×

IMMUNOPOTENTIATING COMPOUNDS

  • US 20090232844A1
  • Filed: 03/23/2007
  • Published: 09/17/2009
  • Est. Priority Date: 03/23/2006
  • Status: Active Grant
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.

View all claims
  • 2 Assignments
Timeline View
Assignment View
    ×
    ×