Medicinal chemistry articles within Nature

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  • Article
    | Open Access

    Unimolecular integration of NMDA receptor antagonism with GLP-1 receptor agonism effectively reverses obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease.

    • Jonas Petersen
    • , Mette Q. Ludwig
    •  & Christoffer Clemmensen

  • Article
    | Open Access

    Accuracy of free-energy calculations can be improved by constructing an experimental benchmark for solid–solid free-energy differences, quantifying statistical errors for the computed free energies and placing both hydrate and anhydrate crystal structures on the same energy landscape.

    • Dzmitry Firaha
    • , Yifei Michelle Liu
    •  & Marcus A. Neumann

  • Article |

    A new type of transformation converting a heteroaromatic carbon atom into a nitrogen atom, turning quinolines into quinazolines to enable manipulation of molecular properties, is reported.

    • Jisoo Woo
    • , Colin Stein
    •  & Mark D. Levin

  • Article |

    Bitopic functionalized ligands based on fentanyl can target the sodium ion-binding site of the mu-opioid receptor and selectively modulate downstream signalling pathways, potentially leading to safer analgesics.

    • Abdelfattah Faouzi
    • , Haoqing Wang
    •  & Susruta Majumdar

  • Article
    | Open Access

    The superchaotropic nature of globular boron cluster anions enables direct passage of a wide range of molecules across lipid membranes.

    • Andrea Barba-Bon
    • , Giulia Salluce
    •  & Werner M. Nau

  • Article |

    A synthetic strategy for the stereoselective preparation of sulfinate esters and related sulfur stereogenic centres via asymmetric condensation expands the drug discovery toolbox for these compounds.

    • Xin Zhang
    • , Esther Cai Xia Ang
    •  & Choon-Hong Tan

  • Article |

    A lead-optimization strategy combining porin permeation properties and biochemical potency leads to development of a new class of antibiotic based on broad inhibition of penicillin-binding proteins from Gram-negative bacteria.

    • Thomas F. Durand-Reville
    • , Alita A. Miller
    •  & Ruben A. Tommasi

  • Article |

    Psychedelic alkaloids served as lead structures for the development of tabernanthalog, a non-hallucinogenic and non-toxic analogue that reduces alcohol- and heroin-seeking behaviour and produces antidepressant-like effects in rodents.

    • Lindsay P. Cameron
    • , Robert J. Tombari
    •  & David E. Olson

  • Article |

    Modular synthesis and structural biology are used to design and characterize group A streptogramin antibiotics, one of which has activity against streptogramin-resistant strains and demonstrates efficacy in a mouse model of bacterial infection.

    • Qi Li
    • , Jenna Pellegrino
    •  & Ian B. Seiple

  • Article |

    A manganese-catalysed oxidative C(sp3)–H methylation method allows a methyl group to be selectively installed into medicinally important heterocycles, providing a way to improve pharmaceuticals and better understand the ‘magic methyl effect’.

    • Kaibo Feng
    • , Raundi E. Quevedo
    •  & M. Christina White

  • Article |

    The MYST acetyltransferase HBO1 is a critical regulator in maintaining leukaemia stem cells, and a small-molecule inhibitor of HBO1 is developed that shows efficacy against a range of acute myeloid leukaemia cells.

    • Laura MacPherson
    • , Juliana Anokye
    •  & Mark A. Dawson

  • Article |

    High-resolution crystal structures of the rat succinate receptor SUCNR1 in an inactive confirmation, and the humanized rat SUCNR1 bound to an antagonist, provide insights into the structure of these receptors and the species selectivity of antagonist binding.

    • Matthias Haffke
    • , Dominique Fehlmann
    •  & Veli-Pekka Jaakola

  • Article |

    A class of chimeric synthetic antibiotics that bind to lipopolysaccharide and BamA shows potent activity against multidrug-resistant Gram-negative bacteria, with the potential to address life-threatening infections.

    • Anatol Luther
    • , Matthias Urfer
    •  & Daniel Obrecht

  • Article |

    Using a make-on-demand library that contains hundreds-of-millions of molecules, structure-based docking was used to identify compounds that, after synthesis and testing, are shown to interact with AmpC β-lactamase and the D4 dopamine receptor with high affinity.

