Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides

Efange, Simon M. N.; Michelson, Robert H.; Knusel, B.; Hefti, Franz; Boudreau, Robert J.; Thomas, J. R.; Tennison, J.R.

doi:10.1016/0969-8051(93)90083-7

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…12 Accordingly, radiolabeled ligands of σ receptors have been synthesized and evaluated as malignant melanoma imaging agents. [13][14][15] σ Receptors have been detected on other different types of tumor cells (breast carcinoma, prostate tumor, colon, lung, brain, and kidney tumors) and have also been detected in healthy tissues such as liver, kidney, and brain. 12,[16][17][18][19][20] However, clinical studies have demonstrated a very high specificity of 123 I-BZA for malignant melanoma and metastases.…”

Section: Introductionmentioning

confidence: 99%

“…Benzamides seem to be co-localized in the melanocytes of the pigmented cells, and their uptake has been correlated to melanin production, suggesting a nonreceptor binding uptake mechanism. ,− On the other hand, benzamides are known to show high affinity for the σ-1 receptor, which has been detected on malignant melanoma tumor cells . Accordingly, radiolabeled ligands of σ receptors have been synthesized and evaluated as malignant melanoma imaging agents. − σ Receptors have been detected on other different types of tumor cells (breast carcinoma, prostate tumor, colon, lung, brain, and kidney tumors) and have also been detected in healthy tissues such as liver, kidney, and brain. ,− However, clinical studies have demonstrated a very high specificity of 123 I-BZA for malignant melanoma and metastases . Hence a single drug-receptor binding mechanism is insufficient to explain the specific uptake of benzamide derivatives by malignant melanoma tumor cells, and recent results published are in favor of a melanin binding mechanism …”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Biodistribution of a New Oxo-technetium-99m Bis(aminothiol) Complex as a Potential Melanoma Tracer

et al. 2001

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[123I]-N-(2-Diethylaminoethyl)-4-iodobenzamide (123I-BZA) has been the best scintigraphic agent described so far for malignant melanoma and ocular melanoma diagnosis. We replaced 123I by the more convenient radioisotope 99mTc and synthesized four bis(aminoethanethiol) derivatives. We describe the synthesis of a new oxo-technetium complex (TcO-Cf), prepared in very high yield (radiochemical yield > 95%), that exhibits an affinity for the pigmented tumor cells. This complex was evaluated in vivo in mice bearing C57Bl6 murine melanoma. After injection, a rapid decrease in the radioactivity levels was noted for all tissues and organs except for eyes (1.26 %ID/g at 1 h and 2.69 %ID/g at 24 h postinjection) and the tumor (1.19 %ID/g at 1 h and 0.80 %ID/g at 24 h postinjection), suggesting a specific in vivo binding of this complex to the pigmented cells. These results were compared with those already published for three other technetium-99m bis(aminothiol) complexes with benzamide derivatives.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Biodistribution of a New Oxo-technetium-99m Bis(aminothiol) Complex as a Potential Melanoma Tracer

et al. 2001

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“…The Williamson reaction of 4-nitroguaialcol 2 with dibromoalkanes followed by N-alkylation provided piperidine, morpholine, and piperazine derivatives 6 – 17 . 4-Substituted piperidinyl derivatives, 18 – 20 , were synthesized by the Mitsunobu reaction of 2 with corresponding 4-(hydroxyalkyl)piperidine fragments, , followed by an N -Boc deprotection reaction to afford 21 and 23 . Compounds 21 and 23 were then reductively methylated to provide 22 and 24 .…”

Section: Resultsmentioning

confidence: 99%

Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design

et al. 2017

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Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer's disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.

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“…Distribution studies in nude mice implanted with human malignant melanoma showed high tumor uptake of both tracers. [176]. The highest uptake of [ 131 I] IPAB was confirmed to be greatest in human non-small cell lung carcinoma [105] and human prostate tumor DU-145 [173] compared with the uptake in all other organ investigated in nude mice.…”

Section: Benzamidsmentioning

confidence: 98%

Sigma Receptor Ligands: Possible Application as Therapeutic Drugs and as Radiopharmaceuticals

Hashimoto¹,

Ishiwata²

2006

CPD

106

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Sigma receptors are classified into sigma(1) and sigma(2) subtypes. These subtypes display a different tissue distribution and a distinct physiological and pharmacological profile in the central and peripheral nervous system. The characterization of these subtypes and the discovery of new specific sigma receptor ligands demonstrated that sigma receptors are novel targets for the therapeutic treatment of neuropsychiatric diseases (schizophrenia, depression, and cognition), brain ischemia, and cocaine addiction. Furthermore, imaging of sigma(1) receptors in the human brain using specific PET radioligands has started. In addition, the two sigma receptor subtypes are also expressed on tumor cells, where they could be of prognostic relevance. The ability of sigma(2) receptor agonists to inhibit tumor cell proliferation through mechanisms that might involve apoptosis, intracellular Ca(2+), and sphingolipids has promoted the development of sigma(2) receptor agonists as novel therapeutic drugs for treating cancer. Consequently, sigma(2) receptor ligands have been demonstrated to be potentially useful tumor imaging ligands. In this article, we focus on the sigma receptor ligands as therapeutic agents and as radiopharmaceuticals.

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Synthesis and biological evaluation of radioiodinated N-2-(4-piperidyl)ethyl benzamides

Cited by 8 publications

References 19 publications

Synthesis and Biodistribution of a New Oxo-technetium-99m Bis(aminothiol) Complex as a Potential Melanoma Tracer

Synthesis and Biodistribution of a New Oxo-technetium-99m Bis(aminothiol) Complex as a Potential Melanoma Tracer

Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design

Sigma Receptor Ligands: Possible Application as Therapeutic Drugs and as Radiopharmaceuticals

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