Synthesis and Bioactivities Evaluation of Novel 1-(1,3,5-Triazin-6-yl)-3-methyl-4-(5-phenyl-1,3,4-oxadiazol-2-yl) pyrazole†

doi:10.7503/cjcu20170239

Abstract

Abstract:

Eighteen novel multi-heterocyclic molecules[7A(a—f), 7B(a—f), 7C(a—f)] were designed and synthesized by hybrid-linking 1,3,4-oxadiazole and 1,3,5-triazine onto pyrazole. The structures of all the compounds were confirmed by IR, NMR and HRMS. The inhibitory activities of target molecules against protein tyrosine phosphatase 1B(PTP1B) and cell division cycle 25 phosphatase B(Cdc25B) were evaluated. As a result, all of the target molecules behave good inhibitory activities against PTP1B and Cdc25B, in which nine compounds show excellent inhibitory activities, respectively. The inhibitory activities of nine compounds are better than the reference oleanolic acid and Na₃VO₄, respectively. The nine compounds are expected to become potential inhibitors of PTP1B and Cdc25B.

Key words: Pyrazole, 1,3,4-Oxadiazole, 1,3,5-Triazine, PTP1B inhibitor, Cdc25B inhibitor

CLC Number:

O626

TrendMD:

ZHANG Chenglu, SUN Xiaona, LI Chuanyin, CAI Jiying, WANG Jing, LI Yizheng, WANG Huayu. Synthesis and Bioactivities Evaluation of Novel 1-(1,3,5-Triazin-6-yl)-3-methyl-4-(5-phenyl-1,3,4-oxadiazol-2-yl) pyrazole^†[J]. Chem. J. Chinese Universities, 2017, 38(10): 1764.

Figures/Tables 7

Fig.1 Some clinical drugs containing pyrazole, 1,3,5-triazine and 1,3,4-oxadiazole

Scheme 1 Synthetic routes of the target compoundsa. R=H; b. R=CH3; c. R=OH; d. R=OCH3; e. R=Cl; f. R=NH2.

Table 1 Melting points for compounds 1A—1C and 2A

Compd.	m. p.(Ref. )/℃	Compd.	m. p.(Ref. )/℃
1A	173.1—173.9(173—174^[21])	1C	112.9—113.7(112—115^[21])
1B	114.6—115.5(114—117^[21])	2A	171.7—172.6(171—173^[14])

Table 2 Appearance, yields, melting points, IR and HRMS data for compounds 2B, 2C, 3A—3C,4A—4C, 5A—5C, 7A(a—f), 7B(a—f) and 7C(a—f)

