Berhane, Ilyas published the artcileThieno[2,3-d]pyrimidine-Based Positive Allosteric Modulators of Human Mas-Related G Protein-Coupled Receptor X1 (MRGPRX1), Application In Synthesis of 439692-55-4, the main research area is MRGPRX1 pos allosteric modulator neuropathic pain analgesic.
Mas-related G protein-coupled receptor X1 (MRGPRX1) is a human sensory neuron-specific receptor and potential target for the treatment of pain. Pos. allosteric modulators (PAMs) of MRGPRX1 have the potential to preferentially activate the receptors at the central terminals of primary sensory neurons and minimize itch side effects caused by peripheral activation. Using a high-throughput screening (HTS) hit, a series of thieno[2,3-d]pyrimidine-based mols. were synthesized and evaluated as human MRGPRX1 PAMs in HEK293 cells stably transfected with human MrgprX1 gene. An iterative process to improve potency and metabolic stability led to the discovery of orally available 6-(tert-butyl)-5-(3,4-dichlorophenyl)-4-(2-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine (1t), which can be distributed to the spinal cord, the presumed site of action, following oral administration. In a neuropathic pain model induced by sciatic nerve chronic constriction injury (CCI), compound 1t (100 mg/kg, po) reduced behavioral heat hypersensitivity in humanized MRGPRX1 mice, demonstrating the therapeutic potential of MRGPRX1 PAMs in treating neuropathic pain.
Journal of Medicinal Chemistry published new progress about Analgesics. 439692-55-4 belongs to class pyrimidines, name is Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-, and the molecular formula is C10H11ClN2S, Application In Synthesis of 439692-55-4.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia