Synthesis of some N-[4-(benzothiazole-2yl) phenyl]-2-aryloxyacetamide derivatives and their anticancer activities

Figures & data

Table 1.  Some characteristic of the compounds.

Comp.	R	R’	X	mp (°C)	Yield (%)	Molecular Formula	Analyses calc./found (%) C H N
3	H	H	O	174	70	C21H16N2O2S.1/2H2O	68.29 4.34	7.59
							68.19 4.33	7.60
4	H	4-Cl	O	222	78	C21H15ClN2O2S.H2O	61.21 3.67	6.81
							61.01 3.63	6.77
5	H	3-Cl	O	233	74	C21H15ClN2O2S.H2O	61.21 3.67	6.81
							61.01 3.63	6.77
6	H	2-Cl	O	207	72	C21H15ClN2O2S.H2O	61.21 3.67	6.81
							61.01 3.63	6.77
7	H	4-OCH3	O	176	75	C22H18N2O3S	67.6 4.65	7.17
							67.5 4.63	7.15
8	H	3-OCH3	O	160	71	C22H18N2O3S	67.6 4.65	7.17
							67.5 4.63	7.15
9	H	2-OCH3	O	132	68	C22H18N2O3S	67.6 4.65	7.17
							67.5 4.63	7.15
10	H	4-CH3	O	198	73	C22H18N2O2S.3H2O	61.67 4.20	6.54
							61.80 4.17	6.52
11	H	3-CH3	O	222	69	C22H18N2O2S.3H2O	61.67 4.20	6.54
							61.80 4.17	6.52
12	H	2-CH3	O	159	67	C22H18N2O2S.3H2O	61.67 4.20	6.54
							61.80 4.17	6.52
13	3-Cl	H	O	92	73	C21H15ClN2O2S.H2O	61.38 3.68	6.79
							61.01 3.63	6.77
14	3-Cl	4-CH3	O	266	76	C22H17ClN2O2S. H2O	61.94 4.02	6.63
							61.82 3.98	6.55
15	3-Cl	3-CH3	O	259	74	C22H17ClN2O2S. H2O	61.94 4.02	6.63
							61.82 3.98	6.55
16	3-Cl	2-CH3	O	186	71	C22H17ClN2O2S. H2O	61.94 4.02	6.63
							61.82 3.98	6.55
17	3-Cl	4-Cl	O	204	78	C21H14Cl2N2O2S	58.75 3.29	6.53
							58.71 3.29	6.52
18	3-Cl	3-Cl	O	214	75	C21H14Cl2N2O2S	58.75 3.29	6.53
							58.71 3.29	6.52
19	3-Cl	2-Cl	O	224	70	C21H14Cl2N2O2S	58.75 3.29	6.53
							58.71 3.29	6.52
20	3-Cl	4-OCH3	O	161	73	C22H17ClN2O3S.1/2H2O	60.90 3.92	6.46
							60.79 3.91	6.42
21	3-Cl	3-OCH3	O	149	69	C22H17ClN2O3S.1/2H2O	60.90 3.92	6.46
							60.79 3.91	6.42
22	3-Cl	2-OCH3	O	162	64	C22H17ClN2O3S.1/2H2O	60.90 3.92	6.46
							60.79 3.91	6.42
23	2-OCH3	H	O	167	62	C22H18N2O3S	67.67 4.65	7.17
							67.63 4.61	7.15
24	2-OCH3	4-CH3	O	174	61	C23H20N2O3S	68.30 4.98	6.93
			O				68.27 4.97	6.91
25	2-OCH3	4-Cl		181	66	C22H17ClN2O3S.1/2H2O	60.90 3.92	6.46
							60.79 3.91	6.42
26	2-OCH3	4-OCH3	O	152	63	C23H20N2O4S	65.70 4.79	6.66
							65.67 4.80	6.68
27	2-CH3	H	O	186	65	C22H18N2O2S	70.57 4.85	7.48
							70.49 4.81	7.51
28	2-CH3	4-CH3	O	157	64	C23H20N2O2S	71.11 5.19	7.21
							71.08 5.08	7.19
29	2-CH3	2-CH3	O	200	62	C23H20N2O2S	71.11 5.19	7.21
							71.08 5.08	7.19
30	2-CH3	4-Cl	O	185	68	C22H17ClN2O2S	64.62 4.19	6.85
							64.59 4.19	6.83
31	2-CH3	2-Cl	O	203	63	C22H17ClN2O2S	64.62 4.19	6.85
							64.59 4.19	6.83
32	2-CH3	4-OCH3	O	208	65	C23H20N2O3S	68.30 4.98	6.93
							68.25 4.95	6.92
33	2-CH3	2-OCH3	O	162	61	C23H20N2O3S	68.30 4.98	6.93
							68.25 4.95	6.92
34	H	H	S	94	60	C21H16N2OS2.H2O	64.42 4.25	7.18
							63.95 4.06	7.10
35	H	4-Cl	S	211	67	C21H15ClN2OS2	61.38 3.68	6.82
							61.34 3.68	6.81
36	H	4-CH3	S	115	63	C22H18N2OS2.2H2O	61.90 4.22	6.50
							61.89 4.19	6.47
37	3-Cl	H	S	123	67	C21H15ClN2OS2	61.38 3.68	6.82
							61.35 3.67	6.79
38	3-Cl	4-Cl	S	102	74	C21H14Cl2N2OS2.3/2H2O	53.35 2.96	5.93
							53.28 2.95	5.91
39	3-Cl	4-CH3	S	105	69	C22H17ClN2OS2. 2H2O	57.27 3.69	6.07
							57.25 3.65	6.05

