Synthesis and in vitro antitumor and antimicrobial activity of some 2,3-diaryl-7-methyl-4,5,6,7-tetrahydroindazole and 3,3a,4,5,6,7-hexahydroindazole derivatives

Figures & data

Table 1.  Physicochemical and analytical data of compounds 2–10.

Compound number	X	R	M.P. (°C)	Yield (%)	Mol. Formula (Mol. Weight)	Analysis
						Calculated/Found (%)
						C	H	N	S
2a	H		199–200	88	C20H23N3O2S	65.01	6.27	11.37	8.68
					(369.48)	64.95	6.33	11.45	8.59
2b	Cl		202–203	84	C20H22ClN3O2S	59.47	5.49	10.40	7.94
					(403.93)	59.30	5.60	10.27	8.05
2c	CH3		204–206	85	C21H25N3O2S	65.77	6.57	10.96	8.36
					(383.51)	65.58	6.74	11.20	8.15
3a	H		150–152	72	C20H21N3O2S	65.37	5.76	11.44	8.73
					(367.46)	65.40	5.70	11.35	8.90
3b	Cl		148–149	70	C20H20ClN3O2S	59.77	5.02	10.46	7.98
					(401.91)	59.85	4.96	10.50	8.04
3c	CH3		126–127	68	C21H23N3O2S	66.12	6.08	11.01	8.41
					(381.49)	66.12	6.08	11.01	8.41
4a	H	cyclohexyl	149–150	72	C27H34N4O3S	65.56	6.93	11.33	6.48
					(494.65)	65.45	7.10	11.50	6.40
4b	H	C6H5	138–139	75	C27H28N4O3S)	66.37	5.78	11.47	6.56
					(488.60)	66.15	5.92	11.55	6.77
4c	H	1-naphthyl	196–198	77	C31H30N4O3S	69.12	5.61	10.40	5.95
					(538.66)	69.03	5.80	10.50	5.78
4d	CH3	cyclohexyl	206–207	74	C28H36N4O3S	66.11	7.13	11.01	6.30
					9508.68)	66.20	7.05	10.88	6.46
4e	CH3	C6H5	158–160	75	C28H30N4O3S	66.91	6.02	11.15	6.38
					(502.63)	67.01	5.92	11.33	6.30
4f	CH3	1-naphthyl	169–170	78	C32H32N4O3S	69.54	5.84	10.14	5.80
					(552.69)	69.48	5.96	10.20	5.76
5a	H	cyclohexyl	134–136	70	C27H32N4O3S	65.83	6.55	11.37	6.51
					(492.63)	66.01	6.39	11.26	6.70
5b	H	C6H5	162–164	72	C27H26N4O3S	66.65	5.39	11.51	6.59
					(486.59)	66.54	5.47	11.60	6.65
5c	H	1-naphthyl	148–149	75	C31H28N4O3S	69.38	5.26	10.44	5.98
					(536.64)	69.12	5.44	10.60	5.73
5d	CH3	C6H5	172–173	78	C28H28N4O3S	67.18	5.64	11.19	6.41
					(500.61)	66.95	5.82	11.36	6.27
5e	CH3	1-naphthyl	156–157	75	C32H30N4O3S	69.80	5.49	10.17	5.82
					(550.67)	69.69	5.60	10.25	5.92
6a	H	C6H5	162–163	89	C27H28N4O2S2	64.26	5.59	11.10	12.71
					(504.67)	64.07	5.74	10.96	12.90
6b	H	CH2C6H5	128–129	72	C28H30N4O2S2	64.84	5.83	10.80	12.36
