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Compd.	R	Appearance	Yield/%	mp/℃
8a	Ph	White solid	67	101-102
8b	2-CH₃Ph	White solid	79	100-101
8c	3-CH₃Ph	White solid	72	102-103
8d	4-CH₃Ph	White solid	71	103-104
8e	2-FPh	White solid	63	104-106
8f	3-FPh	White solid	61	107-109
8g	4-FPh	White solid	55	98-99
8h	2-ClPh	White solid	58	108-110
8i	3-ClPh	White solid	56	100-102
8j	4-ClPh	White solid	48	185-186
8k	2-BrPh	White solid	52	102-103
8l	3-BrPh	White solid	49	103-104
8m	4-BrPh	White solid	43	121-122
8n	PhCH₂	White solid	73	116-118
8o	2-FPhCH₂	White solid	41	188-190
8p	4-FPhCH₂	White solid	55	214-215
8q	PhCH₂CH₂	White solid	73	114-115

Compd.

Appearance

Yield/%

mp/℃

White solid

101-102

2-CH₃Ph

White solid

100-101

3-CH₃Ph

White solid

102-103

4-CH₃Ph

White solid

103-104

2-FPh

White solid

104-106

3-FPh

White solid

107-109

4-FPh

White solid

98-99

2-ClPh

White solid

108-110

3-ClPh

White solid

100-102

4-ClPh

White solid

185-186

2-BrPh

White solid

102-103

3-BrPh

White solid

103-104

4-BrPh

White solid

121-122

PhCH₂

White solid

116-118

2-FPhCH₂

White solid

188-190

4-FPhCH₂

White solid

214-215

PhCH₂CH₂

White solid

114-115

Compd.	R	Appearance	Yield/%	mp/℃
8a	Ph	White solid	67	101-102
8b	2-CH₃Ph	White solid	79	100-101
8c	3-CH₃Ph	White solid	72	102-103
8d	4-CH₃Ph	White solid	71	103-104
8e	2-FPh	White solid	63	104-106
8f	3-FPh	White solid	61	107-109
8g	4-FPh	White solid	55	98-99
8h	2-ClPh	White solid	58	108-110
8i	3-ClPh	White solid	56	100-102
8j	4-ClPh	White solid	48	185-186
8k	2-BrPh	White solid	52	102-103
8l	3-BrPh	White solid	49	103-104
8m	4-BrPh	White solid	43	121-122
8n	PhCH₂	White solid	73	116-118
8o	2-FPhCH₂	White solid	41	188-190
8p	4-FPhCH₂	White solid	55	214-215
8q	PhCH₂CH₂	White solid	73	114-115

Compd.

Appearance

Yield/%

mp/℃

White solid

101-102

2-CH₃Ph

White solid

100-101

3-CH₃Ph

White solid

102-103

4-CH₃Ph

White solid

103-104

2-FPh

White solid

104-106

3-FPh

White solid

107-109

4-FPh

White solid

98-99

2-ClPh

White solid

108-110

3-ClPh

White solid

100-102

4-ClPh

White solid

185-186

2-BrPh

White solid

102-103

3-BrPh

White solid

103-104

4-BrPh

White solid

121-122

PhCH₂

White solid

116-118

2-FPhCH₂

White solid

188-190

4-FPhCH₂

White solid

214-215

PhCH₂CH₂

White solid

114-115

Compd.	¹H NMR, ¹³C NMR and MS
8a	¹H NMR (400 MHz, DMSO) δ_H: 10.05 (s, 1H), 9.00 (d, J = 8.3 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.23-7.31 (m, 6H, ArH), 7.18 (d, J = 7.8 Hz, 1H), 7.15 (s, 2H), 7.01-7.06 (m, 1H), 6.13 (s, 1H), 4.75-4.81 (m, 1H), 3.71 (s, 3H), 2.83-3.11 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 119.8, 124.0, 126.8, 128.5, 129.2, 129.7, 137.9, 139.0, 143.2, 149.6, 162.8, 168.6, 170.0; ESI MS (m/z): 424.3 [M+H]⁺
8b	¹H NMR (400 MHz, CDCl₃) δ_H: 8.14 (s, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.26-7.29 (m, 5H), 7.13-7.17 (m, 2H), 7.05-7.09 (m, 1H), 6.45 (s, 1H), 5.37 (s, 2H), 5.03-5.08 (m, 1H), 3.88 (s, 3H), 3.24-3.39 (m, 2H), 2.06 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 17.5, 37.2, 55.2, 62.8, 110.9, 124.0, 126.0, 126.5, 127.1, 128.8, 129.4, 130.6, 131.0, 134.9, 136.3, 142.3, 147.7, 162.8, 168.1, 169.3; ESI MS (m/z): 438.5 [M+H]⁺
8c	¹H NMR (400 MHz, DMSO) δ_H: 9.96 (s, 1H), 8.99 (d, J = 8.2 Hz, 1H), 7.30-7.37 (m, 4H), 7.24-7.27 (m, 2H), 7.17-7.20 (m, 2H), 7.16 (s, 2H), 6.85-6.87 (m, 1H), 6.12 (s, 1H), 4.75-4.80 (m, 1H), 3.71 (s, 3H), 2.85-3.10 (m, 2H), 2.25 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 21.6, 37.5, 55.1, 62.3, 110.7, 117.0, 120.2, 124.6, 126.8, 128.5, 129.0, 129.7, 138.0, 138.4, 138.9, 143.2, 149.7, 162.7, 168.6, 169.9; ESI MS (m/z): 438.3 [M+H]⁺
8d	¹H NMR (400 MHz, DMSO) δ_H: 9.94 (s, 1H), 8.99 (d, J = 7.5 Hz, 1H), 7.42-7.44 (m, 2H), 7.19-7.29 (m, 5H), 7.16 (s, 2H), 7.09-7.11 (m, 2H), 6.13 (s, 1H), 4.77-4.82 (m, 1H), 3.71 (s, 3H), 2.86-3.09 (m, 2H), 2.22 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 20.9, 37.6, 55.1, 62.3, 110.7, 119.7, 126.7, 128.5, 129.6, 129.7, 132.8, 136.5, 138.0, 143.2, 149.7, 162.7, 168.6, 169.8; ESI MS (m/z): 438.0 [M+H]⁺
8e	¹H NMR (400 MHz, DMSO) δ_H: 8.39 (s, 1H), 8.04 (d, J = 10.2 Hz, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.19-7.27 (m, 5H), 6.99-7.04 (m, 3H), 6.31 (s, 1H), 5.06-5.12 (m, 1H), 3.84 (s, 3H), 3.13-3.42 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 18.3, 37.3, 55.1, 62.9, 111.6, 115.0, 115.2, 122.8, 124.4, 125.3, 127.1, 128.8, 129.2, 136.2, 142.0, 147.6, 151.9, 154.3, 162.8, 168.2, 169.3; ESI MS (m/z): 442.4 [M+H]⁺
8f	¹H NMR (400 MHz, CDCl₃) δ_H: 8.02 (s, 1H), 7.88 (d, J = 9.8 Hz, 1H), 7.19-7.26 (m, 5H), 6.45 (s, 1H), 6.39-6.41 (m, 2H), 5.84 (s, 2H), 4.96-5.01 (m, 1H), 3.86 (s, 3H), 3.18-3.36 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 37.7, 55.4, 62.8, 98.5, 103.6, 111.3, 120.0, 121.5, 126.9, 128.6, 129.3, 136.4, 142.1, 147.5, 149.9, 156.9, 162.4, 168.3, 168.5; ESI MS (m/z): 442.1 [M+H]⁺
8g	¹H NMR (400 MHz, DMSO) δ_H: 10.19 (s, 1H), 9.03 (d, J = 8.2 Hz, 1H), 7.55-7.58 (m, 2H), 7.24-7.37 (m, 5H), 7.11-7.20 (m, 4H), 6.21 (s, 1H), 4.73-4.79 (m, 1H), 3.72 (s, 3H), 2.87-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.6, 55.2, 62.4, 110.8, 115.7, 115.9, 121.5, 121.6, 126.8, 128.6, 129.7, 135.5, 137.9, 149.2, 157.4, 159.7, 162.5, 168.8, 169.9; ESI MS (m/z): 441.9 [M+H]⁺
8h	¹H NMR (400 MHz, DMSO) δ_H: 9.59 (s, 1H), 9.06 (d, J = 8.4 Hz, 1H), 7.73-7.69 (m, 1H), 7.39 (d, J = 5.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.15-7.18 (m, 3H), 7.12 (s, 2H), 7.04-7.07 (m, 2H), 5.09-4.79 (m, 1H), 3.69 (s, 3H), 2.91-3.19 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.7, 56.5, 62.3, 110.8, 126.1, 126.6, 126.8, 126.9, 127.9, 128.6, 129.8, 129.9, 134.9, 138.1, 143.1, 149.7, 162.9, 168.7, 170.4; ESI MS (m/z): 458.2 [M+H]⁺
8i	¹H NMR (400 MHz, DMSO) δ_H: 10.30 (s, 1H), 9.03 (d, J = 8.1 Hz, 1H), 7.77 (s, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.24-7.34 (m, 5H), 7.18 (d, J = 9.0 Hz, 1H), 7.16 (s, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.18 (s, 1H), 4.73-4.78 (m, 1H, CH), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 118.2, 119.2, 122.7, 126.8, 128.6, 129.7, 130.9, 133.5, 137.9, 140.6, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 458.3 [M+H]⁺
8j	¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.03 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 7.7 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 7.23-7.27 (m, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.17 (s, 2H), 6.18 (s, 1H), 4.74-4.79 (m, 1H), 3.71 (s, 3H), 2.87-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 126.9, 127.5, 128.6, 129.2, 129.7, 137.9, 138.1, 143.3, 149.7, 162.8, 168.7, 170.3; ESI MS (m/z): 458.3 [M+H]⁺
8k	¹H NMR (400 MHz, DMSO) δ_H: 9.61 (s, 1H), 9.05 (d, J = 8.6 Hz, 1H), 7.59-7.66 (m, 2H), 7.34-7.39 (m, 3H), 7.25 (t, J = 15.6 Hz, 2H), 7.18-7.22 (m, 1H), 7.16 (s, 2H), 7.11-7.13 (m, 1H), 6.05 (s, 1H), 4.90-4.96 (m, 1H), 3.69 (s, 3H), 2.89-3.24 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.6, 62.3, 110.8, 117.9, 126.8, 127.1, 127.6, 128.6, 129.8, 133.2, 136.2, 138.1, 143.1, 149.7, 162.9, 168.6, 170.33; ESI MS (m/z): 504.2 [M+H]⁺
8l	¹H NMR (400 MHz, DMSO) δ_H: 10.28 (s, 1H), 9.04 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.43-7.45 (m, 1H), 7.29 (d, 2H), 7.24-7.27 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.77 (m, 1H), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.4, 55.2, 62.3, 118.5, 121.9, 122.0, 126.6, 126.9, 128.6, 129.7, 131.3, 137.8, 140.7, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 503.9 [M+H]⁺
8m	¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.02 (d, J = 8.2 Hz, 1H), 7.47-7.54 (m, 4H), 7.23-7.30 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.78 (m, 1H), 3.71 (s, 3H), 2.87-3.07 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 111.5, 121.7, 126.8, 128.6, 129.7, 132.1, 137.9, 138.5, 143.3, 149.7, 162.8, 168.6, 170.3; ESI MS (m/z): 504.3 [M+H]⁺
8n	¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.6 Hz, 1H), 8.26 (t, J = 12.0 Hz, 1H), 7.24-7.28 (m, 6H), 7.17-7.22 (m, 4H), 7.13 (s, 2H), 6.08 (s, 1H), 4.61-4.66 (m, 1H), 4.30 (d, J = 8.6 Hz, 2H), 3.63 (s, 3H), 2.78-3.12 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 42.6, 54.5, 62.2, 110.5, 126.7, 127.3, 127.6, 128.6, 128.7, 129.7, 138.3, 139.4, 143.0, 149.8, 162.7, 168.7, 170.9; ESI MS (m/z): 438.5 [M+H]⁺
8o	¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.8 Hz, 1H), 8.29 (t, J = 12.2 Hz, 1H), 7.24-7.25 (m, 4H), 7.19-7.22 (m, 3H), 7.07-7.12 (m, 4H), 6.11 (s, 1H), 4.59-4.64 (m, 1H), 4.28 (d, J = 3.6 Hz, 2H), 3.65 (s, 3H), 2.74-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 135.7, 138.3, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.3 [M+H]⁺
8p	¹H NMR (400 MHz, DMSO) δ_H: 8.93 (d, J = 8.0 Hz, 1H), 8.28 (t, J = 12.4 Hz, 1H), 7.22-7.25 (m, 4H), 7.18-7.20 (m, 3H), 7.07-7.13 (m, 4H), 6.11 (s, 1H), 4.58-4.64 (m, 1H), 4.28 (d, J = 4.0 Hz, 2H), 3.65 (s, 3H), 2.78-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 138.2, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.0 [M+H]⁺
8q	¹H NMR (400 MHz, DMSO) δ_H: 8.84 (d, J = 8.4 Hz, 1H), 7.92 (t, J = 6.6 Hz, 1H), 7.25-7.27 (m, 1H), 7.23-7.24 (m, 5H), 7.18 (d, J = 4.2 Hz, 2H), 7.16-7.17 (m, 4H), 6.13 (s, 1H), 4.51-4.57 (m, 1H), 3.69 (s, 3H), 3.26 (d, J = 5.9 Hz, 2H), 2.97-3.00 (m, 2H), 2.64-2.77 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 35.6, 37.4, 54.4, 55.3, 62.3, 63.5, 110.5, 126.6, 126.7, 128.5, 128.7, 129.1, 129.7, 138.4, 139.7, 143.1, 149.9, 162.7, 168.7, 170.9; ESI MS (m/z): 452.5 [M+H]⁺

Compd.

¹H NMR, ¹³C NMR and MS

¹H NMR (400 MHz, DMSO) δ_H: 10.05 (s, 1H), 9.00 (d, J = 8.3 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.23-7.31 (m, 6H, ArH), 7.18 (d, J = 7.8 Hz, 1H), 7.15 (s, 2H), 7.01-7.06 (m, 1H), 6.13 (s, 1H), 4.75-4.81 (m, 1H), 3.71 (s, 3H), 2.83-3.11 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 119.8, 124.0, 126.8, 128.5, 129.2, 129.7, 137.9, 139.0, 143.2, 149.6, 162.8, 168.6, 170.0; ESI MS (m/z): 424.3 [M+H]⁺

¹H NMR (400 MHz, CDCl₃) δ_H: 8.14 (s, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.26-7.29 (m, 5H), 7.13-7.17 (m, 2H), 7.05-7.09 (m, 1H), 6.45 (s, 1H), 5.37 (s, 2H), 5.03-5.08 (m, 1H), 3.88 (s, 3H), 3.24-3.39 (m, 2H), 2.06 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 17.5, 37.2, 55.2, 62.8, 110.9, 124.0, 126.0, 126.5, 127.1, 128.8, 129.4, 130.6, 131.0, 134.9, 136.3, 142.3, 147.7, 162.8, 168.1, 169.3; ESI MS (m/z): 438.5 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 9.96 (s, 1H), 8.99 (d, J = 8.2 Hz, 1H), 7.30-7.37 (m, 4H), 7.24-7.27 (m, 2H), 7.17-7.20 (m, 2H), 7.16 (s, 2H), 6.85-6.87 (m, 1H), 6.12 (s, 1H), 4.75-4.80 (m, 1H), 3.71 (s, 3H), 2.85-3.10 (m, 2H), 2.25 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 21.6, 37.5, 55.1, 62.3, 110.7, 117.0, 120.2, 124.6, 126.8, 128.5, 129.0, 129.7, 138.0, 138.4, 138.9, 143.2, 149.7, 162.7, 168.6, 169.9; ESI MS (m/z): 438.3 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 9.94 (s, 1H), 8.99 (d, J = 7.5 Hz, 1H), 7.42-7.44 (m, 2H), 7.19-7.29 (m, 5H), 7.16 (s, 2H), 7.09-7.11 (m, 2H), 6.13 (s, 1H), 4.77-4.82 (m, 1H), 3.71 (s, 3H), 2.86-3.09 (m, 2H), 2.22 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 20.9, 37.6, 55.1, 62.3, 110.7, 119.7, 126.7, 128.5, 129.6, 129.7, 132.8, 136.5, 138.0, 143.2, 149.7, 162.7, 168.6, 169.8; ESI MS (m/z): 438.0 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 8.39 (s, 1H), 8.04 (d, J = 10.2 Hz, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.19-7.27 (m, 5H), 6.99-7.04 (m, 3H), 6.31 (s, 1H), 5.06-5.12 (m, 1H), 3.84 (s, 3H), 3.13-3.42 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 18.3, 37.3, 55.1, 62.9, 111.6, 115.0, 115.2, 122.8, 124.4, 125.3, 127.1, 128.8, 129.2, 136.2, 142.0, 147.6, 151.9, 154.3, 162.8, 168.2, 169.3; ESI MS (m/z): 442.4 [M+H]⁺

