druglikeness

Question 1

what are rotatable bonds?

Answer 1

Rotatable bonds are defined as any single bond, not in a ring, bound to a nonterminal heavy (i.e., non-hydrogen) atom. Excluded from the count are amide C-N bonds because of their high rotational energy barrier.

Question 2

if the compound in oral drugs forms many hydrogen or ionic bonds with water.

Answer 2

De-solvation and formation of a neutral molecule is unfavourable

Question 3

why are too many hydrogen bond donors or acceptors in oral drugs undesirable?

Answer 3

because then the drug will not easily get from the gut into the blood stream.
There are some exceptions to this restriction – carbohydrates have special transport mechanisms.

Question 4

Absorption and Bioavailability are likely to be successful if oral drugs follow lipinski rule of five and an additional rule proposed by D.F. Veber. what are these rules?

Answer 4

1. molecular weight < 500 amu
2. logP < 5
3. < 5 H-bond donors (sum of NH and OH)
4. < 10 H-bond acceptors (sum of N and O)
5. < 10 rotatable bonds

Question 5

Drug molecules that do not obey the Lipinski rule of 5

Answer 5

atorvastatin- MW
doxycycline-HBA/HBD
liothyronine- MW
bexarotene- log p
olmesartan- MW/ HBA
acarbose-MW/HBA
ethopropazine- log p

Question 6

what can be used to measure molecular size?

Answer 6

molecular weight

Question 7

what else can be used to measure molecular weight?

Answer 7

Electron density
Polar surface area
Van der Waals surface
Molar refractivity

Question 8

why is the 1-octanol most frequently used lipid phase?

Answer 8

because It has a polar and non polar region (like the phospholipids that constitute biological membranes)
Po/w is fairly easy to measure
Po/w often correlates well with many biological properties
It can be predicted fairly accurately using computational models