Bikunin and α1-microglobulin in human zona pellucida and connective tissue

The occurrence of bikunin and ·₁-microglobuli n was investigated in human ovary and Fallopian tubes. Bikunin and ·₁-microglobulin are transcribed in the liver from a common gene. Bikunin immunoreactivity was detected in the zona pellucida. A positive reaction for bikunin was also observed in connective tissue of the oviduct. In addition, mast cells showed a more intense posi tive reaction than the surrounding connective tissue. Specific displaceable ·₁-microglobulin immunoreactivity was revealed in the zona pellucida. The data suggest that bikunin and ·₁- microglobulin are trapped in the zona pellucida. This revised version was published online in November 2006 with corrections to the Cover Date.     

Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition

Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration.