{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gomez-Angel AR"],"funding":["Royal Society","European Commission","UK Research and Innovation"],"pagination":["29292-29303"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12356528"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["147(32)"],"pubmed_abstract":["Fragment-based drug discovery (FBDD) is a key strategy employed in the hit-to-lead phase of pharmaceutical development. The rate-limiting step of this process is often identifying and optimizing synthetic chemistry suitable for fragment elaboration, especially in three dimensions (3-D). To address this limitation, we herein present a modular platform for the systematic and programmable elaboration of two-dimensional (2-D) fragment hits into lead-like 3-D compounds, utilizing nine bifunctional building blocks that explore a range of vectors in 3-D. The building blocks comprise (i) rigid sp<sup>3</sup>-rich bicyclic cyclopropane-based structures to fix the vectors and (ii) two synthetic handles─a protected cyclic amine and a cyclopropyl <i>N-</i>methyliminodiacetic acid (MIDA) boronate. To v"],"journal":["Journal of the American Chemical Society"],"pubmed_title":["Modular Synthetic Platform for the Elaboration of Fragments in Three Dimensions for Fragment-Based Drug Discovery."],"pmcid":["PMC12356528"],"funding_grant_id":["675899, FRAGNET","INFR1191028","EP/V048139/1"],"pubmed_authors":["Donald JR","Palmer CJ","Lincoln J","Lucas SCC","Appiani R","Gomez-Angel AR","Yao SY","Fusani L","Klein HF","Firth JD","O'Brien P","Storer RI"],"additional_accession":[]},"is_claimable":false,"name":"Modular Synthetic Platform for the Elaboration of Fragments in Three Dimensions for Fragment-Based Drug Discovery.","description":"Fragment-based drug discovery (FBDD) is a key strategy employed in the hit-to-lead phase of pharmaceutical development. The rate-limiting step of this process is often identifying and optimizing synthetic chemistry suitable for fragment elaboration, especially in three dimensions (3-D). To address this limitation, we herein present a modular platform for the systematic and programmable elaboration of two-dimensional (2-D) fragment hits into lead-like 3-D compounds, utilizing nine bifunctional building blocks that explore a range of vectors in 3-D. The building blocks comprise (i) rigid sp<sup>3</sup>-rich bicyclic cyclopropane-based structures to fix the vectors and (ii) two synthetic handles─a protected cyclic amine and a cyclopropyl <i>N-</i>methyliminodiacetic acid (MIDA) boronate. To v","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-01T18:45:01.919Z","creation":"2026-04-07T17:09:33.511Z"},"accession":"S-EPMC12356528","cross_references":{"pubmed":["40737445"],"doi":["10.1021/jacs.5c08786"]}}