Guanidinium and aminoimidazolinium derivatives of N-(4-piperidyl)propanamides as potential ligands for μ opioid and I2-imidazoline receptors: synthesis and pharmacological screening

Montero, Ana; Goya, Pilar; Jagerovic, Nadine; Callado, Luís F.; Meana, J. Javier; Girón, Rocı́o; Goicoechea, Carlos; Martín, M. I. Fernández San

doi:10.1016/s0968-0896(01)00356-x

Cited by 29 publications

(32 citation statements)

References 18 publications

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“…Thus fentanyl derivatives that incorporate guanidinium and 2-aminoimidazolinium groups were designed and synthesized, which incorporate both μ-opioid and I 2 -imidazoline receptor pharmacophores [140,141]. This publication was likely the first attempt for creation of bivalent ligands based on fentanyl as the μ- component.…”

Section: Insertion Of Substituents Other Than Methyl Into the Differementioning

confidence: 99%

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

2014

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Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed.

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Section: Insertion Of Substituents Other Than Methyl Into the Differementioning

confidence: 99%

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

2014

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“…Alternatively, these cardiovascular dysfunctions could be treated by the use of verapamil-analogue calcium antagonists as zatebradine (27 ), a benzazepinone derivative with vasodilator and bradycardic properties [17]. Bisi and collaborators [18] exploited the MH as strategy in the design of new cardioactive hybrid molecules (28)(29)(30)(31)(32)(33), in which the arylalkyl sub-unity of the lateral chain of 27 was replaced by the 2-hydroxy-3-aryloxypropylamine group (A), a peculiar structural sub-unity of β-blockers (Fig. (4)).…”

Section: Cardioactive Agentsmentioning

confidence: 99%

“…The evaluation of the bioprofile of this series lead to the initial identification of the prototype 86 ( Fig. (12 )), which presented high affinity to the µ-opioid receptor (K i = 23 nM), but low affinity to I 2 -IBS receptor (K i ~2000 nM) [33]. Previous SAR study involving a series of aliphatic bis-guanidine alkaloids demonstrated that the increase of the methylenic bridge between the two basic subunities leads to an increase in the I 2 -IBS affinity [32].…”

Section: Analgesic Anti-inflammatory and Antithro-mbotic Agentsmentioning

confidence: 99%

“…An interesting strategy consists of the combination, in only one molecule, of the pharmacophorical sub-unities of opioid agents and of ligands of the subtype I 2 of the imidazoline receptor (IBS), aiming at a synergic and controlled antinociceptive effect, considering the recent evidences demonstrating that some I 2 -IBS ligands can attenuate the opioid tolerance [33].…”

Section: Analgesic Anti-inflammatory and Antithro-mbotic Agentsmentioning

confidence: 99%

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Molecular Hybridization: A Useful Tool in the Design of New Drug Prototypes

Viegas-Junior

Danuello²,

Bolzani³

et al. 2007

CMC

1,016

395

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Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can result in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this paper, we described several examples of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infectious, anticancer, cardio- and neuroactive properties.

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“…IBS ligands were reported to modulate antinociception [121,122], tolerance [123][124][125], and dependence [126][127][128] induced by opioids. In a preliminary study [129], fentanyl (58) and the guanidine moiety, which mimics an endogenous I 2 -IBS ligand agmatine (59) [130], were chosen as the opioid and I 2 -IBS pharmacophores, respectively, to provide twin drugs 61 and 62. Compounds 61 and 62 decreased the binding affinities for IBS, while 61b and 62b, having an acyclic guanidine moiety, maintained the affinities for opioid receptors (Fig.…”

Section: Opioid and Imidazoline Binding Site Pharmacophoresmentioning

confidence: 99%

Twin and Triplet Drugs in Opioid Research

Fujii

2010

Topics in Current Chemistry

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Twin and triplet drugs are defined as compounds that contain respectively two and three pharmacophore components exerting pharmacological effects in a molecule. The twin drug bearing the same pharmacophores is a "symmetrical twin drug", whereas that possessing different pharmacophores is a "nonsymmetrical twin drug." In general, the symmetrical twin drug is expected to produce more potent and/or selective pharmacological effects, whereas the nonsymmetrical twin drug is anticipated to show both pharmacological activities stemming from the individual pharmacophores (dual action). On the other hand, nonsymmetrical triplet drugs, which have two of the same pharmacophores and one different moiety, are expected to elicit both increased pharmacological action and dual action. The two identical portions could bind the same receptor sites simultaneously while the third portion could bind a different receptor site or enzyme. This review will mainly focus on the twin and triplet drugs with an evaluation of their in vivo pharmacological effects, and will also include a description of their pharmacology and synthesis.

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Guanidinium and aminoimidazolinium derivatives of N-(4-piperidyl)propanamides as potential ligands for μ opioid and I2-imidazoline receptors: synthesis and pharmacological screening

Cited by 29 publications

References 18 publications

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

Molecular Hybridization: A Useful Tool in the Design of New Drug Prototypes

Twin and Triplet Drugs in Opioid Research

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