Solid-Phase Synthesis of Tetrahydro-1,4-benzodiazepine-2-one Derivatives as a β-Turn Peptidomimetic Library

Im, Il; Webb, Thomas R.; Gong, Young‐Dae; Kim, Jae-Il; Kim, Yong-Chul

doi:10.1021/cc034039m

Cited by 35 publications

(28 citation statements)

References 27 publications

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“…Kim reported the synthesis of β-turn mimetics based on the immobilization of the benzodiazepine building block and its subsequent modification on the solid phase [38]. The benzodiazepine derivative 90 was pre-synthesized in the solution phase in four steps from 2-nitro-5-hydroxybenzaldehyde 88.…”

Section: Tetrahydrobenzo[e][14]diazepin-2-onesmentioning

confidence: 99%

Solid-Phase Synthesis of Seven-Membered Heterocycles with Two Nitrogen Atoms

Fülöpová

Soural

2017

Topics in Heterocyclic Chemistry

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Due to the importance of diazepines and diazepanes in medicinal chemistry and chemical biology, their preparation from diverse starting materials has been frequently reported. In this chapter, we summarize all strategies employing the method of solid-phase synthesis. More than seventeen different types of target compounds are accessible. The individual approaches are grouped according to the type of the target scaffold.

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Section: Tetrahydrobenzo[e][14]diazepin-2-onesmentioning

confidence: 99%

Solid-Phase Synthesis of Seven-Membered Heterocycles with Two Nitrogen Atoms

Fülöpová

Soural

2017

Topics in Heterocyclic Chemistry

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“…This system was successfully used for peptide library purification, 163 as well as for low-weight molecule libraries. 164,165 A natural product library including several hundred compounds was effectively purified with the use of an updated FlashMaster II, 166 capable of 10 fully automated independent separations in one run (Figure 3.25).…”

Section: Characterization and Purificationmentioning

confidence: 99%

Practical Aspects of Combinatorial Solid‐Phase Synthesis

Hlaváč¹,

Soural²,

Krchňák³

2011

Solid‐Phase Organic Synthesis

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“…0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Loop cluster β-turn mimetic scaffolds The green horizontal bars represent data which support the hypothesis of structural matches that correlate with biological activity; the yellow bars are neutral and the red bar represents data that challenge the hypothesis The b-turn mimetic scaffold 17 [47][48][49] has an average RMSD of 0.43 and corresponds to one reported synthesis and activity in relation to corticotropin releasing factor (CRF) [80]. The b-turn mimetics 10 [38,39] and 11 [38,39] matched the loop clusters. The R-groups, R4, R2 and R1, of 10 are the only match (high RMS of 0.61) with the R-groups, R1, R2 and R4, of loop cluster 8.…”

Section: Biologically Relevant Descriptorsmentioning

confidence: 99%

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions

Tran

Kulis

Long

et al. 2010

J Comput Aided Mol Des

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Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

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Solid-Phase Synthesis of Tetrahydro-1,4-benzodiazepine-2-one Derivatives as a β-Turn Peptidomimetic Library

Cited by 35 publications

References 27 publications

Solid-Phase Synthesis of Seven-Membered Heterocycles with Two Nitrogen Atoms

Solid-Phase Synthesis of Seven-Membered Heterocycles with Two Nitrogen Atoms

Practical Aspects of Combinatorial Solid‐Phase Synthesis

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions

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