Solid-Phase Synthetic Route to Multiple Derivatives of a Fundamental Peptide Unit

Scott, William L.; Zhou, Ziniu; Zajdel, Paweł; Pawłowski, Maciej; O’Donnell, Martin J.

doi:10.3390/molecules15074961

Cited by 5 publications

(6 citation statements)

References 13 publications

(20 reference statements)

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“…The designed pilot library was obtained according to the multistep solid-phase synthesis protocol which took advantage from construction of 1,2,4-triazin-6(1H)-one moiety from the Fmoc-protected glycine. This approach extends solidsupported methods using amino acid residues as starting building blocks for construction of heterocyclic compounds (15).…”

Section: Resultsmentioning

confidence: 97%

“…General procedure for cleavage/cyclization (11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Solution of hydrazine monohydrate (30 eq, 2.4 mmol, 120 mg) in dioxane (1.5 mL) was added to resin-bound products 10 (125 mg each), and the reactors were placed at 90°C for 36 h. The filtrate was recovered, and the resin was washed with dioxane (3 9 1 mL). The combined fractions were subsequently evaporated under vacuum, dissolved in MeCN/H 2 O (50/50; v/v), and lyophilized to yield a white foam which was further purified using preparative liquid chromatograph coupled to mass spectrometer.…”

Section: Procedures For Alkylation Of Resin 3 With 1-bromo-4-chlorobutmentioning

confidence: 99%

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Solid‐Supported Synthesis and 5‐HT₇/5‐HT_1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

et al. 2015

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A series of arylpiperazinylbutyl derivatives of 4,5-dihydro-1,2,4-triazine-6(1H)-ones was designed and synthesized according to the new solid-supported methodology. In this approach, triazinone scaffold was constructed from the Fmoc-protected glycine. The library representatives showed different levels of affinity for 5-HT7 and 5-HT1A receptors; compounds 13, 14 and 18-20 were classified as dual 5-HT7 /5-HT1A receptors ligands. The structure-affinity relationship analysis revealed that the receptor affinity and selectivity of the tested compounds depended on the kind of substituent in position 3 of triazinone fragment as well as substitution pattern of the phenylpiperazine moiety.

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Section: Resultsmentioning

confidence: 97%

Section: Procedures For Alkylation Of Resin 3 With 1-bromo-4-chlorobutmentioning

confidence: 99%

Solid‐Supported Synthesis and 5‐HT₇/5‐HT_1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

et al. 2015

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“…Flexible synthetic routes are sought that increase the diversity of molecule types available to D3. We recently reported a solid-phase synthetic route to derivatives of the generic fundamental peptide unit 1 [5]. Many variations of R 1 , R 2 , and R 3 are permitted on this inherently biomimetic scaffold.…”

Section: Introductionmentioning

confidence: 99%

“…Many variations of R 1 , R 2 , and R 3 are permitted on this inherently biomimetic scaffold. We also published a synthetic route to 2 giving access to selective binding agents for subclasses of 5-hydroxytryptamine receptors [5,6,7]. Derivatives of scaffold 2 showed central nervous system activity [6].…”

Section: Introductionmentioning

confidence: 99%

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Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations

2016

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Abstract:A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to the Distributed Drug Discovery (D3) project. Using a BAL-based solid-phase synthetic sequence the proline or proline homologue subunit is both constructed and incorporated into the peptidomimetic by an α-alkylation, hydrolysis and intramolecular cyclization sequence. Further transformations on solid-phase provide access to a variety of piperazine derivatives representing a class of molecules known to exhibit central nervous system activity. The procedure works well with proline cores, but with larger six-and seven-membered ring homologues the nature of the carboxylic acid acylating the cyclic amine can lead to side reactions and result in poor overall yields.

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Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications

et al. 2021

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For almost 40 years, difluoromethylene phosphonates have proven to be versatile molecular tools in biochemical studies owing to their close resemblance to naturally occurring phosphates and phosphonates. As bioisosteric, non‐hydrolyzable analogs of these essential molecules, difluoromethylene phosphonates can target the critical parts of the cellular machinery and therefore exhibit a diverse spectrum of biological activity. In the past ten years, there have appeared many new methods for the synthesis of difluoromethylene phosphonates. Most notably, photoredox catalysis has firmly entered the field, while cross‐coupling and nucleophilic strategies have met considerable elaboration and refinement, entirely in accord with the current trends in synthetic organic chemistry. Herein, we introduce difluoromethylene phosphonates as a distinct, high‐tech subclass of synthetic phosphonates resulting from the research efforts on the cross‐section of organophosphorus, organofluorine, and bioorganic chemistry. We then proceed to the discussion of general methods for the preparation of difluoromethylene phosphonates, comprehensively reviewing reactions developed in the past 15 years while providing the context of earlier works where appropriate. Finally, we present selected examples of molecules with high biological activity, their biological targets, and the synthetic steps employed for their preparation.

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Solid-Phase Synthetic Route to Multiple Derivatives of a Fundamental Peptide Unit

Cited by 5 publications

References 13 publications

Solid‐Supported Synthesis and 5‐HT₇/5‐HT_1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

Solid‐Supported Synthesis and 5‐HT₇/5‐HT_1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations

Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications

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Solid-Phase Synthetic Route to Multiple Derivatives of a Fundamental Peptide Unit

Cited by 5 publications

References 13 publications

Solid‐Supported Synthesis and 5‐HT7/5‐HT1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

Solid‐Supported Synthesis and 5‐HT7/5‐HT1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations

Recent Advances in Synthesis of Difluoromethylene Phosphonates for Biological Applications

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Solid‐Supported Synthesis and 5‐HT₇/5‐HT_1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

Solid‐Supported Synthesis and 5‐HT₇/5‐HT_1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one