4-N-苯胺基喹啉衍生物的合成及胆碱酯酶抑制活性

doi:10.7503/cjcu20160880

摘要/Abstract

摘要：

设计合成了一系列4-N-苯胺基喹啉类衍生物, 采用Ellman法测定了目标化合物对乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)的抑制活性. 结果表明, 当喹啉环上连有伸长的吡啶季铵盐片段时, 可显著提高目标化合物的胆碱酯酶抑制作用. 化合物16对AChE和BChE具有明显的双重抑制作用, 其IC₅₀值分别为0.92和14.20 μmol/L, 抑制效果强于阳性对照药加兰他敏.

关键词: 4-N-苯胺基喹啉类衍生物, 胆碱酯酶抑制活性, 构效关系

Abstract:

A series of 4-N-Phenylaminoquinoline derivatives was designed and synthesized, and their anti-cholinesterase activities were evaluated using Ellman assay. The results demonstrated that the stretched-out quaternary pyridine in quinoline ring greatly improved the cholinesterase inhibition of target compounds. Compound 16 exhibited the most potent inhibitory activities against both acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) from the prepared series, with IC₅₀ values of 0.92 and 14.20 μmol/L, respectively, which showed superior activitities compared with the reference drug galanthamine. These results suggest that compound 16 may be valuable as a new parent compound for further structural modifications.

Key words: 4-N-Phenylaminoquinoline derivatives, Anti-cholinesterase activity, Structure-activity relationship(Ed.: P, H, F, K)

中图分类号:

O626.32

TrendMD:

刘玉明, 田丽珺, 胡栋, 聂建兵. 4-N-苯胺基喹啉衍生物的合成及胆碱酯酶抑制活性. 高等学校化学学报, 2017, 38(3): 392.

LIU Yuming, TIAN Lijun, HU Dong, NIE Jianbing. yntheses and Anti-cholinesterase Activity of 4-N-Phenylaminoquinoline Derivatives ^†. Chem. J. Chinese Universities, 2017, 38(3): 392.

图/表 4

参考文献 40

[1]	Alzheimer’s Association, Alzheimers Dement., 2012, 8(2), 131—168
[2]	Zhang Y., Xu Y., Nie H., Wu Y., Zhang L., Zhang M., J. Clin. Neurosci., 2012, 19(10), 1333—1337
[3]	Singh M., Kaur M., Kukreja H., Chugh R., Silakari O., Singh D., Eur. J. Med. Chem., 2013, 70, 165—188
[4]	Savini L., Gaeta A., Fattorusso C., Catalanotti B., Campiani G., Chiasserini L., Pellerano C., Novellino E., McKissic D., Saxena A., J. Med. Chem., 2003, 46(1), 1—4
[5]	Eskander M. F., Nagykery N. G., Leung E. Y., Khelghati B., Geula C., Brain Res., 2005, 1060(1/2), 144—152
[6]	Yang W. C., Sun Q., Yu N. X., Zhu X. L., Yang G. F., Acta Pharm. Sin., 2012, 47(3), 313—321
	(杨文超, 孙琦, 喻宁熙, 朱晓磊, 杨光富. 药学学报, 2012, 47(3), 313—321)
[7]	Pan L., Tan J., Hou J., Huang S., Gu L., Huang Z., Bioorg. Med. Chem. Lett., 2008, 18(13), 3790—3793
[8]	Tang Q., Zhao Y., Du X., Chong L., Gong P., Guo C., Eur. J. Med. Chem., 2013, 69, 77—89
[9]	Hu H., Jiang M. Y., Xie L. J., Hu G., Zhang G. R., Zhang L. X., Zhou S. G., Zhang M. H., Gong P., Chem. Res. Chinese Universities, 2015, 31(5), 746—755
[10]	Ongarora D. S. B., Strydom N., Wicht K., Njoroge M., Wiesner L., Egan T., Wittlin S., Jurva U., Masimirembwa C. M., Chibale K., Bioorg. Med. Chem. Lett., 2015, 23(17), 5419—5432
[11]	Xia S. W., Mao Y. P., Xue Q. Q., Yu L. M., Chem. J. Chinese Universities, 2011, 32(10), 2415—2420
	(夏树伟, 毛雅嫔, 薛倩倩, 于良民. 高等学校化学学报, 2011, 32(10), 2415—2420)
[12]	Liu M., Liu Y., Zhou S., Zhang X., Yu S. J., Li Z. M., Chem. Res. Chinese Universities, 2016, 32(4), 600—606
[13]	Guo Y. B., Liu H. B., Xu M., Chin. J. Org. Chem., 2012, 32(2), 413—419
	(郭永彪, 刘海波, 许明. 有机化学, 2012, 32(2), 413—419)
[14]	Luo W., Huang K., Zhang Z., Hong C., Wang C. J., Acta Pharm. Sin., 2013, 48(2), 269—275
	(罗稳, 黄凯, 张震, 洪琛, 王超杰. 药学学报, 2013, 48(2), 269—275)
[15]	Rosini M., Andrisano V., Bartolini M., Bolognesi M. L., Hrelia P., Minarini A., Tarozzi A., Melchiorre C., J. Med. Chem., 2005, 48(2), 360—363
[16]	Savini L., Campiani G., Garta A., Pellerano C., Fattorusso C., Chiasserini L., Fedorko J. M., Saxena A., Bioorg. Med. Chem. Lett., 2001, 11(13), 1779—1782
[17]	Aguado F., Badía A., Baños J., Bosch F., Bozzo C., Camps P., Contreras J., Dierssen M., Escolano C., Görbig D., Muñoz-Torrero D., Pujol M., Simón M., Vázquez M., Vivas N., Eur. J. Med. Chem., 1994, 29(3), 205—221
[18]	Wang L., Esteban G., Ojima M., Bautista-Aguilera O., Inokuchi T., Moraleda I., Iriepa I., Samadi A., Youdim M. B. H., Romero A., Soriano E., Herrero R., Fernández A. P. F., Ricardo-Martínez-Murillo Marco-Contelles J., Unzeta M., Eur. J. Med. Chem., 2014, 80, 543—561
[19]	Wang X., Xia C., Chen S., Tan J., Ou T., Huang S., Li D., Gu L., Huang Z., Eur. J. Med. Chem., 2015, 89, 349—361
[20]	Tasso B., Catto M., Nicolotti O., Novelli F., Tonelli M., Giangreco I., Pisani L., Sparatore A., Boido V., Carotti A., Sparatore F., Eur. J. Med. Chem., 2011, 46(6), 2170—2184
[21]	Najafi Z., Saeedi M., Mahdavi M., Sabourian R., Khanavi M., Tehrani M. B., Moghadam F. H., Edraki N., Karimpor-Razkenari E., Sharifzadeh M., Foroumadi A., Shafiee A., Akbarzadeh T., Bioorg. Chem., 2016, 67, 84—94
[22]	Mantoani S., Chierrito T., Vilela A., Cardoso C., Martinez A., Carvalho I., Molecules,2016, 21(2), 193-1—12
[23]	Go M., Ngiam T., Lim L., Eur. J. Med. Chem., 1986, 21(1), 81—85
[24]	Nguyen T., Yang T., Go M., Bioorg. Med. Chem. Lett., 2014, 24(7), 1830—1838
[25]	Cheng J., Zhai H., Bai J., Tang J., Lv L., Sun B., Tetrahedron Lett., 2014, 55(30), 4044—4046
[26]	Benek O., Musilek K., Horova A., Dohnal V., Dolezal R., Kuca K., Med. Chem., 2015, 11(1), 21—29
[27]	Bohn P., Fur N. L., Hagues G., Costentin J., Torquet N., Papamicael C., Marsais F., Levacher V., Org. Biomol. Chem., 2009, 7(12), 2612—2618
[28]	Pierre B., Fabienne G., Cyril P., Méziane I., Martine D., Vincent G., Florent A., Mihaela-Liliana T., Francis M., Louisa B., Vincent L., ACS Chem. Neurosci., 2015, 6(5), 737—744
[29]	Wang J.F., The Synthesis and Research of 5,7-Dichloro-4-hydroxyquinoline, Dalian University of Technology, Dalian, 2006
	(王继凤. 5,7-二氯-4-羟基喹啉的合成与研究, 大连: 大连理工大学, 2006)
[30]	Joly R., Warnant J., Goffinet B., Dichloroquinolines FR 1514280, 1968-02-23
[31]	Werbel L. M., Kesten S. J., Turner W. R., Eur. J. Med. Chem., 1993, 28(11), 837—852
[32]	Li S., Zhao Y., Wang K., Gao Y., Han J., Cui B., Gong P., Bioorg. Med. Chem., 2013, 21(11), 2843—2855
[33]	Kormos C. M., Jin C., Cueva J. P., Runyon S. P., Thomas J. B., Brieaddy L. E., Mascarella S. W., Navarro H. A., Gilmour B. P., Carroll F. I., J. Med. Chem., 2013, 56(11), 4551—4567
[34]	Khurana J., Chauhan S., Bansal G., Monatshefte für Chemie, 2004, 135(1), 83—87
[35]	Kokatla H. P., Yoo E., Salunke D. B., Sil D., Ng C. F., Balakrishna R., Malladi S. S., Fox L. M., David S. A., Org. Biomol. Chem., 2013, 11(7), 1179—1198
[36]	Gao Z. Z., Yang L. G., Bai D., Chen L. X., Tao Z., Xiao X., Chem. J. Chinese Universities, 2017, 38(2), 212—216
	(高中政, 杨立国, 白东, 陈丽霞, 陶朱, 肖昕. 高等学校化学学报, 2017, 38(2), 212—216)
[37]	Otevrel J., Bobal P., Zadrazilova I., Govender R., Pesko M., Keltosova S., Koleckarova P., Marsalek P., Imramovsky A., Coffey A., O’Mahony J., Kollar P., Cizek A., Kralova K., Jampilek J., Molecules,2013, 18(9), 10648—10670
[38]	Pearl I. A., Mccoy J. F., J. Am. Chem. Soc., 1947, 69(12), 3071—3072
[39]	Cai J., Sun M., Wu X. Q., Chen J. Q., Wang P., Zong X., Ji M., Eur. J. Med. Chem., 2013, 63, 702—712
[40]	Nishino S., Hirotsu K., Shima H., Harada T., Oda H., Takahashi T., Suzuki S., Process for Producing Quinazolin-4-one Derivative, WO 2003064399, 2003-08-07
	S

Compd.	Appearance	Yield(%)	m. p./℃	HR-ESI-MS(Calcd.), m/z
6a	Yellow solid	82.3	274—276(274—276^[37])	255.0743(255.0689)[M+H]⁺
6b	Yellow solid	86.4	280—283(279—281^[37])	269.0888(269.0846)[M+H]⁺
6c	Slightly yellow solid	78.0	297—299(298—299^[37])	271.0679(271.0638)[M+H]⁺
6d	Slightly yellow solid	75.1	>300(303—305^[37])	271.0683(271.0638)[M+H]⁺
6e	White solid	56.1	241—243(241—243^[37])	289.0342(289.0299)[M+H]⁺
6f	White solid	80.9	261—263(261—262^[37])	289.0343(289.0299)[M+H]⁺
6g	Slightly yellow solid	75.2	292—294(292—293^[37])	289.0320(289.0299)[M+H]⁺
6h	White solid	50.2	>300	322.9936(322.9910)[M+H]⁺
6i	White solid	43.4	>300	319.0454(319.0405)[M+H]⁺
6j	White solid	42.9	>300	353.0038(353.0015)[M+H]⁺
7	White solid	88.4	61—63(63—64^[38])	181.0505(181.0501)[M-H]^-
8	White solid	79.2	100—102(99—100^[39])
9	Yellow solid	86.2	65—67(66—68^[39])	326.0403(326.0407)[M+Na]⁺
10	White solid	87.4	98—99(97—98^[39])	274.0858(274.0846)[M+H]⁺
11	White solid	82.0	165—166(164—165^[40])	258.0535(258.0533)[M-H]^-
12	Yellow solid	83.1	184—186	329.0545(329.0540)[M-H]^-
13	Grey-white solid	30.9	270—272	313.0594(313.0591)[M+H]⁺
14	Grey-white solid	88.6	121—123	331.0260(331.0252)[M+H]⁺
15	Yellow solid	74.5	169—171	422.0691(422.0674)[M+H]⁺
16	Red solid	66.7	229—232	465.1364(465.1330)[M-Cl]⁺
17	Yellow solid	77.8	163—165	435.1586(435.1588)[M-Cl]⁺

