F. Huang, Z. Zeng, W. Zhang et al.
European Journal of Medicinal Chemistry 222 (2021) 113542
7.40 (m, 2H), 7.40 - 7.34 (m, 2H), 7.30 (s, 1H), 7.14 (d, J ¼ 8.6 Hz, 2H),
7.01 (dd, J ¼ 2.6, 9.4 Hz,1H), 6.73 (dt, J ¼ 2.4, 8.9 Hz,1H), 5.18 (s, 2H),
8.4 Hz, 1H), 7.10 (d, J ¼ 7.7 Hz, 1H), 7.08 (s, 1H), 7.03 - 6.97 (m, 2H),
6.73 (dd, J ¼ 2.4, 8.1 Hz, 1H), 3.78 (s, 3H), 3.58 (s, 2H), 2.15 (s, 3H);
3.57 (s, 2H), 2.15 (s, 3H); 13C NMR (151 MHz, CDCl3)
d
¼ 175.51,
13C NMR (151 MHz, DMSO‑d6)
d
¼ 172.10, 162.85 (d, J ¼ 243.2 Hz,
163.02 (d, J ¼ 246.5 Hz, 1C), 158.93, 146.16 (d, J ¼ 8.8 Hz, 1C), 139.30,
138.95, 136.70, 130.98 (s, 2C), 130.71, 129.84 (d, J ¼ 2.2 Hz, 1C),
129.61 (d, J ¼ 2.2 Hz,1C),128.98,128.67 (s, 2C),128.13,127.56 (s, 2C),
123.61 (d, J ¼ 8.8 Hz, 1C), 114.84 (s, 2C), 110.56 (d, J ¼ 23.1 Hz, 1C),
105.62 (d, J ¼ 23.1 Hz, 1C), 70.12, 31.30, 10.61. HRMS (ESI) calcd for
1C), 159.70, 147.37 (d, J ¼ 8.8 Hz, 1C), 140.02, 138.35, 137.93, 132.48
(d, J ¼ 2.2 Hz, 1C), 131.23, 130.20, 130.04 (d, J ¼ 2.2 Hz, 1C), 123.74 (d,
J ¼ 8.8 Hz, 1C), 121.80, 114.70, 114.59, 110.71 (d, J ¼ 23.1 Hz, 1C),
106.34 (d, J ¼ 24.2 Hz, 1C), 55.60, 31.56, 10.70. HRMS (ESI) calcd for
C
20H17FNaOþ3 [MþNaþ]: 347.1054; found: 347.1056.
C
26H21FNaOþ3 [MþNaþ]: 423.1367; found: 423.1359.
4.1.12. (Z)-2-(5-fluoro-2-methyl-1-(3-methylbenzylidene)-1H-
inden-3-yl) acetic acid (11Z)
4.1.7. (Z)-2-(1-(3-(benzyloxy)benzylidene)-5-fluoro-2-methyl-1H-
inden-3-yl) acetic acid (6b)
Yellow solid; yield 63%; M.p.142e144 ꢀC. 1H NMR (600 MHz,
Yellow solid; yield 73%; M.p.169e171 ꢀC; 1H NMR (600 MHz,
CDCl3)
(d, J ¼ 8.8 Hz, 1H), 6.54 (t, J ¼ 8.7 Hz, 1H), 3.56 (s, 2H), 2.37 (s,
3H),2.18 (s, 3H); 13C NMR (151 MHz, CDCl3)
d
¼ 7.29 (m, 3H), 7.24e7.27 (m, 1H), 7.15e7.19 (m, 2H), 6.86
CDCl3)
d
¼ 7.40e7.44 (m, 2H), 7.37 (t, J ¼ 7.4 Hz, 2H), 7.30e7.35 (m,
2H), 7.22e7.28 (m, 1H), 7.17 (s, 1H), 7.06e7.12 (m, 2H), 6.99 (dd,
J ¼ 8.3, 2.2 Hz, 1H), 6.86 (dd, J ¼ 8.8, 2.2 Hz, 1H), 6.53 (td, J ¼ 8.8,
2.3 Hz, 1H), 5.06 (s, 2H) 3.57 (s, 2H), 2.19 (s, 3H); 13C NMR (151 MHz,
d
¼ 177.0, 163.1 (d,
J ¼ 249.8 Hz), 146.2 (d, J ¼ 8.8 Hz), 140.1, 138.9, 138.2, 136.5, 131.0,
130.0, 129.9, 129.0, 128.5 (d, J ¼ 4.4 Hz), 128.4, 126.4, 123.9 (d,
J ¼ 8.8 Hz), 110.7 (d, J ¼ 22.0 Hz), 105.7 (d, J ¼ 23.1 Hz), 31.5, 21.4,
10.6; HRMS (ESI) calcd for C20H17FNaOþ2 [MþNaþ]: 331.1105; found:
331.1100. HPLC purity: 97.86%.
CDCl3)
d
¼ 176.6, 163.1 (d, J ¼ 246.5 Hz), 158.8, 146.2 (d, J ¼ 8.8 Hz),
140.4, 138.8, 137.9, 136.8, 130.4, 130.2 (d, J ¼ 2.2 Hz), 129.7 (d,
J ¼ 3.3 Hz), 129.7, 128.6 (2C), 128.1, 127.5 (2C), 124.0 (d, J ¼ 8.8 Hz),
122.0, 115.2, 115.1, 110.8 (d, J ¼ 22.0 Hz), 105.8 (d, J ¼ 23.1 Hz), 70.0,
31.4, 10.6; HPLC purity: 99.81%.
