Nitrogen-containing heterocycle derivatives, pharmaceutical compositions, and methods of use thereof as antiviral agents

• US 20070219239A1
• Filed: 02/09/2007
• Published: 09/20/2007
• Est. Priority Date: 02/10/2006
• Status: Abandoned Application

• Current Assignee: Transtech Pharma Incorporated
• Original Assignee: Transtech Pharma Incorporated
• Inventors: Andrews, Robert, Mjalli, Adnan, Arimilli, Murty, Rothlein, Robert, Cooper, Jeremy, AlTel, Taleb
• Application Number:
  US11/704,763
• Publication Number:
  US 20070219239A1
• Time in Patent Office: Days
• US Class Current: 514/307
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07D 233/64 with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• CPC Class Codes: C07D 401/02 containing two hetero rings
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present application provides nitrogen-containing heterocycle derivatives that are antiviral compounds that may be useful in the treatment of a viral infection. Compounds of Formula (I) and pharmaceutical compositions comprising a compound of Formula (I) may be administered to a subject for antiviral therapy or prophylaxis.

Claims

1. A compound of Formula (I):

wherein

V is C, W is N—

R¹¹, O, or S, X is C, Y is N, Z is C—

R¹², when sides a, b, and d are single bonds, and sides c and e are double bonds;

V is C, W is N, X is C, Y is N—

R¹¹, O, or S, Z is C—

R¹², when sides a, c, and d are single bonds, and sides b and e are double bonds;

V is C, W is N, X is C, Y is C—

R¹², Z is N—

R¹¹, O, or S when sides b, e, and d are single bonds, and sides a and c are double bonds;

V is C, W is C—

R¹², X is N, Y is C—

R¹³, Z is N, when sides b, c, and e are single bonds, and sides a and d are double bonds;

V is N, W is C—

R¹², X is C, Y is N, Z is C—

R¹³, when sides a, c, and e are single bonds, and sides b and d are double bonds;

V is C, W is N—

R¹¹, O, or S, X is C, Y is C—

R¹², Z is N when sides a, b, and d are single bonds, and sides c and e are double bonds;

wherein

R¹¹ is R^d;

R¹² and R¹³ are independently selected from R^f;

G¹ is selected from the group consisting of;

cycloalkyl, heterocyclyl, aryl, heteroaryl, fused arylcycloalkyl, fused cycloalkylaryl, fused cycloalkylheteroaryl, fused heterocyclylaryl, and fused heterocyclylheteroaryl group, wherein G¹ is optionally substituted with substituents independently selected from R⁵, wherein R⁵ is R^b,

G² is selected from the group consisting of;

cycloalkyl, heterocyclyl, aryl, heteroaryl, fused arylcycloalkyl, fused cycloalkylaryl, fused cycloalkylheteroaryl, fused heterocyclylaryl, and fused heterocyclylheteroaryl group, wherein G² is optionally substituted with substituents independently selected from R⁶, wherein R⁶ is R^b,

R¹ is R^b,

R¹² is R^f,

R³ and R⁴ are independently selected from R^f and R^g,

L¹, L², and L⁵ are independently selected from the group consisting of a direct bond, —

C_1-10 alkylene, —

C_2-10 alkenylene, and —

C_2-10 alkynylene;

wherein alkylene, alkenylene, and alkynylene are optionally substituted 1 to 4 times with R^f,

L³ and L⁴ are independently selected from the group consisting of a direct bond, —

C_1-10 alkylene, —

C_2-10 alkenylene, —

C_2-10 alkynylene, arylene, and heteroarylene;

wherein alkylene, alkenylene, and alkynylene are optionally substituted 1 to 4 times with R^f, and arylene and heteroarylene are optionally substituted 1 to 4 times with R^b,

Y¹ and Y² are independently selected from the group consisting of a direct bond, —

O—

, —

N(R¹⁶)—

, —

C(O)—

, —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)C(O)N(R¹⁷)—

, —

N(R¹⁶)C(O)O—

, —

OC(O)N(R¹⁶)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

N(R¹⁶)SO₂N(R⁷)—

, —

C(R^f)═

C(R^g)—

, —

C≡

C—

, —

N═

N—

, and —

N(R¹⁶)—

N(R¹⁷)—

;

wherein

R¹⁶ and R¹⁷ are independently selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -aryl, -cycloalkyl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are optionally substituted 1 to 4 times with R^f;

