Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives

Figures & data

Figure 1.  Structure of triclosan.

Scheme 1.  Synthesis of the oxadiazole thiones, triazoles, and pyrazoline derivatives of diphenyl ethers.

Ar, ortho-, meta-, or para- phenoxy phenyl (a, b, c) in case of oxadiazolethione (5a, 5b, and 5c) and triazole derivatives (7a, 7b, and 7c). Ar, meta-phenoxy phenyl for (9).

Table 1.  Structures of the compounds synthesised and some of their physical properties.

Code	Structure	Mw	Yield%	mp °C	Elemental analysis Calculated (found)
5a		270.31	87	122	C-62.21% (62.19%)H-3.73% (3.53%)N-10.36% (10.25%)
5b		270.31	85	154	C-62.21% (62.19%)H-3.73% (3.63%)N-10.36% (10.35%)
5c		270.31	70	190	C-62.21% (62.19%)H-3.73% (3.53%)N-10.36% (10.25)
7a		345.42	88	270	C-69.54% (69.55%)H-4.38% (4.36%)N-12.17% (12.16%)
7b		345.42	86	268	C-69.54% (69.55%)H-4.38%(4.36%)N-12.17% (12.16%)
7c		345.42	78	188	C-69.54%(69.55%)H-4.38%(4.36%)N-12.17% (12.16%)
9		419.47	65	130	C-77.31% (77.11%)H-5.05% (5%)N-10.02%(10%)
10a		313.35	65	78	C-80.49% (80.39%)H-4.82% (4.83%)N-4.47% (4.45%)
10b		347.79	70	82	C-72.52% (72.49%)H-4.06% (4.03%)N-4.03% (4.05%)
10c		343.38	60	100	C-80.75% (80.69%)H-4.52% (4.53%)N-4.48% (4.45%)

Scheme 2.  Synthesis of isoxazoles

Ar, meta-phenoxy phenyl; R = H (10a), 4-chloro (10b), and 4-methoxy (10c).

Table 2.  Biological activity of the diphenyl ether derivatives against H37Rv strain of M. tuberculosis and inhibitory activity against ENR.

Code	M. tuberculosis Inhibition (%)^a	Inhibition of ENR (%)^b
5a	100	0
5b	100	1
5c	100	Nd
7a	100	0
7b	100	0
7c	100	0
9	100	3
10a	100	27
10b	100	16
10c	100	1
Triclosan	100	100

^aAt 1 µg/mL concentration, which corresponds to 2.4–3.7 µM.

^bAt 100 µM.