sja-6017 and Retinal-Diseases

sja-6017 has been researched along with Retinal-Diseases* in 1 studies

Other Studies

1 other study(ies) available for sja-6017 and Retinal-Diseases

Article	Year
Exploration of orally available calpain inhibitors 2: peptidyl hemiacetal derivatives. Journal of medicinal chemistry, 2006, Jun-29, Volume: 49, Issue:13 We previously reported a potent calpain inhibitor 1 (SJA6017, N-(4-fluorophenyl)-l-valyl-l-leucinal), which displayed relatively low oral bioavailability (BA). Replacing the metabolically labile aldehyde moiety of 1with more chemically stable warheads, such as a cyclic hemiacetal, hydrazone, and alpha-ketoamide, provided the inhibitors with improved in vitro metabolic stability. Cyclic hemiacetal 2 was the most stable of these compounds. The optimization of 2 led to hemiacetal 8 (SNJ-1715) which exhibited high potency, good aqueous solubility, excellent oral BA, and prolonged plasma half-life in rats. Furthermore, 8 showed neuroprotective efficacy via oral administration in a rat retinal ischemia model. Topics: Administration, Oral; Animals; Calpain; Cell Line; Dipeptides; Drug Stability; Half-Life; Humans; Ischemia; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Solubility; Stereoisomerism; Structure-Activity Relationship; Thiourea	2006

Article

Year

Exploration of orally available calpain inhibitors 2: peptidyl hemiacetal derivatives.

Journal of medicinal chemistry, 2006, Jun-29, Volume: 49, Issue:13

We previously reported a potent calpain inhibitor 1 (SJA6017, N-(4-fluorophenyl)-l-valyl-l-leucinal), which displayed relatively low oral bioavailability (BA). Replacing the metabolically labile aldehyde moiety of 1with more chemically stable warheads, such as a cyclic hemiacetal, hydrazone, and alpha-ketoamide, provided the inhibitors with improved in vitro metabolic stability. Cyclic hemiacetal 2 was the most stable of these compounds. The optimization of 2 led to hemiacetal 8 (SNJ-1715) which exhibited high potency, good aqueous solubility, excellent oral BA, and prolonged plasma half-life in rats. Furthermore, 8 showed neuroprotective efficacy via oral administration in a rat retinal ischemia model.

Topics: Administration, Oral; Animals; Calpain; Cell Line; Dipeptides; Drug Stability; Half-Life; Humans; Ischemia; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Solubility; Stereoisomerism; Structure-Activity Relationship; Thiourea

2006