¹H NMR (400 MHz, CDCl₃) δ_H: 8.02 (s, 1H), 7.88 (d, J = 9.8 Hz, 1H), 7.19-7.26 (m, 5H), 6.45 (s, 1H), 6.39-6.41 (m, 2H), 5.84 (s, 2H), 4.96-5.01 (m, 1H), 3.86 (s, 3H), 3.18-3.36 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 37.7, 55.4, 62.8, 98.5, 103.6, 111.3, 120.0, 121.5, 126.9, 128.6, 129.3, 136.4, 142.1, 147.5, 149.9, 156.9, 162.4, 168.3, 168.5; ESI MS (m/z): 442.1 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 10.19 (s, 1H), 9.03 (d, J = 8.2 Hz, 1H), 7.55-7.58 (m, 2H), 7.24-7.37 (m, 5H), 7.11-7.20 (m, 4H), 6.21 (s, 1H), 4.73-4.79 (m, 1H), 3.72 (s, 3H), 2.87-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.6, 55.2, 62.4, 110.8, 115.7, 115.9, 121.5, 121.6, 126.8, 128.6, 129.7, 135.5, 137.9, 149.2, 157.4, 159.7, 162.5, 168.8, 169.9; ESI MS (m/z): 441.9 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 9.59 (s, 1H), 9.06 (d, J = 8.4 Hz, 1H), 7.73-7.69 (m, 1H), 7.39 (d, J = 5.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.15-7.18 (m, 3H), 7.12 (s, 2H), 7.04-7.07 (m, 2H), 5.09-4.79 (m, 1H), 3.69 (s, 3H), 2.91-3.19 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.7, 56.5, 62.3, 110.8, 126.1, 126.6, 126.8, 126.9, 127.9, 128.6, 129.8, 129.9, 134.9, 138.1, 143.1, 149.7, 162.9, 168.7, 170.4; ESI MS (m/z): 458.2 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 10.30 (s, 1H), 9.03 (d, J = 8.1 Hz, 1H), 7.77 (s, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.24-7.34 (m, 5H), 7.18 (d, J = 9.0 Hz, 1H), 7.16 (s, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.18 (s, 1H), 4.73-4.78 (m, 1H, CH), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 118.2, 119.2, 122.7, 126.8, 128.6, 129.7, 130.9, 133.5, 137.9, 140.6, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 458.3 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.03 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 7.7 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 7.23-7.27 (m, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.17 (s, 2H), 6.18 (s, 1H), 4.74-4.79 (m, 1H), 3.71 (s, 3H), 2.87-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 126.9, 127.5, 128.6, 129.2, 129.7, 137.9, 138.1, 143.3, 149.7, 162.8, 168.7, 170.3; ESI MS (m/z): 458.3 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 9.61 (s, 1H), 9.05 (d, J = 8.6 Hz, 1H), 7.59-7.66 (m, 2H), 7.34-7.39 (m, 3H), 7.25 (t, J = 15.6 Hz, 2H), 7.18-7.22 (m, 1H), 7.16 (s, 2H), 7.11-7.13 (m, 1H), 6.05 (s, 1H), 4.90-4.96 (m, 1H), 3.69 (s, 3H), 2.89-3.24 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.6, 62.3, 110.8, 117.9, 126.8, 127.1, 127.6, 128.6, 129.8, 133.2, 136.2, 138.1, 143.1, 149.7, 162.9, 168.6, 170.33; ESI MS (m/z): 504.2 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 10.28 (s, 1H), 9.04 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.43-7.45 (m, 1H), 7.29 (d, 2H), 7.24-7.27 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.77 (m, 1H), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.4, 55.2, 62.3, 118.5, 121.9, 122.0, 126.6, 126.9, 128.6, 129.7, 131.3, 137.8, 140.7, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 503.9 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.02 (d, J = 8.2 Hz, 1H), 7.47-7.54 (m, 4H), 7.23-7.30 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.78 (m, 1H), 3.71 (s, 3H), 2.87-3.07 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 111.5, 121.7, 126.8, 128.6, 129.7, 132.1, 137.9, 138.5, 143.3, 149.7, 162.8, 168.6, 170.3; ESI MS (m/z): 504.3 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.6 Hz, 1H), 8.26 (t, J = 12.0 Hz, 1H), 7.24-7.28 (m, 6H), 7.17-7.22 (m, 4H), 7.13 (s, 2H), 6.08 (s, 1H), 4.61-4.66 (m, 1H), 4.30 (d, J = 8.6 Hz, 2H), 3.63 (s, 3H), 2.78-3.12 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 42.6, 54.5, 62.2, 110.5, 126.7, 127.3, 127.6, 128.6, 128.7, 129.7, 138.3, 139.4, 143.0, 149.8, 162.7, 168.7, 170.9; ESI MS (m/z): 438.5 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.8 Hz, 1H), 8.29 (t, J = 12.2 Hz, 1H), 7.24-7.25 (m, 4H), 7.19-7.22 (m, 3H), 7.07-7.12 (m, 4H), 6.11 (s, 1H), 4.59-4.64 (m, 1H), 4.28 (d, J = 3.6 Hz, 2H), 3.65 (s, 3H), 2.74-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 135.7, 138.3, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.3 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 8.93 (d, J = 8.0 Hz, 1H), 8.28 (t, J = 12.4 Hz, 1H), 7.22-7.25 (m, 4H), 7.18-7.20 (m, 3H), 7.07-7.13 (m, 4H), 6.11 (s, 1H), 4.58-4.64 (m, 1H), 4.28 (d, J = 4.0 Hz, 2H), 3.65 (s, 3H), 2.78-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 138.2, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.0 [M+H]⁺

¹H NMR (400 MHz, DMSO) δ_H: 8.84 (d, J = 8.4 Hz, 1H), 7.92 (t, J = 6.6 Hz, 1H), 7.25-7.27 (m, 1H), 7.23-7.24 (m, 5H), 7.18 (d, J = 4.2 Hz, 2H), 7.16-7.17 (m, 4H), 6.13 (s, 1H), 4.51-4.57 (m, 1H), 3.69 (s, 3H), 3.26 (d, J = 5.9 Hz, 2H), 2.97-3.00 (m, 2H), 2.64-2.77 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 35.6, 37.4, 54.4, 55.3, 62.3, 63.5, 110.5, 126.6, 126.7, 128.5, 128.7, 129.1, 129.7, 138.4, 139.7, 143.1, 149.9, 162.7, 168.7, 170.9; ESI MS (m/z): 452.5 [M+H]⁺

