E.M.H. Ali et al.
Bioorganic & Medicinal Chemistry 31 (2021) 115969
C), 138.85 (Ar-C), 138.43 (Ar-C), 129.66 (Ar-C), 129.55 (Ar-C), 129.27
(Ar-C), 129.03 (Ar-C), 128.79 (Ar-C), 125.73 (Ar-C), 120.99 (Ar-C),
113.95 (Ar-C), 113.85 (Ar-C), 112.24 (Ar-C), 105.92 (Ar-C), 55.25
(OCH3), 44.01 (CH2CH2NHSO2), 41.63 (CH2CH2NHSO2). LC/MS (ESI)
544.3 (M+1) +. HRMS calculated for C29H26FN5O3S is 543.1740 found:
544.1804 (M+H).
δ 159.7 (Ar-C), 158.71 (Ar-C), 146.87 (Ar-C), 138.73 (Ar-C), 129.77 (Ar-
C), 129.54 (Ar-C), 129.26 (Ar-C), 129.08 (Ar-C), 128.85 (Ar-C), 128.36
(Ar-C), 125.65 (Ar-C), 120.93 (Ar-C), 113.92 (Ar-C), 111.74 (Ar-C),
105.81 (Ar-C), 55.3 (OCH3), 40.1 (CH2CH2CH2NHSO2), 38.34
(CH2CH2CH2NHSO2), 29.93 (CH2CH2CH2NHSO2). LC/MS (ESI) 574.1
(M+).
5.1.6.8. N-(2-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imidazol-5-yl)pyr-
5.1.6.12. 4-Bromo-N-(3-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imida-
zol-5-yl)pyridin-2-yl)amino)propyl)benzenesulfonamide (9c). Yield: 70%.
m.p.: 120–122 ◦C. HPLC purity 96.8% 1H NMR (400 MHz, CDCl3) δ 7.96
(d, J = 6.72 Hz, 2H, Ar-H), 7.82 (d, J = 5.56 Hz, 1H, Ar-H), 7.64 (d, J =
8.6 Hz, 2H, Ar-H), 7.57 (d, J = 8.6 Hz, 2H, Ar-H), 7.4 (d, J = 7.4 Hz, 2H,
Ar-H), 7.29 (q, J = 5.16 Hz, 2H, Ar-H), 7.06 (d, J = 7.24 Hz, 2H, Ar-H),
6.91 (t, J = 1.76 Hz, 1H, Ar-H), 6.74 (s, 1H, Ar-H), 6.66 (d, J = 4.96 Hz,
1H, Ar-H), 4.84 (s, 1H, NH), 3.76 (s, 3H, OCH3), 3.33 (q, J = 5.8 Hz, 2H,
CH2CH2CH2NHSO2), 2.93 (t, J = 5.6 Hz, 2H, CH2CH2CH2NHSO2), 1.64
(m, 2H, CH2CH2CH2NHSO2). 13C NMR (100 MHz, CDCl3) δ 159.74 (Ar-
C), 158.57 (Ar-C), 139.31 (Ar-C), 132.24 (Ar-C), 129.83 (Ar-C), 129.51
(Ar-C), 129.12 (Ar-C), 128.88 (Ar-C), 128.48 (Ar-C), 127.2 (Ar-C),
125.63 (Ar-C), 120.92 (Ar-C), 114.03 (Ar-C), 113.93 (Ar-C), 111.71 (Ar-
idin-2-yl)amino)ethyl)-4-(trifluoromethyl)benzenesulfonamide
(8h).
Yield: 60%. m.p.: 110–112 ◦C. 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J =
6.6 Hz, 2H, Ar-H), 7.79 (d, J = 5.52 Hz, 1H, Ar-H), 7.64 (s, 1H, Ar-H),
7.61 (s, 1H, Ar-H), 7.57 (s, 1H, Ar-H), 7.55 (d, J = 1.72 Hz, 2H, Ar-
H), 7.38 (m, 3H, Ar-H), 7.25 (d, J = 8 Hz, 1H, Ar-H), 7.05 (d, J =
5.92 Hz, 2H, Ar-H), 6.88 (dd, J = 1.75 Hz, 1H, Ar-H), 6.71 (s, 1H, Ar-H),
6.67 (d, J = 4 Hz, 1H, Ar-H), 4.94 (s, 1H, NH), 3.75 (s, 3H, OCH3), 3.38
(t, J = 4.84 Hz, 2H, CH2CH2NHSO2), 3.08 (t, J = 5.32 Hz, 2H,
CH2CH2NHSO2). 13C NMR (100 MHz, CDCl3) δ 159.73 (Ar-C), 158.41
(Ar-C), 146.89 (Ar-C), 146.43 (Ar-C), 139.03 (Ar-C), 132.25 (Ar-C),
129.79 (Ar-C), 129.51 (Ar-C), 129.12 (Ar-C), 128.87 (Ar-C), 127.34 (Ar-
C), 125.63 (Ar-C), 120.93 (Ar-C), 113.93 (Ar-C), 112.26 (Ar-C), 105.95
(Ar-C), 55.32 (OCH3), 44.31 (CH2CH2NHSO2), 41.68 (CH2CH2NHSO2).
C),
55.33
(OCH3),
40.09
(CH2CH2CH2NHSO2),
38.35
LC/MS (ESI) 594.2 (M+1) +
.
(CH2CH2CH2NHSO2), 29.93 (CH2CH2CH2NHSO2). LC/MS (ESI) 618.1
(M+).
5.1.6.9. 4-Methoxy-N-(2-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imida-
zol-5-yl)pyridin-2-yl)amino)ethyl)benzenesulfonamide (8i). Yield: 64%.
m.p.: 101–103 ◦C. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 6.8 Hz, 2H,
Ar-H), 7.74 (d, J = 5.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.84 Hz, 2H, Ar-H),
7.33 (m, 3H, Ar-H), 7.2 (t, J = 7.8 Hz, 1H, Ar-H), 7.03 (d, J = 7.88 Hz,
2H, Ar-H), 6.87 (d, J = 8.88 Hz, 2H, Ar-H), 6.83 (dd, J = 1.16 Hz, 1H, Ar-
H), 6.68 (s, 1H, Ar-H), 6.59 (d, J = 8 Hz, 1H, Ar-H), 5.04 (s, 1H, NH),
3.78 (s, 3H, OCH3), 3.71 (s, 3H, OCH3), 3.33 (d, J = 4.48 Hz, 2H,
CH2CH2NHSO2), 3.03 (t, J = 5.08 Hz, 2H, CH2CH2NHSO2). 13C NMR
(100 MHz, CDCl3) δ 162.75 (Ar-C), 159.59 (Ar-C), 158.52 (Ar-C), 147.04
(Ar-C), 146.65 (Ar-C), 131.32 (Ar-C), 129.63 (Ar-C), 129.01 (Ar-C),
128.94 (Ar-C), 128.77 (Ar-C), 125.74 (Ar-C), 121 (Ar-C), 114.22 (Ar-C),
113.82 (Ar-C), 112.13 (Ar-C), 105.83 (Ar-C), 55.55 (OCH3), 55.25
(OCH3), 43.7 (CH2CH2NHSO2), 41.55 (CH2CH2NHSO2). LC/MS (ESI)
556.3 (M+).
5.1.6.13. 4-Fluoro-N-(3-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imida-
zol-5-yl)pyridin-2-yl)amino)propyl)benzenesulfonamide (9d). Yield: 72%.