					(518.69)	65.02	5.68	10.89	12.21
6c	Cl	C6H5	172–174	75	C27H27ClN4O2S2	60.15	5.05	10.39	11.90
					(539.11)	60.23	4.98	10.26	12.10
6d	Cl	CH2C6H5	136–137	72	C28H29ClN4O2S2	60.80	5.28	10.13	11.59
					(553.14)	60.44	5.37	10.06	11.78
6e	Cl	COC6H5	140–142	70	C28H27ClN4O3S2	59.30	4.80	9.88	11.31
					(567.12)	59.21	4.89	10.01	11.25
6f	CH3	C6H5	122–123	88	C28H30N4O2S2	64.84	5.83	10.80	12.36
					(518.69)	65.00	5.67	10.90	12.25
6g	CH3	CH2C6H5	160–161	66	C29H32N4O2S2	65.38	6.05	10.52	12.04
					(532.72)	68.18	6.22	10.44	12.13
6h	CH3	COC6H5	140–142	72	C29H30N4O3S2	63.71	5.53	10.25	11.73
					(546.70)	63.90	5.48	10.47	11.68
7a	H	C6H5	212–214	78	C29H28N4O3S2	63.95	5.18	10.29	11.77
					(544.69)	64.04	5.10	10.06	12.01
7b	H	CH2C6H5	126–128	65	C29H28N4O3S2	64.49	5.41	10.03	11.48
					(558.71)	64.22	5.60	9.89	11.63
7c	Cl	COC6H5	162–164	72	C30H27ClN4O4S2	59.35	4.48	9.23	10.56
					(607.14)	59.52	4.21	9.44	10.10
7d	CH3	C6H5	187–188	74	C30H30N4O3S2	64.49	5.41	10.03	11.48
					(558.71)	64.77	5.23	10.12	11.39
7e	CH3	CH2C6H5	137–138	70	C31H32N4O3S2	65.01	5.63	9.78	11.20
					(572.74)	64.88	5.92	9.54	11.47
7f	CH3	COC6H5	150–152	72	C31H30N4O4S2	63.46	5.15	9.55	10.93
					(586.72)	63.21	5.36	9.40	11.09
8a	H	C6H5	168–169	75	C35H32N4O2S2	69.51	5.33	9.26	10.60
					(604.78)	69.86	5.18	9.14	10.82
8b	H	CH2C6H5	112–113	62	C36H34N4O2S2	69.87	5.54	9.05	10.36
					(618.81)	70.06	5.39	9.17	10.24
8c	CH3	C6H5	122–123	64	C36H34N4O2S2	69.87	5.54	9.05	10.36
					(618.81)	69.99	5.35	9.21	10.18
9a	H	C6H5	134–135	67	C30H30N4O3S2	64.49	5.41	10.03	11.48
					(558.71)	64.30	5.67	9.95	11.64
9b	CH3	C6H5	130–132	65	C31H32N4O3S2	65.01	5.63	9.78	11.20
					(572.74)	64.86	5.99	9.90	11.03
9c	CH3	CH2C6H5	122–124	62	C32H34N4O3S2	65.50	5.84	9.55	10.93
					(586.77)	65.77	5.60	9.37	10.74
10a	H	C6H5	174–176	70	C30H30N4O3S2	64.49	5.41	10.03	11.48
					(558.71)	64.27	5.70	9.89	11.66
10b	H	CH2C6H5	136–138	69	C31H32N4O3S2	65.01	5.63	9.78	11.20
					(572.74)	64.85	5.81	10.01	11.14
10c	CH3	C6H5	162–164	74	C31H32N4O3S2	65.0164.91	5.63	9.78	11.20
					(572.74)	64.91	5.77	9.92	11.08

