An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1 H -indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3 . Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major . Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR- 13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1–3 Å. MM/GBSA binding free energies illustrated the high stability of TryR- 13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.

In the title compound, C 9 H 8 ClN 3 O 2 , the orientation of the ethyl substituent is partly determined by an intramolecular C-HÁ Á ÁCl hydrogen bond. The indazole moiety is slightly folded with an angle of 0.70 (8) between the fiveand six-membered rings. In the crystal, molecules pack in layers parallel to [100] through C-HÁ Á Á(ring) and N . . . OÁ Á Á(ring) interactions.

The asymmetric unit of the title compound, C 11 H 11 N 3 O 4 , comprises two independent molecules, both of which display positional disorder of their ethyl chains in 0.868 (4):0.132 (4) and 0.839 (4):0.161 (4) ratios. The packing is directed by a combination of C-HÁ Á ÁO hydrogen bonds and N-OÁ Á Á interactions between nitro groups and the aromatic rings. Structure descriptionAs a continuation of our studies of N-substituted indazole derivatives and their potential pharmacological activities (Boulhaoua et al., 2016;Mohamed Abdelahi et al., 2017), we now describe the synthesis and structure of the title compound.The asymmetric unit comprises two independent molecules differing primarily in the orientations of the ester groups (Fig. 1). The dihedral angle between the five-and sixmembered rings making up the imidazole rings are 1.12 (3) in the molecule containing N1 and N2 and 1.28 (3) in the other. In both molecules, the ethyl groups are approximately 15% disordered.The packing is directed by a combination of C-HÁ Á ÁO hydrogen bonds (Table 1) and N-OÁ Á Á contacts between nitro groups and the six-membered rings of the indazole moieties. Fig. 1 shows the C8-H8AÁ Á ÁO5 hydrogen bond occurring within the asymmetric unit as well as the N3-O3Á Á Á(C12-C17 ring) interaction [OÁ Á Á = 3.131 (1) Å , N-OÁ Á Á = 102.81 (9) ] The second N-OÁ Á Á interaction occurs between N6-O7 and the centroid of the C1-C6 ring at x, y, z + 1 [OÁ Á Á = 3.14 (1) Å , N-OÁ Á Á = 109.16 (9) ]. The combination of hydrogen bonds and N-OÁ Á Á interactions leads to a layer structure parallel to (100) (Figs. 2 and 3).

In the title molecule, C 9 H 7 N 3 O 3 , the indazole moiety is essentially planar and the mean plane of the acetyl substituent is twisted by 5.3 (1) from its plane. In the crystal, weak C-HÁ Á ÁO and C-HÁ Á ÁN hydrogen bonds form layers parallel to (102), which are associated through -stacking interactions to form a threedimensional network. The structure was refined as a two-component twin. Structure descriptionThe diverse pharmacological properties exhibited by 1H-indazoles have sparked the emergence of novel methods toward their synthesis. Indazole is a frequently found motif in drug substances with important biological activities such as antimicrobial (Li et al., 2003), anti-inflammatory (Lin et al., 2008) and anticancer effects (Zhu et al., 2007). The crystal structure study of the title compound constitutes a continuation of our previous work on indazole derivatives (Mohamed Abdelahi et al., 2017;El Brahmi et al., 2012).The indazole moiety is planar to within 0.0093 (16) Å for (C6) with an r.m.s. deviation from the mean plane of 0.005 Å . The acetyl group is slightly twisted out of the indazole plane, as indicated by the dihedral angle of 5.3 (1) between it and the N2/C8/C9/O1 plane. This orientation may be due in part to the intramolecular C2-H2Á Á ÁO1 hydrogen bond (Table 1 and Fig. 1).In the crystal, the molecules form dimers through pairwise C7-H7Á Á ÁN1 hydrogen bonds which are linked into sheets parallel to (102) by C4-H4Á Á ÁO1 hydrogen bonds (Table 1 and Fig. 2). The sheets stack along the a-axis direction and are associated through head-to-head -stacking interactions (Fig. 3) with centroidÁ Á Ácentroid distances of 3.892 (1) Å .

No abstract