Compd.	Appearance	Yield(%)	m. p./℃	HRMS(positive-SIMS) m/z(calcd. ), [M+H]⁺	IR(KBr), $ν ˙$ /cm^-1
2B	White solid	75	192.3—193.2	278.2023(278.2015)	3350, 3288, 2940, 1627, 1105
2C	White solid	78	202.6—203.1	250.1711(250.1702)	3352, 3285, 2933, 1625, 1110
3A	White solid	88	78.6—79.5	394.2128(394.2125)	3332, 2940, 2850, 1740, 1690, 1375, 1250
3B	White solid	86	86.8—87.2	390.2546(390.2539)	3312, 2935, 2850, 1728, 1680, 1370, 1250
3C	White solid	71	125.0—126.0	362.2235(362.2226)	3340, 2940, 2860, 1735, 1670, 1375, 1252
4A	Yellow solid	55	230.2—230.9	404.1962(404.1968)	3030, 2962, 1740, 1690, 1634, 1375, 1250,
					1110
4B	Yellow solid	61	137.1—138.0	400.2375(400.2383)	3031, 2951, 1730, 1670, 1630, 1370, 1230,
					1110
4C	Yellow solid	60	176.6—177.1	372.2079(372.2070)	3030, 2960, 1740, 1675, 1630, 1370, 1250,
					1105
5A	Yellow solid	70	>300	376.1662(376.1655)	3436, 3031, 2950, 1740, 1682, 1630, 1380,
					1250, 1105
5B	Yellow solid	79	>300	372.2078(372.2070)	3440, 3030, 2947, 1760, 1680, 1635, 1380,
					1105
5C	Yellow solid	70	278.9—279.7	344.1766(344.1757)	3430, 3035, 2940, 1745, 1670, 1632, 1375,
					1110
Compd.	Appearance	Yield(%)	m. p./℃	HRMS(positive-SIMS) m/z(calcd. ), [M+H]⁺	IR(KBr), ν˙/cm^-1
7Aa	Yellow solid	67	170.1—170.9	476.2080(476.2085)	3030, 2945, 1634, 1601,1555, 1429, 1380,
					1250,1097, 745
7Ab	Yellow solid	63	168.3—169.7	490.2237(490.2241)	3031, 2930, 1640, 1610, 1541, 1438, 1375,
					1250, 1105, 838
7Ac	Yellow solid	60	280.1—280.9	492.2030(492.2024)	3280, 3030, 2935, 1642, 1621, 1545, 1432,
					1380, 1230, 1105, 840
7Ad	Brownish solid	61	163.4—164.6	506.2186(506.2179)	3030, 2935, 1630, 1601, 1550, 1450, 1380,
					1200, 1100, 841
7Ae	Yellow solid	58	195.6—196.4	510.1691(510.1699)	3030, 2940, 1635, 1613, 1545, 1431, 1380,
					1210, 1100, 824
7Af	Yellow solid	51	202.9—204.1	491.2189(491.2198)	3426, 3030, 2940, 1630, 1610, 1540, 1425,
					1380, 1210, 1092, 835
7Ba	Brownish solid	62	180.0—181.8	472.2495(472.2488)	3030, 2935, 1630, 1610, 1545, 1441, 1375,
					1240, 1090, 709
7Bb	Yellow solid	62	198.7—199.3	486.2652(486.2649)	3030, 2930, 1635, 1615, 1540, 1440, 1375,
					1245, 1100, 845
7Bc	Brownish solid	50	230.2—231.7	488.2444(488.2436)	3260, 3030, 2940, 1635, 1625, 1540, 1445,
					1380, 1200, 1102, 825
7Bd	Yellow solid	68	240.7—242.0	502.2601(502.2606)	3030, 2940, 1631, 1615, 1545, 1438, 1375,
					1225, 1095, 831
7Be	Yellow solid	50	165.3—166.1	506.2105(506.2114)	3030, 2930, 1630, 1610, 1540, 1445, 1375,
					1225, 1100, 811
7Bf	Yellow solid	47	232.8—233.8	487.2604(487.2607)	3425, 3030, 2940, 1635, 1612, 1543, 1445,
					1375, 1220, 1105, 836
7Ca	Brownish solid	67	138.3—139.9	444.2182(444.2174)	3035, 2930, 1635, 1612, 1543, 1435, 1375,
					1235, 1105, 735
7Cb	Yellow solid	52	171.1—172.0	458.2339(458.2347)	3030, 2930, 1651, 1610, 1540, 1430, 1375,
					1220, 1110, 839
7Cc	Yellow solid	40	212.2—213.1	460.2131(460.2139)	3265, 3030, 2940, 1635, 1625, 1540, 1438,
					1380, 1229, 1105, 831
7Cd	Brownish solid	42	222.4—223.4	474.2288(474.2292)	3030, 2940, 1645, 1612, 1540, 1440, 1375,
					1210, 1110, 845
7Ce	Yellow solid	39	175.9—176.5	478.1792(478.1788)	3030, 2945, 1635, 1610, 1535, 1445, 1380,
					1205, 1105, 814
7Cf	Yellow solid	38	222.6—223.2	459.2291(459.2298)	3424, 3030, 2945, 1650, 1615, 1530, 1445,
					1375, 1240, 1115, 845

Table 2 Appearance, yields, melting points, IR and HRMS data for compounds 2B, 2C, 3A—3C,4A—4C, 5A—5C, 7A(a—f), 7B(a—f) and 7C(a—f)