4.1.13. (E)-2-(5-fluoro-1-(3-methylbenzylidene)-1H-inden-3-yl)
acetic acid (11E)
4.1.8. (Z)-2-(1-(3-bromobenzylidene)-5-fluoro-2-methyl-1H-
inden-3-yl) acetic acid (7)
Yellow solid; 1H NMR (600 MHz, CDCl3)
d
¼ 7.58 (dd, J ¼ 5.0,
8.3 Hz, 1H), 7.38 - 7.34 (m, 3H), 7.30 (t, J ¼ 7.5 Hz, 1H), 7.15 (d,
J ¼ 7.3 Hz, 1H), 7.04 (s, 1H), 7.01 (dd, J ¼ 2.2, 8.8 Hz, 1H), 6.92 (dt,
J ¼ 2.2, 8.7 Hz, 1H), 3.66 (s, 2H), 2.39 (s, 3H); 13C NMR (151 MHz,
Yellow solid; yield 70%; M.p.163e163 ꢀC. 1H NMR (600 MHz,
CDCl3)
d
¼ 7.64 (s, 1H), 7.51 (d, J ¼ 8.1 Hz,1H), 7.42 (d, J ¼ 7.7 Hz, 1H),
7.28e7.33 (m, 1H), 7.17 (dd, J ¼ 8.4, 5.1 Hz, 1H), 7.11 (s, 1H), 6.88 (dd,
J ¼ 8.8, 2.4 Hz, 1H), 6.59 (td, J ¼ 8.8, 2.4 Hz, 1H), 3.59 (s, 2H), 2.19 (s,
CDCl3)
d
¼ 176.37, 163.00 (d, J ¼ 246.5 Hz, 1C), 143.11 (d, J ¼ 8.8 Hz,
1C), 138.42, 137.93 (d, J ¼ 2.2 Hz, 1C), 137.60, 136.58, 133.58 (d,
J ¼ 3.3 Hz, 1C), 130.84, 129.45, 129.24, 128.69, 127.32, 127.05, 120.08
(d, J ¼ 8.8 Hz, 1C), 112.06 (d, J ¼ 23.1 Hz, 1C), 106.64 (d, J ¼ 24.2 Hz,
1C), 33.86, 21.47. HRMS (ESI) calcd for C19H15FNaO2þ [MþNaþ]:
317.0948; found: 317.0945.
3H); 13C NMR (151 MHz, CDCl3)
d
¼ 175.6, 163.3 (d, J ¼ 246.5 Hz),
146.4 (d, J ¼ 8.8 Hz),141.2, 138.7, 138.6, 132.0, 131.1, 130.9, 130.1,
129.5, 128.5, 127.8, 123.8 (d, J ¼ 8.8 Hz), 122.6, 110.9 (d, J ¼ 22.0 Hz),
106.0 (d,
J
¼
24.2 Hz), 31.3, 10.5; HRMS (ESI) calcd for
C
19H14BrFNaOþ2 [MþNaþ]: 395.0053; found: 395.0047. HPLC purity:
98.72%.
4.1.14. (Z)-2-(2-methyl-1-(3-methylbenzylidene)-1H-inden-3-yl)
acetic acid (12Z)
4.1.9. (Z)-2-(1-(3-chlorobenzylidene)-5-fluoro-2-methyl-1H-inden-
3-yl) acetic acid (8)
Yellow solid; yield 21%; 1H NMR (600 MHz, CDCl3)
J ¼ 7.7 Hz, 1H), 7.33 (s, 1H), 7.33 - 7.29 (m, 2H), 7.20 (s, 1H), 7.18 (d,
J ¼ 7.2 Hz, 2H), 7.16 (d, J ¼ 7.9 Hz, 1H), 6.89 (dt, J ¼ 1.3, 7.5 Hz, 1H),
3.61 (s, 2H), 2.38 (s, 3H), 2.19 (s, 3H); 13C NMR (151 MHz, CDCl3)
d
¼ 7.36 (d,
Yellow solid; yield 75%; M.p.162e163 ꢀC. 1H NMR (600 MHz,
CDCl3)
1H), 7.11 (s, 1H), 6.88 (dd, J ¼ 8.8, 2.0 Hz, 1H), 6.58 (td, J ¼ 8.8, 2.1 Hz,
1H), 3.58 (s, 2H),2.19 (s, 3H); 13C NMR (151 MHz, CDCl3)
d
¼ 7.47 (s, 1H), 7.33e7.39 (m, 3H), 7.16 (dd, J ¼ 8.3, 5.0 Hz,
d
¼ 176.69, 143.88, 141.16, 138.05, 136.80, 136.74, 134.13, 130.99,
d
¼ 175.8,
130.86, 129.93, 128.83, 128.33, 127.83, 126.38, 124.61, 122.87, 117.99,
31.46, 21.40, 10.48.
