IMMUNOPOTENTIATING COMPOUNDS
First Claim
Patent Images
1. A compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, wherein;
R1 and R2 are each, independently, selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl, —
C(═
O)NR7R8, —
C(═
O)R9, —
C(═
O)OR9, —
S(═
O)qR10, C6-10 aryl-C1-6 alkyl, C6-10 aryloxy-C1-6 alkyl, —
(CH2)mCH═
CH(CH2)nR6, and —
(CH2)mC≡
C(CH2)nR6, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl, C6-10 aryl-C1-6 alkyl and C6-10 aryloxy-C1-6 alkyl is optionally substituted by up to 10 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRa, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd;
or R1 and R2 together with the N atom to which they are attached form a heterocycloalkyl group optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd;
R3 is H, C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl, —
(CH2)mCH═
CH(CH2)nR6, —
(CH2)mC≡
C(CH2)nR6, —
C(═
O)NR7R8, —
C(═
O)R9, —
C(═
O)OR9, or —
S(═
O)qR10, wherein each of the C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rd, and S(═
O)2NRcRd;
R4 and R5 are each, independently, selected from H, C1-6 alkyl, C1-6 alkoxy, halogen, trihalomethyl, —
NR7R8, —
OR9, —
C(═
O)R9, —
C(═
O)OR9, —
C(═
O)NR7R8, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd wherein the C1-6 alkyl or C1-6 alkoxy is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rd, and S(═
O)2NRcRd;
or R4 and R5 together with the two carbon atoms to which they are attached form a 5-7 membered cycloalkyl, a 5-7 membered heterocycloalkyl, or a 5-7 membered heteroaryl group, each optionally substituted by 1, 2, 3, 4 or 5 R12;
each R6 is independently H, halo, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C(═
O)OH, or C(═
O)O—
(C1-6 alkyl), wherein each of the C1-6 alkyl, C2-6 alkenyl and C6-10 aryl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;
R7 and R8 are each, independently, selected from H, C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, C6-10 aryl-C1-6 alkyl, C6-10 aryloxy-C1-6 alkyl, —
(CH2)mCH═
CH(CH2)nR11, and —
(CH2)mC≡
C(CH2)nR11, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, C6-10 aryl-C1-6 alkyl and C6-10 aryloxy-C1-6 alkyl is optionally substituted by up to 10 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;
or R7 and R8 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, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRcC(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;
each R9 is independently H, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, or C1-6 alkyl optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rd′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;
each R10 is independently C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, trihalomethyl, or —
NR7R8, wherein each of the C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, and C6-10 aryl-C1-6 alkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
S(═
O)2OH, S(O)2Rb′
, and S(═
O)2NRc′
Rd′
;
each R11 is independently H, halo, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C(═
O)OH, or C(═
O)O—
(C1-6 alkyl), wherein each of the C1-6 alkyl, C2-6 alkenyl and C6-10 aryl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa″
, SRa″
, C(═
O)Rb″
, C(═
O)NRc″
Rd″
, C(═
O)ORa″
, C(═
S)NRc″
Rd″
, OC(═
O)Rb″
, OC(═
O)NRc″
Rd″
, NRc″
Rd″
, NRc″
C(O)Rb″
, NRc″
C(═
O)ORa″
, NRc″
S(═
O)2Rb″
, S(═
O)Rb″
, S(═
O)NRc″
Rd″
, S(═
O)2OH, S(═
O)2Rb″
, and S(═
O)2NRc″
Rd″
;
each R12 is independently C1-6 alkyl, C1-6 alkoxy, halogen, trihalomethyl, —
NR7R8, —
OR9, —
C(═
O)R9, —
C(═
O)OR9, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd, or —
C(═
O)NR7R8, wherein the C1-6 alkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd;
Ra, Ra′
and Ra″
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;
Rb, Rb′
and Rb′
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;
Rc and Rd are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;
or Rc and Rd together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
Rc′
and Rd′
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;
or Rc′
and Rd′
together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
Rc″
and Rd″
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;
or Rc″
and Rd″
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.