Compd.	¹H NMR, ¹³C NMR and MS
8a	¹H NMR (400 MHz, DMSO) δ_H: 10.05 (s, 1H), 9.00 (d, J = 8.3 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.23-7.31 (m, 6H, ArH), 7.18 (d, J = 7.8 Hz, 1H), 7.15 (s, 2H), 7.01-7.06 (m, 1H), 6.13 (s, 1H), 4.75-4.81 (m, 1H), 3.71 (s, 3H), 2.83-3.11 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 119.8, 124.0, 126.8, 128.5, 129.2, 129.7, 137.9, 139.0, 143.2, 149.6, 162.8, 168.6, 170.0; ESI MS (m/z): 424.3 [M+H]⁺
8b	¹H NMR (400 MHz, CDCl₃) δ_H: 8.14 (s, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.26-7.29 (m, 5H), 7.13-7.17 (m, 2H), 7.05-7.09 (m, 1H), 6.45 (s, 1H), 5.37 (s, 2H), 5.03-5.08 (m, 1H), 3.88 (s, 3H), 3.24-3.39 (m, 2H), 2.06 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 17.5, 37.2, 55.2, 62.8, 110.9, 124.0, 126.0, 126.5, 127.1, 128.8, 129.4, 130.6, 131.0, 134.9, 136.3, 142.3, 147.7, 162.8, 168.1, 169.3; ESI MS (m/z): 438.5 [M+H]⁺
8c	¹H NMR (400 MHz, DMSO) δ_H: 9.96 (s, 1H), 8.99 (d, J = 8.2 Hz, 1H), 7.30-7.37 (m, 4H), 7.24-7.27 (m, 2H), 7.17-7.20 (m, 2H), 7.16 (s, 2H), 6.85-6.87 (m, 1H), 6.12 (s, 1H), 4.75-4.80 (m, 1H), 3.71 (s, 3H), 2.85-3.10 (m, 2H), 2.25 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 21.6, 37.5, 55.1, 62.3, 110.7, 117.0, 120.2, 124.6, 126.8, 128.5, 129.0, 129.7, 138.0, 138.4, 138.9, 143.2, 149.7, 162.7, 168.6, 169.9; ESI MS (m/z): 438.3 [M+H]⁺
8d	¹H NMR (400 MHz, DMSO) δ_H: 9.94 (s, 1H), 8.99 (d, J = 7.5 Hz, 1H), 7.42-7.44 (m, 2H), 7.19-7.29 (m, 5H), 7.16 (s, 2H), 7.09-7.11 (m, 2H), 6.13 (s, 1H), 4.77-4.82 (m, 1H), 3.71 (s, 3H), 2.86-3.09 (m, 2H), 2.22 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 20.9, 37.6, 55.1, 62.3, 110.7, 119.7, 126.7, 128.5, 129.6, 129.7, 132.8, 136.5, 138.0, 143.2, 149.7, 162.7, 168.6, 169.8; ESI MS (m/z): 438.0 [M+H]⁺
8e	¹H NMR (400 MHz, DMSO) δ_H: 8.39 (s, 1H), 8.04 (d, J = 10.2 Hz, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.19-7.27 (m, 5H), 6.99-7.04 (m, 3H), 6.31 (s, 1H), 5.06-5.12 (m, 1H), 3.84 (s, 3H), 3.13-3.42 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 18.3, 37.3, 55.1, 62.9, 111.6, 115.0, 115.2, 122.8, 124.4, 125.3, 127.1, 128.8, 129.2, 136.2, 142.0, 147.6, 151.9, 154.3, 162.8, 168.2, 169.3; ESI MS (m/z): 442.4 [M+H]⁺
8f	¹H NMR (400 MHz, CDCl₃) δ_H: 8.02 (s, 1H), 7.88 (d, J = 9.8 Hz, 1H), 7.19-7.26 (m, 5H), 6.45 (s, 1H), 6.39-6.41 (m, 2H), 5.84 (s, 2H), 4.96-5.01 (m, 1H), 3.86 (s, 3H), 3.18-3.36 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 37.7, 55.4, 62.8, 98.5, 103.6, 111.3, 120.0, 121.5, 126.9, 128.6, 129.3, 136.4, 142.1, 147.5, 149.9, 156.9, 162.4, 168.3, 168.5; ESI MS (m/z): 442.1 [M+H]⁺
8g	¹H NMR (400 MHz, DMSO) δ_H: 10.19 (s, 1H), 9.03 (d, J = 8.2 Hz, 1H), 7.55-7.58 (m, 2H), 7.24-7.37 (m, 5H), 7.11-7.20 (m, 4H), 6.21 (s, 1H), 4.73-4.79 (m, 1H), 3.72 (s, 3H), 2.87-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.6, 55.2, 62.4, 110.8, 115.7, 115.9, 121.5, 121.6, 126.8, 128.6, 129.7, 135.5, 137.9, 149.2, 157.4, 159.7, 162.5, 168.8, 169.9; ESI MS (m/z): 441.9 [M+H]⁺
8h	¹H NMR (400 MHz, DMSO) δ_H: 9.59 (s, 1H), 9.06 (d, J = 8.4 Hz, 1H), 7.73-7.69 (m, 1H), 7.39 (d, J = 5.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.15-7.18 (m, 3H), 7.12 (s, 2H), 7.04-7.07 (m, 2H), 5.09-4.79 (m, 1H), 3.69 (s, 3H), 2.91-3.19 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.7, 56.5, 62.3, 110.8, 126.1, 126.6, 126.8, 126.9, 127.9, 128.6, 129.8, 129.9, 134.9, 138.1, 143.1, 149.7, 162.9, 168.7, 170.4; ESI MS (m/z): 458.2 [M+H]⁺
8i	¹H NMR (400 MHz, DMSO) δ_H: 10.30 (s, 1H), 9.03 (d, J = 8.1 Hz, 1H), 7.77 (s, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.24-7.34 (m, 5H), 7.18 (d, J = 9.0 Hz, 1H), 7.16 (s, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.18 (s, 1H), 4.73-4.78 (m, 1H, CH), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 118.2, 119.2, 122.7, 126.8, 128.6, 129.7, 130.9, 133.5, 137.9, 140.6, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 458.3 [M+H]⁺
8j	¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.03 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 7.7 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 7.23-7.27 (m, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.17 (s, 2H), 6.18 (s, 1H), 4.74-4.79 (m, 1H), 3.71 (s, 3H), 2.87-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 126.9, 127.5, 128.6, 129.2, 129.7, 137.9, 138.1, 143.3, 149.7, 162.8, 168.7, 170.3; ESI MS (m/z): 458.3 [M+H]⁺
8k	¹H NMR (400 MHz, DMSO) δ_H: 9.61 (s, 1H), 9.05 (d, J = 8.6 Hz, 1H), 7.59-7.66 (m, 2H), 7.34-7.39 (m, 3H), 7.25 (t, J = 15.6 Hz, 2H), 7.18-7.22 (m, 1H), 7.16 (s, 2H), 7.11-7.13 (m, 1H), 6.05 (s, 1H), 4.90-4.96 (m, 1H), 3.69 (s, 3H), 2.89-3.24 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.6, 62.3, 110.8, 117.9, 126.8, 127.1, 127.6, 128.6, 129.8, 133.2, 136.2, 138.1, 143.1, 149.7, 162.9, 168.6, 170.33; ESI MS (m/z): 504.2 [M+H]⁺
8l	¹H NMR (400 MHz, DMSO) δ_H: 10.28 (s, 1H), 9.04 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.43-7.45 (m, 1H), 7.29 (d, 2H), 7.24-7.27 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.77 (m, 1H), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.4, 55.2, 62.3, 118.5, 121.9, 122.0, 126.6, 126.9, 128.6, 129.7, 131.3, 137.8, 140.7, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 503.9 [M+H]⁺
8m	¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.02 (d, J = 8.2 Hz, 1H), 7.47-7.54 (m, 4H), 7.23-7.30 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.78 (m, 1H), 3.71 (s, 3H), 2.87-3.07 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 111.5, 121.7, 126.8, 128.6, 129.7, 132.1, 137.9, 138.5, 143.3, 149.7, 162.8, 168.6, 170.3; ESI MS (m/z): 504.3 [M+H]⁺
8n	¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.6 Hz, 1H), 8.26 (t, J = 12.0 Hz, 1H), 7.24-7.28 (m, 6H), 7.17-7.22 (m, 4H), 7.13 (s, 2H), 6.08 (s, 1H), 4.61-4.66 (m, 1H), 4.30 (d, J = 8.6 Hz, 2H), 3.63 (s, 3H), 2.78-3.12 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 42.6, 54.5, 62.2, 110.5, 126.7, 127.3, 127.6, 128.6, 128.7, 129.7, 138.3, 139.4, 143.0, 149.8, 162.7, 168.7, 170.9; ESI MS (m/z): 438.5 [M+H]⁺
8o	¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.8 Hz, 1H), 8.29 (t, J = 12.2 Hz, 1H), 7.24-7.25 (m, 4H), 7.19-7.22 (m, 3H), 7.07-7.12 (m, 4H), 6.11 (s, 1H), 4.59-4.64 (m, 1H), 4.28 (d, J = 3.6 Hz, 2H), 3.65 (s, 3H), 2.74-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 135.7, 138.3, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.3 [M+H]⁺
8p	¹H NMR (400 MHz, DMSO) δ_H: 8.93 (d, J = 8.0 Hz, 1H), 8.28 (t, J = 12.4 Hz, 1H), 7.22-7.25 (m, 4H), 7.18-7.20 (m, 3H), 7.07-7.13 (m, 4H), 6.11 (s, 1H), 4.58-4.64 (m, 1H), 4.28 (d, J = 4.0 Hz, 2H), 3.65 (s, 3H), 2.78-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 138.2, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.0 [M+H]⁺
8q	¹H NMR (400 MHz, DMSO) δ_H: 8.84 (d, J = 8.4 Hz, 1H), 7.92 (t, J = 6.6 Hz, 1H), 7.25-7.27 (m, 1H), 7.23-7.24 (m, 5H), 7.18 (d, J = 4.2 Hz, 2H), 7.16-7.17 (m, 4H), 6.13 (s, 1H), 4.51-4.57 (m, 1H), 3.69 (s, 3H), 3.26 (d, J = 5.9 Hz, 2H), 2.97-3.00 (m, 2H), 2.64-2.77 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 35.6, 37.4, 54.4, 55.3, 62.3, 63.5, 110.5, 126.6, 126.7, 128.5, 128.7, 129.1, 129.7, 138.4, 139.7, 143.1, 149.9, 162.7, 168.7, 170.9; ESI MS (m/z): 452.5 [M+H]⁺

Compd.

¹H NMR, ¹³C NMR and MS

Compd.	MIC/μg·mL^-1
8a	128.	64.	128.	64.
8b	> 128.	128.	128.	128.
8c	64.	> 128.	> 128.	> 128.
8d	32.	32.	64.	32.
8e	64.	16.	32.	16.
8f	16.	> 128.	> 128.	> 128.
8g	8.	4.	4.	4.
8h	32.	32.	32.	32.
8i	32.	128.	128.	128.
8j	16.	8.	8.	8.
8k	64.	128.	64.	128.
8l	32.	> 128.	> 128.	> 128.
8m	64.	128.	64.	> 128.
8n	16.	32.	64.	32.
8o	128.	16.	32.	16.
8p	16.	2.	2.	2.
8q	> 128.	128.	64.	128.
Ciprofloxacin	0.5	2.	4.	> 128.

Compd.

MIC/μg·mL^-1

S. aureus

E. coli

P. aeruginosa

FREC

128.

64.

128.

64.

> 128.

128.

64.

> 128.

32.

64.

32.

64.

16.

32.

16.

> 128.

32.

128.

16.

64.

128.

64.

128.

32.

> 128.

64.

128.

64.

> 128.

16.

32.

64.

32.

128.

16.

32.

16.

> 128.

128.

64.

128.

Ciprofloxacin

0.5

> 128.

Compd.	MIC/μg·mL^-1
8a	128.	64.	128.	64.
8b	> 128.	128.	128.	128.
8c	64.	> 128.	> 128.	> 128.
8d	32.	32.	64.	32.
8e	64.	16.	32.	16.
8f	16.	> 128.	> 128.	> 128.
8g	8.	4.	4.	4.
8h	32.	32.	32.	32.
8i	32.	128.	128.	128.
8j	16.	8.	8.	8.
8k	64.	128.	64.	128.
8l	32.	> 128.	> 128.	> 128.
8m	64.	128.	64.	> 128.
8n	16.	32.	64.	32.
8o	128.	16.	32.	16.
8p	16.	2.	2.	2.
8q	> 128.	128.	64.	128.
Ciprofloxacin	0.5	2.	4.	> 128.

