Synthesis of (+)-cis-N-(4-Isothiocyanatobenzyl)-N-normetazocine, an Isothiocyanate Derivative of N-Benzylnormetazocine as Acylant Agent for the σ1 Receptor

Ronsisvalle, Giuseppe; Prezzavento, Orazio; Marrazzo, Agostino; Vittorio, F; Massimino, Michele; Murari, G; Spampinato, Santi

doi:10.1021/jm010501a

Cited by 9 publications

(1 citation statement)

References 14 publications

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“…19 Briefly, each tube containing 500 µg of membrane protein was incubated for 150 min at 37 °C with [ 3 H]-(+)-pentazocine (3 nM) in 50 mM Tris-HCl pH 7.4. Non-specific binding was determined using 10 µM haloperidol.…”

Section: Issn 1424-6376mentioning

confidence: 99%

1-Phenyl-3-azabicyclo[3.1.0]hexane derivatives as new ligands for sigma receptors

Marrazzo¹,

Pappalardo²,

Prezzavento³

et al. 2004

Arkivoc

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A series of 1-phenyl-3-azabicyclo[3.1.0]hexanes were synthesized as more conformationally restricted prototypical σ ligands 3-phenylpiperidines with the aim to developing new σ ligands. Compared with 3-phenylpiperidines reported by Largent et al., binding data showed that conformational restriction was not detrimental for σ receptor affinity. Specifically, except for secondary amine 4, all racemic 1-phenyl-3-azabicyclo[3.1.0]hexane derivatives (12-19) showed moderate to high affinity for both σ 1 and σ 2 receptors. Dextrorotatory isomers with the same configuration of 3-phenylpiperidines to C-1 carbon linked to the phenyl ring showed a better affinity and selectivity for σ 1 receptors compared to the respective levorotatory isomers. Compounds (+)-14 and (+)-15 displayed very high affinity for σ 1 (Ki = 0.9 and 2.3 nM respectively) but low selectivity for receptor subtypes. Compound (+)-18 with N-phenethyl substituent embodies the highest selectivity for σ 1 receptors.

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Section: Issn 1424-6376mentioning

confidence: 99%

1-Phenyl-3-azabicyclo[3.1.0]hexane derivatives as new ligands for sigma receptors

Marrazzo¹,

Pappalardo²,

Prezzavento³

et al. 2004

Arkivoc

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An Efficient and Practical Method for Highly Chemoselective Hydrogenation of Nitrobenzylamines to Aminobenzylamine Hydrochlorides

et al. 2007

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A comparative molecular field analysis (CoMFA) study using semiempirical, density functional, ab initio methods and pharmacophore derivation using DISCOtech on sigma 1 ligands

2004

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Abstract:The Comparative Molecular Field Analysis (CoMFA) was developed to investigate a threedimensional quantitative structure activity relationship (3D-QSAR) model of ligands for the sigma 1 receptor. The starting geometry of sigma-1 receptor ligands was obtained from the Tripos force field minimizations and conformations were decided from DISCOtech using the SYBYL 6.8. program. The structures of 48 molecules were fully optimized at the ab initio HF/3-21G* and semiempirical AM1 calculations using GAUSSIAN 98. The electrostatic charges were calculated using several methods such as semiempirical AM1, density functional B3LYP/3-21G*, and ab initio HF/3-21G*, MP2/3-21G* calculations within GAUSSIAN 98. Using the optimized geometries, the CoMFA results derived from the HF/3-21G method were better than those from AM1. The best CoMFA was obtained from HF/3-21G* optimized geometry and charges (R 2 ϭ 0.977). Using the optimized geometries, the CoMFA results derived from the HF/3-21G methods were better than those from AM1 calculations. The training set of 43 molecules gave higher R 2 (0.989 -0.977) from HF/3-21G* optimized geometries than R 2 (0.966 -0.911) values from AM1 optimized geometries. The test set of five molecules also suggested that HF/3-21G* optimized geometries produced good CoMFA models to predict bioactivity of sigma 1 receptor ligands but AM1 optimized geometries failed to predict reasonable bioactivity of sigma 1 receptor ligands using different calculations for atomic charges.

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Synthesis of (+)-cis-N-(4-Isothiocyanatobenzyl)-N-normetazocine, an Isothiocyanate Derivative of N-Benzylnormetazocine as Acylant Agent for the σ₁ Receptor

Cited by 9 publications

References 14 publications

1-Phenyl-3-azabicyclo[3.1.0]hexane derivatives as new ligands for sigma receptors

1-Phenyl-3-azabicyclo[3.1.0]hexane derivatives as new ligands for sigma receptors

An Efficient and Practical Method for Highly Chemoselective Hydrogenation of Nitrobenzylamines to Aminobenzylamine Hydrochlorides

A comparative molecular field analysis (CoMFA) study using semiempirical, density functional, ab initio methods and pharmacophore derivation using DISCOtech on sigma 1 ligands

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