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. Author manuscript; available in PMC: 2020 Aug 7.
Published in final edited form as: ARKIVOC. 2018 Mar 11;2018(4):158–182. doi: 10.24820/ark.5550190.p010.460

Table 2.

In vitro In vitro microsomal stability of SH-053-2'F-S-CH3 (2) analogs.

Entry Structure at C(3) with C(8)-ethynyl Microsomal stability (HLM) after 2 hr Microsomal stability (MLM) after 2 hr
  Half-life (min) % remaining Half-life (min) % remaining

2 ester CO2CH2CH3 < 5b < 5.0b 155 ± 9d 78.0 ± 0.2d
3   CO2CH2CH3e < 5b < 5.0b 46 ± 3 16.0 ± 0.4
4a   CO2CH3f 10 ± 1d 2.0 ± 0.3d 116 ± 13 41.0 ± 0.6
4b   CO2CH2CH3f < 5b < 5.0b < 5b < 5.0b
5a   CO2CH3 119 ± 21d 43.0 ± 0.4d 216 ± 28 62.0 ± 0.5
5b   CO2CH2CH2CH3 < 5c < 5.0c 24 ± 0d 12.0 ± 0.2d
5c   CO2CH(CH3)2 57 ± 2d 47.0 ± 0.2d 227 ± 16d 83.0 ± 0.1d
5d   CO2C(CH3)3 514 ± 115d 89.0 ± 0.2d 196 ± 20d 78.0 ± 0.2d
5f   CO2CH2CF3 < 5a < 5.0a < 5b < 5.0b
5g   CO2-cyclopropyl < 5a < 5.0a 19 ± 2d 11.0 ± 0.2d

6 acid COOH 358 ± 56 74.0 ± 0.4 139 ± 11d 54.0 ± 0.3d

7 thioester COSCH2CH3 101 ± 19 28.0 ± 0.3 46 ± 6 9.0 ± 0.5

8a amide CONHCH3 1780 ± 39 92.0 ± 0.3 845 ± 5 86.0 ± 0.2
8b   CONHCH2CH3 1978 ± 50 93.0 ± 0.3 1961 ± 46 92.0 ± 0.3
8c   CONH-cyclopropyl 1625 ± 803d 89.0 ± 0.4d 320 ± 34d 72.0 ± 0.3d
8d   CONHCH(CH3)2 107 ± 10 38.0 ± 0.5 28 ± 0 75.0 ± 0.3
8e   CONHC(CH3)3 205 ± 14 63.0 ± 0.3 142 ± 9 52.0 ± 0.3
8f   CON(CH3)2 59 ± 5d 41.0 ± 0.9d 24 ± 2d 19.0 ± 0.9d

9a 1,2,4-oxadiazole 3-CH3 866 ± 213 86.0 ± 0.3 443 ± 66 81.0 ± 0.4
9b 3-CH2CH3 563 ± 123 80.0 ± 0.4 213 ± 17 63.0 ± 0.3
9c 3-CH(CH3)2 2584 ± 1920 91.0 ± 0.3 500 ± 109 79.0 ± 0.5

10 nitrile CN 41 ± 5 9.0 ± 0.3 58 ± 6 17.0 ± 0.6
a

Compound was not detected after 10 minutes.

b

Compound was not detected after 20 minutes.

c

Compound was not detected after 30 minutes.

d

Compound was assessed at 1-hour incubation time.

e

C(8)-cyclopropyl.

f

C(8)-bromo. (see Supplementary material for details)