R^b is

a) -cycloalkyl,

b) -cyano,

c) —

OR^d,

d) —

NO₂,

e) -halogen,

f) —

S(O)_mR^d,

g) —

SR^d,

h) —

S(O)₂OR^d,

i) —

S(O)_mNR^dR^e,

j) —

NR^dR^e,

k) —

O(CR^fR^g)_nNR^dR^e,

l) —

C(O)R^d,

m) —

CO₂R^d,

n) —

CO₂(CR^fR^g)_nC(O)NR^dR^e,

o) —

OC(O)R^d,

p) —

C(O)NR^dR^e,

q) —

NR^dC(O)R^e,

r) —

OC(O)NR^dR^e,

s) —

NR^dC(O)OR^e,

t) —

NR^dC(O)NR^dR^e,

u) —

CF₃,

v) —

OCF₃,

w) -haloalkyl,

x) -haloalkoxy,

y) —

C_1-10 alkyl,

z) —

C_2-10 alkenyl,

aa) —

C_2-10 alkynyl,

bb) —

C_1-10 alkylene-aryl,

cc) —

C_1-10 alkylene-heteroaryl, or

dd) -heteroaryl,

wherein alkyl, alkenyl, alkynyl, aryl, heteroaryl, and cycloalkyl groups are optionally substituted 1-4 times with a group independently selected from R^c;

R^c is

a) -halogen,

b) -amino,

c) -carboxy,

d) —

C_1-4 alkyl,

e) —

O—

C_1-4 alkyl,

f) -cycloalkyl,

g) —

O-cycloalkyl,

h) -aryl,

i) —

C_1-4 alkylene-aryl,

j) -hydroxy,

k) —

CF₃,

l) -haloalkyl,

m) -haloalkoxy,

n) —

O-aryl,

o) -heteroaryl,

p) -heteroaryl-C_1-10 alkyl,

q) heterocyclyl,

r) —

CO₂—

C_1-10 alkyl, or

s) —

CO₂—

C_1-10 alkyl-aryl,

R^d and R^e are independently selected from hydrogen, C_1-10 alkyl, C_2-10 alkenyl, C_2-10 alkynyl, cycloalkyl, —

C_1-10 alkylene-cycloalkyl, aryl, heterocyclyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl groups are optionally substituted with one to four substituents independently selected from R^c;

or R^dand R^e together with the atoms to which they are attached form a heterocyclic ring of 5 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and nitrogen and optionally substituted with 1-3 times with R^c,

R^f and R^g are independently selected from hydrogen, C_1-10 alkyl, cycloalkyl, —

C_1-10 alkylene-cycloalkyl, and aryl, wherein alkyl, cycloalkyl, and aryl groups are optionally substituted with one to four substituents independently selected from R^c;

or R^f and R^g together with the carbon to which they are attached form a ring of 5 to 7 members containing 0-2 heteroatoms independently selected from oxygen, sulfur and nitrogen optionally substituted with 1-3 times with R^c;

m is an integer from 1 to 2,

n is an integer from 1 to 10,

u is an integer from 0 to 2,

v is an integer from 0 to 2,

w is an integer from 0 to 1,

or pharmaceutically acceptable salt, solvate, or prodrug thereof.

2. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein G¹ is isoquinoline-3-yl, quinoline-2-yl, quinoline-3-yl, pyridine-2-yl, pyridine-3-yl, phenyl, or naphthyl-2-yl, wherein G¹ may be substituted or unsubstituted.

3. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein G¹ is isoquinoline-3-yl, pyridine-2-yl, or pyridine-3-yl, wherein G¹ is unsubstituted.

4. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein G² is phenyl, pyridine, pyrimidine, pyridazine, or pyrazine,

wherein G² is optionally substituted 1 to 4 times with R⁶, wherein R⁶ is R^b.

5. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein V is C, W is N—

R¹¹, O, or S, X is C, Y is N, Z is C—

R¹², sides a, b, and d are single bonds, and sides c and e are double bonds.

6. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein V is C, W is N—

R¹¹, X is C, Y is N, Z is C—

R¹², sides a, b, and d are single bonds, and sides c and e are double bonds.

7. The compound of Formula (I) in claim 6 or a pharmaceutically acceptable salt thereof, wherein R¹¹ and R¹² are hydrogen.

8. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is 0, v is 1, L¹ is a direct bond, L² is a direct bond, Y¹ is —

N(R¹⁶)C(O)—

, and R¹² is R^f.

9. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is 0, v is 1, L¹ is a direct bond, L² is a direct bond,

R¹² is hydrogen, C_1-10 alkyl, cycloalkyl, phenyl, or —

C_1-10 alkylene-phenyl, wherein alkyl, cycloalkyl, and phenyl are substituted or unsubstituted, and

Y¹ is —

N(R¹⁶)C(O)—

, wherein R¹⁶ is hydrogen, C_1-10 alkyl, cycloalkyl, or phenyl, wherein alkyl, cycloalkyl, and phenyl are substituted or unsubstituted.

10. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is 0, v is 1, L¹ is a direct bond, L² is a direct bond,

Y¹ is selected from the group consisting of a —

O—

, —

N(R¹⁶)—

, —

C(O)—

, —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)C(O)N(R¹⁷)—

, —

N(R¹⁶)C(O)O—

, —

OC(O)N(R¹⁶)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

N(R¹⁶)SO₂N(R¹⁷)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ and R¹⁷ are independently selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -aryl, -cycloalkyl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are substituted or unsubstituted; and

R¹² is C_1-10 alkyl, cycloalkyl, phenyl, or —

C_1-10 alkylene-phenyl, wherein alkyl, cycloalkyl, and phenyl are substituted or unsubstituted.

11. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is 0, v is 1, L¹ is a direct bond, L² is a direct bond,

Y¹ is selected from the group consisting of a —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ is selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -aryl, -cycloalkyl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are substituted or unsubstituted; and

R¹² is C_1-10 alkyl, -cycloalkyl, -phenyl, or —

C_1-10 alkylene-phenyl, wherein alkyl, cycloalkyl, and phenyl are substituted or unsubstituted.

12. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein u is 0, v is 1, L¹ is a direct bond, L² is a direct bond,

Y¹ is selected from the group consisting of a —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ is selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -cycloalkyl, -aryl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are substituted or unsubstituted; and

R¹² is methyl, ethyl, propyl, isopropyl, tert-butyl, isobutyl, 1-ethyl-propyl, and (1-halo-1-methyl)-ethyl.

13. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein L³, L⁴, and L⁵ are direct bonds, and w is 1.

14. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein L³, L⁴, and L⁵ are direct bonds, w is 1, and

Y² is selected from the group consisting of a —

O—

, —

N(R¹⁶)—

, —

C(O)—

, —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)C(O)N(R¹⁷)—

, —

N(R¹⁶)C(O)O—

, —

OC(O)N(R¹⁶), —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, —

S—

, —

S(O)—

, —

S(O)₂—

, —

N(R¹⁶)SO₂N(R¹⁷)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ and R¹⁷ are independently selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -aryl, -cycloalkyl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are substituted or unsubstituted.

15. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein L³, L⁴, and L⁵ are direct bonds, w is 1, and

Y² is selected from the group consisting of a —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ is selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -aryl, -cycloalkyl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are substituted or unsubstituted.

16. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein L³, L⁴, and L⁵ are direct bonds, w is 1,

Y² is selected from the group consisting of —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ is selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -cycloalkyl, -aryl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are substituted or unsubstituted;

R³ is H,

R⁴ is —

C_1-10 alkyl, -cycloalkyl, —

C_1-10 alkylene-cycloalkyl, and -aryl, wherein alkyl, cycloalkyl, and aryl groups are substituted or unsubstituted, and

G² is phenyl substituted from 1 to 4 times with R⁶.

17. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein L³, L⁴, and L⁵ are direct bonds, w is 1,

Y² is selected from the group consisting of —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ is selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -cycloalkyl, -aryl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are optionally substituted with R^f;

R³ is H,

R⁴ is —

C_1-10 alkyl, -cycloalkyl, —

C_1-10 alkylene-cycloalkyl, and -aryl, wherein alkyl, cycloalkyl, and aryl groups are substituted or unsubstituted, and

G² is phenyl substituted from 1 to 4 times with R⁶, wherein G² is substituted with at least one halogen.

18. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein L³, L⁴, and L⁵ are direct bonds, w is 1,

Y² is selected from the group consisting of —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ is selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -cycloalkyl, -aryl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are substituted or unsubstituted;

R³ is H,

R⁴ is —

C_1-10 alkyl, -cycloalkyl, —

C_1-10 alkylene-cycloalkyl, and -aryl, wherein alkyl, cycloalkyl, and aryl groups are substituted or unsubstituted, and

G² is para-halophenyl.

19. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein the group -L³-Y²-L⁴-(C(R³)(R⁴))-L⁵-G² is taken together to form the group

wherein

Y² is selected from the group consisting of —

C(O)N(R¹⁶)—

, —

N(R¹⁶)C(O)—

, —

N(R¹⁶)SO₂—

, —

SO₂N(R¹⁶)—

, —

C(O)—

O—

, —

O—

C(O)—

, and —

C(R^f)═

C(R^g)—

;

wherein

R¹⁶ is selected from the group consisting of;

-hydrogen, —

C_1-10 alkyl, -cycloalkyl, -aryl, and —

C_1-10 alkylene-aryl, wherein alkyl, cycloalkyl, and aryl are optionally substituted with R^f;

R⁴ is R^b,

R⁶ is R^b, and

p is an integer from 0 to 4.

20. The compound of Formula (I) in claim 27 or a pharmaceutically acceptable salt thereof, wherein Y² is —

C(O)NH—

, R⁴ is —

C_1-4 alkyl, p is 1, and R⁶ is halo.

21. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein the group -L³-Y²-L⁴-(C(R³)(R⁴))-L⁵-G² is taken together to form the group

wherein

L⁴ is imidazole, oxazole, or thiazole,

R⁴ is R^b,

R⁶ is R^b, and

p is an integer from 0 to 4.

22. The compound of Formula (I) in claim 29 or a pharmaceutically acceptable salt thereof, wherein Y² is imidazole, R⁴ is —

C_1-4 alkyl, p is 1, and R⁶ is halo.

23. The compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the formula (Ia)

wherein

G¹, R¹², R⁴, R⁵, R¹¹, R¹², L¹, L², L³, L⁴, L⁵, Y¹, Y², and v are as defined in claim 1, and p is an integer from 0 to 4.

24. The compound of Formula (Ia) in claim 23 or a pharmaceutically acceptable salt thereof, G¹ is isoquinoline-3-yl, quinoline-2-yl, quinoline-3-yl, pyridine-2-yl, pyridine-3-yl, phenyl, or naphthyl-2-yl, wherein G¹ may be substituted or unsubstituted.

25. The compound of Formula (Ia) in claim 23 or a pharmaceutically acceptable salt thereof, wherein G¹ is isoquinoline-3-yl, pyridine-2-yl, or pyridine-3-yl, wherein G¹ is unsubstituted.

26. The compound of Formula (Ia) in claim 23 or a pharmaceutically acceptable salt thereof, wherein R¹¹ and R¹² are independently selected from the group consisting of hydrogen, C_1-10 alkyl, cycloalkyl, phenyl, and —

C_1-10 alkylene-phenyl.

27. The compound of Formula (Ia) in claim 23 or a pharmaceutically acceptable salt thereof, wherein R¹¹ and R¹² are hydrogen.

28. A pharmaceutical composition comprising a compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient, diluent, or mixture thereof.

29. The pharmaceutical composition of claim 28, further comprising a therapeutically effective amount of the compound of Formula (I) or a pharmaceutically acceptable salt thereof.