Compd.	Appearance	Yield(%)	m. p./℃	HRMS(positive-SIMS) m/z(calcd. ), [M+H]⁺	IR(KBr), $ν ˙$ /cm^-1
2B	White solid	75	192.3—193.2	278.2023(278.2015)	3350, 3288, 2940, 1627, 1105
2C	White solid	78	202.6—203.1	250.1711(250.1702)	3352, 3285, 2933, 1625, 1110
3A	White solid	88	78.6—79.5	394.2128(394.2125)	3332, 2940, 2850, 1740, 1690, 1375, 1250
3B	White solid	86	86.8—87.2	390.2546(390.2539)	3312, 2935, 2850, 1728, 1680, 1370, 1250
3C	White solid	71	125.0—126.0	362.2235(362.2226)	3340, 2940, 2860, 1735, 1670, 1375, 1252
4A	Yellow solid	55	230.2—230.9	404.1962(404.1968)	3030, 2962, 1740, 1690, 1634, 1375, 1250,
					1110
4B	Yellow solid	61	137.1—138.0	400.2375(400.2383)	3031, 2951, 1730, 1670, 1630, 1370, 1230,
					1110
4C	Yellow solid	60	176.6—177.1	372.2079(372.2070)	3030, 2960, 1740, 1675, 1630, 1370, 1250,
					1105
5A	Yellow solid	70	>300	376.1662(376.1655)	3436, 3031, 2950, 1740, 1682, 1630, 1380,
					1250, 1105
5B	Yellow solid	79	>300	372.2078(372.2070)	3440, 3030, 2947, 1760, 1680, 1635, 1380,
					1105
5C	Yellow solid	70	278.9—279.7	344.1766(344.1757)	3430, 3035, 2940, 1745, 1670, 1632, 1375,
					1110
Compd.	Appearance	Yield(%)	m. p./℃	HRMS(positive-SIMS) m/z(calcd. ), [M+H]⁺	IR(KBr), ν˙/cm^-1
7Aa	Yellow solid	67	170.1—170.9	476.2080(476.2085)	3030, 2945, 1634, 1601,1555, 1429, 1380,
					1250,1097, 745
7Ab	Yellow solid	63	168.3—169.7	490.2237(490.2241)	3031, 2930, 1640, 1610, 1541, 1438, 1375,
					1250, 1105, 838
7Ac	Yellow solid	60	280.1—280.9	492.2030(492.2024)	3280, 3030, 2935, 1642, 1621, 1545, 1432,
					1380, 1230, 1105, 840
7Ad	Brownish solid	61	163.4—164.6	506.2186(506.2179)	3030, 2935, 1630, 1601, 1550, 1450, 1380,
					1200, 1100, 841
7Ae	Yellow solid	58	195.6—196.4	510.1691(510.1699)	3030, 2940, 1635, 1613, 1545, 1431, 1380,
					1210, 1100, 824
7Af	Yellow solid	51	202.9—204.1	491.2189(491.2198)	3426, 3030, 2940, 1630, 1610, 1540, 1425,
					1380, 1210, 1092, 835
7Ba	Brownish solid	62	180.0—181.8	472.2495(472.2488)	3030, 2935, 1630, 1610, 1545, 1441, 1375,
					1240, 1090, 709
7Bb	Yellow solid	62	198.7—199.3	486.2652(486.2649)	3030, 2930, 1635, 1615, 1540, 1440, 1375,
					1245, 1100, 845
7Bc	Brownish solid	50	230.2—231.7	488.2444(488.2436)	3260, 3030, 2940, 1635, 1625, 1540, 1445,
					1380, 1200, 1102, 825
7Bd	Yellow solid	68	240.7—242.0	502.2601(502.2606)	3030, 2940, 1631, 1615, 1545, 1438, 1375,
					1225, 1095, 831
7Be	Yellow solid	50	165.3—166.1	506.2105(506.2114)	3030, 2930, 1630, 1610, 1540, 1445, 1375,
					1225, 1100, 811
7Bf	Yellow solid	47	232.8—233.8	487.2604(487.2607)	3425, 3030, 2940, 1635, 1612, 1543, 1445,
					1375, 1220, 1105, 836
7Ca	Brownish solid	67	138.3—139.9	444.2182(444.2174)	3035, 2930, 1635, 1612, 1543, 1435, 1375,
					1235, 1105, 735
7Cb	Yellow solid	52	171.1—172.0	458.2339(458.2347)	3030, 2930, 1651, 1610, 1540, 1430, 1375,
					1220, 1110, 839
7Cc	Yellow solid	40	212.2—213.1	460.2131(460.2139)	3265, 3030, 2940, 1635, 1625, 1540, 1438,
					1380, 1229, 1105, 831
7Cd	Brownish solid	42	222.4—223.4	474.2288(474.2292)	3030, 2940, 1645, 1612, 1540, 1440, 1375,
					1210, 1110, 845
7Ce	Yellow solid	39	175.9—176.5	478.1792(478.1788)	3030, 2945, 1635, 1610, 1535, 1445, 1380,
					1205, 1105, 814
7Cf	Yellow solid	38	222.6—223.2	459.2291(459.2298)	3424, 3030, 2945, 1650, 1615, 1530, 1445,
					1375, 1240, 1115, 845

Table 3 1H NMR for compounds 2B, 2C, 3A—3C, 4A—4C, 5A—5C, 7A(a—f), 7B(a—f) and 7C(a—f)*

