Similarities in Bioanalogous Structural Transformation Patterns

In vivo high throughput screening (HTS) has been adopted by most of the larger crop protection companies as an important tool for the discovery of new agrochemicals. There has been a paradigm shift in capabilities from screening a few thousand compounds a year to several hundred thousand and the quantity of screening sample required has fallen dramatically. The unifying goal now bringing together screens and inputs is the need to maximise the flow of useful information from HTS and thereby minimise the time taken to discover robust leads and new products. This review examines the positive changes that have occurred towards targeted design and selection of chemical inputs for agrochemical discovery over the last ten years and corresponding developments in HTS assays, data analysis and the logistics of compound storage and dispensing.

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“…between heterocycles used in both insecticidal pyrethroids and herbicidal PPGO inhibitors [14] (Fig. 1).…”

Section: Selection Of 'Ag-like' Privileged Building Blocksmentioning

confidence: 99%

Targeting Chemical Inputs and Optimising HTS for Agrochemical Discovery

Smith¹,

Delaney²,

Robinson³

et al. 2005

CCHTS

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“…In general, a bioisostere is typically defined as a pair of substructures that exhibit similar physicochemical properties while also conveying similar biological properties to a molecule, and several reviews have been published on the topic. [3][4][5][6][7] However, the bioisostere is more accurately labeled as a concept as this definition is functionally inadequate.…”

Section: Introductionmentioning

confidence: 99%

Rationalizing Lead Optimization by Associating Quantitative Relevance with Molecular Structure Modification

Raymond

Watson

Mahoui

2009

J. Chem. Inf. Model.

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Historically, one of the characteristic activities of the medicinal chemist has been the iterative improvement of lead compounds until a suitable therapeutic entity is achieved. Often referred to as lead optimization, this process typically takes the form of minor structural modifications to an existing lead in an attempt to ameliorate deleterious attributes while simultaneously trying to maintain or improve desirable properties. The cumulative effect of this exercise performed over the course of several decades of pharmaceutical research by thousands of trained researchers has resulted in large collections of pharmaceutically relevant chemical structures. As far as the authors are aware, this work represents the first attempt to use that data to define a framework to quantifiably catalogue and summate this information into a medicinal chemistry expert system. A method is proposed that first comprehensively mines a compendium of chemical structures compiling the structural modifications, abridges them to rectify artificially inflated support levels, and then performs an association rule mining experiment to ascribe relative confidences to each transformation. The result is a catalogue of statistically relevant structural modifications that can potentially be used in a number of pharmaceutical applications.

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“…[2][3][4][5][6] Especially, the study for the change of heterocyclic group is actively working. 7 The common ones of eight types in hererocyclic group are cyclopentane, tetrahydrophthalimide and bicyclic five-membered heterocyclic analogues.…”

Section: Introductionmentioning

confidence: 99%

3D-QSARs of Herbicidal 2-N-Phenylisoindolin-1-one Analogues as a New Class of Potent Inhibitors of Protox

2009

Bulletin of the Korean Chemical Society

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3D-QSARs for the inhibition activities against protox by herbicidal 2-N-phenylisoindolin-1-one derivatives were studied quantitatively using CoMFA and CoMSIA methods. 0.909). Also, the relative contribution of the optimized CoMSIA model 2 showed the steric (24.6%), electrostatic (31.0%), hydrophobic (ClogP, 23.4%) and H-bond acceptor field (21.0%), respectively. From the results of the contour maps, the protox inhibition activities are expected to increase when steric favor and H-bond acceptor favor groups are substituted on R2 position and positive favor group are substituted on C2, C3, and C5 atom in phenyl ring of R2 position. And the inhibition activities are expected to increase when hydrophobic favor group is substituted on C1 and C3 atom in phenyl ring of R2 position and Cl atom of R1 position and hydrophilic favor groups are substituted on C4 atom in phenyl ring of R2 position and the terminal group of R1 position.

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Similarities in Bioanalogous Structural Transformation Patterns

Cited by 4 publications

References 0 publications

Targeting Chemical Inputs and Optimising HTS for Agrochemical Discovery

Targeting Chemical Inputs and Optimising HTS for Agrochemical Discovery

Rationalizing Lead Optimization by Associating Quantitative Relevance with Molecular Structure Modification

3D-QSARs of Herbicidal 2-N-Phenylisoindolin-1-one Analogues as a New Class of Potent Inhibitors of Protox

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