m.p.: 112–114 ◦C. HPLC purity 97.4%, 1H NMR (400 MHz, CDCl3) δ 7.94
(t, J = 1.8 Hz, 2H, Ar-H), 7.77 (m, 3H, Ar-H), 7.35 (d, J = 6.76 Hz, 3H,
Ar-H), 7.22 (t, J = 8.04 Hz, 1H, Ar-H), 7.08 (t, J = 8.56 Hz, 1H, Ar-H),
7.02 (d, J = 5.68 Hz, 2H, Ar-H), 6.86 (t, J = 1.84 Hz, 1H, Ar-H), 6.67 (s,
1H, Ar-H), 6.59 (d, J = 5.04 Hz, 1H, Ar-H), 4.7 (s, 1H, NH), 3.71 (s, 3H,
OCH3), 3.25 (d, J = 8 Hz, 2H, CH2CH2CH2NHSO2), 2.88 (t, J = 5.64 Hz,
2H, CH2CH2CH2NHSO2), 1.58 (t, J = 8 Hz, 2H, CH2CH2CH2NHSO2). 13
C
NMR (100 MHz, CDCl3) δ 166.08 (Ar-C), 163.55 (Ar-C), 159.63 (Ar-C),
158.84 (Ar-C), 146.96 (Ar-C), 146.72 (Ar-C), 136.2 (Ar-C), 129.69 (Ar-
C), 129.03 (Ar-C), 128.81 (Ar-C), 125.71 (Ar-C), 120.96 (Ar-C), 116.07
(Ar-C), 113.91 (Ar-C), 111.77 (Ar-C), 105.75 (Ar-C), 55.25 (OCH3),
40.12 (CH2CH2CH2NHSO2), 38.33 (CH2CH2CH2NHSO2), 29.86
(CH2CH2CH2NHSO2). 19F NMR (400 MHz, DMSO‑d6) ꢀ 107.17 (d, 1F, J
= 8.00 Hz). LC/MS (ESI) 558.1 (M+).
5.1.6.10. N-(3-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imidazol-5-yl)pyr-
idin-2-yl)amino)propyl)benzenesulfonamide (9a). Yield: 65%. m.p.: 105
◦C. HPLC purity 96.4%, 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 6.76
Hz, 2H, Ar-H), 7.8 (m, 3H, Ar-H), 7.51 (t, J = 4.8 Hz, 1H, Ar-H), 7.43 (t,
J = 7.76 Hz, 2H, Ar-H), 7.36 (m, J = 6.8 Hz, 3H, Ar-H), 7.24 (t, J = 8.04
Hz, 1H, Ar-H), 7.05 (d, J = 5.75 Hz, 2H, Ar-H), 6.87 (t, J = 4 Hz, 1H, Ar-
H), 6.68 (s, 1H, Ar-H), 6.62 (d, J = 3.72 Hz, 1H, Ar-H), 4.74 (s, 1H, NH),
3.73 (s, 3H, OCH3), 3.28 (t, J = 5.92 Hz, 2H, CH2CH2CH2NHSO2), 2.92
(t, J = 5.76 Hz, 2H, CH2CH2CH2NHSO2), 1.6 (t, J = 5.8 Hz, 2H,
CH2CH2CH2NHSO2). 13C NMR (100 MHz, CDCl3) δ 159.66 (Ar-C),
158.77 (Ar-C), 146.9 (Ar-C), 146.69 (Ar-C), 140.08 (Ar-C), 132.41 (Ar-
C), 129.59 (Ar-C), 129.03 (Ar-C), 128.83 (Ar-C), 126.86 (Ar-C), 125.68
(Ar-C), 120.95 (Ar-C), 113.96 (Ar-C), 113.82 (Ar-C), 111.73 (Ar-C),
55.29 (OCH3), 40.17 (CH2CH2CH2NHSO2), 38.37 (CH2CH2CH2NHSO2),
29.91 (CH2CH2CH2NHSO2). LC/MS (ESI) 540.1 (M+).