Compd.	¹H NMR(500 MHz), δ
2B	6.10(s, 1H), 4.01(s, 2H), 3.75(t, J=4.9 Hz, 8H), 1.66—1.62(m, 12H)
2C	6.15(s, 1H), 3.99(s, 2H), 3.55—3.50(m, 8H), 2.05—1.89(m, 8H)
3A	7.68(s, 1H), 4.21(q, J=7.2 Hz, 2H), 3.79—3.71(m, 16H), 3.36(s, 2H), 2.27(s, 3H), 1.30(t, J=7.2 Hz, 3H)
3B	7.61(s, 1H), 4.17(q, J=7.1 Hz, 2H), 3.74(t, J=4.9 Hz, 8H), 3.34(s, 2H), 2.15(s, 3H), 1.63—1.50(m, 12H), 1.29
	(t, J=7.1 Hz, 3H)
3C	7.65(s, 1H), 4.17(q, J=7.1 Hz, 2H), 3.57—3.50(m, 8H), 3.43(s, 2H), 2.15(s, 3H), 2.0—1.86(m, 8H), 1.28(t,
	J=7.1 Hz, 3H)
4A	8.86(s, 1H), 4.26(q, J=7.1 Hz, 2H), 3.81—3.65(m, 16H), 2.43(s, 3H), 1.31(t, J=7.1 Hz, 3H)
4B	9.04(s, 1H), 4.34(q, J=7.0 Hz, 2H), 3.71(t, J=4.9 Hz, 8H), 2.58(s, 3H), 1.67—1.53(m, 12H), 1.37(t, J=7.0 Hz,
	3H)
4C	8.95(s, 1H), 4.31(q, J=7.1 Hz, 2H), 3.71—3.59(m, 8H), 2.56(s, 3H), 2.10—1.87(m, 8H), 1.37(t, J=7.1 Hz, 3H)
5A	12.63(s,1H), 8.92(s, 1H), 3.80—3.63(m, 16H), 2.41(s, 3H)
5B	12.38(s, 1H), 9.02(s, 1H), 3.74(t, J=5.0 Hz, 8H), 2.58(s, 3H), 1.63—1.52(m, 12H)
5C	12.11(s, 1H),9.06(s, 1H), 3.80—3.59(m, 8H), 2.58(s, 3H), 1.95—1.86(m, 8H)
7Aa	8.96(s, 1H), 7.87(d, J=7.5 Hz, 2H), 7.75—7.60(m, 3H), 3.79—3.62(m, 16H), 2.34(s, 3H)
Compd.	¹H NMR(500 MHz), δ
7Ab	8.91(s, 1H), 8.01(d, J=8.5 Hz, 2H), 7.43(d, J=8.5 Hz, 2H), 3.74—3.60(m, 16H), 2.42(s, 3H), 2.33(s, 3H)
7Ac	10.17(s, 1H), 8.90(s, 1H), 8.12(d, J=8.5 Hz, 2H), 7.40(d, J=8.5 Hz, 2H), 3.79—3.62(m, 16H), 2.34(s, 3H)
7Ad	8.90(s, 1H), 8.06(d, J=8.6 Hz, 2H), 7.16(d, J=8.6 Hz, 2H), 3.85(s, 3H), 3.81—3.62(m, 16H), 2.39(s, 3H)
7Ae	8.90(s, 1H), 8.13(d, J=8.25 Hz, 2H), 7.62(d, J=8.3 Hz, 2H), 3.75—3.55(m, 16H), 2.41(s, 3H)
7Af	8.89(s, 1H), 7.90(d, J=8.2 Hz, 2H), 6.71(d, J=8.2 Hz, 2H), 5.60(s, 2H), 3.76—3.61(m, 16H), 2.40(s, 3H)
7Ba	8.82(s, 1H), 7.90(d, J=7.7 Hz, 2H), 7.64—7.51(m, 3H), 3.49(t, J=4.9 Hz, 8H), 2.36(s, 3H), 1.88—1.61(m, 12H)
7Bb	8.83(s, 1H), 8.01(d, J=8.5 Hz, 2H), 7.43(d, J=8.5 Hz, 2H), 3.74(t, J=4.9 Hz, 8H), 2.49(s, 3H), 2.36(s, 3H),
	1.61—1.51(m, 12H)
7Bc	10.13(s, 1H), 8.83(s, 1H), 8.09(d, J=8.5 Hz, 2H), 7.23(d, J=8.5 Hz, 2H), 3.75(t, J=4.9 Hz, 8H), 2.41(s, 3H),
	1.61—1.51(m, 12H)
7Bd	8.83(s, 1H), 8.04(d, J=8.6 Hz, 2H), 7.10(d, J=8.6 Hz, 2H), 3.80(s, 3H), 3.69(t, J=4.9 Hz, 8H), 2.41(s, 3H),
	1.60—1.50(m, 12H)
7Be	8.83(s, 1H), 8.09(d, J=8.3 Hz, 2H), 7.57(d, J=8.3 Hz, 2H), 3.72(t, J=4.9 Hz, 8H), 2.40(s, 3H), 1.61—1.51
	(m, 12H)
7Bf	8.83(s, 1H), 7.81(d, J=8.2 Hz, 2H), 6.70(d, J=8.2 Hz, 2H), 5.61(s, 2H), 3.73(t, J=4.9 Hz, 8H), 2.41(s, 3H),
	1.60—1.52(m, 12H)
7Ca	8.82(s, 1H), 7.91(d, J=7.5 Hz, 2H), 7.64—7.48(m, 3H), 3.56—3.46(m, 8H), 2.40(s, 3H), 1.92—1.82(m, 8H)
7Cb	8.82(s, 1H), 7.98(d, J=8.5 Hz, 2H), 7.39(d, J=8.5 Hz, 2H), 3.57—3.45(m, 8H), 2.42(s, 3H), 2.36(s, 3H),
	1.92—1.84(m, 8H)
7Cc	10.12(s, 1H), 8.86(s, 1H), 7.99(d, J=8.5 Hz, 2H), 7.32(d, J=8.5 Hz, 2H), 3.56—3.45(m, 8H), 2.42(s, 3H),
	1.93—1.84(m, 8H)
7Cd	8.82(s, 1H), 8.02(d, J=8.6 Hz, 2H), 7.16(d, J=8.6 Hz, 2H), 3.85(s, 3H), 3.53—3.48(m, 8H), 2.39(s, 3H),
	1.88—1.79(m, 8H)
7Ce	8.82(s, 1H), 8.17(d, J=8.3 Hz, 2H), 7.60(d, J=8.3 Hz, 2H), 3.57—3.48(m, 8H), 2.42(s, 3H), 1.92—1.85(m, 8H)
7Cf	8.83(s, 1H), 7.89(d, J=8.2 Hz, 2H), 6.80(d, J=8.2 Hz, 2H), 5.60(s, 2H), 3.50—3.41(m, 8H), 2.42(s, 3H),
	1.87—1.80(m, 8H)

Table 3 1H NMR for compounds 2B, 2C, 3A—3C, 4A—4C, 5A—5C, 7A(a—f), 7B(a—f) and 7C(a—f)*

Compd.	¹H NMR(500 MHz), δ
2B	6.10(s, 1H), 4.01(s, 2H), 3.75(t, J=4.9 Hz, 8H), 1.66—1.62(m, 12H)
2C	6.15(s, 1H), 3.99(s, 2H), 3.55—3.50(m, 8H), 2.05—1.89(m, 8H)
3A	7.68(s, 1H), 4.21(q, J=7.2 Hz, 2H), 3.79—3.71(m, 16H), 3.36(s, 2H), 2.27(s, 3H), 1.30(t, J=7.2 Hz, 3H)
3B	7.61(s, 1H), 4.17(q, J=7.1 Hz, 2H), 3.74(t, J=4.9 Hz, 8H), 3.34(s, 2H), 2.15(s, 3H), 1.63—1.50(m, 12H), 1.29
	(t, J=7.1 Hz, 3H)
3C	7.65(s, 1H), 4.17(q, J=7.1 Hz, 2H), 3.57—3.50(m, 8H), 3.43(s, 2H), 2.15(s, 3H), 2.0—1.86(m, 8H), 1.28(t,
	J=7.1 Hz, 3H)
4A	8.86(s, 1H), 4.26(q, J=7.1 Hz, 2H), 3.81—3.65(m, 16H), 2.43(s, 3H), 1.31(t, J=7.1 Hz, 3H)
4B	9.04(s, 1H), 4.34(q, J=7.0 Hz, 2H), 3.71(t, J=4.9 Hz, 8H), 2.58(s, 3H), 1.67—1.53(m, 12H), 1.37(t, J=7.0 Hz,
	3H)
4C	8.95(s, 1H), 4.31(q, J=7.1 Hz, 2H), 3.71—3.59(m, 8H), 2.56(s, 3H), 2.10—1.87(m, 8H), 1.37(t, J=7.1 Hz, 3H)
5A	12.63(s,1H), 8.92(s, 1H), 3.80—3.63(m, 16H), 2.41(s, 3H)
5B	12.38(s, 1H), 9.02(s, 1H), 3.74(t, J=5.0 Hz, 8H), 2.58(s, 3H), 1.63—1.52(m, 12H)
5C	12.11(s, 1H),9.06(s, 1H), 3.80—3.59(m, 8H), 2.58(s, 3H), 1.95—1.86(m, 8H)
7Aa	8.96(s, 1H), 7.87(d, J=7.5 Hz, 2H), 7.75—7.60(m, 3H), 3.79—3.62(m, 16H), 2.34(s, 3H)
Compd.	¹H NMR(500 MHz), δ
7Ab	8.91(s, 1H), 8.01(d, J=8.5 Hz, 2H), 7.43(d, J=8.5 Hz, 2H), 3.74—3.60(m, 16H), 2.42(s, 3H), 2.33(s, 3H)
7Ac	10.17(s, 1H), 8.90(s, 1H), 8.12(d, J=8.5 Hz, 2H), 7.40(d, J=8.5 Hz, 2H), 3.79—3.62(m, 16H), 2.34(s, 3H)
7Ad	8.90(s, 1H), 8.06(d, J=8.6 Hz, 2H), 7.16(d, J=8.6 Hz, 2H), 3.85(s, 3H), 3.81—3.62(m, 16H), 2.39(s, 3H)
7Ae	8.90(s, 1H), 8.13(d, J=8.25 Hz, 2H), 7.62(d, J=8.3 Hz, 2H), 3.75—3.55(m, 16H), 2.41(s, 3H)
7Af	8.89(s, 1H), 7.90(d, J=8.2 Hz, 2H), 6.71(d, J=8.2 Hz, 2H), 5.60(s, 2H), 3.76—3.61(m, 16H), 2.40(s, 3H)
7Ba	8.82(s, 1H), 7.90(d, J=7.7 Hz, 2H), 7.64—7.51(m, 3H), 3.49(t, J=4.9 Hz, 8H), 2.36(s, 3H), 1.88—1.61(m, 12H)
7Bb	8.83(s, 1H), 8.01(d, J=8.5 Hz, 2H), 7.43(d, J=8.5 Hz, 2H), 3.74(t, J=4.9 Hz, 8H), 2.49(s, 3H), 2.36(s, 3H),
	1.61—1.51(m, 12H)
7Bc	10.13(s, 1H), 8.83(s, 1H), 8.09(d, J=8.5 Hz, 2H), 7.23(d, J=8.5 Hz, 2H), 3.75(t, J=4.9 Hz, 8H), 2.41(s, 3H),
	1.61—1.51(m, 12H)
7Bd	8.83(s, 1H), 8.04(d, J=8.6 Hz, 2H), 7.10(d, J=8.6 Hz, 2H), 3.80(s, 3H), 3.69(t, J=4.9 Hz, 8H), 2.41(s, 3H),
	1.60—1.50(m, 12H)
7Be	8.83(s, 1H), 8.09(d, J=8.3 Hz, 2H), 7.57(d, J=8.3 Hz, 2H), 3.72(t, J=4.9 Hz, 8H), 2.40(s, 3H), 1.61—1.51
	(m, 12H)
7Bf	8.83(s, 1H), 7.81(d, J=8.2 Hz, 2H), 6.70(d, J=8.2 Hz, 2H), 5.61(s, 2H), 3.73(t, J=4.9 Hz, 8H), 2.41(s, 3H),
	1.60—1.52(m, 12H)
7Ca	8.82(s, 1H), 7.91(d, J=7.5 Hz, 2H), 7.64—7.48(m, 3H), 3.56—3.46(m, 8H), 2.40(s, 3H), 1.92—1.82(m, 8H)
7Cb	8.82(s, 1H), 7.98(d, J=8.5 Hz, 2H), 7.39(d, J=8.5 Hz, 2H), 3.57—3.45(m, 8H), 2.42(s, 3H), 2.36(s, 3H),
	1.92—1.84(m, 8H)
7Cc	10.12(s, 1H), 8.86(s, 1H), 7.99(d, J=8.5 Hz, 2H), 7.32(d, J=8.5 Hz, 2H), 3.56—3.45(m, 8H), 2.42(s, 3H),
	1.93—1.84(m, 8H)
7Cd	8.82(s, 1H), 8.02(d, J=8.6 Hz, 2H), 7.16(d, J=8.6 Hz, 2H), 3.85(s, 3H), 3.53—3.48(m, 8H), 2.39(s, 3H),
	1.88—1.79(m, 8H)
7Ce	8.82(s, 1H), 8.17(d, J=8.3 Hz, 2H), 7.60(d, J=8.3 Hz, 2H), 3.57—3.48(m, 8H), 2.42(s, 3H), 1.92—1.85(m, 8H)
7Cf	8.83(s, 1H), 7.89(d, J=8.2 Hz, 2H), 6.80(d, J=8.2 Hz, 2H), 5.60(s, 2H), 3.50—3.41(m, 8H), 2.42(s, 3H),
	1.87—1.80(m, 8H)

