Thiazole benzamide derivatives and pharmaceutical compositions for inhibiting cell proliferation

A compound represented by Formula (I):

• wherein:
• R1 and R2 are each independently hydrogen, or —CH2—R10, a C2-C11 alkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, amino alkyl, aryl, or cycloalkyl group unsubstituted or substituted with one or more R10 substituents selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—RaO—, —ORb, —CO—Rc, O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—ORc, ═O, ═S, SO2—Rc, —SO—Rc, —NRdRc, —CO—NRdRe, —O—CO—NRdRe, —NRc—CO—NRdRe, —NRc—CO—Re, NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRc, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are defined above, where R1 and R2 are not both hydrogen;
• or
• R1 or R2, together with the
• and two adjacent carbon atoms of the phenyl ring of Formula (I), forms a 5- or 6-membered ring structure fused to the phenyl ring of Formula (I) and unsubstituted or substituted with one or more substituents independently selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRe, —O—CO—NRdRe, —NRc—CO—NRdRe, —NRc—CO—Rc, —NRc—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRc, —SO—NRdRc, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRc, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are as defined above;
• or
• R1 and R2, taken together with the nitrogen atom to which they are bonded, form a monocyclic or fused or non-fused polycyclic structure which may contain one to three additional heteroatoms, the structure being unsubstituted or substituted with one or more substituents selected from the group consisting alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRc, —O—CO—NRdRc, —NRc—CO—NRdRc, —NRc—CO—Rc, —NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—O—Rc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRcCS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRe, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRc, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRcCO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, and unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are defined above;
• R3 is an aryl, alkyl, or cycloalkyl group, unsubstituted or substituted with one or more substituents independently selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRc, —O—CO—NRdRe, —NRc—CO—NRdRe, —NRc—CO—Rc, —NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—Rc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRc, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, and unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are defined above;
• and
• Y is hydrogen, alkyl, heteroalkyl, haloalkyl, halocycloalkyl, cycloalkyl, NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, ═O, ═S, —NRdRe, —CO—NRdRe, —O—CO—NRdRc, —NRc—CO—Re, —NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc-CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—SO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRe, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, and cycloalkyl, Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl alkenyl, alkynyl, —CORf, —COORf, —O—CO—Rf, —O—CO—Rf, —OH, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl;
• or a pharmaceutically acceptable salt of said compound, or a pharmaceutically acceptable prodrug of said compound.