Stereospecific activity of two glutamate analogs

Two glutamic acid analogs, (+)‐(S)‐ and (–)‐(R)‐4‐(2,2‐diphenyl‐1,3,2‐oxazaborolidin‐5‐oxo)propionic acid ((+)‐(S)‐ and (–)‐(R)‐Trujillon, respectively), were prepared. The stereospecific activity of their pharmacological properties was studied. The median convulsant dose (CD 50 ) and median lethal dose (LD 50 ) were analyzed in female Swiss Webster mice and their effects in vivo on unitary electrical activity in globus pallidus neurons were elucidated in male Wistar rats. Compounds were characterized by 1 H, 13 C, and 11 B nuclear magnetic resonance. The LD 50 of (+)‐(S)‐Trujillon was 449.08 mg/kg and it increased spontaneous motor activity, while with (–)‐(R)‐Trujillon there was no mortality up to 1,000 mg/kg and it decreased spontaneous motor activity. The CD 50 in experiments with (+)‐(S)‐Trujillon was 199.34 mg/kg. Unitary recording in globus pallidus neurons showed i.v. administration (+)‐(S)‐Trujillon (50 mg/kg) increased frequency 79.0 ± 23.0% in relation to basal response. (–)‐(R)‐Trujillon and (+)‐(S)‐glutamate (50 mg/kg each) did not provoke changes in spontaneous basal firing. Local infusion of (+)‐(S)‐Trujillon (1 nMol) increased spontaneous firing in most neurons tested by 269.0 ± 83.0% in relation to basal values. Intrapallidal infusion of (–)‐(R)‐Trujillon (1 nMol) and saline solution did not cause statistically significant changes in globus pallidus spiking. Results showed that (+)‐(S)‐Trujillon crosses the blood–brain barrier and has stereospecific activity. Chirality 16:586–591, 2004. © 2004 Wiley‐Liss, Inc.