Compd.	Appearance	Yield(%)	m. p./℃	HR-ESI-MS(Calcd.), m/z
6a	Yellow solid	82.3	274—276(274—276^[37])	255.0743(255.0689)[M+H]⁺
6b	Yellow solid	86.4	280—283(279—281^[37])	269.0888(269.0846)[M+H]⁺
6c	Slightly yellow solid	78.0	297—299(298—299^[37])	271.0679(271.0638)[M+H]⁺
6d	Slightly yellow solid	75.1	>300(303—305^[37])	271.0683(271.0638)[M+H]⁺
6e	White solid	56.1	241—243(241—243^[37])	289.0342(289.0299)[M+H]⁺
6f	White solid	80.9	261—263(261—262^[37])	289.0343(289.0299)[M+H]⁺
6g	Slightly yellow solid	75.2	292—294(292—293^[37])	289.0320(289.0299)[M+H]⁺
6h	White solid	50.2	>300	322.9936(322.9910)[M+H]⁺
6i	White solid	43.4	>300	319.0454(319.0405)[M+H]⁺
6j	White solid	42.9	>300	353.0038(353.0015)[M+H]⁺
7	White solid	88.4	61—63(63—64^[38])	181.0505(181.0501)[M-H]^-
8	White solid	79.2	100—102(99—100^[39])
9	Yellow solid	86.2	65—67(66—68^[39])	326.0403(326.0407)[M+Na]⁺
10	White solid	87.4	98—99(97—98^[39])	274.0858(274.0846)[M+H]⁺
11	White solid	82.0	165—166(164—165^[40])	258.0535(258.0533)[M-H]^-
12	Yellow solid	83.1	184—186	329.0545(329.0540)[M-H]^-
13	Grey-white solid	30.9	270—272	313.0594(313.0591)[M+H]⁺
14	Grey-white solid	88.6	121—123	331.0260(331.0252)[M+H]⁺
15	Yellow solid	74.5	169—171	422.0691(422.0674)[M+H]⁺
16	Red solid	66.7	229—232	465.1364(465.1330)[M-Cl]⁺
17	Yellow solid	77.8	163—165	435.1586(435.1588)[M-Cl]⁺

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
6h	6.50(d, J=6.9 Hz, 1H), 7.59(br s, 2H), 7.79(br s, 1H), 7.83(dd, J=2.0, 9.1 Hz, 1H), 8.04(d, J=2.0 Hz, 1H), 8.46(d, J=6.9 Hz, 1H), 8.61(d, J=9.1 Hz, 1H)	103.2, 118.1, 118.6, 121.8, 127.2, 130.5, 131.3, 132.7, 132.9, 135.2, 137.4, 141.6, 142.6, 145.7, 158.5
6i	3.80(s, 3H), 6.34(d, J=6.9 Hz, 1H), 7.12(dd, J=3.0, 9.0 Hz, 1H), 7.22(d, J=3.0 Hz, 1H), 7.62(d, J=9.0 Hz, 1H), 7.88(dd, J=2.0, 9.1 Hz, 1H), 8.28(d, J=2.0 Hz, 1H), 8.57(d, J=6.9 Hz, 1H), 8.99(d, J=9.1 Hz, 1H), 11.46(br s, 1H, NH)	56.4, 101.4, 115.4, 116.0, 116.4, 119.7, 122.5, 126.7, 128.1, 131.7, 135.2, 139.0, 139.4, 143.8, 155.7, 159.7
6j	3.85(s, 3H), 6.28(br s, 1H), 7.26(s, 1H), 7.61(d, J=8.5 Hz, 1H), 7.77(s, 1H), 7.91(br s, 1H), 8.42(br s, 1H), 8.47(d, J=8.5 Hz, 1H)	57.2, 102.8, 112.9, 118.2, 119.9, 122.0, 125.2, 125.9, 126.5, 131.0, 135.1, 137.6, 148.0, 150.0, 150.6, 154.9
12	2.21(m, 2H), 3.78(s, 3H), 3.79(t, J=6.4 Hz, 2H), 4.22(t, J=5.9 Hz, 2H), 6.66(d, J=6.1 Hz, 1H), 7.25(s, 1H), 7.53(s, 1H), 8.02(dd, J=6.1, 13.2 Hz, 1H), 13.93(d, J=13.2 Hz, 1H)	31.6, 41.9, 55.9, 65.7, 100.2, 108.4, 112.7, 113.4, 136.2, 138.2, 144.9, 153.1, 168.1
13	2.27(m, 2H), 3.82(t, J=6.4 Hz, 2H), 3.90(s, 3H), 4.21(t, J=6.1 Hz, 2H), 7.19(s, 1H), 7.60(s, 1H), 9.08(s, 1H)	31.4, 41.8, 55.8, 65.5, 101.9, 105.4, 122.2, 130.4, 134.5, 140.7, 148.1, 152.4, 166.6
14	2.29(m, 2H), 3.83(t, J=6.4 Hz, 2H), 4.02(s, 3H), 4.36(t, J=5.9 Hz, 2H), 7.52(s, 1H), 7.58(s, 1H), 9.17(s, 1H)	31.4, 41.8, 56.3, 65.9, 102.9, 109.0, 120.4, 132.6, 139.8, 142.7, 146.4, 152.1, 154.2
15	2.26(m, 2H), 3.78( s, 3H), 3.81(t, J=6.4 Hz, 2H), 4.28(t, J=5.8 Hz, 2H), 7.08(d, J=8.6 Hz, 2H), 7.36(d, J=8.6 Hz, 2H), 7.39(s, 1H), 7.56(s, 1H), 8.94(s, 1H), 9.80(s, 1H, NH)	31.9, 42.3, 56.3, 65.8, 104.1, 109.9, 115.4, 122.0(2C), 128.0, 129.5(2C), 130.3, 141.0, 141.2, 144.9, 146.9, 149.7, 153.3
16	2.56(m, 2H), 3.73( s, 3H), 4.36(t, J=5.4 Hz, 2H), 4.86(t, J=6.2 Hz, 2H), 7.10(d, J=8.6 Hz, 2H), 7.34(d, J=8.6 Hz, 2H), 7.38(s, 1H), 7.78(s, 1H), 8.14(t-like, J=6.9 Hz, 2H), 8.63(t, J=7.8 Hz, 1H), 8.92(s, 1H), 9.17(d, J=5.8 Hz, 2H), 10.12(s, 1H, NH)		30.0, 56.5, 59.7, 66.9, 104.4, 109.8, 115.9, 121.5(2C), 127.6, 128.4(2C), 129.4(2C), 130.3, 140.9, 141.2, 145.0, 145.5(2C), 145.8, 146.8, 149.5, 152.8
17	2.69(m, 2H), 3.68( s, 3H), 4.40(t, J=5.4 Hz, 2H), 4.97(t, J=6.6 Hz, 2H), 6.97(d, J=8.0 Hz, 2H), 7.17(s, 1H), 7.32(s, 1H),7.34(d, J=8.0 Hz, 2H), 8.14(t-like, J=6.6 Hz, 2H), 8.31(s, 1H), 8.65(t, J=7.7 Hz, 1H), 9.14(d, J=5.6 Hz, 2H)		29.8, 54.8, 59.7, 66.4, 101.2, 102.4, 118.6, 119.5(2C), 126.4, 128.0, 128.1(2C), 128.6(2C), 130.0, 131.1, 132.7, 140.5, 145.0(2C), 145.4, 150.1, 150.5