30. The pharmaceutical composition of claim 29, further comprising one or more additional therapeutic agents.

31. The pharmaceutical composition of claim 30, wherein the additional therapeutic agent is an antiviral agent selected from the group consisting of:

AZT, abacavir, ddC, ddI, d4T, 3TC, ZDV, tenofovir, nevirapine, pentafuside, amprenavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquanivir, lamivudine, foscarnet, acyclovir, cidofovir, ganciclovir, valaciclovir, amantadine, rimantadine, zanamivir, and oseltamivir.

32. The pharmaceutical composition of claim 28 in the form of an oral, rectal, nasal, topical (including ocular, buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural) dosage.

33. The pharmaceutical composition of claim 28, wherein said compound of Formula (I) is a dose of less than 1,000 mg/kg of body weight per day.

34. A method comprising administering to a subject the compound of Formula (I) in claim 1, or a pharmaceutically acceptable salt thereof.

35. The method of claim 34, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof is an amount sufficient to reduce a viral load in a subject.

36. The method of claim 34, wherein said compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered as a dose of less than 1,000 mg/kg of body weight of the subject per day.

37. A method of treating a viral condition comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

38. The method of treating a viral condition of claim 37, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof or the pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered to a subject prophylactically, or prior to the onset of or diagnosis of a viral infection.

39. The method of claim 37, wherein the viral condition is associated with a virus selected from the group consisting of:

Adenoviridae including adenovirus, Hepadnaviridae including hepatitis B virus (HBV), Herpesviridae including herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), thymidine kinase-deficient (TK⁻

) HSV-1, varicella-zoster virus (TK⁺ and TK⁻

VZV), cytomegalovirus (CMV), human herpesvirus type 6 (HHV-6), and feline herpesvirus, Poxviridae including vaccinia virus, Papillomaviridae including human papilloma virus, and Polyomaviridae including polyoma virus.

40. The method of claim 37, wherein the viral condition is associated with a virus selected from the group consisting of:

Retroviridae including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), simian immunodeficiency virus (SIV), and moloney murine sarcoma virus, Coronaviridae including feline (FIPV) corona virus, human (SARS) CoV, and mouse hepatitis virus, Flaviviridae including flavivirus (yellow fever virus (YFV), dengue-type 2 virus, and modoc virus (murine flavivirus)), hepacivirus (hepatitis A, B, or C), and pestivirus (bovine viral diarrhea virus (BVDV)), Picornaviridae including coxsackie B virus, polio virus, and rhinovirus, Alphaviridae including sindbis virus, Arenaviridae including arenaviruses (Tacaribe), Bunyaviridae including punta toro, Orthomyxoviridae including influenza A, B, and C virus, Paramyxoviridae including respiratory syncytial virus (RSV) and parainfluenza-3 virus, and Reoviridae including reo-1 virus.

41. The method of claim 37, wherein the viral condition is associated with a virus selected from the group consisting of:

Poxviridae including vaccinia virus.

42. The method of claim 37, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered as a pharmaceutical composition and the pharmaceutical compositions is administered orally, rectally, nasally, topically (including ocular, buccal and sublingual), vaginally or parenterally (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural).

43. The method of claim 42, wherein the pharmaceutical composition is administered orally.

44. The method of claim 37, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered as a dose of less than 1,000 mg/kg of body weight of the subject per day.

45. The method of claim 37, wherein the compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered in conjunction with one or more other therapeutic agents used to treat conditions associated with a viral infection in a subject.

46. The method of claim 45, wherein the additional therapeutic agent is selected from the group consisting of:

AZT, abacavir, ddC, ddI, d4T, 3TC, ZDV, tenofovir, nevirapine, pentafuside, amprenavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquanivir, lamivudine, foscarnet, acyclovir, cidofovir, ganciclovir, valaciclovir, amantadine, rimantadine, zanamivir, and oseltamivir.

47. A method for inhibiting propagation of a virus comprising administering to a subject in need thereof a compound of Formula (I) in claim 1 or a pharmaceutically acceptable salt thereof.

48. The method of claim 47, wherein the virus is selected from the group consisting of Poxviridae including vaccinia virus.