New Diarylmethylpiperazines as Potent and Selective Nonpeptidic δ Opioid Receptor Agonists with Increased In Vitro Metabolic Stability was written by Plobeck, Niklas;Delorme, Daniel;Wei, Zhong-Yong;Yang, Hua;Zhou, Fei;Schwarz, Peter;Gawell, Lars;Gagnon, Helene;Pelcman, Benjamin;Schmidt, Ralf;Yue, Shi Yi;Walpole, Christopher;Brown, William;Zhou, Edward;Labarre, Maryse;Payza, Kemal;St-Onge, Stephane;Kamassah, Augustus;Morin, Pierre-Emmanuel;Projean, Denis;Ducharme, Julie;Roberts, Edward. And the article was included in Journal of Medicinal Chemistry in 2000.Electric Literature of C11H14INO This article mentions the following:
Nonpeptide δ opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews anal. of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl(1-piperazinyl)methyl]benzamide which retained potent binding affinity and selectivity to the human δ receptor (IC50 = 11 nM, μ/δ = 740, κ/δ > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced mol. weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for δ receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for δ binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the Ph group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)methyl]benzamide which had an improved in vitro binding profile (IC50 = 0.5 nM, μ/δ = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80. In the experiment, the researchers used many compounds, for example, N,N-Diethyl-4-iodobenzamide (cas: 77350-52-8Electric Literature of C11H14INO).
N,N-Diethyl-4-iodobenzamide (cas: 77350-52-8) belongs to iodide derivatives. Organic iodides can be alkyl, alkenyl, or alkynyl, and all of them are very reactive toward with many kinds of nucleophiles. A typical method for synthesis of aromatic iodides is diazotization of primary aromatic amines followed by treatment of potassium iodide. Aliphatic alcohols are converted to alkyl iodides by treating with hydrogen iodide.Electric Literature of C11H14INO
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com