Nampt modulators

A compound of Formula (II):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• n is 0 to 6;
• Y1 is
• and R1 is selected from the group consisting of
• or
• Y1 is
• and R1 is selected from the group consisting of
• or
• Y1 is —C(O)—N(Rq)—(Rs), wherein Rq is H or C1-C6 alkyl, and Rs is C3-C8 cycloalkyl, optionally substituted C6-C14 aryl, optionally substituted 5- to 18-membered heteroaryl, or —(C1-C6 alkylene)-(optionally substituted C6-C14 aryl), and R1 is selected from the group consisting of
• or
• Y1 is —C(O)—Rb, wherein Rb is optionally substituted 3- to 18-membered heterocycloalkyl, and
• R1 is
• or
• Y1 is —N(Rt)—C(O)Ru, wherein Rt is H or C1-C6 alkyl, and Ru is optionally substituted C6-C14 aryl, optionally substituted 5- to 18-membered heteroaryl, or —(C1-C6 alkylene)-(5- to 18-membered heteroaryl), and R1 is
• or
• Y1 is
• and R1 is
• wherein
• R2a and R2b are each independently halo, —O(C1-C6 alkyl), C1-C6 alkyl substituted with —OH, —C(O)NR2cR2d, or —N(R2e)C(O)(C1-C6 alkyl);
• and
• R2c, R2d, and R2e are each independently hydrogen or C1-C6 alkyl;
• G1 is CH or N;
• p1 and p2 are each independently 0, 1, or 2;
• q1 and q2 are each independently 1 or 2;
• r is 1, 2, or 3;
• wherein, when Y1 is
• then n is 4, 5, or 6;
• when Y1 is
• and r is 1, then n is 2, 3, 4, 5, or 6;
• and
• when Y1 is —C(O)—N(Rq)—(Rs), —C(O)—Rb, —N(Rt)—C(O)Ru, or
• then n is 4 or 5;
• and
• R3 is selected from the group consisting of:
• i. unsubstituted C1-C6 alkyl;
• ii. C6-C14 aryl;
• iii. optionally substituted 5- to 18-membered heteroaryl;
• iv. —NR3aR3b, wherein
• R3a and R3b are each independently selected from the group consisting of hydrogen, C6-C14 aryl, 5- to 18-membered heteroaryl, —(C1-C6 alkylene)-(C6-C14 aryl), and —(C1-C6 alkylene)-(5- to 18-membered heteroaryl);
• v. —OR3c, wherein
• R3, is C6-C14 aryl, 5- to 18-membered heteroaryl, or —(C1-C6 alkylene)-(5- to 18-membered heteroaryl);
• vi. —C(O)R3d, wherein
• R3d is selected from the group consisting of —NR 3R3g;
• C3-C8 cycloalkyl;
• C3-C8 cycloalkyl substituted with optionally substituted C6-C14 aryl;
• C3-C8 cycloalkenyl;
• optionally substituted C6-C14 aryl;
• optionally substituted —(C1-C6 alkylene)-(C6-C14 aryl);
• optionally substituted 3- to 18-membered heterocycloalkyl;
• and optionally substituted 5- to 18-membered heteroaryl,
• wherein
• R3f and R3g are each independently selected from the group consisting of:
• (a) hydrogen,
• (b) optionally substituted C1-C6 alkyl,
• (c) C6-C14 aryl,
• (d) optionally substituted 3- to 18-membered heterocycloalkyl,
• (e) optionally substituted 5- to 18-membered heteroaryl,
• (f) optionally substituted C3-C10 cycloalkyl;
• and
• (g) optionally substituted C3-C10 cycloalkenyl;
• vii. C1-C6 alkyl substituted with one or more —OH, —C(O)NR3hR3i, optionally substituted C6-C14 aryl, optionally substituted 3- to 18-membered heterocycloalkyl, optionally substituted 5- to 18-membered heteroaryl, —N(R3p)—C(O)R3, —S(O)2—Rr, or —C(O)—Rs,
• wherein
• R3h and R3i are each independently selected from C1-C6 alkyl and —(C1-C6 alkylene)-(C6-C14 aryl),
• R3p is H or C1-C6 alkyl,
• R3q is C3-C8 cycloalkyl, optionally substituted 3- to 18-membered heterocycloalkyl, or optionally substituted 5- to 18-membered heteroaryl,
• R3r is C6-C14 aryl or 5- to 18-membered heteroaryl, and
• R3s is optionally substituted 3- to 18-membered heterocycloalkyl;
• viii. —C(O)OR3j, wherein
• R3j is hydrogen or C1-C6 alkyl;
• ix. —NHC(O)R3k, wherein
• R3k is optionally substituted C6-C14 aryl, optionally substituted —(C1-C6 alkylene)-(C6-C14 aryl), or optionally substituted 5- to 18-membered heteroaryl;
• x. —NHC(O)OR31, wherein
• R3l is hydrogen or C1-C6 alkyl;
• xi. —NHSO2R3m, wherein
• R3m is optionally substituted 5- to 18-membered heteroaryl, optionally substituted C6-C14 aryl, or —(C1-C6 alkylene)-(C6-C14 aryl), each of which is optionally substituted;
• and
• xii. —SO2R3n;
• wherein
• R3n is C1-C6 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C6-C14 aryl, or optionally substituted —(C1-C6 alkylene)-(C6-C14 aryl);
• R4 is phenyl or —C(O)NH—CH2-phenyl;
• R5′ and R5b are independently selected from the group consisting of hydrogen, methyl, and —NHC(O)O(C1-C6 alkyl);
• and
• R6 is selected from the group consisting of —C(O)OC(CH3)3, —NHC(O)O(C1-C6 alkyl), —C(O)-(optionally substituted phenyl), —C(O)—(C1-C6 alkylene)-(optionally substituted phenyl), —C(O)-(optionally substituted 3- to 18-membered heterocycloalkyl), —C(O)-(optionally substituted 5- to 18-membered heteroaryl), —C(O)—(C1-C6 alkylene)-(optionally substituted 5- to 18-membered heteroaryl), and 5- to 18-membered heteroaryl,
• provided that, when R6 is —C(O)-(substituted phenyl), —C(O)—(C1-C6 alkylene)-(optionally substituted phenyl), —C(O)-(optionally substituted 3- to 18-membered heterocycloalkyl), —C(O)-(optionally substituted 5- to 18-membered heteroaryl), —C(O)—(C1-C6alkylene)-(optionally substituted 5- to 18-membered heteroaryl), or 5- to 18-membered heteroaryl, then (1) n is 4 or 5, and (2) R1 is selected from the group consisting of
• wherein
• (1) when Y1 is
• and n is 0 or 1, then R1 is selected from the group consisting of
• and
• (2) when Y1 is
• and n is 0, then R1 is selected from the group consisting of