Table 1 SAR of the tricyclic compounds

From: Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders

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CPD-ID

m

X

R2

R3

R4

Y

hNNMT IC50 (µM)

mNNMT IC50 (µM)

(1)

2

CH

H

Me

H

NH

0.13 ± 0.08

0.18 ± 0.01

(2)

2

CF

H

Me

H

NH

0.059 ± 0.004

0.33 ± 0.13

(3)

2

CF

F

Me

H

NH

0.19 ± 0.13

1.2 ± 0.75

(4)

2

N

H

Me

H

NH

0.36 ± 0.10

0.77 ± 0.04

(5)

3

CH

H

Me

H

NH

 > 30

ND

(6)

1

CH

H

Me

H

NH

0.034 ± 0.001

0.20 ± 0.02

(7)

1

CH

H

Me

H

O

0.18 ± 0.02

0.38 ± 0.02

(8)

1

CF

H

Me

H

NH

0.039 ± 0.004

1.1 ± 0.5

(9)

1

CF

F

Me

H

NH

0.49 ± 0.04

 > 3

(10)

1

CF

H

Et

H

NH

0.074 ± 0.030

 > 3

(11)

1

CH

H

Me

F

NH

 > 1

ND

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