Compd.

MIC/μg·mL^-1

S. aureus

E. coli

P. aeruginosa

FREC

128.

64.

128.

64.

> 128.

128.

64.

> 128.

32.

64.

32.

64.

16.

32.

16.

> 128.

32.

128.

16.

64.

128.

64.

128.

32.

> 128.

64.

128.

64.

> 128.

16.

32.

64.

32.

128.

16.

32.

16.

> 128.

128.

64.

128.

Ciprofloxacin

0.5

> 128.

Bacterial species		Ciprofloxacin + 8p	Oxacillin + 8p	Gentamicin + 8p	Tigecycline + 8p
S. aureus	MIC	1/16MIC + 1/2MIC	1/16MIC + 1/2MIC	1/8MIC + 1/2MIC	1/16MIC + 1/2MIC
FICI	1.7	0.4	0.5	1.2
E. coli	MIC	1/4MIC + 1/2MIC	1/2MIC + 1/2MIC	1/8MIC + 1/2MIC	1/16MIC + 1/2MIC
FICI	0.4	1.3	0.4	0.9
P. aeruginosa	MIC	1/2MIC + 1/2MIC	1/2MIC + 1/2MIC	1/4MIC + 1/2MIC	1/4MIC + 1/2MIC
FICI	0.4	1.4	0.5	0.8
FREC	MIC	1/2MIC + 1/2MIC	1/2MIC + 1/2MIC	1/4MIC + 1/2MIC	1/4MIC + 1/2MIC
FICI	0.4	0.8	0.5	1.2

Bacterial species

Ciprofloxacin + 8p

Oxacillin + 8p

Gentamicin + 8p

Tigecycline + 8p

S. aureus

MIC

1/16MIC + 1/2MIC

1/8MIC + 1/2MIC

1/16MIC + 1/2MIC

FICI

1.7

0.4

0.5

1.2

E. coli

MIC

1/4MIC + 1/2MIC

1/2MIC + 1/2MIC

1/8MIC + 1/2MIC

1/16MIC + 1/2MIC

FICI

0.4

1.3

0.4

0.9

P. aeruginosa

MIC

1/2MIC + 1/2MIC

1/4MIC + 1/2MIC

FICI

0.4

1.4

0.5

0.8

FREC

MIC

1/2MIC + 1/2MIC

1/4MIC + 1/2MIC

FICI

0.4

0.8

0.5

1.2

Bacterial species		Ciprofloxacin + 8p	Oxacillin + 8p	Gentamicin + 8p	Tigecycline + 8p
S. aureus	MIC	1/16MIC + 1/2MIC	1/16MIC + 1/2MIC	1/8MIC + 1/2MIC	1/16MIC + 1/2MIC
FICI	1.7	0.4	0.5	1.2
E. coli	MIC	1/4MIC + 1/2MIC	1/2MIC + 1/2MIC	1/8MIC + 1/2MIC	1/16MIC + 1/2MIC
FICI	0.4	1.3	0.4	0.9
P. aeruginosa	MIC	1/2MIC + 1/2MIC	1/2MIC + 1/2MIC	1/4MIC + 1/2MIC	1/4MIC + 1/2MIC
FICI	0.4	1.4	0.5	0.8
FREC	MIC	1/2MIC + 1/2MIC	1/2MIC + 1/2MIC	1/4MIC + 1/2MIC	1/4MIC + 1/2MIC
FICI	0.4	0.8	0.5	1.2

Bacterial species

Ciprofloxacin + 8p

Oxacillin + 8p

Gentamicin + 8p

Tigecycline + 8p

S. aureus

MIC

1/16MIC + 1/2MIC

1/8MIC + 1/2MIC

1/16MIC + 1/2MIC

FICI

1.7

0.4

0.5

1.2

E. coli

MIC

1/4MIC + 1/2MIC

1/2MIC + 1/2MIC

1/8MIC + 1/2MIC

1/16MIC + 1/2MIC

FICI

0.4

1.3

0.4

0.9

P. aeruginosa

MIC

1/2MIC + 1/2MIC

1/4MIC + 1/2MIC

FICI

0.4

1.4

0.5

0.8

FREC

MIC

1/2MIC + 1/2MIC

1/4MIC + 1/2MIC

FICI

0.4

0.8

0.5

1.2

含苯丙氨酸残基的拟肽衍生物的设计、合成与抗菌活性研究

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汪晴 , 钱春丽 , 佘慧娴 , 杨家强 ^*

药学学报 | 研究论文 2026,61(9): 3442-3447

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药学学报 |研究论文 2026 , 61 (9) : 3442 -3447

含苯丙氨酸残基的拟肽衍生物的设计、合成与抗菌活性研究

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汪晴, 钱春丽, 佘慧娴, 杨家强^*

作者信息

遵义医科大学药学院, 贵州遵义 563000

通讯作者:

杨家强，Tel: 86-851-28642339，E-mail: yjqcn@126.com

作者简介:

作者贡献:

汪晴负责理化与活性数据整理、分析及论文撰写等; 钱春丽负责化学合成; 佘慧娴参与构效关系分析; 杨家强负责论文指导与修改等工作。

Design, synthesis and antibacterial activities of peptidomimetic derivatives containing phenylalanine

Qing WANG, Chun-li QIAN, Hui-xian SHE, Jia-qiang YANG^*

Affiliations

College of Pharmacy, Zunyi Medical University, Zunyi 563000, China

出版时间: 2026-09-12 doi: 10.16438/j.0513-4870.2026-0196

文章导航

摘要

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运用分子杂合策略, 将药效片段氨基噻唑肟与苯丙氨酸组合, 设计合成了17个含苯丙氨酸残基的拟肽衍生物进行抗菌活性研究。结果表明, 该类化合物对所测试细菌有不同程度的抑制作用, 尤以化合物8p最为突出, 对大肠埃希菌(E. coli)、绿脓杆菌(P. aeruginosa) 和耐氟喹诺酮大肠杆菌(fluoroquinolone-resistant E. coli, FREC) 的最小抑菌浓度(minimum inhibitory concentration, MIC) 均为2 μg·mL^-1, 抗E. coli、P. aeruginosa与对照药环丙沙星相当, 抗FREC活性远优于对照药; 同时, 化合物8p与部分抗菌药物联用, 具有协同作用。其较显著的抗菌及增效作用具有进一步开发的潜力。

关键词

氨基噻唑肟 / 苯丙氨酸残基 / 拟肽衍生物 / 合成 / 抗菌活性

Abstract

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Using a molecular hybridization strategy, 17 peptidomimetic derivatives of phenylalanine were designed and synthesized by combining an aminothiazole oxime scaffold with phenylalanine for antibacterial activity studies. The results showed that these compounds exhibited varying degrees of inhibitory activity against the tested bacterial strains, with compound 8p being particularly outstanding. It demonstrated minimal inhibitory concentrations (MIC) of 2 μg·mL^-1 against E. coli, P. aeruginosa, and fluoroquinolone-resistant E. coli (FREC). Its activity against E. coli and P. aeruginosa was comparable to that of the reference drug ciprofloxacin, while its efficacy against FREC was significantly superior to the reference drug. Meanwhile, compound 8p exhibited synergistic effects when combined with certain antibacterial agents. Its relatively significant antibacterial activities and synergistic enhancement warrant further investigation.

Key words

aminothiazole oxime / phenylalanine / peptidomimetic derivative / synthesis / antibacterial activity

引用本文

汪晴, 钱春丽, 佘慧娴, 杨家强. 含苯丙氨酸残基的拟肽衍生物的设计、合成与抗菌活性研究. 药学学报, 2026 , 61 (9) : 3442 -3447 . DOI: 10.16438/j.0513-4870.2026-0196

Qing WANG, Chun-li QIAN, Hui-xian SHE, Jia-qiang YANG. Design, synthesis and antibacterial activities of peptidomimetic derivatives containing phenylalanine[J]. Acta Pharmaceutica Sinica, 2026 , 61 (9) : 3442 -3447 . DOI: 10.16438/j.0513-4870.2026-0196

正文

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天然抗菌肽是宿主防御系统的一部分, 具有广谱抗菌、作用快速且不易产生耐药性等优点, 但存在稳定性差、成本高和生物利用度低等缺陷^{[1, 2]}。而拟肽类化合物旨在模仿天然抗菌肽的优势, 通过保留或模拟其关键的药效团, 来克服其局限性^[3-5]。其中, 含苯丙氨酸残基的拟肽衍生物近年在抗菌药物的设计中呈现巨大潜力^[6]。2017年, Su等^[7]设计合成的含苯丙氨酸残基的共聚肽, 对金黄色葡萄球菌(S. aureus) 的MIC值达到2 μg·mL^-1; 2021年, Peng等^[8]用疏水性苯丙氨酸取代质子凝集素肽中的氨基酸, 能显著提高对S. aureus和枯草芽孢杆菌(B. subtilis) 的抑制作用, MIC值达4 μg·mL^-1; 2025年, 本课题组^[9]设计合成的含苯丙氨酸残基的拟肽类蛇床子素衍生物对E. coli、耐甲氧西林金黄色葡萄球菌(methicillin-resistance S. aureus, MRSA) 和耐氟喹诺酮大肠杆菌(fluoroquinolone-resistant E. coli, FREC) 的MIC值分别达2、16和4 μg·mL^-1, 苯丙氨酸残基的引入有助于提高抗革兰阴性菌活性。