Table 2.  ¹H-NMR spectral data of compounds^a (2–10).

Compound number	X	R	H-4,5,6 cyclohexyl (m, 6H)	CH3 (d, 3H)	H-7 (m, 1H)	H-3a (m, 1H)	H-3 (d, 1H)	Ar-H (m)	Others
2a	H		1.46–1.74	1.28	3.04	3.67	5.38	6.85–7.58 (11H)^b
2b	Cl		1.42–1.75	1.28	2.94	3.70	4.95	6.82–7.88 (10H)^b
2c	CH3		1.38–1.69	1.27	3.03	3.64	5.31	6.76–7.92 (10H)^b	2.31 (s, 3H, Tol-CH3)
3a	H		1.52–2.35	1.26	3.08	–	–	6.82–7.68 (11H)^b
3b	Cl		1.45–1.62	1.27	3.10	–	–	6.77–7.82 (10H)^b
3c	CH3		1.62–2.28	1.30	3.12	–	–	6.90–7.82 (10H)^b	2.35 (s, 3H, Tol-CH3)
4a	H	cyclohexyl	1.14–2.74^c	1.24	3.10	3.78	5.44	7.14–8.11 (9H)	9.1 (s, 1H, NH), 9.6 (s, 1H, NH)
4b	H	C6H5	1.36–1.72	1.27	2.98	3.62	5.32	6.83–7.55 (14H)	8.93 (s, 1H, NH), 9.25 (s, 1H, NH)
4c	H	1-naphthyl	1.38–1.80	1.25	3.02	3.71	5.38	6.98–8.02 (16H)	9.11 (s, 1H, NH), 9.72 (s, 1H, NH)
4d	CH3	cyclohexyl	1.22–2.68^c	1.23	3.14	3.65	5.52	7.23–7.92 (8H)	2.32 (s, 3H, Tol-CH3), 9.23 (s, 1H, NH), 9.58 (s, 1H, NH)
4e	CH3	C6H5	1.39–1.79	1.27	3.06	3.63	5.42	7.02–7.98 (13H)	2.35 (s, 3H, Tol-CH3), 9.32 (s, 1H, NH), 9.63 (s, 1H, NH)
5a	H	cyclohexyl	1.18–2.60^c	1.27	3.11	–	–	7.04–7.99 (8H)	9.25 (s, 1H, NH), 9.48 (s, 1H, NH)
5b	H	C6H5	1.35–2.28	1.28	3.05	–	–	7.02–8.05 (13H)	9.32 (s, 1H, NH), 9.43 (s, 1H, NH)
5c	H	1-naphthyl	1.38–2.17	1.28	3.07	–	–	7.18–8.06 (15H)	9.04 (s, 1H, NH), 9.65 (s, 1H, NH)
5d	CH3	C6H5	1.42–2.30	1.27	3.10	–	–	7.12–8.15 (13H)	2.38 (s, 3H, Tol-CH3), 9.26 (s, 1H, NH), 9.42 (s, 1H, NH)
5e	CH3	1-naphthyl	1.29–2.26	1.26	3.18	–	–	7.24–8.12 (15H)	2.34 (s, 3H, Tol-CH3), 9.15 (s, 1H, NH), 9.61 (s, 1H, NH)
6a	H	C6H5	1.48–1.75	1.24	3.68	3.65	5.24	6.92–7.80 (14H)	9.02 (s, 1H, NH), 9.78 (s, 1H, NH)
6b	H	CH2C6H5	1.39–1.72	1.26	3.58	3.92	5.25	7.02–7.82 (14H)	4.75 (d, 2H, CH2- C6H5), 9.13 (s, 1H, NH), 9.92 (s, 1H, NH)
6c	Cl	C6H5	1.41–1.78	1.24	3.42	3.70	5.21	6.87–7.84 (13H)	9.24 (s, 1H, NH), 9.63 (s, 1H, NH)
6d	Cl	CH2C6H5	1.39–1.67	1.23	3.38	3.62	5.14	7.11–7.89 (13H)	4.72 (d, 2H, CH2), 9.08 (s, 1H, NH), 9.52 (s, 1H, NH)
