Nguyen, Thuy published the artcileDiarylureas Containing 5-Membered Heterocycles as CB1 Receptor Allosteric Modulators: Design, Synthesis, and Pharmacological Evaluation, COA of Formula: C4H11NO2, the main research area is diarylurea heterocycle synthesis SAR cannabinoid CB1 receptor; CB1 receptor; PSNCBAM-1; allosteric modulators; diarylurea; five-membered heterocycles; structure−activity relationship.
Allosteric modulators have attracted significant interest as an alternate strategy to modulate CB1 receptor signaling for therapeutic benefits that may avoid the adverse effects associated with orthosteric ligands. Here we extended our previous structure-activity relationship studies on the diarylurea-based CB1 neg. allosteric modulators (NAMs) by introducing five-membered heterocycles to replace the 5-pyrrolidinylpyridinyl group in PSNCBAM-1 (1), one of the first generation CB1 allosteric modulators. Many of these compounds had comparable potency to 1 in blocking the CB1 agonist CP55,940 stimulated calcium mobilization and [35S]GTP-γ-S binding. Similar to 1, most compounds showed pos. cooperativity by increasing [3H]CP55,940 binding, consistent with the pos. allosteric modulator (PAM)-antagonist mechanism. Interestingly, these compounds exhibited differences in ability to increase specific binding of [3H]CP55,940 and decrease binding of the antagonist [3H]SR141716. In saturation binding studies, only increases in [3H]CP55,940 Bmax, but not Kd, were observed, suggesting that these compounds stabilize low affinity receptors into a high affinity state. Among the series, the 2-pyrrolyl analog (I) exhibited greater potency than 1 in the [35S]GTP-γ-S binding assay and significantly enhanced the maximum binding level in the [3H]CP5,5940 binding assay, indicating greater CB1 receptor affinity and/or cooperativity.
ACS Chemical Neuroscience published new progress about Central nervous system disease. 22483-09-6 belongs to class alcohols-buliding-blocks, name is 2,2-Dimethoxyethanamine, and the molecular formula is C4H11NO2, COA of Formula: C4H11NO2.
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