Table 1 hAChE inhibitory activity and h5-HT4R affinity for benzisoxazole derivatives 11–16, 21–23, 32a–e and 33.

From: Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT4 receptors activities for the treatment of Alzheimer’s disease

Compound

IC50 hAChE (nM) % inhibition at 10−6 M

Ki h5-HT4R (nM) % inhibition at 10−6 M/10−8 M

X

R1

R2

 

donecopride

 

16 ± 5 (n = 2)

8.5 ± 0.3 (n = 3)

11

O

H

n.d.

24%

9.6 ± 1.6 (n = 3)

100%/67%

12

O

H

n.d.

33%

42.4 ± 12.2 (n = 3)

99%/29%

13

O

H

n.d.

8%

20.8 ± 12.5 (n = 3)

100%/59%

14

O

441 ± 63 (n = 2)

82%

2.7 ± 0.4 (n = 3)

100%/99%

15

O

939 ± 40 (n = 2)

82%

3.0 ± 0.4 (n = 3)

100%/94%

16

O

n.d.

23%

4.1 ± 0.4 (n = 3)

100%/100%

21

CH2

H

240 ± 59 (n = 2)

84%

139 ± 9 (n = 3)

89%/4%

22

CH2

H

35.7 ± 9.4 (n = 2)

96%

263 ± 11 (n = 3)

78%/8%

23

CH2

H

n.d.

11%

n.d.

87%/8%

32a

CH2

63.5 ± 19.2 (n = 2)

94%

59 ± 8.5 (n = 3)

100%/13%

32b

CH2

200 ± 32 (n = 2)

87%

80.5 ± 9.9 (n = 3)

100%/16%

32c

CH2

n.d.

42%

219 ± 65 (n = 3)

100%/4%

32d

CH2

1001 ± 84 (n = 2)

52%

616 ± 67 (n = 3)

100%/0%

32e

CH2

n.d.

10%

2920 ± 781 (n = 3)

96%/0%

33

CH2

OH

97.3 ± 1.5 (n = 2)

87%

37 ± 10.5 (n = 3)

100%/29%

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