Skip to main content
. Author manuscript; available in PMC: 2016 Sep 1.
Published in final edited form as: Bioorg Med Chem. 2015 Jul 16;23(17):5709–5724. doi: 10.1016/j.bmc.2015.07.013

Table 3.

6-Amino tetrahydroisoquinoline orexin antagonists.

graphic file with name nihms709265u4.jpg
No. R R′ OX1 Ke (nM)a OX2 Ke (nM)a
25a Methyl Methyl 1370 ± 100 b
25b n-Propyl H >10000 b
25c n-Propyl Methyl 619 ± 96 b
25d n-Propyl n-Propyl 2350 ± 490 b
25e iso-Propyl H >10000 b
25f Cyclopropylmethyl H >10000 b
25g Cyclopropylmethyl Methyl 1400 ± 240 b
25h Benzyl H 1100 ± 290 b
25i Benzyl Methyl >10000 b
25j graphic file with name nihms709265t3.jpg H 2180 ± 360c b
25k 3-Phenylpropyl H 1180 ± 80 b
25l 4-Phenoxybutyl H 2080 ± 20 b
25m 4-Pyridylmethyl H >10,000 b
25n 3-Pyridylmethyl H 1270 ± 110 b
25o graphic file with name nihms709265t4.jpg H >10000 b
25p Pyrrolidine 2480 ± 6 b
25q Piperidine >10000 b
25r n-Pentyl H >10000 b
25s n-Pentyl Methyl >10000 b
25t n-Hexyl H >10000 b
25u n-Hexyl Methyl >10000 b
26a graphic file with name nihms709265t5.jpg H 427 ± 69 b
26b graphic file with name nihms709265t6.jpg H >10000 b
26c graphic file with name nihms709265t7.jpg H 809 ± 200 b
26d graphic file with name nihms709265t8.jpg H 591 ± 67 >10000
26e graphic file with name nihms709265t9.jpg H 1010 ± 200d b
26f graphic file with name nihms709265t10.jpg H 1600 ± 190 b
26g graphic file with name nihms709265t11.jpg H >10000 b
26h graphic file with name nihms709265t12.jpg H >10000 b
27 Methylsulfanyl H >10000 b
28a Acetyl H >10000 b
28b Hexanoyl H >10000 >10000
28c Benzoyl H >10000 b
23a Methyl carbamoyl H 2400 ± 320 >10000
23b Ethyl carbamoyl H >10000 >10000
28d PhNHCO H >10000 b
28e n-Hexyl-NHCO H 5230 ± 680 b
a

Ke values are the mean ± SEM of three independent experiments performed in duplicate. Results where Ke > 10 μM are N=2.

b

Less than 50% inhibition at 10 μM.

c

Pre-incubation of antagonist and receptor was 45 min.

d

Pre-incubation of antagonist and receptor was 1 hr.