Activity against Trypanosoma cruzi of New Analogues of Nifurtimox

Abstract

Ten new derivatives 1 structurally related to Nifurtimox have been synthesized from 5‐nitrofurfural and the corresponding N‐aminoheterocyclic compounds. Physical data, spectroscopic characteristics and biological properties have been examined. An unusual long‐range coupling constant in the pyrazolyl derivative 1b has been observed. Compounds in which the heterocyclic counterparts are 1,2,4‐triazol‐4‐yl and pyridin‐1‐yl groups clearly show s superior activity against Trypanosoma cruzi.

Molecular structure in the solid state (X‐Ray diffraction) and in solution (1H and 13C NMR) of nifurtimox and two pyrazol‐1‐Yl analogs

“…3(6) 125.5(4) 119.5(6) 121 . I (4) 115.5 (6) 116.1(3) 121.8(6) 123.9(3) 112.7 (7) 113.0 (5) 105.1 (7) 106.2(4) 01 5-N13-C2-X1 -2.0(10) 0.4 (5) Xi-C5-C6-N7 -3.9(11) -0.5 (6) C5-C6-N7-N8 179.8 (7) 180.5 (3) C6-N7-N8-N9 ~ 4.2(11) 2.2 (5) Conformation and configuration of compounds 1, 2 and 3 in solution (lH and 13C NMR study).-These molecules present several structural problems : i) the configuration of the C6-N7 double bond; ii) the conformation about the C5C6 single bond;…”

“…Synthesis of compounds 2 and 3 has been (4) or will be described elsewhere (7). X-Ray Crystallography.-The main characteristics of the X-ray analysis are given in Table 1.…”

“…By analogy, a compound 2 where a 1-pyrazolyl residue replaces the thiazine 1,l-dioxide ring was designed, synthesized (4), and biologically evaluated (4)(5)(6). It shows powerful antiprotozoal properties.…”

A New Analogue of Nifurtimox

“…This chemical was also found to be mutagenic in bacteria (Nagel, 1987). These drawbacks led to the synthesis of a new series of nifurtimox analogues with activity against Trypanosoma cruzi (Mester et al, 1987), among them compound (1). As the knowledge of the threedimensional structure of this compound is necessary to try to understand its behaviour at the molecular level, a crystal-structure determination was undertaken.…”