6e	Cl	COC6H5	1.40–1.82	1.25	3.02	3.74	5.16	7.16–7.79 (13H)	9.18 (s, 1H, NH), 9.63 (s, 1H, NH)
6f	CH3	C6H5	1.37–1.67	1.25	3.00	3.72	5.32	6.78–7.90 (13H)	2.32 (s, 3H, Tol-CH3), 9.21 (s, 1H, NH), 9.78 (s, 1H, NH)
6g	CH3	CH2C6H5	1.34–1.69	1.28	3.14	3.66	5.04	7.13–8.11 (13H)	2.29 (s, 3H, Tol-CH3), 4.29 (d, 2H, CH2), 9.03 (s, 1H, NH), 9.49 (s, 1H, NH)
6h	CH3	COC6H5	1.44–1.78	1.31	3.06	3.72	5.12	7.16–8.03 (13H)	2.34 (s, 3H, Tol-CH3), 9.14 (s, 1H, NH), 9.55 (s, 1H, NH)
7a	H	C6H5	1.42–1.72	1.28	3.10	3.64	5.34	6.92–7.85 (14H)	4.30 (s, 2H, CH2)
7b	H	CH2C6H5	1.45–1.75	1.29	3.03	3.78	5.22	7.01–8.10 (14H)	4.16 (s, 2H, CH2), 4.82 (s, 2H, CH2- C6H5)
7c	Cl	COC6H5	1.40–1.74	1.28	3.06	3.77	5.25	6.88–7.82 (13H)	4.33 (s, 2H, CH2)
7d	CH3	C6H5	1.43–1.69	1.26	3.12	3.69	5.43	7.14–7.92 (13H)	2.31 (s, 3H, Tol-CH3), 4.13 (s, 2H, CH2)
7e	CH3	CH2C6H5	1.39–1.72	1.24	3.34	3.84	5.68	7.12–7.85 (13H)	2.34 (s, 3H, Tol-CH3), 4.24 (s, 2H, CH2), 4.80 (s, 2H, CH2)
7f	CH3	COC6H5	1.40–1.75	1.25	3.24	3.75	5.52	7.09–7.88 (13H)	2.30 (s, 3H, Tol-CH3), 4.19 (s, 2H, CH2)
8a	H	C6H5	1.38–1.85	1.29	2.98	3.65	5.28	6.80–7.75 (19H)	5.78 (s, 1H, H-5 thiazole)
8b	H	CH2C6H5	1.37–1.75	1.26	3.01	3.68	5.10	6.70–7.88 (19H)	4.75(s, 2H,CH2), 5.89 (s, 1H, H-5 thiazole)
8c	CH3	C6H5	1.36–1.78	1.28	3.05	3.72	5.15	6.80–7.95 (18H)	2.35 (s, 3H, Tol-CH3), 5.74 (s, 1H, H-5 thiazole)
9a	H	C6H5	1.38–1.85	1.26	3.25^d	3.68	5.10	6.70–7.88 (14H)
9b	CH3	C6H5	1.35–1.90	1.32	3.19^d	3.72	5.30	6.92–7.82 (13H)	2.32 (s, 3H, Tol-CH3)
9c	CH3	CH2C6H5	1.41–1.72	1.23	3.09^d	3.74	5.48	6.88–7.90 (13H)	2.31 (s, 3H, Tol-CH3), 4.75 (d, 2H, CH2- C6H5)
10a	H	C6H5	1.34–1.78	1.29	2.99	3.70	5.29	6.88–7.82 (14H)	4.40 (s, 2H, H-4 thiazine), 5.42 (s, 2H, H-6 thiazine)
10b	H	CH2C6H5	1.37–1.79	1.20	3.12	3.78	5.34	6.94–7.82 (14H)	4.42 (s, 2H, H-4 thiazine), 5.62 (s, 2H, H-6 thiazine)
10c	CH3	C6H5	1.40–1.68	1.29	3.20	3.69	5.21	6.86–7.78 (13H)	2.34 (s, 3H, Tol-CH3), 4.38 (s, 2H, H-4 thiazine), 5.54 (s, 2H, H-6 thiazine)