Scheme 1.  Synthesis of compounds 3–39. Reagents and conditions: (a) PPA/MW, 125°C, 35 minutes (b) DMF/Et₃N (c) acetonitril, K₂CO₃, heating at reflux.

Table 2.  Anticancer activity of some compounds as % growth.

Comp.	L	NSCLC	CC	CNSC	M	OC	RC	PC	BC	Mean
3	81.18	87.51	97.78	96.22	98.48	97.75	90.17	96.00	81.00	91.70
7	88.17	96.37	106.39	96.22	111.31	101.84	97.97	100.56	89.87	99.36
13	106.10	90.05	105.47	98.10	102.18	93.60	101.25	100.07	90.65	98.51
17	101.52	96.11	105.79	103.08	111.04	98.62	108.34	101.85	98.19	103.04
20	87.84	83.30	100.15	89.58	102.33	88.74	94.60	92.80	81.53	91.53
25	77.14	40.58	62.38	29.64	64.12	36.06	46.04	65.94	43.81	50.94
26	92.33	76.34	82.77	72.16	86.91	81.18	81.74	89.83	68.77	80.99
35	84.81	91.88	99.23	92.57	107.2	91.83	93.84	79.57	80.56	93.50
38	49.23	49.54	51.77	62.01	82.98	60.39	54.65	30.93	67.05	59.73

Table 3.  Mean logGI₅₀ values of compounds 25 and 38 and control anticancer agents.

Comp.	L	NSCLC	CC	CNSC	M	OC	RC	PC	BC	MG_MID
25	−4.32	−5.42	−4.91	−5.11	−5.21	−5.26	−5.33	−5.26	−5.17	−5.14
38	−5.32	−5.38	−5.45	−5.22	−5.25	−5.34	−5.41	−5.62	−5.41	−5.36
A	−5.48	−5.17	−5.11	−5.12	−5.08	−5.18	−4.99	−4.49	−4.79	−5.09
B	−6.39	−6.20	−6.14	−6.18	−6.08	−6.45	−6.17	−6.41	−6.05	−6.20

A: Melphalan, B: Cisplatin.