163.3 (d, J ¼ 244.3 Hz),146.4 (d, J ¼ 8.8 Hz),141.2,138.6,138.4,134.5,
130.8, 129.8, 129.5 (d, J ¼ 2.2 Hz), 129.1, 128.6, 128.2, 127.4, 123.8 (d,
J ¼ 8.8 Hz), 110.9 (d, J ¼ 23.1 Hz), 106.0 (d, J ¼ 23.1 Hz), 31.3, 10.5;
HRMS (ESI) calcd for C19H14ClFNaOþ2 [MþNaþ]: 351.0559; found:
351.0553. HPLC purity: 99.32%.
4.1.15. (E)-2-(1-(3-methylbenzylidene)-1H-inden-3-yl) acetic acid
(12E)
Yellow solid, 1H NMR (600 MHz, CDCl3)
d
¼ 7 7.69 (d, J ¼ 7.2 Hz,
1H), 7.44 (s, 1H), 7.39e7.42 (m, 2H), 7.31e7.34 (m, 2H), 7.29 (d,
J ¼ 9.0 Hz, 1H), 7.27 (d, J ¼ 4.8 Hz, 1H), 7.15 (d, J ¼ 7.5 Hz, 1H), 7.00 (s,
4.1.10. (Z)-2-(5-fluoro-1-(3-hydroxybenzylidene)-2-methyl-1H-
inden-3-yl) acetic acid (9)
1H), 3.71 (s, 2H), 2.40 (s, 3H); 13C NMR (151 MHz, CDCl3)
d
¼ 176.14,
Yellow solid; yield 45%; M.p. 172e177 ꢀC. 1H NMR (600 MHz,
141.29, 139.00, 138.64, 138.33, 137.95, 136.81, 130.86, 129.26, 128.71,
128.64, 127.43, 127.35, 125.57, 125.25, 119.10, 119.04, 33.89, 21.47.
HRMS (ESI) calcd for C19H15O2ꢃ [Mꢃ]: 275.1078; found: 275.1081.
DMSO‑d6)
d
¼ 9.64 (br. s., 1H), 7.30 - 7.27 (m, 3H), 7.01 (dd, J ¼ 2.5,
9.3 Hz, 1H), 6.93 (d, J ¼ 8.1 Hz, 1H), 6.92 (s, 1H), 6.82 (dd, J ¼ 2.3,
8.2 Hz, 1H), 6.74 (dt, J ¼ 2.4, 9.0 Hz, 1H), 3.57 (s, 2H), 2.14 (s, 3H); 13
C
NMR (151 MHz, DMSO‑d6)
d
¼ 172.11, 162.80 (d, J ¼ 243.2 Hz, 1C),
4.2. Materials for biological assays
157.87, 147.29 (d, J ¼ 8.8 Hz, 1C), 139.75, 138.39, 137.81, 132.27 (d,
J ¼ 2.2 Hz, 1C), 131.60, 130.15, 130.08 (d, J ¼ 2.2 Hz, 1C), 123.80 (d,
J ¼ 8.8 Hz, 1C), 120.22, 116.04, 115.87, 110.66 (d, J ¼ 23.1 Hz, 1C),
106.24 (d, J ¼ 23.1 Hz, 1C), 31.55, 10.71. HRMS (ESI) calcd for
Insulin (I9278), dexamethasone (D2915), IBMX (I5879),
b-
Glycerophosphate disodium salt hydrate (G9422), -ascorbic acid
L
(A4544), D-(þ)-Glucose (G7021), WY-14643 (C7081), GW501516
(43732), rosiglitazone (R2408), Oil Red O (O0625) Solutol HS 15
(70142-34-6), and Alizarin Red S (A5533) were purchased from
Sigma-Aldrich; Alkaline phosphatase Kit (P0321) and COX-2
enzyme immune assay kit (S0168) were purchased from Beyo-
time Biotechnology (China). IPTG Dioxane Free (A600168) and
Imidazole (A600277) were purchased from Sangon Biotech (China).
C
19H16FOþ3 [MþHþ]: 311.1078; found: 311.1078. HPLC purity: 97.34%.
4.1.11. (Z)-2-(5-fluoro-1-(3-methoxybenzylidene)-2-methyl-1H-
inden-3-yl) acetic acid (10)
Yellow solid; yield 43%; M.p. 131e133 ꢀC. 1H NMR (600 MHz,
DMSO‑d6)
d
¼ 7.41 (t, J ¼ 7.9 Hz, 1H), 7.34 (s, 1H), 7.25 (dd, J ¼ 5.3,
10