Synthesis of cyclic RGD derivatives via solid phase macrocyclization using the Heck reaction

Akaji, Kenichi; Teruya, Kenta; Akaji, Masako; Aimoto, S.

doi:10.1016/s0040-4020(01)00113-2

Cited by 36 publications

(23 citation statements)

References 35 publications

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“…88 Heck methodology was also employed in the solid phase construction of cyclic RGD peptidomimetic 126 (Scheme 2h). 89 Zapf and coworkers designed and synthesized the aminobased bridged benzannulated macrocyclic structure 129 via the Buchwald-Hartwig reaction (Scheme 2i). 90 Balraju and Iqbal also employed the Buchwald-Hartwig C-N coupling reaction for macrocyclization in the construction of bridged benzannulated macrocycle 131 constrained with a diphenylamine linker (Scheme 2j).…”

Section: Transition Metal Catalyzed Coupling Reactionsmentioning

confidence: 99%

Importance and synthesis of benzannulated medium-sized and macrocyclic rings (BMRs)

2014

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Cyclic molecular frameworks, especially the benzannulated medium-sized and macrocyclic ring (BMR) systems, constitute an integral component of a large number of biologically significant natural or synthetic molecules. Many of these BMR compounds are either approved as drugs or have reached the late developmental stages in clinical trials. Such cyclic systems have been shown to possess great potential, especially in the discovery of new anticancer leads. Efforts from synthetic chemists have led to the development of elegant new strategies for the construction of BMR scaffolds of medicinalimportance. This review intends to highlight the importance of benzannulated medium-sized and macrocyclic rings (BMRs) and the strategies developed over the years for their synthesis.

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Section: Transition Metal Catalyzed Coupling Reactionsmentioning

confidence: 99%

Importance and synthesis of benzannulated medium-sized and macrocyclic rings (BMRs)

2014

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“…(11)) [51]. Given their flexibility, these compounds displayed an aspecific activity against v 3 and IIb 3 receptors, which was in the nanomolar range when a -amino acid sugar was incorporated within the cycle (compounds (60) and (61)). This result was supported by the analysis of the 3D arrangement of the most active compound (61), which was found to lie between the typical kinked conformation of v 3 -selective antagonists and the extended one required for targeting IIb 3 integrin.…”

Section: Rgd-based Semipeptides Containing Monocyclic Turn-inducing Mmentioning

confidence: 99%

“…Only a small number of additional examples have been reported to complete the scenario of RGD-based semipeptides [46,[56][57][58][59][60][61][62]. Interestingly, modern trends in organic chemistry are significantly affecting the search for innovative synthetic protocols to efficiently forge macrocyclic RGD-based structures.…”

Section: Rgd-based Semipeptides Containing Monocyclic Turn-inducing Mmentioning

confidence: 99%

Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides

Auzzas

Zanardi²,

Battistini³

et al. 2010

CMC

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The outstanding physio-pathological role played by integrin receptors in living subjects motivates the enormous interest shown by scientists worldwide for this topic. More than twenty years of research has spanned across the structural and functional elucidation of these proteins and over their antagonism-based biomedical applications. The proof-of concept stage, aimed at identifying potent inhibitors, covered a decade of studies, and paved the way for a more advanced era of research where these antagonist molecules were thrown into the deep end of applicative studies. This review intends to summarize the major efforts conducted thus far and focuses on the design, synthesis and biomedical applications of cyclic RGD-containing alpha(v)beta(3) integrin antagonists, in both their small and macromolecular formats. In particular, Chapters 1 and 2 offer a comprehensive outlook on the rational basis for the design of integrin inhibitors, Chapter 3 chronicles the biological and medical applications of monofunctional RGD integrin ligands both in their monomeric and multimeric asset, and Chapter 4 illustrates the potential of RGD-based multifunctional systems in molecular medicine.

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“…The first demonstration of a Pd(0) process on the solid phase actually involved Heck chemistry and was directed toward the synthesis of small libraries containing 20-to 24-membered macrocycles (94, Scheme 11.10). 198 Analogous procedures were employed for the assembly of macrocyclic RGD mimetics 199,200 and b-turn mimics (97, Figure 11.12, site of reaction and palladium species employed indicated) 201 on the solid phase. For these conversions, it was postulated that an intramolecular hydrogen bond in the precursor assisted in the formation of the cycle.…”

Section: Heckmentioning

confidence: 99%

The Synthesis of Macrocycles for Drug Discovery

Peterson¹

2014

Macrocycles in Drug Discovery

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Despite the attractive nature of macrocyclic compounds for use in new pharmaceutical discovery, applications have been hindered due to the lack of appropriate synthetic methods, in particular for the construction of libraries of such molecules. However, over the last decade, a number of effective and versatile methodologies suitable for macrocyclic scaffolds have been developed and applied successfully. These include classical coupling and substitution reactions, ring-closing metathesis (RCM), cycloaddition (“click”) chemistry, multicomponent reactions (MCR), numerous organometallic-mediated processes and others. This chapter presents a comprehensive compilation of these strategies and provides examples of their use in drug discovery, along with a description of those approaches that have proven effective for the assembly of macrocyclic libraries suitable for screening.

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Synthesis of cyclic RGD derivatives via solid phase macrocyclization using the Heck reaction

Cited by 36 publications

References 35 publications

Importance and synthesis of benzannulated medium-sized and macrocyclic rings (BMRs)

Importance and synthesis of benzannulated medium-sized and macrocyclic rings (BMRs)

Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides

The Synthesis of Macrocycles for Drug Discovery

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Synthesis of cyclic RGD derivatives via solid phase macrocyclization using the Heck reaction

Cited by 36 publications

References 35 publications

Importance and synthesis of benzannulated medium-sized and macrocyclic rings (BMRs)

Importance and synthesis of benzannulated medium-sized and macrocyclic rings (BMRs)

Targeting &#945;v&#946;3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides

The Synthesis of Macrocycles for Drug Discovery

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Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides