Table 2 Expansion of the SAR.

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

CPD-ID

X

R1

R2

R3

R4

hNNMT IC50 (µM)

mNNMT IC50 (µM)

(12)

O

H

H

Me

H

0.18 ± 0.02

0.38 ± 0.02

(13)

S

H

H

Me

H

0.86 ± 0.06

0.20 ± 0.02

(14)

–NCN

H

H

Me

H

0.25 ± 0.07

0.72 ± 0.07

(15)

–NAc

H

H

Me

H

 > 30

ND

(16)

––NMe

H

H

Me

H

 > 30

ND

(17)

–NCON(Me)2

H

H

Me

H

 > 30

ND

(18)

O

F

H

Me

H

0.069 ± 0.036

 > 3

(19)

O

F

F

Me

H

 > 1

ND

(20)

––NMe

F

H

Me

H

 > 3

ND

(21)

O

F

H

–CH2CF3

H

 > 30

ND

(22)

O

H

H

–CH2CH2–(4F-phenyl)

H

 > 30

ND

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