Table 4 13C NMR for compounds 5A—5C, 7A(a—f), 7B(a—f) and 7C(a—f)*

Compd.	¹³C NMR(500 MHz), δ
5A	172.05, 170.86, 166.52, 140.33, 136.66, 104.32, 64.88, 43.97, 13.56
5B	172.21, 170.63, 166.25, 140.82, 136.73, 104.25, 47.72, 25.65, 22.18, 13.75
5C	172.18, 170.77, 166.33, 141.15, 136.23, 104.37, 54.68, 25.32, 13.68
7Aa	170.57, 166.58, 162.52, 141.16, 140.30, 137.58, 133.83, 131.27, 129.39, 127.27, 104.28, 64.96, 44.78, 13.82
7Ab	170.56, 166.57, 162.54, 141.05, 140.35, 137.57, 135.24, 129.35, 127.20, 125.27, 104.27, 64.86, 44.57, 20.37, 13.97
7Ac	170.56, 166.59, 162.57, 146.29, 141.17, 137.54, 136.68, 131.26, 124.27, 122.13, 104.25, 64.57, 44.28, 13.90
7Ad	170.23, 166.44, 162.54, 148.29, 141.34, 138.66, 137.52, 131.68, 123.25, 120.14, 104.25, 64.28, 55.18, 44.39, 13.92
7Ae	170.48, 166.25, 162.33, 141.06, 140.12, 137.28, 132.29, 125.23, 122.82, 120.35, 104.27, 64.57, 44.35, 13.92
7Af	170.48, 166.62, 162.19, 141.26, 139.55, 137.33, 132.12, 125.76, 122.93, 120.34, 104.58, 64.29, 44.47, 13.83
7Ba	170.27, 166.47, 162.47, 141.12, 140.44, 137.54, 133.82, 131.27, 129.25, 127.26, 104.10, 47.64, 25.06, 22.37, 13.83
7Bb	170.45, 166.52, 162.54, 141.17, 139.86, 137.58, 135.25, 129.34, 127.20, 125.16, 104.27, 47.58, 25.62, 22.27,
	20.32, 13.67
7Bc	170.87, 166.48, 162.57, 146.27, 141.28, 137.39, 136.52, 131.79, 124.64, 122.36, 104.20, 47.56, 25.36, 22.13, 13.97
7Bd	170.29, 166.48, 162.39, 148.29, 141.37, 137.23, 136.58, 131.54, 123.25, 120.38, 104.25, 55.29, 47.64, 25.36,
	22.77, 13.97
7Be	170.43, 166.06, 162.32, 141.12, 140.01, 137.35, 132.59, 125.22, 122.37, 120.45, 104.43, 47.28, 25.62, 22.39, 13.66
7Bf	170.48, 166.25, 162.15, 141.23, 140.21, 137.22, 132.34, 125.35, 122.87, 120.28, 104.37, 47.25, 25.42, 22.77, 13.98
7Ca	170.55, 166.58, 162.32, 141.23, 139.88, 137.63, 133.25, 131.27, 129.42, 127.16, 104.15, 54.76, 25.03, 13.82
7Cb	170.27, 166.42, 162.38, 141.22, 140.22, 137.61, 135.24, 129.35, 127.10, 125.28, 104.07, 54.97, 25.38, 22.02, 13.79
7Cc	170.31, 166.28, 162.38, 146.27, 141.17, 137.58, 136.25, 131.25, 124.30, 122.23, 104.05, 54.28, 25.66, 13.62
7Cd	170.28, 166.34, 162.25, 148.17, 141.32, 137.55, 136.82, 131.43, 123.57, 120.26, 104.25, 56.27, 54.28, 25.66, 13.82
7Ce	170.29, 166.42, 162.27, 141.02, 139.95, 137.25, 132.28, 125.23, 122.45, 120.46, 104.25, 54.28, 25.46, 13.93
7Cf	170.48, 166.27, 162.38, 141.27, 140.78, 137.33, 132.14, 125.78, 122.28, 120.34, 104.25, 54.28, 25.34, 13.92

