Table 4 Estimated BBB permeabilities of 8–11 and reference compound

From: Rivastigmine and metabolite analogues with putative Alzheimer’s disease-modifying properties in a Caenorhabditis elegans model

Compoundsa

Mean Papp

(10−6 cm/s)

Carbamate Papp/Phenol Papp

Permeability categoryb

3-((Ethyl(methyl)carbamoyl)oxy)benzoic acidc

3.64

46.8

Moderate

10

9.15

8.09

High

9

22.3

0.93

High

11

33.6

1.28

High

Racemic rivastigmine (8)

33.8

1.31

High

  1. aValues are mean of at least two independent experiments using an MDR1-MDCKII cell-based model. Replicate Papp values were within 5% of the mean. The test concentration was 2 µM with 2.5 h incubation. Pgp efflux ratios: 3-((ethyl(methyl)carbamoyl)oxy)benzoic acid, 0.50; 10, 1.55; galantamine, 0.97; 9, 0.72; donepezil, 0.82; 11, 0.73; racemic rivastigmine (8), 0.76; (S)-rivastigmine [(S)-8], 0.75
  2. bLow permeability: Papp  ≤  1.0 ( × 10−6 cm/s); Moderate permeability: 1.0 <  Papp  < 5.5 ( × 10−6 cm/s); High permeability: Papp  ≥  5.5 ( × 10−6 cm/s). The boundaries for low and high permeability categories are equivalent to 50 and 80% of the calculated fraction absorbed (Fa) in humans
  3. cThe synthesis of this compound is described in the Supplementary Methods
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