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. Author manuscript; available in PMC: 2009 Oct 30.
Published in final edited form as: J Med Chem. 2006 May 18;49(10):2939–2952. doi: 10.1021/jm051262k

Table 3.

In Vitro Activities of 3-Mono-, Di-, and Trifluoromethyl-7-substituted-THIQs.

graphic file with name nihms64101f10.jpg
R3= CH2F (a)a R3= CHF2 (b)a R3= CF3 (c)b
Compd R7 PNMTc α2c,d Sele PNMTc α2c,d Sele PNMTc α2c,d Sele
11a–c Br 0.023 6.4 280 0.094 230 2400 3.2 >1000 >310
12a–c CF3 0.030 41 1400 0.067 190 2800 0.98 >1000 >1000
13a–c I 0.054 7.1 130 0.20 >1000 >5000 1.9 >1000 >530
14a–c SO2NHCH2CF3 0.13 1200 9200 0.25 >1000 >4000 9.4 >1000 >110
15a–c NO2 0.15 76 510 0.17 >1000 >5800 2.3 1400 610
16a–c SO2NH2 0.15 680 4500 0.68 >1000 >1500 8.0 >1000 >125
17a–c SO2NH(p-C6H4Cl) 0.27 140 520 0.90 >1000 >1100 15 >1000 >67
18a–c CN 0.80 460 570 3.1 >1000 >320 21 2900 140
19a–c H 0.82 3.8 4.6 3.4 150 44 23 400 17
20a–c SO2CH3 1.1 230 210 6.0 2500 420 41 3900 95
21a–c SO2NHEt 1.4 550 390 3.2 >1000 >310 60 >1000 >17
22a–c SO2NHPr 1.7 610 360 2.1 >1000 >480 — — —
23a–c SO2NH(CH2)3OCH3 2.6 750 290 5.3 >1000 >190 13 >1000 >77
24a–c SO2NHBu 3.4 260 76 5.6 >1000 >180 — — —
25a–c SO2NH(p-C6H4NO2) 7.7 >1000 >130 37 >1000 >27 110 >1000 >9.1
a

Data for compounds 11a–25a found in refs. 48 and 44.

b

Data for compounds 11c–13c, 15c, 16c, and 18c–21c found in refs. 23 and 24.

c

Standard error of the mean was not greater than 10%.

d

In vitro activities for the inhibition of [3H]clonidine binding to the α2-adrenoceptor.

e

Selectivity α2 Ki /hPNMT Ki.