Development of fluorinated and methoxylated benzothiazole derivatives as highly potent and selective cannabinoid CB2 receptor ligands

Development of the High-Affinity Carborane-Based Cannabinoid Receptor Type 2 PET Ligand [18F]LUZ5-d8

“…This leads to the assumption that cytochrome P450-catalyzed functionalization reactions (phase I), such as oxidation, are not involved in the metabolism of this class of compounds in MLMs. However, the use of human liver microsomes (HLMs) instead of MLMs might provide a different picture, as species differences are described well in the literature , and were already reported for CB 2 R ligands by Aly et al However, as discussed in the section In Vivo Metabolism, radiometabolites were detected in plasma from rodents after administration of [ 18 F]­LUZ5- d 8 . These findings suggest further in vitro investigations with regard to conjugation reactions (phase II), to understand the complexity of the processes taking place in vivo .…”

Synthesis, Structure–Activity Relationships, Radiofluorination, and Biological Evaluation of [18F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET

“…Besides quinolinones, − naphthyridones, − and thiazoles, − indole − is one of the most widely investigated scaffolds in the medicinal chemistry of CB2R-targeted small molecules. As the most broadly used substitution pattern, the N -alkyl-3-carbonyl indole plays a central role; however, the cannabinoid receptor ligands based on this scaffold most often suffer from low selectivity against CB1R as, e.g., JWH-018 and the more recently reported compound GBD-003 (Figure ).…”

Synthesis and Antimicrobial, Anticancer and Anti-Oxidant Activities of Novel 2,3-Dihydropyrido[2,3-d]pyrimidine-4-one and Pyrrolo[2,1-b][1,3]benzothiazole Derivatives via Microwave-Assisted Synthesis

“…Pyrido [2,3-d]pyrimidine ring systems have assorted biological and pharmacological activities such as being analgesic, anti-inflammatory [1-3], antitubercular [4], antimicrobial [5][6][7], a threonine tyrosine kinase (TTK) inhibitor [8], an adenosine kinase inhibitor [9], antiviral [10], antioxidant [11][12][13][14], a dihydrofolate reductase inhibitor [15,16], and an efficient glucosidase inhibitor [17,18]. Moreover, the 1,3-benzothiazole nucleus is a highly significant scaffold in the drug design, due to important pharmacological and medicinal activities, such as being antiviral [19], antituberculosis [20], an identifier of selective CB2 receptor ligands [21], antitumor [22][23][24], antimicrobial [25][26][27], anticonvulsant [28], a schistosome BCL-2 inhibitor [29], antidiabetic [30], antioxidant [31], an anti-Alzheimer drug [32] and a urease inhibitor [33] among the heterocyclic compounds containing a pyrimidine and benzothiazole nucleus that exhibits biological activity [34][35][36] (Figure 1). kinase (TTK) inhibitor [8], an adenosine kinase inhibitor [9], antiviral [10], antioxidant [11][12][13]…”

“…kinase (TTK) inhibitor [8], an adenosine kinase inhibitor [9], antiviral [10], antioxidant [11][12][13][14], a dihydrofolate reductase inhibitor [15,16], and an efficient glucosidase inhibitor [17,18]. Moreover, the 1,3-benzothiazole nucleus is a highly significant scaffold in the drug design, due to important pharmacological and medicinal activities, such as being antiviral [19], antituberculosis [20], an identifier of selective CB2 receptor ligands [21], antitumor [22][23][24], antimicrobial [25][26][27], anticonvulsant [28], a schistosome BCL-2 inhibitor [29], antidiabetic [30], antioxidant [31], an anti-Alzheimer drug [32] and a urease inhibitor [33] among the heterocyclic compounds containing a pyrimidine and benzothiazole nucleus that exhibits biological activity [34][35][36] (Figure 1). Accordingly, with all of the previous observations of the biological importance and in continuation of our program in the synthesis of pyrido [2,3-d]pyrimidine [37], this study aims to design and develop highly selective and efficacious antimicrobial and anticancer agents of a novel series of pyrido [2,3-d]pyrimidine derivatives bearing different heterocyclic and aryl moieties such as benzothiazole, thiophene, furan, piperonal, naphthalene, and fluorophenyl as a side chain and various aryl derivatives by the microwave irradiation technique.…”