a-438079 and Peripheral-Nervous-System-Diseases

a-438079 has been researched along with Peripheral-Nervous-System-Diseases* in 1 studies

Other Studies

1 other study(ies) available for a-438079 and Peripheral-Nervous-System-Diseases

Article	Year
Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists. Journal of medicinal chemistry, 2006, Jun-15, Volume: 49, Issue:12 1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution on the tetrazole was examined. Compounds were evaluated for activity to inhibit calcium flux in both human and rat recombinant P2X(7) cell lines using fluorometric imaging plate reader technology. Analogues were also assayed for their ability to inhibit IL-1beta release and to inhibit P2X(7)-mediated pore formation in human THP-1 cells. Compound 15d was advanced to efficacy studies in a model of neuropathic pain where significant reversal of mechanical allodynia was observed at doses that did not affect motor coordination. Topics: Analgesics; Animals; Cell Line; Humans; Interleukin-1; Ligation; Motor Activity; Pain; Patch-Clamp Techniques; Peripheral Nervous System Diseases; Physical Stimulation; Purinergic P2 Receptor Antagonists; Pyridines; Rats; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Spinal Nerves; Stereoisomerism; Structure-Activity Relationship; Tetrazoles; Touch	2006

Article

Year

Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists.

Journal of medicinal chemistry, 2006, Jun-15, Volume: 49, Issue:12

1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution on the tetrazole was examined. Compounds were evaluated for activity to inhibit calcium flux in both human and rat recombinant P2X(7) cell lines using fluorometric imaging plate reader technology. Analogues were also assayed for their ability to inhibit IL-1beta release and to inhibit P2X(7)-mediated pore formation in human THP-1 cells. Compound 15d was advanced to efficacy studies in a model of neuropathic pain where significant reversal of mechanical allodynia was observed at doses that did not affect motor coordination.

Topics: Analgesics; Animals; Cell Line; Humans; Interleukin-1; Ligation; Motor Activity; Pain; Patch-Clamp Techniques; Peripheral Nervous System Diseases; Physical Stimulation; Purinergic P2 Receptor Antagonists; Pyridines; Rats; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Spinal Nerves; Stereoisomerism; Structure-Activity Relationship; Tetrazoles; Touch

2006