	US 7,521,062 B2
	Thiosemicarbazones as anti-virals and immunopotentiators
Paul A. Barsanti, Pleasant Hill, Calif. (US); Nathan Brammeier, Walnut Creek, Calif. (US); Anthony Diebes, Minnetonka, Minn. (US); Liana Marie Lagniton, Berkeley, Calif. (US); Simon Ng, Walnut Creek, Calif. (US); Zhi-Jie Ni, Fremont, Calif. (US); Keith B. Pfister, San Ramon, Calif. (US); Casey Philbin, Columbus, Ohio (US); Nicholas Valiante, Walnut Creek, Calif. (US); Allan S. Wagman, Belmont, Calif. (US); Weibo Wang, Moraga, Calif. (US); and Amy J. Weiner, Fairfield, Calif. (US)
Assigned to Novartis Vaccines & Diagnostics, Inc., Emeryville, Calif. (US)
Filed on Dec. 29, 2003, as Appl. No. 10/748,071.
Claims priority of provisional application 60/436472, filed on Dec. 27, 2002.
Claims priority of provisional application 60/436638, filed on Dec. 30, 2002.
Claims priority of provisional application 60/438987, filed on Jan. 10, 2003.
Prior Publication US 2005/0069555 A1, Mar. 31, 2005
Int. Cl. A61K 39/00 (2006.01); A61K 31/40 (2006.01); A61K 31/44 (2006.01); A61K 31/175 (2006.01); A61K 39/095 (2006.01); A61K 45/00 (2006.01)

U.S. Cl. 424—278.1 [514/357; 514/408; 514/582; 552/517; 424/184.1]

40 Claims

1. A composition comprising:

a vaccine in an amount effective to stimulate a cell—mediated immune response; and

a vaccine adjuvant comprising a thiosemicarbazone or derivative thereof,

wherein the thiosemicarbazone is a compound of formula I:

wherein:

E is absent or selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, and substituted heteroaryl;

L is absent or is selected from the group consisting of oxo, amino, alkylene, substituted alkylene, alkoxy, alkylamino, aminoalkyl, heterocyclyl, carbocyclyl, and carbonyl;

W is absent or selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, and substituted heteroaryl;

X is a absent or is selected from the group consisting of oxo, amino, alkylene, substituted alkylene, alkoxy, alkylamino, aminoalkyl, heterocyclyl, carbocyclyl, and carbonyl;

Y is selected from the group consisting of cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, heteroaryl, and substituted heteroaryl;

Y′ is absent or is selected from the group consisting of F, Cl, Br, I, nitro, alkyl, substituted alkyl, heterocyclyl, substituted heterocyclyl, amino, alkylamino, and dialkylamino;

Y″ is absent or is selected from the group consisting of F, Cl, Br, I, nitro, alkyl, substituted alkyl, heterocyclyl, substituted heterocyclyl, amino, alkylamino, and dialkylamino;

R′ is H, alkyl, or substituted alkyl;

R″ is H, or

R′ and R″ are taken together to form a heterocyclic ring;

Z and Z′ are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, alkoxy, substituted alkoxy, aminocarbonyl, alkoxycarbonyl, carboxyl sulfonyl, methanesulfonyl, and substituted or unsubstituted alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, heteroarylcarbonyloxy, heteroaralkylcarbonyloxy, alkylaminocarbonyloxy, arylaminocarbonyloxy, formyl, loweralkylcarbonyl, loweralkoxycarbonyl, aminocarbonyl, aminoaryl, alkylsulfonyl, sulfonamido, aminoalkoxy, alkylamino, heteroarylamino, alkylcarbonylamino, alkylaminocarbonylamino, arylaminocarbonylamino, aralkylcarbonylamino, heteroarylcarbonylamino, arylcarbonylamino, cycloamidino, cycloalkyl, cycloimido, arylsulfonyl and arylsulfonamido; or

Z and Z′ are taken together to form a heterocyclic group, which may be optionally substituted;

the tautomers and the pharmaceutically acceptable salts, esters, or prodrugs thereof.