Table 4 13C NMR for compounds 5A—5C, 7A(a—f), 7B(a—f) and 7C(a—f)*

Compd.	¹³C NMR(500 MHz), δ
5A	172.05, 170.86, 166.52, 140.33, 136.66, 104.32, 64.88, 43.97, 13.56
5B	172.21, 170.63, 166.25, 140.82, 136.73, 104.25, 47.72, 25.65, 22.18, 13.75
5C	172.18, 170.77, 166.33, 141.15, 136.23, 104.37, 54.68, 25.32, 13.68
7Aa	170.57, 166.58, 162.52, 141.16, 140.30, 137.58, 133.83, 131.27, 129.39, 127.27, 104.28, 64.96, 44.78, 13.82
7Ab	170.56, 166.57, 162.54, 141.05, 140.35, 137.57, 135.24, 129.35, 127.20, 125.27, 104.27, 64.86, 44.57, 20.37, 13.97
7Ac	170.56, 166.59, 162.57, 146.29, 141.17, 137.54, 136.68, 131.26, 124.27, 122.13, 104.25, 64.57, 44.28, 13.90
7Ad	170.23, 166.44, 162.54, 148.29, 141.34, 138.66, 137.52, 131.68, 123.25, 120.14, 104.25, 64.28, 55.18, 44.39, 13.92
7Ae	170.48, 166.25, 162.33, 141.06, 140.12, 137.28, 132.29, 125.23, 122.82, 120.35, 104.27, 64.57, 44.35, 13.92
7Af	170.48, 166.62, 162.19, 141.26, 139.55, 137.33, 132.12, 125.76, 122.93, 120.34, 104.58, 64.29, 44.47, 13.83
7Ba	170.27, 166.47, 162.47, 141.12, 140.44, 137.54, 133.82, 131.27, 129.25, 127.26, 104.10, 47.64, 25.06, 22.37, 13.83
7Bb	170.45, 166.52, 162.54, 141.17, 139.86, 137.58, 135.25, 129.34, 127.20, 125.16, 104.27, 47.58, 25.62, 22.27,
	20.32, 13.67
7Bc	170.87, 166.48, 162.57, 146.27, 141.28, 137.39, 136.52, 131.79, 124.64, 122.36, 104.20, 47.56, 25.36, 22.13, 13.97
7Bd	170.29, 166.48, 162.39, 148.29, 141.37, 137.23, 136.58, 131.54, 123.25, 120.38, 104.25, 55.29, 47.64, 25.36,
	22.77, 13.97
7Be	170.43, 166.06, 162.32, 141.12, 140.01, 137.35, 132.59, 125.22, 122.37, 120.45, 104.43, 47.28, 25.62, 22.39, 13.66
7Bf	170.48, 166.25, 162.15, 141.23, 140.21, 137.22, 132.34, 125.35, 122.87, 120.28, 104.37, 47.25, 25.42, 22.77, 13.98
7Ca	170.55, 166.58, 162.32, 141.23, 139.88, 137.63, 133.25, 131.27, 129.42, 127.16, 104.15, 54.76, 25.03, 13.82
7Cb	170.27, 166.42, 162.38, 141.22, 140.22, 137.61, 135.24, 129.35, 127.10, 125.28, 104.07, 54.97, 25.38, 22.02, 13.79
7Cc	170.31, 166.28, 162.38, 146.27, 141.17, 137.58, 136.25, 131.25, 124.30, 122.23, 104.05, 54.28, 25.66, 13.62
7Cd	170.28, 166.34, 162.25, 148.17, 141.32, 137.55, 136.82, 131.43, 123.57, 120.26, 104.25, 56.27, 54.28, 25.66, 13.82
7Ce	170.29, 166.42, 162.27, 141.02, 139.95, 137.25, 132.28, 125.23, 122.45, 120.46, 104.25, 54.28, 25.46, 13.93
7Cf	170.48, 166.27, 162.38, 141.27, 140.78, 137.33, 132.14, 125.78, 122.28, 120.34, 104.25, 54.28, 25.34, 13.92

