Immunopotentiating compounds

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, wherein:

R 1 and R 2 are each, independently selected from —(CH 2 ) m CH═CH(CH 2 ) n R 6 and C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, CN, NO 2 , C 1-6 alkoxy and C 1-6 haloalkoxy;

R 3 is H, C 1-6 alkyl, C 6-10 aryl, heterocyclyl, C 3-14 cycloalkyl, —(CH 2 ) m CH═CH(CH 2 ) n R 6 , —(CH 2 ) m C≡C(CH 2 ) n R 6 , —C(═O)NR 7 R 8 , —C(═O)R 9 , —C(═O)OR 9 , or —S(═O) q R 10 , wherein each of the C 1-6 alkyl, C 6-10 aryl, heterocyclyl, C 3-14 cycloalkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a , SR a , C(═O)R b , C(═O)NR c R d , C(═O)OR a , C(═S)NR c R d , OC(═O)R b , OC(═O)NR c R d , NR c R d , NR c C(═O)R b , NR c C(═O)OR a , NR c S(═O) 2 R b , S(═O)R b , S(═O)NR c R d , S(═O) 2 OH, S(═O) 2 R b , and S(═O) 2 NR c R d ;

R 4 and R 5 are each, independently, selected from H, C 1-6 alkyl, C 1-6 alkoxy, halogen, trihalomethyl, —NR 7 R 8 , —OR 9 , —C(═O)R 9 , —C(═O)OR 9 , —C(═O)NR 7 R 8 , NR c C(═O)R b , NR c C(═O)OR a , NR c S(═O) 2 R b , S(═O)R b , S(═O)NR c R d , S(═O) 2 OH, S(═O) 2 R b , and S(═O) 2 NR c R d wherein the C 1-6 alkyl or C 1-6 alkoxy is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a , SR a , C(═O)R b , C(═O)NR c R d , C(═O)OR a , C(═S)NR c R d , OC(═O)R b , OC(═O)NR c R d , NR c R d , NR c C(═O)R b , NR c C(═O)OR a , NR c S(═O) 2 R b , S(═O)R b , S(═O)NR c R d , S(═O) 2 OH, S(═O) 2 R b , and S(═O) 2 NR c R d ;

each R 6 is independently H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 6-10 aryl, C(═O)OH, or C(═O)O—(C 1-6 alkyl), wherein each of the C 1-6 alkyl, C 2-6 alkenyl and C 6-10 aryl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a′ , SR a′ , C(═O)R b′ , C(═O)NR c′ R d′ , C(═O)OR a′ , C(═S)NR c′ R d′ , OC(═O)R b′ , OC(═O)NR c′ R d′ , NR c′ R d′ , NR c C(═O)R b′ , NR c′ C(═O)OR a′ , NR c′ S(═O) 2 R b′ , S(═O)R b′ , S(═O)NR c′ R d′ , S(═O) 2 OH, S(═O) 2 R b′ , and S(═O) 2 NR c′ R d′ ;

R 7 and R 8 are each, independently, selected from H, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 6-10 aryl, C 6-10 aryl-C 1-6 alkyl, C 6-10 aryloxy-C 1-6 alkyl, —(CH 2 ) m CH═CH(CH 2 ) n R 11 , and —(CH 2 ) m C≡C(CH 2 ) n R 11 , wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, C 6-10 aryl, C 6-10 aryl-C 1-6 alkyl and C 6-10 aryloxy-C 1-6 alkyl is optionally substituted by up to 10 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a′ , SR a′ , C(═O)R b′ , C(═O)NR c′ R d′ , C(═O)OR a′ , C(═S)NR c′ R d′ , OC(═O)R b′ , OC(═O)NR c′ R d′ , NR c′ R d′ , NR c′ C(═O)R b′ , NR c′ C(═O)OR a′ , NR c′ S(═O) 2 R b′ , S(═O)R b′ , S(═O)NR c′ R d′ , S(═O) 2 OH, S(═O) 2 R b′ , and S(═O) 2 NR c′ R d′ ;

or R 7 and R 8 together with the N atom to which they are attached form a heterocyclyl group optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a′ , SR a′ , C(═O)R b′ , C(═O)NR c′ R d′ , C(═O)OR a′ , C(═S)NR c′ R d′ , OC(═O)R b′ , OC(═O)NR c′ R d′ , NR c′ R d′ , NR c′ C(═O)R b′ , NR c′ C(═O) OR a′ , NR c′ S(═O) 2 R b′ , S(═O)R b′ , S(═O)NR c′ R d′ , S(═O) 2 OH, S(═O) 2 R b′ , and S(═O) 2 NR c′ R d′ ;

each R 9 is independently H, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, or C 1-6 alkyl optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a′ , SR a′ , C(═O)R b′ , C(═O)NR c′ R d′ , C(═O)OR a′ , C(═S)NR c′ R d′ , OC(═O)R b′ , OC(═O)NR c′ R d′ , NR c′ R d′ , NR c′ C(═O)R d′ , NR c′ C(═O)OR a′ , NR c′ S(═O) 2 R b′ , S(═O)R b′ , S(═O)NR c′ R d′ , S(═O) 2 OH, S(═O) 2 R b′ , and S(═O) 2 NR c′ R d′ ;

