New pyrano[2,3-c]pyridazine derivatives with antimicrobial activity synthesized using piperidine as the organocatalyst

Figures & data

Scheme 1. Mechanism for the synthesis of 2a–e. Reagents and conditions: arylbenzylidine, piperidine, EtOH, reflux 3 h.

Scheme 2. Synthesis of compounds 3a–c, 4a–c. Reagents and conditions: (i) CS₂, piperidine, EtOH, reflux 4 h and (ii) CS₂, EtOH, reflux 4 h.

Scheme 3. Synthesis of compounds 5,6. Reagents and conditions: (i) NaN₃, NH₄Cl, DMF, reflux 5 h and (ii) C₆H₅CHO, EtOH, piperidine, reflux 2 h.

Scheme 4. Synthesis of compounds 7–9. Reagents and conditions: (i) HCOOH, EtOH, reflux 6 h; (ii) (Ac) 2O, EtOH, reflux 6 h and (iii) HCONH₂, EtOH, reflux 6 h.

Scheme 5. Synthesis of compounds 10,11. Reagents and conditions: (i) NH₂NH₂.H₂O, EtOH, reflux 3 h and (ii) CH₂ (CN)₂, piperidine, EtOH, reflux 10 h.

Figure 1. Inhibition zones (mm) and MIC (µ/ml) of compounds 3a–c and chloramphenicol against Klebsiella pneumonia, Escherichia coli, Enterococcusi fecalis and S. aureus strains.

Figure 2. Inhibition zones (mm) and MIC (µ/ml) of compounds 3a,c and 4a,c and Nystatin against Aspergillus flavus and Candida albicans strains.

Table 1. Minimal inhibitory concentrations (MIC, µg/ml) and zones of inhibition (mm) of compounds (2b–e, 3a–c and 4a–c).

	Bacteria
Compound	Gram-negative bacteria		Gram-positive bacteria		Fungi
number	Klebsiella pneumonia	Escherichia coli	Enterococcusi fecalis	Staphylococcus aureus	Aspergillus flavus	Candida albicans
2b	–	–	–	–	–	–
2c	–	–	–	–	–	–
2d	–	–	–	–	–	–
2e	–	–	–	–	–	–
3a	10 (29)	10 (28)	15 (18)	10 (29)	5 (30)	10 (27)
3b	10 (28)	15 (29)	15 (30)	15 (32)	–	–
3c	10 (28)	10 (28)	15 (16)	15 (28)	10 (26)	15 (27)
4a	–	–	–	–	10 (28)	10 (29)
4b	–	–	–	–	–	–
4c	–	–	–	–	15 (32)	20 (35)
Reference drug
Chloramphenicol	2.5 (39)	2.5 (38)	2.5 (37)	2.5 (38)	–	–
Nystatin	–	–	–	–	2.5 (35)	5 (30)