Table 3.
Proposed structural guidelines for the design of synthetic large MC libraries for use in the discovery of oral drugs
| Property | Observed Rangea |
|---|---|
| Ring Size (R) | 14–38 |
| Number of Substituents | 4.4 (3–8) |
| Large substituents (≥5 HA)b | 1.9 (1–3) |
| Small Substituents (2–4 HA)b | 2.4 (1–6) |
| Proportion of HA that are in Substituents | 47% (40–59%) |
|
Number of
Peripheral Groupsc |
5–12 |
| Polar/Nonpolar balance, Substituents | ~30/70 |
|
Polar/Nonpolar balance,
Peripheral Groups |
~60/40 |
| Degrees of Unsaturation in Ring | ~0.4R – 4 (±3) |
| N:O ratio | 0.25:1 (0–0.4:1) |
| Chiral Centers | 15 (9–18) |
a
Mean (10–90% range).
b
HA = Heavy (i.e. non-hydrogen) atoms.
c
Peripheral groups are groups connected to the MC ring that contain only a single HA (see text).