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Accused Products
Abstract
The invention provides novel compositions comprising Imidazopyridine compounds. Also provided are methods of administering the compositions in an effective amount to enhance the immune response of a subject. Further provided are novel compositions and methods of administering the compositions in combination with (an)other agent(s).
-
Citations
115 Claims
-
1. A compound of Formula (I):
-
or a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, wherein; R1 and R2 are each, independently, selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl, —
C(═
O)NR7R8, —
C(═
O)R9, —
C(═
O)OR9, —
S(═
O)qR10, C6-10 aryl-C1-6 alkyl, C6-10 aryloxy-C1-6 alkyl, —
(CH2)mCH═
CH(CH2)nR6, and —
(CH2)mC≡
C(CH2)nR6, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl, C6-10 aryl-C1-6 alkyl and C6-10 aryloxy-C1-6 alkyl is optionally substituted by up to 10 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRa, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd;or R1 and R2 together with the N atom to which they are attached form a heterocycloalkyl group optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd;R3 is H, C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl, —
(CH2)mCH═
CH(CH2)nR6, —
(CH2)mC≡
C(CH2)nR6, —
C(═
O)NR7R8, —
C(═
O)R9, —
C(═
O)OR9, or —
S(═
O)qR10, wherein each of the C1-6 alkyl, C6-10 aryl, heterocyclyl, C3-14 cycloalkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rd, and S(═
O)2NRcRd;R4 and R5 are each, independently, selected from H, C1-6 alkyl, C1-6 alkoxy, halogen, trihalomethyl, —
NR7R8, —
OR9, —
C(═
O)R9, —
C(═
O)OR9, —
C(═
O)NR7R8, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd wherein the C1-6 alkyl or C1-6 alkoxy is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rd, and S(═
O)2NRcRd;or R4 and R5 together with the two carbon atoms to which they are attached form a 5-7 membered cycloalkyl, a 5-7 membered heterocycloalkyl, or a 5-7 membered heteroaryl group, each optionally substituted by 1, 2, 3, 4 or 5 R12; each R6 is independently H, halo, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C(═
O)OH, or C(═
O)O—
(C1-6 alkyl), wherein each of the C1-6 alkyl, C2-6 alkenyl and C6-10 aryl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;R7 and R8 are each, independently, selected from H, C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, C6-10 aryl-C1-6 alkyl, C6-10 aryloxy-C1-6 alkyl, —
(CH2)mCH═
CH(CH2)nR11, and —
(CH2)mC≡
C(CH2)nR11, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, C6-10 aryl-C1-6 alkyl and C6-10 aryloxy-C1-6 alkyl is optionally substituted by up to 10 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;or R7 and R8 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, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRcC(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;each R9 is independently H, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, or C1-6 alkyl optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rd′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
, S(═
O)2OH, S(═
O)2Rb′
, and S(═
O)2NRc′
Rd′
;each R10 is independently C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, trihalomethyl, or —
NR7R8, wherein each of the C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, and C6-10 aryl-C1-6 alkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa′
, SRa′
, C(═
O)Rb′
, C(═
O)NRc′
Rd′
, C(═
O)ORa′
, C(═
S)NRc′
Rd′
, OC(═
O)Rb′
, OC(═
O)NRc′
Rd′
, NRc′
Rd′
, NRcC(═
O)Rb′
, NRc′
C(═
O)ORa′
, NRc′
S(═
O)2Rb′
, S(═
O)Rb′
, S(═
O)NRc′
Rd′
S(═
O)2OH, S(O)2Rb′
, and S(═
O)2NRc′
Rd′
;each R11 is independently H, halo, C1-6 alkyl, C2-6 alkenyl, C6-10 aryl, C(═
O)OH, or C(═
O)O—
(C1-6 alkyl), wherein each of the C1-6 alkyl, C2-6 alkenyl and C6-10 aryl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa″
, SRa″
, C(═
O)Rb″
, C(═
O)NRc″
Rd″
, C(═
O)ORa″
, C(═
S)NRc″
Rd″
, OC(═
O)Rb″
, OC(═
O)NRc″
Rd″
, NRc″
Rd″