5.1.6.14. 3-Chloro-N-(3-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imida-
zol-5-yl)pyridin-2-yl)amino)propyl1)benzenesulfonamide (9e). Yield: 71%.
m.p.: 113–115 ◦C. HPLC 97.3%, H NMR (400 MHz, CDCl3) δ 7.94 (t, J
= 1.36 Hz, 2H, Ar-H), 7.78 (m, 2H, Ar-H), 7.64 (d, J = 7.8 Hz, 1H, Ar-H),
7.47 (q, J = 0.8 Hz, 1H, Ar-H), 7.35 (m, 4H, Ar-H), 7.22 (t, J = 8.04 Hz,
1H, Ar-H), 7.02 (d, J = 6.12 Hz, 2H, Ar-H), 6.86 (t, J = 1.8 Hz, 1H, Ar-H),
6.67 (s, 1H, Ar-H), 6.61 (d, J = 5.04 Hz, 1H, Ar-H), 4.71 (s, 1H, NH),
3.71 (s, 3H, OCH3), 3.27 (d, J = 5.76 Hz, 2H, CH2CH2CH2NHSO2), 2.9 (t,
J = 5.6 Hz, 2H, CH2CH2CH2NHSO2), 1.59 (t, J = 5.72 Hz, 2H,
CH2CH2CH2NHSO2). 13C NMR (100 MHz, CDCl3) δ 159.63 (Ar-C),
158.81 (Ar-C), 146.67 (Ar-C), 141.98 (Ar-C), 135.1 (Ar-C), 132.46 (Ar-
C), 130.36 (Ar-C), 129.55 (Ar-C), 128.83 (Ar-C), 126.95 (Ar-C), 125.69
(Ar-C), 124.93 (Ar-C), 120.97 (Ar-C), 113.89 (Ar-C), 111.77 (Ar-C),
105.79 (Ar-C), 55.27 (OCH3), 40.14 (CH2CH2CH2NHSO2), 38.32
(CH2CH2CH2NHSO2), 29.94 (CH2CH2CH2NHSO2). LC/MS (ESI) 574.1
(M+1) +. HRMS calculated for C30H28ClN5O3S is 573.1601 found :
574.1689 (M+H).
5.1.6.11. 4-Chloro-N-(3-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imida-
zol-5-yl)pyridin-2-yl)amino)propyl)benzenesulfonamide (9b). Yield: 65%.
m.p.: 108–110 ◦C. HPLC purity 97.1% 1H NMR (400 MHz, CDCl3) δ 7.95
(d, J = 6.52 Hz, 2H, Ar-H), 7.82 (d, J = 5.52 Hz, 1H, Ar-H), 7.7 (d, J =
8.64 Hz, 2H, Ar-H), 7.39 (q, J = 6.72 Hz, 4H, Ar-H), 7.29 (d, J = 2.36 Hz,
1H, Ar-H), 7.25 (d, J = 8.04 Hz, 1H, Ar-H), 7.05 (d, J = 6.8 Hz, 2H, Ar-
H), 6.89 (t, J = 1.76 Hz, 1H, Ar-H), 6.71 (s, 1H, Ar-H), 6.63 (d, J = 4.76
Hz, 1H, Ar-H), 4.73 (s, 1H, NH), 3.75 (s, 3H, OCH3), 3.31 (q, J = 5.64 Hz,
2H, CH2CH2CH2NHSO2), 2.91 (t, J = 5.68 Hz, 2H, CH2CH2CH2NHSO2),
1.62 (t, J = 5.8 Hz, 2H, CH2CH2CH2NHSO2). 13C NMR (100 MHz, CDCl3)
5.1.6.15. 2,6-dichloro-N-(3-((4-(4-(3-methoxyphenyl)-2-phenyl-1H-imi-
dazol-5-yl)pyridin-2-yl)amino)propyl)benzenesulfonamide
(9f). Yield:
63%. m.p.: 117–119 ◦C. HPLC purity 95.8%, 1H NMR (400 MHz, CDCl3)
δ 7.94 (d, J = 6.84 Hz, 2H, Ar-H), 7.82 (d, J = 5.36 Hz, 1H, Ar-H), 7.41
(d, J = 7.88 Hz, 2H, Ar-H), 7.35 (d, J = 7.52 Hz, 2H, Ar-H), 7.26 (m, 3H,
Ar-H), 7.02 (s, 2H, Ar-H), 6.84 (d, J = 7.56 Hz, 1H, Ar-H), 6.63 (d, J =
16