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. 2020 Feb 1;30(3):126751. doi: 10.1016/j.bmcl.2019.126751

Table 1.

Comparison of thieno[3,2-d]pyrimidine amides 4a with thieno[2,3-d]pyrimidine amides 5.

graphic file with name fx2.jpg

NR1R2 Compound Notumb
IC50 (nM)		 MLMc
Cli (μL/min/mg)		 MDCK-MDR1c
AB/BA Papp (×10−6 cm/s) and efflux ratio (ER)
–NMe2 4a 7.5 ± 12.4
5a 15 ± 6 360
graphic file with name fx3.gif 4b 91 ± 67
5b 220 ± 12
graphic file with name fx4.gif 4c 18 ± 8.7 >500 40/38 0.95
5c 69 ± 10
graphic file with name fx5.gif 4d 7.1 ± 4.1 24 7.9/65 8.2
5d 5.8 ± 4.0 19 12/66 5.5
graphic file with name fx6.gif 4e 1.5 ± 0.1 19 3.8/14 3.7
5e 2.7 ± 0.5 65 14/82 5.9
graphic file with name fx7.gif 4f 1.1 ± 0.3 29 0.95/93 98
5f 3.2 ± 0.1 13 0.6/56 93
a

See Ref. 12.

b

All values are geometric mean ± s.d. of n = 2–6 experiments quoted to 2 s.f. Differences of <2-fold should not be considered significant. For details of the assay protocol, see reference 15.

c

MLM, MDCK-MDR1 and additional in vitro ADME studies reported in this work were independently performed by GVK Biosciences (Hyderabad, India. https://www.gvkbio.com/discovery-services/biology-services/dmpk-services/) or Cyprotex (Macclesfield, UK. https://www.cyprotex.com/admepk).