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
6h	6.50(d, J=6.9 Hz, 1H), 7.59(br s, 2H), 7.79(br s, 1H), 7.83(dd, J=2.0, 9.1 Hz, 1H), 8.04(d, J=2.0 Hz, 1H), 8.46(d, J=6.9 Hz, 1H), 8.61(d, J=9.1 Hz, 1H)	103.2, 118.1, 118.6, 121.8, 127.2, 130.5, 131.3, 132.7, 132.9, 135.2, 137.4, 141.6, 142.6, 145.7, 158.5
6i	3.80(s, 3H), 6.34(d, J=6.9 Hz, 1H), 7.12(dd, J=3.0, 9.0 Hz, 1H), 7.22(d, J=3.0 Hz, 1H), 7.62(d, J=9.0 Hz, 1H), 7.88(dd, J=2.0, 9.1 Hz, 1H), 8.28(d, J=2.0 Hz, 1H), 8.57(d, J=6.9 Hz, 1H), 8.99(d, J=9.1 Hz, 1H), 11.46(br s, 1H, NH)	56.4, 101.4, 115.4, 116.0, 116.4, 119.7, 122.5, 126.7, 128.1, 131.7, 135.2, 139.0, 139.4, 143.8, 155.7, 159.7
6j	3.85(s, 3H), 6.28(br s, 1H), 7.26(s, 1H), 7.61(d, J=8.5 Hz, 1H), 7.77(s, 1H), 7.91(br s, 1H), 8.42(br s, 1H), 8.47(d, J=8.5 Hz, 1H)	57.2, 102.8, 112.9, 118.2, 119.9, 122.0, 125.2, 125.9, 126.5, 131.0, 135.1, 137.6, 148.0, 150.0, 150.6, 154.9
12	2.21(m, 2H), 3.78(s, 3H), 3.79(t, J=6.4 Hz, 2H), 4.22(t, J=5.9 Hz, 2H), 6.66(d, J=6.1 Hz, 1H), 7.25(s, 1H), 7.53(s, 1H), 8.02(dd, J=6.1, 13.2 Hz, 1H), 13.93(d, J=13.2 Hz, 1H)	31.6, 41.9, 55.9, 65.7, 100.2, 108.4, 112.7, 113.4, 136.2, 138.2, 144.9, 153.1, 168.1
13	2.27(m, 2H), 3.82(t, J=6.4 Hz, 2H), 3.90(s, 3H), 4.21(t, J=6.1 Hz, 2H), 7.19(s, 1H), 7.60(s, 1H), 9.08(s, 1H)	31.4, 41.8, 55.8, 65.5, 101.9, 105.4, 122.2, 130.4, 134.5, 140.7, 148.1, 152.4, 166.6
14	2.29(m, 2H), 3.83(t, J=6.4 Hz, 2H), 4.02(s, 3H), 4.36(t, J=5.9 Hz, 2H), 7.52(s, 1H), 7.58(s, 1H), 9.17(s, 1H)	31.4, 41.8, 56.3, 65.9, 102.9, 109.0, 120.4, 132.6, 139.8, 142.7, 146.4, 152.1, 154.2
15	2.26(m, 2H), 3.78( s, 3H), 3.81(t, J=6.4 Hz, 2H), 4.28(t, J=5.8 Hz, 2H), 7.08(d, J=8.6 Hz, 2H), 7.36(d, J=8.6 Hz, 2H), 7.39(s, 1H), 7.56(s, 1H), 8.94(s, 1H), 9.80(s, 1H, NH)	31.9, 42.3, 56.3, 65.8, 104.1, 109.9, 115.4, 122.0(2C), 128.0, 129.5(2C), 130.3, 141.0, 141.2, 144.9, 146.9, 149.7, 153.3
16	2.56(m, 2H), 3.73( s, 3H), 4.36(t, J=5.4 Hz, 2H), 4.86(t, J=6.2 Hz, 2H), 7.10(d, J=8.6 Hz, 2H), 7.34(d, J=8.6 Hz, 2H), 7.38(s, 1H), 7.78(s, 1H), 8.14(t-like, J=6.9 Hz, 2H), 8.63(t, J=7.8 Hz, 1H), 8.92(s, 1H), 9.17(d, J=5.8 Hz, 2H), 10.12(s, 1H, NH)		30.0, 56.5, 59.7, 66.9, 104.4, 109.8, 115.9, 121.5(2C), 127.6, 128.4(2C), 129.4(2C), 130.3, 140.9, 141.2, 145.0, 145.5(2C), 145.8, 146.8, 149.5, 152.8
17	2.69(m, 2H), 3.68( s, 3H), 4.40(t, J=5.4 Hz, 2H), 4.97(t, J=6.6 Hz, 2H), 6.97(d, J=8.0 Hz, 2H), 7.17(s, 1H), 7.32(s, 1H),7.34(d, J=8.0 Hz, 2H), 8.14(t-like, J=6.6 Hz, 2H), 8.31(s, 1H), 8.65(t, J=7.7 Hz, 1H), 9.14(d, J=5.6 Hz, 2H)		29.8, 54.8, 59.7, 66.4, 101.2, 102.4, 118.6, 119.5(2C), 126.4, 128.0, 128.1(2C), 128.6(2C), 130.0, 131.1, 132.7, 140.5, 145.0(2C), 145.4, 150.1, 150.5

Compd.	IC₅₀/(μmol·L^-1)		Compd.	IC₅₀/(μmol·L^-1)
Compd.	AChE		BChE	AChE	BChE
6a	75.31±0.85	>150	6h	121.50±2.13	>150
6b	121.72±0.06	>150	6i	>150	>150
6c	111.22±2.39	>150	6j	109.68±1.67	>150
6d	94.14±0.52	>150	15	140.91±1.03	>150
6e	116.43±0.34	142.08±0.68	16	0.92±0.05	14.20±0.96
6f	120.29±1.43	>150	17	3.19±0.22	17.43±0.57
6g	136.23±1.45	>150	Galanthamine	2.30±0.03	20.47±1.92