2-氨基噻唑可分别作为氢键供体或受体与靶标结合, 存在于多种药物中^[10]。尤其是在抗菌药物结构中, 能增强细胞膜的通透性, 提高与靶点的亲和力, 进而提升抗菌活性、扩大抗菌谱, 尤其是克服细菌耐药性的重要结构单元^[11-14], 如头孢匹罗、氨曲南和磺胺噻唑等。肟醚作为一种抗菌药效团, 其独特的电子效应和立体取向, 有助于药物分子更精确地与细菌靶点结合, 增强亲和力, 避免被耐药菌产生的灭活酶识别, 在抗菌药物的设计中扮演着重要角色^{[15, 16]}。如在半合成β-内酰胺类抗生素中引入肟醚结构, 提高了对酶的稳定性^[17]; 在喹诺酮类抗菌药物中引入肟醚片段, 增强了与靶标的亲和力^[18]。

基于此, 运用分子杂合策略, 将2-氨基噻唑肟与苯丙氨酸通过酰胺键杂合(设计思路见图 1), 设计系列新型含苯丙氨酸残基的拟肽衍生物进行抗菌活性评价。目标物的合成如路线1所示。

结果与讨论

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1　化合物的合成

在合成中间体1时, 以亚硝酸叔丁酯做肟化剂, 替代亚硝酸钠^[19], 操作简便, 反应易控制, 更绿色环保。在合成中间体5时, 以(C₂H₅O)₃P代替传统的脱水剂浓硫酸^[20], 反应更温和, 收率更高。在合成目标物8时, 以HBTU/DIPEA为缩合剂比以HOBT/EDCI/DMAP为缩合剂有更好的收率。

目标化合物8的相关理化数据见表 1、2。

2　目标化合物的抗菌活性

该类化合物对所测细菌有不同程度的抑制作用(表 3), 化合物8d、8f、8g、8h、8i、8j、8l、8n和8p对S. aureus的MIC分别为32、16、8、32、32、16、32、16和16 μg·mL^-1, 尤以8g最为突出; 化合物8d、8e、8g、8h、8j、8n、8o和8p对E. coli的MIC分别为32、16、4、32、8、32、16和2 μg·mL^-1, 其中, 8g和8o与对照药环丙沙星相当; 化合物8e、8g、8h、8j、8o和8p对P. aeruginosa的MIC分别为32、4、32、8、32和2 μg·mL^-1, 其中, 8o优于对照药; 同时, 该类化合物抗耐药菌FREC活性较显著, 化合物8d、8e、8g、8h、8j、8n、8o和8p对FREC的MIC分别为32、16、4、32、8、32、16和2 μg·mL^-1, 均优于对照药。综合来看, 该类化合物抗革兰阴性菌活性更优。

构效关系分析如下, ①取代基的位置: 对位取代普遍能获得更好的抗菌活性, 尤其是化合物8g (4-FPh) 和8p (4-FPhCH₂) 呈现出较显著的抗菌效果, 可能是氟原子在对位实现了亲脂性、膜穿透性与靶点亲和力的最优平衡; 邻位取代导致抗菌活性大幅降低; 而间位取代对革兰阴性菌几乎无活性；②取代基的电子效应: 吸电子基取代的抗菌活性更优, 大多遵循F > Cl > Br, 给电子基使其活性降低；③取代基的长度: 适中长度的苄基取代对革兰阴性菌活性最好(如8p优于8g), 而连接链延长至苯乙基(8q), 活性降低, 可能是靶点结合口袋对连接链长度较为敏感。

3　化合物8p与抗菌药物联合的抗菌效果及协同作用

化合物8p与不同抗菌药物的联合使用对MIC的影响结果如表 4所示, 化合物8p与环丙沙星联合使用, 对E. coli、P. aeruginosa和FREC有协同作用; 与苯唑西林联合使用, 对S. aureus有协同作用; 与庆大霉素联合使用, 则对所测细菌均有一定的协同作用; 而与替加环素联合使用时, 无协同作用。

4　小结

依据分子杂合原理, 设计合成的部分含苯丙氨酸残基的拟肽衍生物有较显著抗菌活性, 该类化合物的活性受取代基的位置、电子效应和长短等因素的影响较大, 其中, 以化合物8p的抗革兰阴性菌效果最突出, 可作为先导化合物深入研究。

实验部分

收起

用SGW X-显微熔点仪测定熔点Agilent 6460质谱仪; NMR用Brker Avance 400型核磁共振仪测定; 质谱数据用Agilent 6460质谱仪测得。

溴乙酰乙酸乙酯、亚硝酸叔丁酯、硫脲、吡啶、四丁基溴化铵、硫酸二甲酯、亚膦酸三乙酯、三乙胺、促进剂DM、L-苯丙氨酸、苯胺、取代苯胺、取代苄胺、苯乙胺、O-苯并三氮唑-四甲基脲六氟磷酸盐(HBTU)、N, N-二异丙基乙胺(DIPEA)、三氟乙酸均为化学纯, 购于百灵威试剂有限公司, 其余试剂均为分析纯。

1　化合物的合成

1.1　化合物5的合成

在反应瓶中加入8.2 g (0.05 mol) 溴乙酰乙酸乙酯、10 mL丙醇、5.2 g (0.05 mol) 亚硝酸叔丁酯、0.3 mL浓盐酸, 于5~10 ℃下搅拌反应20 h, 完毕, 通氮气除去未反应的亚硝酸叔丁酯, 浓缩溶剂, 得黄色液体, 即化合物1。接着, 将化合物1、3.8 g (0.1 mol) 硫脲、20 mL蒸馏水和4.5 mL吡啶加至反应瓶, 室温搅拌反应3.5 h, 减压过滤, 得浅黄色固体, 即化合物2。然后, 将化合物2、4.8 g (0.046 mol) 碳酸钠、0.1 g四丁基溴化铵和9.8 g (0.046 mol) Me₂SO₄加至反应瓶, 于10~15 ℃搅拌反应4 h; 冰水浴冷却, 减压过滤, 得淡黄色固体, 即化合物3。接下来, 将化合物3、30 mL乙醇和40 mL 1.5 mol·L^-1的NaOH溶液加入反应瓶, 室温搅拌反应2 h, 用10% HCl调pH至7, 减压蒸出乙醇, 乙酸乙酯萃取, 水溶液用10% HCl调节pH至2~3, 冰水浴冷却, 析出固体, 减压过滤, 得白色固体, 即化合物4。最后, 将11.6 g (0.035 mol) 促进剂DM、50 mL 1, 2-二氯乙烷、5.24 g (0.026 mol) 化合物4、0.013 mol三乙胺和0.035 mol亚磷酸三乙酯加至反应瓶中, 于10~15 ℃搅拌反应5 h, 减压过滤, 得淡黄色粉末, 即化合物5。mp 129~131 ℃。¹H NMR (400 MHz, CDCl₃) δ_H: 8.11~8.13 (m, 1H), 7.93~7.95 (m, 1H), 7.51~7.57 (m, 2H), 6.90 (s, 1H), 5.75 (s, 2H), 4.11 (s, 3H)。

1.2　化合物7的合成

以化合物7a为例, 依次称取0.297 g (1.12 mmol) L-苯丙氨酸、0.885 g (2.34 mmol) HBTU、0.56 mL (3.27 mmol) DIPEA、3.5 mL N, N-二甲基甲酰胺和0.085 g (0.93 mmol) 苯胺于反应瓶中, 在0~5 ℃搅拌反应, 薄层色谱跟踪, 2 h反应完毕, 加适量蒸馏水, 过滤, 得白色固体, 即化合物6。再将化合物7、3 mL二氯甲烷和0.68 mL (1.5 mmol) 三氟乙酸加入反应瓶中, 5~10 ℃搅拌反应, 薄层色谱跟踪, 4 h反应完毕, 加适量饱和碳酸氢钠, 析出浅棕色固体, 过滤, 硅胶柱色谱(V_石油醚∶V_乙酸乙酯 = 5∶1) 分离纯化, 得白色固体, 即化合物7a。mp 75~77 ℃。¹H NMR (400 MHz, CDCl₃) δ_H: 9.42 (brs, 1H), 7.61~1.58 (m, 2H), 7.36~7.25 (m, 7H), 7.13~7.09 (m, 1H), 3.74 (dd, J = 9.6, 4.0 Hz, 1H), 3.39~2.80 (m, 2H), 1.46 (brs, 2H)。

