.

[5]  A. Borkhardt,et al.  Solid-Phase Synthesis of Cereblon-Recruiting Selective Histone Deacetylase 6 Degraders (HDAC6 PROTACs) with Antileukemic Activity. , 2022, Journal of medicinal chemistry.

[6]  C. Lemmen,et al.  Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors , 2022, Nature Communications.

[7]  A. Waterson,et al.  Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRASG12C Inhibitor , 2022, Journal of medicinal chemistry.

[8]  D. Kaldre,et al.  Inverse hydride shuttle catalysis enables the stereoselective one-step synthesis of complex frameworks , 2022, Nature Chemistry.

[9]  S. Wessler,et al.  Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases , 2022, Journal of medicinal chemistry.

[10]  D. Ricklin,et al.  Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors , 2022, Nature Communications.

[11]  D. Leonori,et al.  Photoexcited nitroarenes for the oxidative cleavage of alkenes , 2022, Nature.

[12]  K. Houk,et al.  A concise synthesis of tetrodotoxin , 2022, Science.

[13]  M. Windbergs,et al.  Discovery of Inhibitors of DNA Methyltransferase 2, an Epitranscriptomic Modulator and Potential Target for Cancer Treatment. , 2022, Journal of medicinal chemistry.

[14]  M. Schiedel,et al.  Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the Chemokine Receptor CCR2. , 2022, ACS chemical biology.

[15]  Jérémy Merad,et al.  Direct Stereodivergent Olefination of Carbonyl Compounds with Sulfur Ylides , 2022, Journal of the American Chemical Society.

[16]  A. Rentmeister,et al.  Photocaged 5′ cap analogues for optical control of mRNA translation in cells , 2022, Nature Chemistry.

[17]  K. Ashe,et al.  Caspase-2 Inhibitor Blocks Tau Truncation and Restores Excitatory Neurotransmission in Neurons Modeling FTDP-17 Tauopathy. , 2022, ACS chemical neuroscience.

[18]  M. Bischoff,et al.  Regio‐ and Stereoselective Epoxidation and Acidic Epoxide Opening of Antibacterial and Antiplasmodial Chlorotonils Yield Highly Potent Derivatives , 2022, Angewandte Chemie.

[19]  Hana Imrichová,et al.  Functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders , 2022, bioRxiv.

[20]  A. Rentmeister,et al.  Chemo-Enzymatic Modification of the 5' Cap To Study mRNAs. , 2022, Accounts of chemical research.

[21]  H. Natsugari,et al.  Axial chirality and affinity at the GABAA receptor of triazolobenzodiazepines. , 2022, Bioorganic & medicinal chemistry.

[22]  Y. Orba,et al.  Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19 , 2022, Journal of medicinal chemistry.

[23]  Julian E. Fuchs,et al.  A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo , 2022, Nature Communications.

[24]  C. Schofield,et al.  Mass Spectrometric Assays Reveal Discrepancies in Inhibition Profiles for the SARS‐CoV‐2 Papain‐Like Protease , 2022, ChemMedChem.

[25]  John D Lambris,et al.  Compstatins: the dawn of clinical C3-targeted complement inhibition. , 2022, Trends in pharmacological sciences.

[26]  E. Kostenis,et al.  A Chemical Biology Toolbox Targeting the Intracellular Binding Site of CCR9: Fluorescent Ligands, New Drug Leads and PROTACs , 2021, Angewandte Chemie.

[27]  M. Dreyer,et al.  Rational Design of Highly Potent, Selective, and Bioavailable SGK1 Protein Kinase Inhibitors for the Treatment of Osteoarthritis. , 2021, Journal of medicinal chemistry.

[28]  R. Hartmann,et al.  Substrate‐Inspired Fragment Merging and Growing Affords Efficacious LasB Inhibitors , 2021, Angewandte Chemie.

[29]  H. Natsugari,et al.  Atropisomeric Properties of 9-Methyl-1,4-benzodiazepin-2-ones , 2021, Synthesis.

[30]  D. Trauner,et al.  Photoswitchable Serotonins for Optical Control of the 5-HT2A Receptor. , 2021, Angewandte Chemie.

[31]  Sheridan M. Hoy.  Pegcetacoplan: First Approval , 2021, Drugs.

[32]  K. Gajiwala,et al.  An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19 , 2021, Science.

[33]  M. Bogyo,et al.  Selective activation of PFKL suppresses the phagocytic oxidative burst , 2021, Cell.

[34]  S. Knapp,et al.  Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2) , 2021, Cancers.

[35]  E. Isacoff,et al.  Selective Photoswitchable Allosteric Agonist of a G Protein-Coupled Receptor , 2021, Journal of the American Chemical Society.

[36]  K. Becker,et al.  Selective, Modular Probes for Thioredoxins Enabled by Rational Tuning of a Unique Disulfide Structure Motif. , 2021, Journal of the American Chemical Society.

[37]  J. Kim,et al.  A radical approach for the selective C–H borylation of azines , 2021, Nature.