^aSolutions in a mixture of CDCl₃ and DMSO-d₆; ^b(Ar-H + NH₂); ^c(m, 16H, 2cyclohexyl); ^d(m, 5H, H-7 and H-5 & H-6 of thiazine).

Scheme 1.  Scheme 1 Reagents and reaction conditions: (i) ethanol, reflux, 4 h; (ii, iv) Br₂ water, r.t., 3 h; (iii, v) RNCO, anhyd.K₂CO₃, acetone, reflux, 18 h; (vi) RNCS, anhyd. K₂CO₃, acetone, reflux, 10 h.

Scheme 2.  Reagents and reaction conditions: (i) ethyl bromoacetate, anhyd. Na acetate, ethanol, reflux, e h; (ii) phenacyl bromide, anhyd. Na acetate, ethanol, reflux, 3 h; (iii) ethyl 3-bromopropionate, anhyd. Na acetate, ethanol, reflux, 4 h; (iv) 1,3-dichloroacetone, anhyd. Na acetate, ethanol, areflux, 5 h.

Table 3.  Growth inhibitory concentration (GI₅₀, μM) of the active compounds.

Cell Lines	3c	4d	4e	5a	5d	8c
Leukaemia
CCRF-CEM	3.65	18.43	18.67	0.55	2.46	16.71
HL-60 (TB)	NT^a	23.02	18.51	6.20	24.62	15.50
K-562	17.4	13.36	12.70	3.23	12.24	16.01
MOLT-4	10.2	7.70	8.23	1.90	6.11	13.72
RPMI-8226	18.2	5.56	15.41	3.20	7.43	13.63
SR	14.5	6.53	3.01	0.80	2.35	12.06
Non-Small Cell Lung Cancer
A549/ATCC	24.74	13.91	13.21	22.27	27.90	19.81
EKVX	20.21	21.10	13.92	11.62	18.52	22.00
HOP-62	21.41	46.75	18.95	17.55	33.15	42.22
HOP-92	14.60	13.33	15.30	2.79	18.83	19.21
NCI-H226	17.12	20.82	16.01	21.81	16.46	22.22
NCI-H23	23.12	14.85	14.72	11.90	16.90	NT
NCI-H322	19.80	4.98	20.62	4.95	15.84	29.01
NCI-H460	21.32	21.81	22.03	8.93	19.91	16.20
NCI-H522	11.75	6.80	12.66	12.84	11.22	24.61
Colon Cancer
COLO 205	22.14	13.51	19.01	11.81	20.00	24.32
HCC-2998	8.62	11.82	NT	NT	13.81	NT
HCT-116	11.53	16.52	3.40	4.02	20.92	17.90
HCT-15	20.62	20.83	15.52	17.42	16.45	24.32
HT29	22.15	23.86	25.35	24.94	36.78	NT
KM12	16.40	11.92	18.03	13.52	17.51	23.20
SW-620	4.82	16.60	12.92	2.82	12.40	15.9
CNS Cancer
SF-268	21.31	23.24	18.54	12.07	19.77	15.47
SF-295	21.14	18.54	13.07	17.62	33.22	18.92
SF-539	19.01	21.21	13.92	10.06	18.87	18.35
SNB-19	384	22.32	25.78	20.92	31.32	66.77
SNB-75	17.94	44.73	18.36	21.64	23.48	NT
U251	20.14	12.85	13.94	11.57	18.50	19.64
Melanoma
LOX IMVI	19.35	18.43	12.54	1.95	11.37	18.40
M14	20.20	35.70	17.41	19.47	23.74	32.52
SK-MEL-2	12.67	17.56	15.32	15.67	17.15	22.01
SK-MEL-28	18.67	18.32	23.5	17.30	20.44	NT
SK-MEL-5	12.78	14.97	14.26	1.36	13.23	14.1
UACC-257	21.22	22.44	18.49	24.72	17.70	21.43
UACC-62	13.74	11.94	12.28	18.08	11.82	15.05
Ovarian Cancer
IGROV1	3.3	5.8	11.7	11.3	3.8	26.9
OVCAR-3	14.6	14.9	13.7	19.7	33.3	16.2
OVCAR-4	16.4	18.6	16.5	16.8	20.4	NT
OVCAR-5	26.2	28.3	13.1	28.4	31.9	NT
OVCAR-8	35.4	19.7	22.4	27.0	18.9	22.3
SK-OV-3	48.2	21.2	17.9	19.5	17.7	35.1
Renal Cancer
786-0	16.12	29.40	12.61	2.33	22.84	32.57
A498	6.28	22.51	16.0	0.02	19.70	14.76
ACHN	19.89	14.77	13.81	15.6	14.8	21.82
CAKI-1	18.17	17.40	13.66	19.50	16.04	17.16
RXF 393	17.80	18.78	16.70	22.73	16.59	23.80
SN12C	18.11	17.06	14.10	18.94	17.00	16.76
TK-10	20.12	12.34	16.60	1.72	11.32	19.19
UO-31	6.64	11.16	11.72	1.35	8.75	17.74
Prostate Cancer
PC-3	17.12	10.66	14.95	12.61	17.10	22.53
DU-145	15.26	24.61	14.22	15.53	15.93	23.79
Breast Cancer
MCF7	32.43	11.35	18.11	5.94	21.54	5.67
NCI/ADR-RES	22.44	12.74	16.17	17.00	33.81	NT
MDA-MB-231/ATCC	13.85	28.52	11.58	21.89	17.55	15.19
HS 578T	14.57	24.76	18.74	21.15	23.81	19.02
MDA-MB-435	17.92	15.06	17.17	19.54	28.22	18.16
BT-549	NT	17.78	15.47	12.14	18.09	19.28
T-47D	72.23	31.45	35.98	26.47	31.05	36.85