1.3　化合物8的合成

以化合物8a为例, 依次称取0.085 g (0.24 mmol) 化合物6、0.2 mL (0.1 mmol) 三乙胺、10 mL二氯甲烷和0.029 g (0.12 mmol) 化合物7a于反应瓶中, 薄层色谱监测反应, 4 h反应完毕, 浓缩溶剂, 硅胶柱色谱(V_石油醚∶V_乙酸乙酯 = 3∶1) 分离纯化, 得化合物8a。

2　体外抗菌活性测试

S. aureus、E. coli和P. aeruginosa源于北京北纳创联生物技术研究院; 耐药菌株FREC由遵义医科大学附属医院分离提供。以环丙沙星(Oxacillin) 对照药, 采用两倍稀释法测定目标物的MIC, 测试方法参照文献^[21]。

3　联合抗菌活性测试

采用微量稀释法, 调整细菌浓度为10⁵ CFU·mL^-1, 接种于96孔板, 加入不同的抗菌药, 依次倍比稀释, 使其终浓度自32~0.062 5 μg·mL^-1; 再加入相应浓度的目标物, 使其浓度范围为64~0.125 μg·mL^-1; 置37 ℃培养箱孵育24 h, 记录联合使用时的MIC, 并计算抑菌浓度指数(fractional inhibitory concentration index, FICI)。

参考文献

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2026年第61卷第9期

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doi: 10.16438/j.0513-4870.2026-0196

接收时间：2026-02-25
首发时间：2026-10-22
出版时间：2026-09-12

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收稿日期：2026-02-25
修回日期：2026-03-20

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遵义医科大学药学院, 贵州遵义 563000

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杨家强，Tel: 86-851-28642339，E-mail: yjqcn@126.com

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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Compd.	R	Appearance	Yield/%	mp/℃
8a	Ph	White solid	67	101-102
8b	2-CH₃Ph	White solid	79	100-101
8c	3-CH₃Ph	White solid	72	102-103
8d	4-CH₃Ph	White solid	71	103-104
8e	2-FPh	White solid	63	104-106
8f	3-FPh	White solid	61	107-109
8g	4-FPh	White solid	55	98-99
8h	2-ClPh	White solid	58	108-110
8i	3-ClPh	White solid	56	100-102
8j	4-ClPh	White solid	48	185-186
8k	2-BrPh	White solid	52	102-103
8l	3-BrPh	White solid	49	103-104
8m	4-BrPh	White solid	43	121-122
8n	PhCH₂	White solid	73	116-118
8o	2-FPhCH₂	White solid	41	188-190
8p	4-FPhCH₂	White solid	55	214-215
8q	PhCH₂CH₂	White solid	73	114-115

Compd.

