Table 1.

Inhibitory activity of type I compounds 7a-i, 8a-i, 9a-e, 10a-b, 11a-b, 12 and 15a-b against DNA gyrase from E. coli.

Compd.	R1	R2	R3	R4	*	IC50 (nM)a or RA (%)b
						E. coli gyrase
7a	4,5-diBr	iPr	iPr	COOMe	l	94%
7b	4,5-diBr	iPr	Bn	COOMe	l	100%
7c	4,5-diBr	iPr	CH3	COOMe	l	93%
7d	3,4-diCl-5-Me	iPr	Bn	COOMe	l	100%
7e	3,4-diCl-5-Me	iPr	CH3	COOMe	l	66%
7f	3,4-diCl-5-Me	iPr	CH3	COOMe	d	87%
7g	4,5-diBr	CH2CH2NHBoc	H	COOMe	/	53%
7h	4,5-diBr	CH2CH2NHBoc	Bn	COOMe	l	100%
7i	3,4-diCl-5-Me	CH2CH2NHBoc	CH3	COOMe	l	100%
8a	4,5-diBr	iPr	iPr	COOH	l	70%
8b	4,5-diBr	iPr	Bn	COOH	l	100%
8c	4,5-diBr	iPr	CH3	COOH	l	370 ± 160 nM
8d	3,4-diCl-5-Me	iPr	Bn	COOH	l	91%
8e	3,4-diCl-5-Me	iPr	CH3	COOH	l	38 ± 9 nM
8f	3,4-diCl-5-Me	iPr	CH3	COOH	d	41 ± 16 nM
8g	4,5-diBr	CH2CH2NHBoc	H	COOH	/	96%
8h	4,5-diBr	CH2CH2NHBoc	Bn	COOH	l	100%
8i	3,4-diCl-5-Me	CH2CH2NHBoc	CH3	COOH	l	590 ± 20 nM
9a	4,5-diBr	${\text{CH}}_{\text{2}}{\text{CH}}_{\text{2}}{\text{NH}}_{\text{3}}^{+}{\text{Cl}}^{-}$	Bn	COOMe	l	85%
9b	3,4-diCl-5-Me	${\text{CH}}_{\text{2}}{\text{CH}}_{\text{2}}{\text{NH}}_{\text{3}}^{+}{\text{Cl}}^{-}$	CH3	COOMe	l	34 ± 1 nM
9c	4,5-diBr	${\text{CH}}_{\text{2}}{\text{CH}}_{\text{2}}{\text{NH}}_{\text{3}}^{+}{\text{Cl}}^{-}$	H	COOH	l	50%
9d	4,5-diBr	${\text{CH}}_{\text{2}}{\text{CH}}_{\text{2}}{\text{NH}}_{\text{3}}^{+}{\text{Cl}}^{-}$	Bn	COOH	l	370 ± 10 nM
9e	3,4-diCl-5-Me	${\text{CH}}_{\text{2}}{\text{CH}}_{\text{2}}{\text{NH}}_{\text{3}}^{+}{\text{Cl}}^{-}$	CH3	COOH	l	28 ± 7 nM
10a	3,4-diCl-5-Me	iPr	CH3	CONHNH2	l	280 ± 80 nM
10b	3,4-diCl-5-Me	CH2CH2NHBoc	CH3	CONHNH2	l	68%
11a	3,4-diCl-5-Me	iPr	CH3		l	85 ± 7 nM
11b	3,4-diCl-5-Me	CH2CH2NHBoc	CH3		l	1600 ± 200 nM
12	3,4-diCl-5-Me	${\text{CH}}_{\text{2}}{\text{CH}}_{\text{2}}{\text{NH}}_{\text{3}}^{+}{\text{Cl}}^{-}$	CH3		l	13 ± 4 nM
15a	4,5-diBr	iPr	H		/	100%
15b	4,5-diBr	iPr	H		/	87%
novobiocin						170 ± 20 nM

^aConcentration of compound that inhibits the enzyme activity by 50%.

^bResidual activity of the enzyme at 1 μM of the compound.