[38]  Andrew J. Bannister,et al.  Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia , 2021, Nature.

[39]  M. Steinmetz,et al.  In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M , 2021, bioRxiv.

[40]  G. Wolber,et al.  Chemical Evolution of Antivirals Against Enterovirus D68 through Protein‐Templated Knoevenagel Reactions , 2021, Angewandte Chemie.

[41]  R. Hartmann,et al.  Phosphonate as Stable Zinc-binding Group for Inhibitors of Clostridial Collagenase H (ColH) as Pathoblocker Agents. , 2021, ChemMedChem.

[42]  P. Cramer,et al.  Small-molecule inhibitors of human mitochondrial DNA transcription , 2020, Nature.

[43]  M. Steinmetz,et al.  A Robust, GFP-Orthogonal Photoswitchable Inhibitor Scaffold Extends Optical Control over the Microtubule Cytoskeleton. , 2020, Cell chemical biology.

[44]  J. Meiler,et al.  Hydroxamic Acids Immobilized on Resins (HAIRs): Synthesis of Dual‐Targeting HDAC Inhibitors and HDAC Degraders (PROTACs) , 2020, Angewandte Chemie.

[45]  Christian N. Cunningham,et al.  Small Molecule Dysregulation of TEAD Lipidation Induces a Dominant-Negative Inhibition of Hippo Pathway Signaling. , 2020, Cell reports.

[46]  Julian E. Fuchs,et al.  PI by NMR: Probing CH–π Interactions in Protein–Ligand Complexes by NMR Spectroscopy , 2020, Angewandte Chemie.

[47]  Thomas M. Smith,et al.  Discovery of 4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases. , 2020, Journal of medicinal chemistry.

[48]  R. Müller,et al.  Production optimization and biosynthesis revision of corallopyronin A, a potent anti-filarial antibiotic. , 2019, Metabolic engineering.

[49]  William Farnaby,et al.  BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design , 2019, Nature Chemical Biology.

[50]  S. Laufer,et al.  Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology. , 2018, Journal of medicinal chemistry.

[51]  R. Hartmann,et al.  Targeted Endocrine Therapy: Design, Synthesis, and Proof-of-Principle of 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors in Bone Fracture Healing. , 2019, Journal of medicinal chemistry.

[52]  R. Hartmann,et al.  Highly Potent 17β-HSD2 Inhibitors with a Promising Pharmacokinetic Profile for Targeted Osteoporosis Therapy. , 2018, Journal of medicinal chemistry.

[53]  R. Krüger,et al.  Gasdermin D plays a vital role in the generation of neutrophil extracellular traps , 2018, Science Immunology.

[54]  R. Konrat,et al.  Late metabolic precursors for selective aromatic residue labeling , 2018, Journal of Biomolecular NMR.

[55]  M. Pérez,et al.  Caspase-Cleaved Tau Impairs Mitochondrial Dynamics in Alzheimer’s Disease , 2018, Molecular Neurobiology.

[56]  A. Kirschning,et al.  Discovery and Total Synthesis of Natural Cystobactamid Derivatives with Superior Activity against Gram-Negative Pathogens. , 2017, Angewandte Chemie.

[57]  Qingzhong Hu,et al.  Lead Optimization Generates CYP11B1 Inhibitors of Pyridylmethyl Isoxazole Type with Improved Pharmacological Profile for the Treatment of Cushing's Disease. , 2017, Journal of medicinal chemistry.

[58]  K. Zahs,et al.  Caspase-2 cleavage of tau reversibly impairs memory , 2016, Nature Medicine.

[59]  Elisa de Stanchina,et al.  Overcoming mTOR Resistance Mutations with a New Generation mTOR Inhibitor , 2016, Nature.

[60]  R. Müller,et al.  Cystobactamids: myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity. , 2014, Angewandte Chemie.

[61]  Qingzhong Hu,et al.  Potent 11β-hydroxylase inhibitors with inverse metabolic stability in human plasma and hepatic S9 fractions to promote wound healing. , 2014, Journal of medicinal chemistry.

[62]  R. Hartmann,et al.  Lead optimization of 17β-HSD1 inhibitors of the (hydroxyphenyl)naphthol sulfonamide type for the treatment of endometriosis. , 2012, Journal of medicinal chemistry.

[63]  R. Hartmann,et al.  In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives. , 2008, Journal of medicinal chemistry.

[64]  M. Gütschow,et al.  Azadipeptide nitriles: highly potent and proteolytically stable inhibitors of papain-like cysteine proteases. , 2008, Angewandte Chemie.

[65]  R. Hartmann,et al.  Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) for the treatment of estrogen-dependent diseases. , 2008, Journal of medicinal chemistry.

[66]  R. Hartmann,et al.  Aromatase inhibitors. Synthesis and evaluation of mammary tumor inhibiting activity of 3-alkylated 3-(4-aminophenyl)piperidine-2,6-diones. , 1986, Journal of medicinal chemistry.