^aNT: Not Tested.

Figure 1.  Leukaemia Growth inhibitory concentration (GI₅₀, μM) of the active compounds.

Figure 2.  Melanoma Growth inhibitory concentration (GI₅₀, μM) of the active compounds.

Figure 3.  Renal Cancer Growth inhibitory concentration (GI₅₀, μM) of the active compounds.

Table 4.  Median growth inhibitory concentrations (GI₅₀, μM), total growth inhibitory concentrations (TGI, μM) and lethal concentrations (LC₅₀, μM) of in vitro subpanel tumor cell lines.

Compound number	Subpanel Tumor Cell Lines^a									MG-MID^b
	I	II	III	IV	V	VI	VII	VIII	IX	GI50	TGI	LC50
3c	13.08	18.13	15.38	22.2	15.5	24.02	14.81	16.84	30.0	15.60	39.61	78.30
4d	10.43	16.54	16.40	23.6	19.6	18.14	17.42	16.40	20.5	15.91	38.40	77.80
4e	12.55	14.37	15.25	17.01	15.72	16.05	15.03	13.84	18.6	14.40	49.62	88.23
5a	2.45	11.21	12.00	15.82	14.20	20.51	10.41	12.21	17.1	9.22	26.61	69.80
5d	8.70	18.29	19.41	24.71	16.67	20.65	16.51	15.65	21.8	16.64	54.22	91.23
8c	14.19	23.61	20.67	18.58	20.62	25.52	20.82	23.00	18.2	20.04	51.63	90.11
S^c	1.27	1.05	1.21	1.21	1.30	1.163	1.16	NT^d	NT	1.19	1.63	1.99

^aGI₅₀ values against: I, Leukaemia; II, non-small cell lung cancer; III, colon cancer; IV, CNS cancer; V, melanoma; VI, ovarian cancer; VII, renal cancer; VIII, prostate cancer; IX, breast cancer.