Table 5 Inhibiting activity of target compounds against PTP1B and Cdc25B

Compd.	PTP1B^a		Cdc25B^b
Compd.	Inhibition^c(%)	I $C 50 d$ /(μg·mL^-1)	Inhibition^c(%)	I $C 50 d$ /(μg·mL^-1)
7Aa	65.03±3.09	9.04±1.37	88.00±1.36	6.75±0.42
7Ab	73.95±1.99	8.69±1.61	91.30±1.81	5.19±0.35
7Ac	91.02±1.82	1.08±0.07	92.50±0.06	1.59±0.01
7Ad	81.44±3.93	8.01±0.58	81.12±0.16	3.90±0.05
7Ae	90.63±0.51	1.19±0.05	93.74±0.31	1.81±0.04
7Af	93.74±0.87	1.02±0.08	90.02±0.22	1.50±0.21
7Ba	96.77±0.26	2.64±0.01	98.82±0.33	3.11±0.00
7Bb	95.53±0.06	2.53±0.10	95.80±1.49	2.58±0.07
7Bc	98.31±0.54	0.79±0.00	95.45±0.08	0.39±0.02
7Bd	96.81±0.68	1.71±0.34	91.19±1.34	2.47±0.30
7Be	97.08±0.44	1.05±0.01	90.00±6.67	1.34±0.05
7Bf	96.93±0.01	0.74±0.06	96.65±0.16	0.32±0.52
7Ca	76.60±6.47	8.58±1.66	87.34±0.05	6.62±0.36
7Cb	84.00±0.04	8.33±0.08	93.33±0.51	3.16±0.72
7Cc	91.60±0.10	0.84±0.06	97.91±0.34	0.69±0.10
7Cd	86.11±1.29	7.91±1.49	90.98±4.50	3.02±0.21
7Ce	91.09±0.32	1.10±0.07	97.84±0.98	1.43±0.07
7Cf	95.14±0.15	0.89±0.04	93.17±1.30	0.59±0.13

Table 5 Inhibiting activity of target compounds against PTP1B and Cdc25B

Compd.	PTP1B^a		Cdc25B^b
Compd.	Inhibition^c(%)	I $C 50 d$ /(μg·mL^-1)	Inhibition^c(%)	I $C 50 d$ /(μg·mL^-1)
7Aa	65.03±3.09	9.04±1.37	88.00±1.36	6.75±0.42
7Ab	73.95±1.99	8.69±1.61	91.30±1.81	5.19±0.35
7Ac	91.02±1.82	1.08±0.07	92.50±0.06	1.59±0.01
7Ad	81.44±3.93	8.01±0.58	81.12±0.16	3.90±0.05
7Ae	90.63±0.51	1.19±0.05	93.74±0.31	1.81±0.04
7Af	93.74±0.87	1.02±0.08	90.02±0.22	1.50±0.21
7Ba	96.77±0.26	2.64±0.01	98.82±0.33	3.11±0.00
7Bb	95.53±0.06	2.53±0.10	95.80±1.49	2.58±0.07
7Bc	98.31±0.54	0.79±0.00	95.45±0.08	0.39±0.02
7Bd	96.81±0.68	1.71±0.34	91.19±1.34	2.47±0.30
7Be	97.08±0.44	1.05±0.01	90.00±6.67	1.34±0.05
7Bf	96.93±0.01	0.74±0.06	96.65±0.16	0.32±0.52
7Ca	76.60±6.47	8.58±1.66	87.34±0.05	6.62±0.36
7Cb	84.00±0.04	8.33±0.08	93.33±0.51	3.16±0.72
7Cc	91.60±0.10	0.84±0.06	97.91±0.34	0.69±0.10
7Cd	86.11±1.29	7.91±1.49	90.98±4.50	3.02±0.21
7Ce	91.09±0.32	1.10±0.07	97.84±0.98	1.43±0.07
7Cf	95.14±0.15	0.89±0.04	93.17±1.30	0.59±0.13

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