, NRc″
C(O)Rb″
, NRc″
C(═
O)ORa″
, NRc″
S(═
O)2Rb″
, S(═
O)Rb″
, S(═
O)NRc″
Rd″
, S(═
O)2OH, S(═
O)2Rb″
, and S(═
O)2NRc″
Rd″
;each R12 is independently C1-6 alkyl, C1-6 alkoxy, halogen, trihalomethyl, —
NR7R8, —
OR9, —
C(═
O)R9, —
C(═
O)OR9, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd, or —
C(═
O)NR7R8, wherein the C1-6 alkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, oxo, imino, guanidino, amidino, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, ORa, SRa, C(═
O)Rb, C(═
O)NRcRd, C(═
O)ORa, C(═
S)NRcRd, OC(═
O)Rb, OC(═
O)NRcRd, NRcRd, NRcC(═
O)Rb, NRcC(═
O)ORa, NRcS(═
O)2Rb, S(═
O)Rb, S(═
O)NRcRd, S(═
O)2OH, S(═
O)2Rb, and S(═
O)2NRcRd;Ra, Ra′
and Ra″
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocycloalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;Rb, Rb′
and Rb′
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;Rc and Rd are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; or Rc and Rd together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; Rc′
and Rd′
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;or Rc′
and Rd′
together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;Rc″
and Rd″
are each, independently, selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl, wherein each of the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryl-C1-6 alkyl, cycloalkylalkyl and heterocyclylalkyl is optionally substituted by 1, 2 or 3 substituents independently selected from OH, CN, NO2, oxo, C1-6 alkoxy, amino, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl;or Rc″
and Rd″
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. - View Dependent Claims (2, 5, 9, 11, 14, 22, 24, 32, 36, 44, 46, 49, 53, 56, 57, 58, 59, 60, 61, 63, 65, 67, 75, 78, 79, 80, 82, 83, 84, 85, 88, 89, 91, 92, 94, 95, 97, 109, 110)
and the pharmaceutically acceptable salts thereof, tautomers thereof, and pharmaceutically acceptable salts of the tautomers.
-
-
44. The compound of claim 1 wherein R4 and R5 together with the two carbon atoms to which they are attached form a 5-7 membered cycloalkyl, a 5-7 membered heterocycloalkyl, or a 5-7 membered heteroaryl group, each optionally substituted by 1, 2,3, 4 or 5 R12.
-
46. The compound of claim 1 wherein R4 and R5 together with the two carbon atoms to which they are attached form a 5-6 membered heteroaryl group optionally substituted by 1, 2 or 3 R12.
-
49. The compound of claim 1 wherein:
-
each R12 is independently C1-6 alkyl, C6-10 aryl, heterocyclyl, —
NR7R8, —
OR9, —
C(═
O)R9, —
C(═
O)OR9, or —
C(═
O)NR7R8, wherein each of the C1-6 alkyl, C6-10 aryl and heterocyclyl is optionally substituted by 1, 2 or 3 substituents independently selected from halo, OH, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryloxy, C1-6 alkoxy and C1-6 haloalkoxy;R7 and R8 are each, independently, selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, C6-10 aryl-C1-6 alkyl, C6-10 aryloxy-C1-6 alkyl, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, C6-10 aryl-C1-6 alkyl and C6-10 aryloxy-C1-6 alkyl is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, OH, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryloxy, C1-6 alkoxy and C1-6 haloalkoxy; or R7 and R8 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, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryloxy, C1-6 alkoxy and C1-6 haloalkoxy; and each R9 is independently H or C1-6 alkyl optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from halo, OH, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C6-10 aryl, C3-14 cycloalkyl, heterocyclyl, C6-10 aryloxy, C1-6 alkoxy and C1-6 haloalkoxy.
-
-
53. The compound of claim 1 wherein:
-
each R12 is independently C6-10 aryl, azepanyl, morpholino, piperazinyl, piperidinyl, pyrrolidinyl, azetidinyl, aziridinyl, —
NHR8, or —
OR9; andR8 and R9 are each, independently, selected from C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C6-10 aryl, C6-10 aryl-C1-6 alkyl and C6-10 aryloxy-C1-6 alkyl.
