Non-oxidatively metabolized compounds and compositions, synthetic pathways therefor, and uses thereof

1 - 8 . (canceled)

9 . A method of identifying an agonist or antagonist of a receptor or an inhibitor of a protein having known biological activity, the method comprising:

a) identifying one or more compounds having a hydrolysable bond for agonist or antagonist activity with respect to the receptor or protein; and

b) identifying the compounds from (a) that have a combination of three or more of the following characteristics or properties:

i) metabolism by both CYP450 and non-oxidative metabolic enzyme or system of enzymes;

ii) a no n-oxidative metabolic half-life of less than or equal to four hours;

iii) a hydrolyzable bond that can be cleaved nonoxidatively by hydrolytic enzymes;

iv) primary metabolites that are soluble in water at physiological pH and have significantly reduced pharmacological activity compared to the compound;

v) primary metabolites that have negligible inhibitory activity at the IK R (HERG) channel at normal therapeutic concentration of the parent compound in plasma;

vi) the compound and metabolite(s) thereof do not cause metabolic drug-drug interactions when co-administered with one or more other drugs; and

vii) a failure to elevate liver function test values when administered alone.

10 . The method according to claim 1 , wherein (b) consists of identifying compounds from (a) that have at combination of four or more of characteristics or properties i)-vii).

11 . The method according to claim 1 , wherein (b) consists of identifying compounds from (a) that have a combination of five or more of characteristics or properties i)-vii).

12 . The method according to claim 1 , wherein (b) consists of identifying compounds from (a) that have a combination of six or more of characteristics or properties i) -vii).

13 . The method according to claim 1 , wherein (b) consists of identifying compounds from (a) that have a combination of all characteristics or properties i)-vii).

14 . The method according to claim 1 , wherein (b) consists of identifying compounds from (a) that have a combination of characteristics or properties selected from:

a) i, ii, iii;

b) i, ii, iv;

c) i, ii, v;

d) i, ii, vi;

e) i, ii, vii;

f) i, iii, iv;

g) i, iii, v;

h) i, iii, vi;

i) i, iii, vii;

j) i, iv, v;

k) i, iv, vi;

l) i, iv, vii;

m) i, v, vi;

n) i, v, vii;

o) i, vi, vii;

p) ii, iii, iv;

q) ii, iii, v;

r) ii, iii, vi;

s) ii, iii, vii;

t) ii, iv, v;

u) ii, iv, vi;

v) ii, iv, vii;

w) ii, v, vi;

x) ii, v, vii;

y) ii, vi, vii;

z) iii, iv, v;

aa) iii, iv, vi;

bb) iii, iv, vii;

cc) iii, v, vi;

dd) iii, v, vii;

ee) iii, vi, vii;

ff) iv, v, vi;

gg) iv, v, vii;

hh) iv, vi, vii; and

ii) v, vi, vii.

15 . The method according to claim 1 , wherein the receptor or protein is selected from the group consisting of the serotonin tiansporter 5-HTT, CYP3A4, CYP2D6, HMG coA reductase, calcium channel proteins, μ-receptor, peroxisome proliferator-activated receptors, HERG channel proteins, and H 1 -receptors.