^bGI₅₀, TGI and LC₅₀ (μM) full panel mean-graph midpoint (MG-MID) = the average sensitivity of all cell lines towards the test agent.

^cSulofenur; (NSC 656667): NCI cancer screen; August 2004.

^dNT = Not tested.

Figure 4.  Structures of sulofenur A, its congeners B–D and the general structures of the new compounds E and F.

Table 5.  Antimicrobial activity of the target compounds 2–10.

Compound number	S. aureus (ATCC 25923)		B. subtilis (ATCC 6051)		E.coli (ATCC 25922)		P. aeruginosa (ATCC 27853)		C. albicans (ATCC 10231)
	IZ^a	MIC^b	IZ	MIC	IZ	MIC	IZ	MIC	IZ	MIC
2a	10	>200 (540)	9	...c	7	…	NA^d	…	6	…
2b	13	100 (247.6)	14	100 (247.6)	14	200 (495.1)	10	…	12	...
2c	15	100 (260.7)	16	200 (521.5)	8	…	NA	…	14	100
3a	19	100 (272.1)	18	100 (272.1)	10	…	NA	…	9	…
3b	22	100 (248.8)	17	100 (248.8)	14	200 (497.6)	10	…	16	100 (248.8)
3c	24	50 (131)	20	50 (131)	15	200 (524)	11	…	23	100 (262)
4a	19	50 (101.1)	18	100 (202.2)	6	…	NA	…	8	…
4b	16	100 (204.7)	15	200 (409.3)	9	...	NA	...	10	...
4d	18	100 (196.6)	16	200 (393.2)	14	200 (393.2)	12	100 (196.6)	15	100 (196.6)
4e	17	100 (198.9)	15	200 (397.9)	12	200 (397.9)	10	…	9	...
5a	28	12.5 (25.4)	22	50 (101.5)	17	50 (101.5)	14	200 (406)	29	50 (101.5)
5b	20	50 (102.7)	16	100 (205.4)	12	200 (410.8)	10	…	18	50 (102.7)
5d	24	50 (100)	18	100 (200)	16	100 (200)	11	…	20	50 (100)
6a	8	...	6	…	NA	…	10	…	NA	…
6b	7	…	8	...	6	…	5	…	NA	…
6c	9	…	6	…	NA	...	NA	…	NA	…
6f	10	...	8	...	10	...	6	…	9	…
7a	12	>200 (367.2)	10	...	8	...	NA	…	10	...
7b	14	100 (179)	12	200 (358)	15	200 (358)	10	…	12	100 (179)
7c	16	100 (164.7)	14	200 (329.4)	12	200 (329.4)	10	…	9	…
7d	18	100 (179)	15	200 (358)	14	200 (358)	10	…	12	100 (179)
8a	16	100 (165.3)	18	100 (165.3)	14	200 (330.6)	16	200 (330.6)	8	…
8c	18	100 (161.6)	17	100 (161.6)	16	200 (323.2)	NA	…	6	…
9a	12	>200 (358)	9	...	8	...	NA	…	NA	...
9b	18	100 (174.6)	17	50 (87.3)	14	200 349.2)	NA	…	NA	...
10a	14	200 (358)	12	200 (358)	12	...	13	…	NA	...
10b	16	100 (174.6)	14	200 (349.2)	10	…	NA	…	6	…
A*	36	12.5 (31)	30	25 (62)	32	25 (62)	27	50 (124)	…	…
C**	…	…	…	…	…	…	…	…	42	12.5 (36.2)

^aInhibition zone (mm).

^bMinimal Inhibitory Concentration: μg/mL(µM).

^cNot tested.

^dNot active.

A*: Ampicillin trihydrate; C**: Clotrimazole.

Cerecetto H, Gerpe A, González M, Arán VJ, de Ocáriz CO. Pharmacological properties of indazole derivatives: recent developments. Mini Rev Med Chem 2005;5:869–878.

 PubMed Web of Science ®Google Scholar