Crystal structures of two N-phenylated tricyclic benzothiazines with antimalarial activity

Abstract

The crystal structures of two N-phenylated tricyclic benzothiazines were determined 3-amino-7-chloro-9-phenyl-1,9H-pyrazolo-[4,3-b]benzothiazine 4,4-dioxide, C15H11ClN4O2S crystallises in P21/c with a = 11.436 (4)Å, b = 10.894 (3)Å, c = 11.858 (4)Å, β = 95.297 (9)°, V = 1471.0 (8) Å3 and Z = 4, while 2,4-diamino-8-chloro-10H-phenylpyrimido-[5,4-b]benzothiazine 5,5-dioxide, C16H12ClN5O2S crystallises in P21/c with a = 7.496 (2)Å, b = 17.7 28 (4)Å, c = 11.889 (2)Å, (3 = 91.524 (5)°, V = 1579.4 (5)Å3 and Z = 4. Both molecules are essentially planar, including the exocyclic groups. These compounds were promising as inhibitors of hemoglobin hydrolysis, however, their effect as inhibitors of β-hematin formation was marginal. The most active compound to emerge from the in vitro and in vivo murine studies was the pyrimidobezothaizine, suggesting an antimalarial activity via inhibition of haemoglobin hydrolysis, but it was not as efficient as chloroquine.