Appearance

Yield/%

mp/℃

White solid

101-102

2-CH₃Ph

White solid

100-101

3-CH₃Ph

White solid

102-103

4-CH₃Ph

White solid

103-104

2-FPh

White solid

104-106

3-FPh

White solid

107-109

4-FPh

White solid

98-99

2-ClPh

White solid

108-110

3-ClPh

White solid

100-102

4-ClPh

White solid

185-186

2-BrPh

White solid

102-103

3-BrPh

White solid

103-104

4-BrPh

White solid

121-122

PhCH₂

White solid

116-118

2-FPhCH₂

White solid

188-190

4-FPhCH₂

White solid

214-215

PhCH₂CH₂

White solid

114-115

Compd.	¹H NMR, ¹³C NMR and MS
8a	¹H NMR (400 MHz, DMSO) δ_H: 10.05 (s, 1H), 9.00 (d, J = 8.3 Hz, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.23-7.31 (m, 6H, ArH), 7.18 (d, J = 7.8 Hz, 1H), 7.15 (s, 2H), 7.01-7.06 (m, 1H), 6.13 (s, 1H), 4.75-4.81 (m, 1H), 3.71 (s, 3H), 2.83-3.11 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 119.8, 124.0, 126.8, 128.5, 129.2, 129.7, 137.9, 139.0, 143.2, 149.6, 162.8, 168.6, 170.0; ESI MS (m/z): 424.3 [M+H]⁺
8b	¹H NMR (400 MHz, CDCl₃) δ_H: 8.14 (s, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.26-7.29 (m, 5H), 7.13-7.17 (m, 2H), 7.05-7.09 (m, 1H), 6.45 (s, 1H), 5.37 (s, 2H), 5.03-5.08 (m, 1H), 3.88 (s, 3H), 3.24-3.39 (m, 2H), 2.06 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 17.5, 37.2, 55.2, 62.8, 110.9, 124.0, 126.0, 126.5, 127.1, 128.8, 129.4, 130.6, 131.0, 134.9, 136.3, 142.3, 147.7, 162.8, 168.1, 169.3; ESI MS (m/z): 438.5 [M+H]⁺
8c	¹H NMR (400 MHz, DMSO) δ_H: 9.96 (s, 1H), 8.99 (d, J = 8.2 Hz, 1H), 7.30-7.37 (m, 4H), 7.24-7.27 (m, 2H), 7.17-7.20 (m, 2H), 7.16 (s, 2H), 6.85-6.87 (m, 1H), 6.12 (s, 1H), 4.75-4.80 (m, 1H), 3.71 (s, 3H), 2.85-3.10 (m, 2H), 2.25 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 21.6, 37.5, 55.1, 62.3, 110.7, 117.0, 120.2, 124.6, 126.8, 128.5, 129.0, 129.7, 138.0, 138.4, 138.9, 143.2, 149.7, 162.7, 168.6, 169.9; ESI MS (m/z): 438.3 [M+H]⁺
8d	¹H NMR (400 MHz, DMSO) δ_H: 9.94 (s, 1H), 8.99 (d, J = 7.5 Hz, 1H), 7.42-7.44 (m, 2H), 7.19-7.29 (m, 5H), 7.16 (s, 2H), 7.09-7.11 (m, 2H), 6.13 (s, 1H), 4.77-4.82 (m, 1H), 3.71 (s, 3H), 2.86-3.09 (m, 2H), 2.22 (s, 3H); ¹³C NMR (101 MHz, DMSO) δ_C: 20.9, 37.6, 55.1, 62.3, 110.7, 119.7, 126.7, 128.5, 129.6, 129.7, 132.8, 136.5, 138.0, 143.2, 149.7, 162.7, 168.6, 169.8; ESI MS (m/z): 438.0 [M+H]⁺
8e	¹H NMR (400 MHz, DMSO) δ_H: 8.39 (s, 1H), 8.04 (d, J = 10.2 Hz, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.19-7.27 (m, 5H), 6.99-7.04 (m, 3H), 6.31 (s, 1H), 5.06-5.12 (m, 1H), 3.84 (s, 3H), 3.13-3.42 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 18.3, 37.3, 55.1, 62.9, 111.6, 115.0, 115.2, 122.8, 124.4, 125.3, 127.1, 128.8, 129.2, 136.2, 142.0, 147.6, 151.9, 154.3, 162.8, 168.2, 169.3; ESI MS (m/z): 442.4 [M+H]⁺
8f	¹H NMR (400 MHz, CDCl₃) δ_H: 8.02 (s, 1H), 7.88 (d, J = 9.8 Hz, 1H), 7.19-7.26 (m, 5H), 6.45 (s, 1H), 6.39-6.41 (m, 2H), 5.84 (s, 2H), 4.96-5.01 (m, 1H), 3.86 (s, 3H), 3.18-3.36 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ_C: 37.7, 55.4, 62.8, 98.5, 103.6, 111.3, 120.0, 121.5, 126.9, 128.6, 129.3, 136.4, 142.1, 147.5, 149.9, 156.9, 162.4, 168.3, 168.5; ESI MS (m/z): 442.1 [M+H]⁺
8g	¹H NMR (400 MHz, DMSO) δ_H: 10.19 (s, 1H), 9.03 (d, J = 8.2 Hz, 1H), 7.55-7.58 (m, 2H), 7.24-7.37 (m, 5H), 7.11-7.20 (m, 4H), 6.21 (s, 1H), 4.73-4.79 (m, 1H), 3.72 (s, 3H), 2.87-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.6, 55.2, 62.4, 110.8, 115.7, 115.9, 121.5, 121.6, 126.8, 128.6, 129.7, 135.5, 137.9, 149.2, 157.4, 159.7, 162.5, 168.8, 169.9; ESI MS (m/z): 441.9 [M+H]⁺
8h	¹H NMR (400 MHz, DMSO) δ_H: 9.59 (s, 1H), 9.06 (d, J = 8.4 Hz, 1H), 7.73-7.69 (m, 1H), 7.39 (d, J = 5.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.15-7.18 (m, 3H), 7.12 (s, 2H), 7.04-7.07 (m, 2H), 5.09-4.79 (m, 1H), 3.69 (s, 3H), 2.91-3.19 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.7, 56.5, 62.3, 110.8, 126.1, 126.6, 126.8, 126.9, 127.9, 128.6, 129.8, 129.9, 134.9, 138.1, 143.1, 149.7, 162.9, 168.7, 170.4; ESI MS (m/z): 458.2 [M+H]⁺
8i	¹H NMR (400 MHz, DMSO) δ_H: 10.30 (s, 1H), 9.03 (d, J = 8.1 Hz, 1H), 7.77 (s, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.24-7.34 (m, 5H), 7.18 (d, J = 9.0 Hz, 1H), 7.16 (s, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.18 (s, 1H), 4.73-4.78 (m, 1H, CH), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 118.2, 119.2, 122.7, 126.8, 128.6, 129.7, 130.9, 133.5, 137.9, 140.6, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 458.3 [M+H]⁺
8j	¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.03 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 7.7 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 7.23-7.27 (m, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.17 (s, 2H), 6.18 (s, 1H), 4.74-4.79 (m, 1H), 3.71 (s, 3H), 2.87-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 126.9, 127.5, 128.6, 129.2, 129.7, 137.9, 138.1, 143.3, 149.7, 162.8, 168.7, 170.3; ESI MS (m/z): 458.3 [M+H]⁺
8k	¹H NMR (400 MHz, DMSO) δ_H: 9.61 (s, 1H), 9.05 (d, J = 8.6 Hz, 1H), 7.59-7.66 (m, 2H), 7.34-7.39 (m, 3H), 7.25 (t, J = 15.6 Hz, 2H), 7.18-7.22 (m, 1H), 7.16 (s, 2H), 7.11-7.13 (m, 1H), 6.05 (s, 1H), 4.90-4.96 (m, 1H), 3.69 (s, 3H), 2.89-3.24 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 54.6, 62.3, 110.8, 117.9, 126.8, 127.1, 127.6, 128.6, 129.8, 133.2, 136.2, 138.1, 143.1, 149.7, 162.9, 168.6, 170.33; ESI MS (m/z): 504.2 [M+H]⁺
8l	¹H NMR (400 MHz, DMSO) δ_H: 10.28 (s, 1H), 9.04 (d, J = 8.3 Hz, 1H), 7.89 (s, 1H), 7.43-7.45 (m, 1H), 7.29 (d, 2H), 7.24-7.27 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.77 (m, 1H), 3.71 (s, 3H), 2.87-3.09 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.4, 55.2, 62.3, 118.5, 121.9, 122.0, 126.6, 126.9, 128.6, 129.7, 131.3, 137.8, 140.7, 143.3, 149.7, 162.8, 168.7, 170.5; ESI MS (m/z): 503.9 [M+H]⁺
8m	¹H NMR (400 MHz, DMSO) δ_H: 10.22 (s, 1H), 9.02 (d, J = 8.2 Hz, 1H), 7.47-7.54 (m, 4H), 7.23-7.30 (m, 4H), 7.18 (d, J = 7.8 Hz, 1H), 7.16 (s, 2H), 6.17 (s, 1H), 4.72-4.78 (m, 1H), 3.71 (s, 3H), 2.87-3.07 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.5, 55.2, 62.3, 110.7, 111.5, 121.7, 126.8, 128.6, 129.7, 132.1, 137.9, 138.5, 143.3, 149.7, 162.8, 168.6, 170.3; ESI MS (m/z): 504.3 [M+H]⁺
8n	¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.6 Hz, 1H), 8.26 (t, J = 12.0 Hz, 1H), 7.24-7.28 (m, 6H), 7.17-7.22 (m, 4H), 7.13 (s, 2H), 6.08 (s, 1H), 4.61-4.66 (m, 1H), 4.30 (d, J = 8.6 Hz, 2H), 3.63 (s, 3H), 2.78-3.12 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 42.6, 54.5, 62.2, 110.5, 126.7, 127.3, 127.6, 128.6, 128.7, 129.7, 138.3, 139.4, 143.0, 149.8, 162.7, 168.7, 170.9; ESI MS (m/z): 438.5 [M+H]⁺
8o	¹H NMR (400 MHz, DMSO) δ_H: 8.94 (d, J = 7.8 Hz, 1H), 8.29 (t, J = 12.2 Hz, 1H), 7.24-7.25 (m, 4H), 7.19-7.22 (m, 3H), 7.07-7.12 (m, 4H), 6.11 (s, 1H), 4.59-4.64 (m, 1H), 4.28 (d, J = 3.6 Hz, 2H), 3.65 (s, 3H), 2.74-3.08 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 135.7, 138.3, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.3 [M+H]⁺
8p	¹H NMR (400 MHz, DMSO) δ_H: 8.93 (d, J = 8.0 Hz, 1H), 8.28 (t, J = 12.4 Hz, 1H), 7.22-7.25 (m, 4H), 7.18-7.20 (m, 3H), 7.07-7.13 (m, 4H), 6.11 (s, 1H), 4.58-4.64 (m, 1H), 4.28 (d, J = 4.0 Hz, 2H), 3.65 (s, 3H), 2.78-3.10 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 37.3, 41.9, 54.5, 62.3, 110.4, 115.3, 115.5, 126.7, 128.6, 129.5, 129.6, 129.7, 135.6, 138.2, 143.1, 149.8, 160.4, 162.7, 168.7, 170.9; ESI MS (m/z): 456.0 [M+H]⁺
8q	¹H NMR (400 MHz, DMSO) δ_H: 8.84 (d, J = 8.4 Hz, 1H), 7.92 (t, J = 6.6 Hz, 1H), 7.25-7.27 (m, 1H), 7.23-7.24 (m, 5H), 7.18 (d, J = 4.2 Hz, 2H), 7.16-7.17 (m, 4H), 6.13 (s, 1H), 4.51-4.57 (m, 1H), 3.69 (s, 3H), 3.26 (d, J = 5.9 Hz, 2H), 2.97-3.00 (m, 2H), 2.64-2.77 (m, 2H); ¹³C NMR (101 MHz, DMSO) δ_C: 35.6, 37.4, 54.4, 55.3, 62.3, 63.5, 110.5, 126.6, 126.7, 128.5, 128.7, 129.1, 129.7, 138.4, 139.7, 143.1, 149.9, 162.7, 168.7, 170.9; ESI MS (m/z): 452.5 [M+H]⁺

Compd.

¹H NMR, ¹³C NMR and MS

Compd.	MIC/μg·mL^-1
8a	128.	64.	128.	64.
8b	> 128.	128.	128.	128.
8c	64.	> 128.	> 128.	> 128.
8d	32.	32.	64.	32.
8e	64.	16.	32.	16.
8f	16.	> 128.	> 128.	> 128.
8g	8.	4.	4.	4.
8h	32.	32.	32.	32.
8i	32.	128.	128.	128.
8j	16.	8.	8.	8.
8k	64.	128.	64.	128.
8l	32.	> 128.	> 128.	> 128.
8m	64.	128.	64.	> 128.
8n	16.	32.	64.	32.
8o	128.	16.	32.	16.
8p	16.	2.	2.	2.
8q	> 128.	128.	64.	128.
Ciprofloxacin	0.5	2.	4.	> 128.

Compd.

MIC/μg·mL^-1

S. aureus

E. coli

P. aeruginosa

FREC

128.

64.

128.

64.

> 128.

128.

64.

> 128.

32.

64.

32.

64.

16.

32.

16.

> 128.

32.

128.

16.

64.

128.

64.

128.

32.

> 128.

64.

128.

64.

> 128.

16.

32.

64.

32.

128.

16.

32.

16.

> 128.

128.

64.

128.

Ciprofloxacin

0.5

> 128.

Bacterial species		Ciprofloxacin + 8p	Oxacillin + 8p	Gentamicin + 8p	Tigecycline + 8p
S. aureus	MIC	1/16MIC + 1/2MIC	1/16MIC + 1/2MIC	1/8MIC + 1/2MIC	1/16MIC + 1/2MIC
FICI	1.7	0.4	0.5	1.2
E. coli	MIC	1/4MIC + 1/2MIC	1/2MIC + 1/2MIC	1/8MIC + 1/2MIC	1/16MIC + 1/2MIC
FICI	0.4	1.3	0.4	0.9
P. aeruginosa	MIC	1/2MIC + 1/2MIC	1/2MIC + 1/2MIC	1/4MIC + 1/2MIC	1/4MIC + 1/2MIC
FICI	0.4	1.4	0.5	0.8
FREC	MIC	1/2MIC + 1/2MIC	1/2MIC + 1/2MIC	1/4MIC + 1/2MIC	1/4MIC + 1/2MIC
FICI	0.4	0.8	0.5	1.2

Bacterial species

Ciprofloxacin + 8p

Oxacillin + 8p

Gentamicin + 8p

Tigecycline + 8p

S. aureus

MIC

1/16MIC + 1/2MIC

1/8MIC + 1/2MIC

1/16MIC + 1/2MIC

FICI

1.7

0.4

0.5

1.2

E. coli

MIC

1/4MIC + 1/2MIC

1/2MIC + 1/2MIC

1/8MIC + 1/2MIC

1/16MIC + 1/2MIC

FICI

0.4

1.3

0.4

0.9

P. aeruginosa

MIC

1/2MIC + 1/2MIC

1/4MIC + 1/2MIC

FICI

0.4

1.4

0.5

0.8

FREC

MIC

1/2MIC + 1/2MIC

1/4MIC + 1/2MIC

FICI

0.4

0.8

0.5

1.2