2-[2-Chloro-5-(trifluoro­methyl)­phen­yl]hexa­hydro­pyrimidine monohydrate

The mol­ecule of the title compound, C11H12ClF3N2·H2O, is a substituted hexa­hydro­pyrimidine. There are two crystallographically independent mol­ecules (A and B) and two water mol­ecules in the asymmetric unit of the title compound. Inter­molecular C—H⋯Cl (× 2), C—H⋯F, and C—H⋯N (× 2) hydrogen bonds generate S(5) ring motifs. The dihedral angle between the two benzene rings is 8.17 (11)°. The F atoms in mol­ecule B are disordered over four positions with refined site-occupancies of ca 0.35/0.19/0.29/0.17 for the four components. In the crystal structure, mol­ecules are arranged into one-dimensional extended chains along the c axis and are further stacked along the a axis by directed four-membered O—H⋯O—H inter­actions, forming two-dimensional networks parallel to the ac plane. The short distances between the centroids of the benzene rings (3.8002–3.8327 Å) indicate the existence of π–π inter­actions. In addition, the crystal structure is further stabilized by N—H⋯O, O—H⋯N (× 4), N—H⋯Cl and C—H⋯O (× 2) hydrogen-bonding inter­actions

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate