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, C 15 H 11 ClN 4 O 2 S crystallises in P2 1 /c with a = 11.436 (4)Å, b = 10.894 (3)Å, c = 11.858 (4)Å, = 95.297 (9)°, V = 1471.0 (8) Å 3 and Z = 4, while 2,4-diamino-8-chloro-10H-phenylpyrimido-[5,4b]benzothiazine 5,5-dioxide, C 16 H 12 ClN 5 O 2 S crystallises in P2 1 /c with a = 7.496 (2)Å, b = 17.728 (4)Å, c = 11.889 (2)Å, = 91.524 ( 5)°, V = 1579.4 (5)Å 3 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 -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.

Transannular S...N interactions in 10-ethynyl-10H-phenothiazine 5-oxide and 5,5-dioxide

“…The central six-membered rings of (1) and (2) in boat conformations correspond to the usual geometry for phenothiazine 5-oxides and 5,5-dioxides, except for a few examples (Kormos et al, 2012). When one or both benzene rings are removed or replaced by a heteroaromatic ring, however, the resulting 1,4-thiazine 5,5-dioxides are planar (Akkurt et al, 2005;Andreetti et al, 1974;Barazarte et al, 2008Barazarte et al, , 2009Charris et al, 2007;Chia et al, 2008;Fraenkel et al, 1986;Girard et al, 1987;Wang, Mudraboyina et al, 2010;Wang, Wisner & Jennings, 2010) The molecular structure of (2), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres.…”

2,1-Benzothiazine – (quinolin/thiophen)yl hydrazone frameworks as new monoamine oxidase inhibitory agents; synthesis, in vitro and in silico investigation

“…5 Among different heterocyclic compounds, benzothiazine ring systems are one of the supreme targeted areas for the synthetic and clinical interest in the eld of pharmacokinetics as they act as a skeleton with a rich bio-activity prole. [6][7][8] A number of biological potentials have marked benzothiazine based derivatives interesting as antifungal, 9,10 anti-bacterial, 10,11 anti-malarial, 12 anti-oxidant, 13 anti-hypertensive, 14 anti-neoplastic, 15 antiviral, 16,17 and cardio-protective 18 agents. 1,2-Benzothiazines have experimentally proven to be effective as analgesic agents and different candidates have been tested to examine their respective strength as painkillers and anti-inammatory pills.…”