each R 10 is independently C 1-6 alkyl, C 2-6 alkenyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, trihalomethyl, or —NR 7 R 8 , wherein each of the C 1-6 alkyl, C 2-6 alkenyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, and C 6-10 aryl-C 1-6 alkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a′ , SR a′ , C(═O)R b′ , C(═O)NR c′ R d′ , C(═O)OR a′ , C(═S)NR c′ R d′ , OC(═O)R b′ , OC(═O)NR c′ R d′ , NR c′ R d′ , NR c′ C(═O)R b′ , NR c′ C(═O)OR a′ , NR c′ S(═O) 2 R b′ , S(═O)R b′ , S(═O)NR c′ R d′ , S(═O) 2 OH, S(═O) 2 R b′ , and S(═O) 2 NR c′ R d′ ;

each R 11 is independently H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 6-10 aryl, C(═O)OH, or C(═O)O—(C 1-6 alkyl), wherein each of the C 1-6 alkyl, C 2-6 alkenyl and C 6-10 aryl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a″ , SR a″ , C(═O)R b″ , C(═O)NR c″ R d″ , C(═O)OR a″ , C(═S)NR c″ R d″ , OC(═O)R b″ , OC(═O)NR c″ R d″ , NR c″ R d″ , NR c″ C(═O)R b″ , NR c″ C(═O)OR a″ , NR c″ S(═O) 2 R b″ , S(═O)R b″ , S(═O)NR c″ R d″ , S(═O) 2 OH, S(═O) 2 R b″ , and S(═O) 2 NR c″ R d″ ;

R a , R a′ and R a″ are each, independently, selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO 2 , oxo, C 1-6 alkoxy, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;

R b , R b′ and R b″ are each, independently, selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO 2 , oxo, C 1-6 alkoxy, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;

R c and R d are each, independently, selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO 2 , oxo, C 1-6 alkoxy, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;

or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

R c′ and R d′ are each, independently, selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO 2 , oxo, C 1-6 alkoxy, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;

or R c′ and R d′ together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

R c″ and R d″ are each, independently, selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryl-C 1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO 2 , oxo, C 1-6 alkoxy, amino, halo, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;

or R c″ and R d″ together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

m and n are each, independently, selected from 0, 1, 2 and 3; and

each q is independently 0, 1 or 2.

2. The compound of claim 1 , wherein R 1 and R 2 are each, independently, C 1-4 alkyl, wherein the C 1-4 alkyl is optionally substituted by 1, 2, or 3 substituents independently selected from OH and C 1-4 alkoxy.

3. The compound of claim 1 , wherein R 1 is methyl and R 2 is n-propyl.

4. The compound of claim 1 , wherein R 3 is C 1-6 alkyl optionally substituted by 1, 2 or 3 substituents independently selected from halo, CN, NO 2 , C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, OR a , SR a , C(═O)R b , C(═O)NR c R d , C(═O)OR a , C(═S)NR c R d , OC(═O)R b , OC(═O)NR c R d , NR c R d , NR c C(═O)R b , NR c C(═O)OR a , NR c S(═O) 2 R b , S(═O)R b , S(═O)NR c R d , S(═O) 2 OH, S(═O) 2 R b , and S(═O) 2 NR c R d .

5. The compound of claim 1 , wherein R 3 is C 1-6 alkyl optionally substituted by 1 or 2 OH.

6. The compound of claim 1 wherein:

R 4 and R 5 are each, independently, selected from H, C 1-6 alkyl, C 6-10 aryl, —NR 7 R 8 , and —OR 9 , wherein each of the C 1-6 alkyl and C 6-10 aryl is optionally substituted by 1, 2 or 3 substituents independently selected from halo, OH, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-14 cycloalkyl, heterocyclyl, C 6-10 aryloxy, C 1-6 alkoxy and C 1-6 haloalkoxy;

R 7 and R 8 are each, independently, selected from H, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, C 6-10 aryl, C 6-10 aryl-C 1-6 alkyl, C 6-10 aryloxy-C 1-6 alkyl;

or R 7 and R 8 together with the N atom to which they are attached form a heterocyclyl group optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, OH, CN, NO 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryloxy, C 1-6 alkoxy and C 1-6 haloalkoxy; and

R 9 is C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 6-10 aryl, C 6-10 aryl-C 1-6 alkyl, or C 6-10 aryloxy-C 1-6 alkyl.

7. The compound of claim 1 wherein:

R 4 and R 5 are each, independently, selected from H, C 6-10 aryl, azepanyl, morpholino, piperazinyl, piperidinyl, pyrrolidinyl, azetidinyl, aziridinyl, —NHR 8 , and —OR 9 ; and

R 8 and R 9 are each, independently, selected from C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, C 6-10 aryl, C 6-10 aryl-C 1-6 alkyl and C 6-10 aryloxy-C 1-6 alkyl.

8. The compound of claim 1 wherein:

R 1 is methyl;

R 2 is n-propyl;

R 3 is C 3-6 alkyl optionally substituted by OH;

one of R 4 and R 5 is H and the other is selected from C 6-10 aryl, azepanyl, piperidinyl, pyrrolidinyl, azetidinyl, aziridinyl, —NHR 8 , and —OR 9 ; and

R 8 and R 9 are each, independently, C 1-6 alkoxy-C 1-6 alkyl.

9. A compound of claim 1 wherein the compound is selected from the group consisting of:

and the pharmaceutically acceptable salts thereof, tautomers thereof, and pharmaceutically acceptable salts of the tautomers.

10. A pharmaceutical composition, comprising: the compound of claim 1 and a pharmaceutically acceptable excipient.