Synthesis, in vitro and in vivo characterization of new benzoxazole and benzothiazole-based sigma receptor ligands

Exploiting the Power of Stereochemistry in Drug Action: 3-[(2S,6S,11S)-8-Hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-phenylpropanamide as Potent Sigma-1 Receptor Antagonist

“…Recently obtained as a human crystal structure, the sigma-1 receptor (σ1R) is a protein chaperone at the endoplasmic reticulum (ER)–mitochondrion interface . For its modulatory role on potassium and calcium channels, , on different neurotransmitters and on second messenger systems, , σ1R has been proposed as a valuable target for the treatment of different conditions such as depression and anxiety, amnesic and cognitive deficits, psychosis, and persistent pain. , σ1R is widely distributed in key sites for pain neuraxis such as the dorsal horn of the spinal cord, periaqueductal gray matter, locus coeruleus , rostroventral medulla, and dorsal root ganglia …”

“…2 For its modulatory role on potassium and calcium channels, 3,4 on different neurotransmitters 5 and on second messenger systems, 6,7 σ1R has been proposed as a valuable target for the treatment of different conditions such as depression 8 and anxiety, 9 amnesic and cognitive deficits, 10 psychosis, 11 and persistent pain. 12,13 σ1R is widely distributed in key sites for pain neuraxis 14 such as the dorsal horn of the spinal cord, periaqueductal gray matter, locus coeruleus, rostroventral medulla, and dorsal root ganglia. 15 Although σ1R agonists act as an endogenous antiopioid system, σ1R antagonists markedly enhance the morphineinduced antinociception both at central and at peripheral levels.…”

NEW ROUTE FOR THE SYNTHESES OF SOME NOVEL DERIVATIVES OF 3-ARYL BENZO[d] THIAZOLE-2(3H)-IMINE FROM HIGH SUBSTITUTED THIOUREAS

“…Benzothiazole is an organosulfur, as well as organonitrogen heterocyclic compound was a which benzene ring is fused with thiazole [4][5][6][7][8][9][10][11][12][13]. Benzothiazoles are an important class of heterocyclic compounds that act as core nucleus in various drugs such as anticancer [5,14], antileishmanial [15], antimicrobial [9,16], anti-asthmatic [11], antitumor [6], antibacterial [17,18], anti-tubercular, [19] anticonvulsant [4,20], anti-HIV [15,21], anti-inflammatory [5,7], antifungal [9,13], antiproliferative [6,14,21,22], antiviral [23], anti-Alzheimer [10,14], antimalarial [15], and antidiabetic [24][25][26] effects. The related research and developments in BTA-based medicinal chemistry have become a rapidly developing and increasingly active topic [6,19].…”

Synthesis and Pharmacological Evaluation of σ2 Receptor Ligands Based on a 3‐Alkoxyisoxazole Scaffold: Potential Antitumor Effects against Osteosarcoma

“…For example, SW‐43 ( 3 , K i, σ2=18 nM), a fluorescently labeled σ2 receptor ligand, mediated pancreatic cancer cells death by lysosomal membrane permeabilization, while PB‐28 ( 6 , K i , σ1=13.0 nM, K i, σ2=0.28 nM) could induce cell death via mitochondrial superoxide production and caspase activation in pancreatic cancer (Figure 1). [19a,20] For human SK−N‐SH neuroblastoma cells, CM‐572 ( 7 , K i , σ1>10 μM, K i, σ2=14.6 nM) induced an immediate dose‐dependent increase in cytosolic calcium concentration, and the newer benzoxazole and benzothiazole derivatives were reported to inhibit the viability of breast cancer cells [19h,21] . A study with fluorescent probe K05‐138 ( 8 , K i , σ1=1100 nM, K i, σ2=45 nM) suggests that σ2 ligands are internalized by an endocytotic pathway in breast cancer cells [22] .…”