Inhibitors of inv(16) leukemia

A compound of the formula:

• wherein,
• R, R1, R2, R3, R5, R6, R7, may be the same or different, and are independently —OH, —OC1-4 alkyl, —ORa, trifluoroC1-4 alkoxy, —SC1-4 alkyl, —S—Ra, —SO2—C1-4 alkyl, —SO2—Ra, —SOC1-4 alkyl, —SO—Ra, —SO2—NH—Rb, —NRCRd, halo, —C1-4 alkyl, —C5-12 alkyl, —C2-6 alkenyl, —C2-6 alkynyl, —C3-6 cycloalkyl, or phenyl, benzyl, or monocyclic heteroaryl optionally substituted with Rb, —C3-6 cycloalkyl optionally containing O, S, N, or Hydrogen, —OC(O)—Rb, —OC(O)—Rb, —P(O)(ORb)1-2, —P(S)(ORb)1-2, —P(O)(NRCRd)1-2, —P(S)(NRCRd)1-2, —O(CH2—CH2—O)1-4CH3, —CN, —COOH, —NO2, —C(O)—C1-4 alkyl, or —C(O)—Rb;
• Ra is —C3-6 cycloalkyl, —C2-6 alkenyl, —C2-6 alkynyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb;
• Rb is independently H, halo, —OH, —COOH, —C1-4 alkyl, C5-12 alkyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, —C2-6 alkenyl, —C2-6 alkynyl, trifluroC1-4 alkoxy, —OC1-4 alkyl, —O(CH2—CH2—O)1-4CH3, —O-phenyl, —O-benzyl, —NC1-4 alkyl, —N-phenyl, and —N-benzyl, —N-monocyclic heteroaryl ring optionally substituted with Rb;
• RC and Rd are each independently H, —C1-4 alkyl, —C1-4 alkyl, —C(O)—C1-4 alkyl, —C(O)—Re, —C1-4 alkyl-Re, —SO2—Ra, —SO2—C1-4 alkyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, and optionally RC and Rd can be taken together with the nitrogen to which they are attached to form an optionally substituted monocyclic heterocycloalkyl ring optionally containing one or more O, S, N;
• Re is —C3-7 heterocycloalkyl ring optionally containing one or more O, S, N;
• and
• R4 is —C1-4 alkyl, —C5-12 alkyl, cyclopropyl, and phenyl, benzyl or monocyclic heteroaryl optionally substituted with Rb, —C(O)—Rb,
• or a pharmaceutically-acceptable salt, enantiomer, polymorph, derivative, analog, dimer, or tautomer thereof.

A method of preventing or treating inv(16) leukemia is a subject in need thereof, said method comprising administering to said subject a pharmaceutical composition comprising a pharmaceutically acceptable-carrier and a therapeutically effective amount of a compound of the formula:

• where
• R, R1, R2, R3, R5, R6, R7, may be the same or different, and are independently —OH, —OC1-4 alkyl, —ORa, trifluoroC1-4 alkoxy, —SC1-4 alkyl, —S—Ra, —SO2—C1-4 alkyl, —SO2—Ra, —SOC1-4 alkyl, —SO—Ra, —SO2—NH—Rb, —NRCRd, halo, —C1-4 alkyl, —C5-12 alkyl, —C2-6 alkenyl, —C2-6 alkynyl, —C3-6 cycloalkyl, or phenyl, benzyl, or monocyclic heteroaryl optionally substituted with Rb, —C3-6 cycloalkyl optionally containing O, S, N, or Hydrogen, —OC(O)—Rb, —OC(O)—Rb, —P(O)(ORb)1-2, —P(S)(ORb)1-2, —P(O)(NRCRd)1-2, —P(S)(NRCRd)1-2, —O(CH2—CH2—O)1-4CH3, —CN, —COOH, —NO2, —C(O)—C1-4 alkyl, or —C(O)—Rb;
• Ra is —C3-6 cycloalkyl, —C2-6 alkenyl, —C2-6 alkynyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb;
• Rb is independently H, halo, —OH, —COOH, —C1-4 alkyl, C5-12 alkyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, —C2-6 alkenyl, —C2-6 alkynyl, trifluroC1-4 alkoxy, —OC1-4 alkyl, —O(CH2—CH2—O)1-4CH3, —O-phenyl, —O-benzyl, —NC1-4 alkyl, —N-phenyl, and —N-benzyl, —N-monocyclic heteroaryl ring optionally substituted with Rb;
• RC and Rd are each independently H, —C1-4 alkyl, —C1-4 alkyl, —C(O)—C1-4 alkyl, —C(O)—Re, —C1-4 alkyl-Re, —SO2—Ra, —SO2—C1-4 alkyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, and optionally RC and Rd can be taken together with the nitrogen to which they are attached to form an optionally substituted monocyclic heterocycloalkyl ring optionally containing one or more O, S, N;
• Re is —C3-7 heterocycloalkyl ring optionally containing one or more O, S, N;
• and
• R4 is —C1-4 alkyl, —C5-12 alkyl, cyclopropyl, and phenyl, benzyl or monocyclic heteroaryl optionally substituted with Rb, —C(O)—Rb,
• or a pharmaceutically-acceptable salt, enantiomer, polymorph, derivative, analog, dimer, or tautomer thereof.

