Inhibitors of long and very long chain fatty acid metabolism as broad spectrum anti-virals
View Patent ↗The present invention provides methods and compounds for treating viral infections using modulators of host cell enzymes relating to long chain fatty acid and lipid droplet metabolism. It includes a method of treating viral infections using triacsin C and its relatives, analogs and derivatives as well as other inhibitors of long chain fatty acid metabolism and lipid droplet metabolism.
1. A method of treating or preventing viral infection in a mammal, comprising administering to the mammalian subject in need thereof a therapeutically effective amount of an agent that inhibits a long chain fatty acid synthesis enzyme, wherein the virus is human cytomegalovirus (HCMV) and the agent is a compound of Formula VIII
wherein R 1 is selected from H, unsubstituted phenyl; substituted phenyl where substitutents are selected from F, Me, Et, Cl, OMe, OCF 3 and CF 3 ; C 1-6 alkyl; and C 3-6 cycloalkyl;
wherein R 3 and R 4 are independently selected from H; C 1-3 alkyl; and phenyl; or R 3 and R 4 taken together form a cycloalkyl of formula —(CH2) n — where n=2, 3, 4 and 5;
wherein R 5 is selected from methyl; CF 3 ; cyclopropyl; unsubstituted phenyl; mono- and disubstituted phenyl where substitutents are selected from F, Me, Et, CN, iPr, Cl, OMe, OPh, OCF 3 , and CF 3 ; unsubstituted heteroaromatic group; and imidazole;
or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug thereof.
2. The method of claim 1 , wherein R 5 is
3. The method of claim 1 , wherein the compound of Formula VIII is selected from the group consisting of
4. The method of claim 1 , wherein the virus is HCMV, which further comprises administering a therapeutically effective amount of an agent that inhibits HCMV-encoded DNA polymerase, wherein the agent is selected from the group consisting of gancyclovir, valgancyclovir, cidofovir, and foscarnet.