Design and synthesis of a fragment set based on twisted bicyclic lactams

Hassan, Haitham; Marsden, S. P.; Nelson, Adam

doi:10.1016/j.bmc.2018.02.027

Cited by 19 publications

(18 citation statements)

References 31 publications

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“…Nelson and co-workersd escribed the synthesis of at hree-dimensional fragment collectionb ased on twisted bicyclic lactam scaffolds. [224] Again, av ery limited set of key building blocks( i.e.,b icyclic lactamsb earing an additional functional group)w ere preparedand subjected to capping or heterocyclization reactions. Alternatively, the capping reactions could be also performed prior to the bicyclic lactam formation step.…”

Section: Compound Libraries Based On Npsmentioning

confidence: 99%

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

Grygorenko

Volochnyuk

Ryabukhin

et al. 2019

Chemistry A European J

135

123

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All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high‐quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity‐, biology‐, lead‐, or fragment‐oriented syntheses; and DNA‐encoded libraries) are critically surveyed.

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Section: Compound Libraries Based On Npsmentioning

confidence: 99%

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

Grygorenko

Volochnyuk

Ryabukhin

et al. 2019

Chemistry A European J

135

123

View full text Add to dashboard Cite

show abstract

“…In 2018, Marsden, Nelson and co-workers reported the synthesis of a set of bridged lactams with [3.3.1] and [4.3.1] scaffolds as part of their research on fragment-based drug discovery (Figure 11) [28]. This approach nicely utilizes the presence of an additional heteroatom in the twisted amide structure to facilitate the synthesis of starting materials.…”

Section: Synthesis Properties and Reactivity Of Bridged Lactamsmentioning

confidence: 99%

Chemistry of Bridged Lactams: Recent Developments

Szostak

2019

Molecules

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Bridged lactams represent the most effective and wide-ranging method of constraining the amide bond in a non-planar conformation. A previous comprehensive review on this topic was published in 2013 (Chem. Rev. 2013, 113, 5701–5765). In the present review, which is published as a part of the Special Issue on Amide Bond Activation, we present an overview of the recent developments in the field of bridged lactams that have taken place in the last five years and present a critical assessment of the current status of bridged lactams in synthetic and physical organic chemistry. This review covers the period from 2014 until the end of 2018 and is intended as an update to Chem. Rev. 2013, 113, 5701–5765. In addition to bridged lactams, the review covers recent advances in the chemistry of bridged sultams, bridged enamines and related non-planar structures.

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“…(A) Twigg et al ( 2016 ) DOS of partially saturated bicyclic heteroaromatic fragments. (B) Hassan et al ( 2018 ) DOS fragment library based on twisted amides. (C) Mateu et al ( 2018 ) DOS fragment library based on α,α-disubstituted amino esters.…”

Section: The Application Of Dos To Access Novel Fragments With Multipmentioning

confidence: 99%

“…Hassan et al recently disclosed an interesting example via the exploitation of twisted bicyclic amide compounds for the generation of a 3D fragment screening library (Hassan et al, 2018 ). In this work five 3-(ω-carboxylate)-substituted piperidine starting materials were manipulated to produce a 22-member polycyclic library (Figure 2B ).…”

Section: The Application Of Dos To Access Novel Fragments With Multipmentioning

confidence: 99%

Recent Applications of Diversity-Oriented Synthesis Toward Novel, 3-Dimensional Fragment Collections

et al. 2018

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Fragment-based drug discovery (FBDD) is a well-established approach for the discovery of novel medicines, illustrated by the approval of two FBBD-derived drugs. This methodology is based on the utilization of small “fragment” molecules (<300 Da) as starting points for drug discovery and optimization. Organic synthesis has been identified as a significant obstacle in FBDD, however, in particular owing to the lack of novel 3-dimensional (3D) fragment collections that feature useful synthetic vectors for modification of hit compounds. Diversity-oriented synthesis (DOS) is a synthetic strategy that aims to efficiently produce compound collections with high levels of structural diversity and three-dimensionality and is therefore well-suited for the construction of novel fragment collections. This Mini-Review highlights recent studies at the intersection of DOS and FBDD aiming to produce novel libraries of diverse, polycyclic, fragment-like compounds, and their application in fragment-based screening projects.

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Design and synthesis of a fragment set based on twisted bicyclic lactams

Cited by 19 publications

References 31 publications

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

Chemistry of Bridged Lactams: Recent Developments

Recent Applications of Diversity-Oriented Synthesis Toward Novel, 3-Dimensional Fragment Collections

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