A compound of the formula:

• wherein.
• R5 is independently m-, and p-substituted to Pyridine —N, H, —OH, —OC1-4 alkyl, —ORa trifluroC1-4 alkoxy —SC1-4 alkyl, —S—Ra, —SO2—C1-4 alkyl, —SO2—Ra, —SOC1-4 alkyl, —SO—Ra, —SO2—NH—Rb, —NRCRd, halo, —C1-4 alkyl, —C5-12 alkyl, —C2-6 alkenyl, —C2-6 alkynyl, —C3-6 cycloalkyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, —C3-6 cycloalkyl optionally containing O, S, N, or Hydrogen, —OC(O)—Rb, —OC(O)—Rb, —P(O)(ORb)1-2, —P(S)(ORb)1-2, —P(O)(NRCRd)1-2, —P(S)(NRCRd)1-2, —O(CH2—CH2—O)1-4CH3, —CN, —COOH, —NO2, —C(O)—C1-4 alkyl, or —C(O)—Rb;
• each X is independently m-, and p-substituted to Pyridine —N, or independently —O, —NH, or —S, where n is an integer of from 1-10;
• Y is Oxygen, —NH, or —NRf where Rf is methyl or ethyl;
• R, R1, R2, and R3 are independently —OH, —OC1-4 alkyl, —ORa, trifluroC1-4 alkoxy, —SC1-4 alkyl, —S—Ra, —SO2—C1-4 alkyl, —SO2—Ra, —SOC1-4 alkyl, —SO—Ra, —SO2—NH—Rb, —NRCRd, halo, —C1-4 alkyl, —C5-12 alkyl, —C2-6 alkenyl, —C2-6 alkynyl, —C3-6 cycloalkyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, —C3-6 cycloalkyl optionally containing O, S, N, or Hydrogen, —OC(O)—Rb, —OC(O)—Rb, —P(O)(ORb)1-2, —P(S)(ORb)1-2, —P(O)(NRCRd)1-2, —P(S)(NRCRd)1-2, —O(CH2—CH2—O)1-4CH3, —CN, —COOH, —NO2, —C(O)—C1-4 alkyl, or —C(O)—Rb;
• Ra is —C3-6 cycloalkyl, —C2-6 alkenyl, —C2-6 alkynyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb;
• Rb is independently H, halo, —OH, —COOH, —C1-4 alkyl, —C5-12 alkyl, —C2-6 alkenyl, —C2-6 alkynyl, trifluroC1-4 alkoxy, —OC1-4 alkyl, —O(CH2—CH2—O)1-4CH3, —O-phenyl, —O-benzyl, —NC1-4 alkyl, —N-phenyl, and —N-benzyl, —N-monocyclic heteroaryl ring optionally substituted with Rb;
• Rc and Rd are each independently H, —C1-4 alkyl, —C(O)—C1-4 alkyl, —C(O)—Re, —C1-4 alkyl-Re, —SO2—Ra, —SO2—C1-4 alkyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, and RC and Rd taken together with the nitrogen to which they are attached optionally form a substituted monocyclic heterocycloalkyl ring optionally containing one or more of O, S, or N;
• Re is —C3-7 heterocycloalkyl ring optionally containing one or more O, S, or N;
• and
• R4 is —C1-4 alkyl, —C5-12 alkyl, cyclopropyl, phenyl, benzyl, or monocyclic heteroaryl ring, wherein the phenyl, benzyl, or monocyclic heteroaryl ring is optionally substituted with Rb, or —C(O)—Rb;
• or a pharmaceutically-acceptable salt, enantiomer, polymorph, derivative, analog, dimer, or tautomer thereof.