Simple syntheses of N-alkylated spermidine fragments and analogues of the spermine alkaloid kukoamine A

Vassis, Stratos; Karigiannis, George; Balayiannis, George; Militsopoulou, Maria; Mamos, Petros; Francis, George W.; Papaioannou, Dionissios

doi:10.1016/s0040-4039(00)02308-x

Cited by 19 publications

(12 citation statements)

References 18 publications

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“…153 Papaioannou and co-workers have previously synthesized kukoamines, which are spermine alkaloids, as well as derivatives of kukoamines using SPS. 154 Recently, the same group have used reduction of amides as a versatile way to prepare various N-alkylated spermidine derivatives in solution 155 and also linear as well as cyclic polyamines have been synthesized using selective N-tritylation of polyamines. 156,157 B. Structure-Activity Relationship Studies…”

Section: A Novel Synthetic Methodsmentioning

confidence: 99%

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Strømgaard

Mellor

2004

Medicinal Research Reviews

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Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular polyamines are known to modulate the function of these receptors in vivo. In this study, recent developments in the medicinal chemistry of polyamine-based ligands are given, particularly focusing on the use of solid-phase synthesis (SPS) as a tool for the facile generation of libraries of polyamine toxin analogues. Moreover, the recent development of highly potent and very selective AMPAR ligands is described. Additionally, we provide a detailed account on the mechanism and site of action of AMPAR blockade by polyamine-based ligands, including examples of how these ligands are used as tools to study AMPAR, and a comparison with their action on other ionotropic receptors.

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Section: A Novel Synthetic Methodsmentioning

confidence: 99%

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Strømgaard

Mellor

2004

Medicinal Research Reviews

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“…Compound 1 and side chain 5a were treated with PyBOP in the presence of DIPEA in a mixture of THF and DCM, followed by the removal of the Boc group. PD0325901 analogue 7a was obtained in 68% yield (two steps) [15,18]. Derivation of the terminal amine group of 7awith succinic anhydride provided the hemisuccinate ester 8a in 85% yield [19].…”

Section: Scheme 1 Synthesis Of Compounds 5a-ementioning

confidence: 99%

Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy

Hou

Wang

et al. 2013

Molecules

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Two novel series of RGD-MEKI conjugates derived from a MEK1/2 kinase inhibitor-PD0325901-have been developed for integrin receptor mediated anticancer therapy. The first series, alkoxylamine analog RGD-MEKI conjugates 9a-g showed anti-proliferation activity in melanoma A375 cells by the same mechanism as that of PD0325901. PEGylation increased the IC 50 value of 9f three-fold in the A375 assay, and the multi-cRGD peptide cargo significantly improved the receptor specific anti-proliferation activity of 9g in integrin-overexpressing U87 cells. In the second series, RGD-PD0325901 13 exhibited significantly increased antitumor properties compared to the alkoxylamine analogs by both inhibition of the ERK pathway activity and DNA replication of the cancer cells. Furthermore, 13 displayed more potent anti-proliferation activity in the U87 assay than PD0325901 in a dose-dependent manner. All these data demonstrate that RGD-MEKI conjugates with an ester bond linkage enhanced anticancer efficacy with improved targeting capability toward integrin-overexpressing tumor cells.

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“…However, most of the literature involving borane reduction of amides on solid phase concerns polyamine synthesis. In contrast to the work by Houghten, where the polyamine is an intermediate, reports by Papaioannou and co-workers, 154,155 Hall and co-workers, [156][157][158][159][160] and one from our group 161 dealt with the preparation of various polyamine derivatives.…”

Section: Reduction Of Amides/peptidesmentioning

confidence: 77%

“…While Papaioannou and co-workers prepared polyamine derivatives on a trityl resin with decomposition of the borane-amine complex during acidic cleavage, 154,155 Hall's group developed a mild oxidative protocol employing iodine in a DIPEA-acetate buffer (pH ~5) compatible with both Wang and trityl resins. 156,157 This protocol was applied to the preparation of libraries of a variety of polyamine derivatives [e.g., the wasp toxin PhTX-433 (71, ~50% yield), Scheme 14].…”

Section: Reduction Of Amides/peptidesmentioning

confidence: 99%

N-Alkylation Reactions and Indirect Formation of Amino Functionalities in Solid-Phase Synthesis

Olsen¹,

Franzyk²,

Jaroszewski³

2005

Synthesis

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Aliphatic and aromatic amino functionalities are present in a wide variety of natural products and drugs, as well as in synthetic small molecular probes with therapeutic and/or diagnostic potential in drug discovery. As solid-phase synthesis and combinatorial chemistry have emerged as important tools for generation of compound libraries, development of broad-scope and efficient chemistry for the introduction of various functional groups into resinanchored substrates is highly important. Herein, we present a review of the literature concerning formation of the amino functionality on solid phase.

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Simple syntheses of N-alkylated spermidine fragments and analogues of the spermine alkaloid kukoamine A

Cited by 19 publications

References 18 publications

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Synthesis and Biological Evaluation of RGD-Conjugated MEK1/2 Kinase Inhibitors for Integrin-Targeted Cancer Therapy

N-Alkylation Reactions and Indirect Formation of Amino Functionalities in Solid-Phase Synthesis

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