    • Jiankun Lyu
    • , Sheng Wang
    •  & John J. Irwin

  • Letter |

    A system that combines nanoscale synthesis and affinity ranking enables high-throughput screening of reaction conditions and bioactivity for a given protein target, accelerating the process of drug discovery.

    • Nathan J. Gesmundo
    • , Bérengère Sauvagnat
    •  & Tim Cernak

  • Letter |

    Crystal structures of the human cannabinoid receptor 1 (CB1) bound to the agonists AM11542 and AM841 reveal notable structural rearrangements upon receptor activation, and this flexibility may be a common feature among other G-protein-coupled receptors.

    • Tian Hua
    • , Kiran Vemuri
    •  & Zhi-Jie Liu

  • Article |

    Crystal structures of two complexes of the angiotensin II receptor AT2R with distinct tightly bound ligands reveal an active-like state of the receptor, in which helix VIII adopts a non-canonical position that blocks binding of G proteins and β-arrestins.

    • Haitao Zhang
    • , Gye Won Han
    •  & Vadim Cherezov

  • Article |

    The bicyclic azetidines, a class of potent, well-tolerated antimalarial compounds that is active against multiple stages of the Plasmodium life-cycle, has been discovered following screens against libraries of compounds reminiscent of natural products.

    • Nobutaka Kato
    • , Eamon Comer
    •  & Stuart L. Schreiber

  • Letter |

    A selective inhibitor of the kinetoplastid proteasome (GNF6702) is identified that is highly efficacious in vivo, clearing the parasites that cause leishmaniasis, Chagas disease and sleeping sickness from mice, highlighting the possibility of developing a single class of drugs for these neglected diseases.

    • Shilpi Khare
    • , Advait S. Nagle
    •  & Frantisek Supek

  • Article |

    The description of a compound (DDD107498) with antimalarial activity against multiple life-cycle stages of Plasmodium falciparum and good pharmacokinetic and safety properties, with potential for single-dose treatment, chemoprotection and prevention of transmission.

    • Beatriz Baragaña
    • , Irene Hallyburton
    •  & Ian H. Gilbert

  • Article |

    An automated approach designing drug ligands to multi-target profiles (with a 75% prediction success rate) is experimentally validated by the invention of novel ligands tailored to the complex and physiologically-relevant goal of identifying drugs that can specifically target profiles of multiple proteins.

    • Jérémy Besnard
    • , Gian Filippo Ruda
    •  & Andrew L. Hopkins

  • Article |

    The X-ray crystal structure of the human G-protein-coupled receptor protease-activated receptor 1 (PAR1) bound to the antagonist vorapaxar is solved, revealing an unusual method of drug binding that should facilitate the development of improved PAR1-selective antagonists.

    • Cheng Zhang
    • , Yoga Srinivasan
    •  & Brian K. Kobilka

  • News & Views |

    Reagents have been developed that allow carbon—hydrogen bonds on benzene-like compounds called heterocycles to be converted directly into carbon—carbon bonds. The finding will be a boon to medicinal chemists. See Letter p.95

    • William J. Pitts

  • News & Views |

    Developing therapeutic drugs that target peptide receptors is challenging. The structure of one of these G-protein-coupled receptors, NTS1, activated and bound to a peptide, provides an excellent starting point. See Article p.508

    • Felix Hausch
    •  & Florian Holsboer

  • Outlook |

    Several new drugs for treating chronic obstructive pulmonary disease are about to hit the market, with more in the pipeline.

    • Duncan Graham-Rowe

  • News & Views |

    Biochemicals known as prostaglandins are challenging targets for synthetic organic chemistry. Yet by channelling the reactivity of a simple reactant, a powerful synthesis of one such compound has been achieved. See Letter p.278

    • Erik J. Sorensen

  • Editorial |

    Legal actions and oversight are necessary to keep the drug industry in line.

  • News |

    As approvals for engineered food animals stall, pigs may be US regulators’ next challenge.

    • Amy Maxmen

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