-
-
56. The compound of claim 1 wherein each R12 is independently phenyl, piperidinyl, —
- NHCH2CH2—
OCH3 or —
OCH2CH2—
OCH3.
- NHCH2CH2—
-
57. A compound of claim 1 wherein the compound has Formula (II):
or a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer, wherein; one of D1, D2, D3 and D4 is N and the others are each independently CR13; and each R13 is independently selected from H and R12.
-
58. The compound of claim 57 wherein D1 is N.
-
59. The compound of claim 57 wherein D2 is N.
-
60. The compound of claim 57 wherein D3 is N.
-
61. The compound of claim 57 wherein D3 is N.
-
63. The compound of claim 57 wherein at least two R13 are H.
-
65. The compound of claim 57 wherein:
-
R1 and R2 are each, independently, selected from methyl, ethyl, n-propyl and n-butyl; R3 is C3-6 alkyl optionally substituted by OH; each R12 is independently C6-10 aryl, azepanyl, piperidinyl, piperazinyl, pyrrolidinyl, azetidinyl, aziridinyl, —
NHR8, or —
OR9; andR8 and R9 are each, independently, C1-6 alkoxy-C1-6 alkyl.
-
-
67. A compound of claim 57 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.
-
75. A method of inducing an immune response in a subject, comprising:
- administering a compound of claim 1 to the subject in an amount sufficient to induce an immune response in the subject.
-
78. The method of claim 75, wherein the subject is suffering from a microbial infection.
-
79. The method of claim 75, wherein the subject is suffering from a viral infection.
-
80. The method of claim 79, wherein the viral infection is a viral infection caused by the hepatitis C virus (HCV) or by human immunodeficiency virus (HIV).
-
82. The method of claim 75, wherein the subject is suffering from abnormal cellular proliferation or cancer.
-
83. The method of claim 75, wherein the subject is suffering from allergic diseases.
-
84. The method of claim 75, wherein the subject is suffering from asthma.
-
85. The method of claim 75, wherein the subject is suffering from precancerous lesions, wherein the precancerous lesions are actinic keratosis.
-
88. The method of claim 75 wherein the compound is administered topically.
-
89. A pharmaceutical composition, comprising:
- the compound of claim 1 and a pharmaceutically acceptable excipient.
-
91. A method of enhancing the immune response to an antigen in a subject, comprising:
- administering to the subject a composition comprising a compound of claim 1 and an antigen, wherein the immune response to the antigen in the subject is enhanced.
-
92. A composition comprising the compound of claim 1 and an additional immunogenic composition or an antigen.
-
94. The composition of claim 92, further comprising an additional adjuvant.
-
95. The composition of claim 94 wherein the adjuvant is MF59.
-
97. The composition according to claim 92, wherein the antigen is a bacterial antigen or a viral antigen.
-
109. The composition according to claim 97, wherein the antigen is a viral antigen from a virus selected from the group consisting of Hepatitis C virus, Human Immunodeficiency virus, Hepatitis B virus, Human Papilloma virus and Influenza virus.
-
110. The composition according to claim 97, wherein the antigen is an influenza antigen.
-
3-4. -4. (canceled)
-
6-8. -8. (canceled)
-
10. (canceled)
-
12-13. -13. (canceled)
-
15-21. -21. (canceled)
-
23. (canceled)
-
25-31. -31. (canceled)
-
33-35. -35. (canceled)
-
37-43. -43. (canceled)
-
45. (canceled)
-
47-48. -48. (canceled)
-
50-52. -52. (canceled)
-
54-55. -55. (canceled)
-
62. (canceled)
-
64. (canceled)
-
66. (canceled)
-
68-73. -73. (canceled)
-
76-77. -77. (canceled)
-
81. (canceled)
-
86-87. -87. (canceled)
-
90. (canceled)
-
93. (canceled)
-
96. (canceled)
-
98-108. -108. (canceled)
-
111-114. -114. (canceled)
-
115. An immunogenic composition comprising an antigen and an imidazo[1,2-a]quinoxalin-4-amine effective to stimulate a cell mediated response to said antigen.
Specification