A divergent synthetic approach to diverse molecular scaffolds: assessment of lead-likeness using LLAMA, an open-access computational tool

Abstract

Complementary cyclisation reactions of hex-2-ene-1,6-diamine derivatives were exploited in the synthesis of alternative molecular scaffolds. The value of the synthetic approach was analysed using LLAMA, an open-access computational tool for assessing the lead-likeness and novelty of molecular scaffolds.

Design, Synthesis, and Phenotypic Profiling of Pyrano‐Furo‐Pyridone Pseudo Natural Products

“…In contrast, the NP-scores calculated for drugs and closely related molecules show substantial overlap with the majority of the PFP NP-scores, indicating that PFPs may have favorable physicochemical properties for potential drug discovery programs. [25] The vast majority of pseudo NPs (98 %, 158 out of 162 PFPs) fall into the Lipinskisr ule-of-five space [26] exhibiting an ALog P < 5a nd MW < 500 Da. [25] The vast majority of pseudo NPs (98 %, 158 out of 162 PFPs) fall into the Lipinskisr ule-of-five space [26] exhibiting an ALog P < 5a nd MW < 500 Da.…”

A Two‐Step Synthesis of 2‐Spiropiperidines

“…Recently it has been recognised that a very large proportion of these molecules are comparatively two‐dimensional structures containing a high proportion of sp and sp 2 ‐hybridised carbons, and hence, there has been a drive to develop new routes to access the relatively under‐explored sp 3 ‐rich area of chemical space . Consequently, several tools have been developed to assess the degree of three‐dimensionality of small molecules; these include principle moments of inertia (PMI) analysis, plane of best fit analysis and, more recently, lead likeness and molecular analysis (LLAMA) . There is a growing consensus that out of all the sp 3 ‐rich structural types spirocyclic molecules hold a privileged position, as they are conformationally well defined, which allows the functionality on the spirocycle to be elaborated in well‐defined directions .…”

ChemInform Abstract: Evaluating New Chemistry to Drive Molecular Discovery: Fit for Purpose?

“…Thei dentification of potential applications of new synthetic methods may be facilitated by computational tools for the enumeration and analysis of virtual libraries.H erein, we have used our open-access computational tool Lead Likeness And Molecular Analysis (LLAMA); [17] however, other openaccess tools (e.g., KNIME) [18] and many commercial tools are also available.S uch tools could also be used by synthetic chemistry researchers to select reactants that allow the full scope of their methods to be demonstrated. In most cases,we used as tandard set of typical medicinal chemistry capping groups to decorate the scaffolds (see the Supporting Information).…”

“…In most cases,we used as tandard set of typical medicinal chemistry capping groups to decorate the scaffolds (see the Supporting Information). [17] Attempts to capture performance against arange of molecular property measures have been made,for example in aC NS drug-likeness score, [19] am etric capturing the chemical beauty of drugs, [20] and alead-likeness penalty.…”