1345962-48-2Relevant academic research and scientific papers
Discovery of Potent Antiallodynic Agents for Neuropathic Pain Targeting P2X3 Receptors
Jung, Young-Hwan,Kim, Yeo Ok,Lin, Hai,Cho, Joong-Heui,Park, Jin-Hee,Lee, So-Deok,Bae, Jinsu,Kang, Koon Mook,Kim, Yoon-Gyoon,Pae, Ae Nim,Ko, Hyojin,Park, Chul-Seung,Yoon, Myung Ha,Kim, Yong-Chul
, p. 1465 - 1478 (2017)
Antagonism of the P2X3 receptor is one of the potential therapeutic strategies for the management of neuropathic pain because P2X3 receptors are predominantly localized on small to medium diameter C- and Aδ-fiber primary afferent neurons, which are related to the pain-sensing system. In this study, 5-hydroxy pyridine derivatives were designed, synthesized, and evaluated for their in vitro biological activities by two-electrode voltage clamp assay at hP2X3 receptors. Among the novel hP2X3 receptor antagonists, intrathecal treatment of compound 29 showed parallel efficacy with pregabalin (calcium channel modulator) and higher efficacy than AF353 (P2X3 receptor antagonist) in the evaluation of its antiallodynic effects in spinal nerve ligation rats. However, because compound 29 was inactive by intraperitoneal administration in neuropathic pain animal models due to low cell permeability, the corresponding methyl ester analogue, 28, which could be converted to compound 29 in vivo, was investigated as a prodrug concept. Intravenous injection of compound 28 resulted in potent antiallodynic effects, with ED50 values of 2.62 and 2.93 mg/kg in spinal nerve ligation and chemotherapy-induced peripheral neuropathy rats, respectively, indicating that new drug development targeting the P2X3 receptor could be promising for neuropathic pain, a disease with high unmet medical needs.
NOVEL 5-HYDROXY PYRIDINE-BASED COMPOUND FOR USE AS P2X1 AND P2X3 RECEPTOR ANTAGONIST AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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, (2020/05/14)
The present invention relates to novel 5-hydroxy pyridine-based compounds useful as P2X1 and P2X3 receptor antagonists and compositions comprising the same. The compounds according to the present invention have an activity of strongly antagonizing P2X1 an
Design and synthesis of potent and selective P2X3 receptor antagonists derived from PPADS as potential pain modulators
Cho, Joong-Heui,Jung, Kwan-Young,Jung, Younghwan,Kim, Min Hye,Ko, Hyojin,Park, Chul-Seung,Kim, Yong-Chul
, p. 811 - 830 (2013/12/04)
Pyridoxalphosphate-6-azophenyl-2′,4′-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X3 receptor antagonists as potential antinociceptive agents. Based on
NOVEL PYRIDINE CARBOXYLIC ACID BASED COMPOUND USED AS A P2X1 AND P2X3 RECEPTOR ANTAGONIST, A PRODUCTION METHOD FOR THE SAME AND A COMPOSITION COMPRISING THE SAME
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Paragraph 0277; 0278; 0279; 0280, (2013/03/26)
Provided are a novel pyridine carboxylic acid based compound used as a P2X1 and P2X3 receptor antagonist, a production method for the same and a composition comprising the same. The compound according to the present invention is a powerful antagonist of P2X1 and P2X3 receptors, and hence can be used as a drug for treating or preventing diseases involving neurological pain or chronic inflammatory diseases which are diseases caused by P2X1 and P2X3 receptor activity.
