Chalcone derivatives and their use to treat diseases

A compound of Formula I

• or its pharmaceutically acceptable salt or ester, wherein:
• the wavy line indicates that the compound can be in the form of the E- or Z- isomer;
• R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β are independently selected from the group consisting of hydrogen, halogen, nitro, alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, cycloalkylalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, heteroaryl lower alkyl, heterocyclic, heterocyclic lower alkyl, alkylthioalkyl, cycloalkylthioalkyl, arylthio lower alkyl, aralkyl lower thioalkyl, heteroarylthio lower alkyl, heteroaralkyl lower thioalkyl, heterocyclicthio lower alkyl, heterocyclicalkyl lower thioalkyl, lower alkyl S(O)-lower alkyl, lower alkyl-S(O)2-lower alkyl, arylsulfinyl lower alkyl, arylsulfonyl lower alkyl, —C(O)R2, R2C(O)alkyl, aminoalkyl, cycloalkylaminoalkyl, arylamino lower alkyl, heteroarylamino lower alkyl, heterocyclicamino lower alkyl, hydroxyl, hydroxyalkyl, alditol, carbohydrate, polyol alkyl, alkoxy, lower alkoxy, —(O(CH2)2)1-3—O-lower alkyl, polyoxyalkylene, cycloalkyloxy, cycloalkylalkoxy, haloalkoxy, aryloxy, arylalkoxy, heteroaryloxy, heteroarylalkoxy, heteroaryl lower alkoxy, heterocyclicoxy, heterocyclicalkoxy, heterocyclic lower alkoxy, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, alkylamino, acylamino, dialkylamino, cycloalkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclicamino, heterocyclicalkylamino, —NHR2, N(R2)2, —NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, —NHC(O)N(R2)2, thiol, alkylthio, cycloalkylthio, cycloalkylalkylthio, haloalkylthio, arylthio, aralkylthio, heteroarylthio, heteroaralkylthio, heterocyclicthio, heterocyclicalkylthio, alkylsulfonyl, arylsulfonyl, haloalkylsulfonyl, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, sulfonic acid, sulfonate, sulfate, sulfinic acid, sulfenic acid, cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)R2, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2R2, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(CH3)2C(O)OH, —(CH2)yC(O)OH, wherein y is 1, 2, 3, 4, 5, or 6, —PO2H2, —PO3H2, —P(R2)O2H, and phosphate, all of which can be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;
• R1 is independently selected from the group consisting of hydrogen, lower alkyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be optionally substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;
• R2 is independently selected from the group consisting of alkyl, lower alkyl, alkenyl, alkynyl, carbocycle, cycloalkyl, aryl, heteroaryl, heterocyclic, arylalkyl, heteroarylalkyl, and heterocyclicalkyl, wherein all may be substituted by one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;
• R7 and R8 are independently selected from the group consisting of alkyl, alkenyl and aryl and linked together forming a 4- to 12-membered monocyclic, bicylic, tricyclic or benzofused ring;
• wherein one of R2β, R3β, R4β, R5β or R6β, or one of R2α, R3α, R4α, R5α or R6α must be a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl;
• wherein when one of R2β, R3β, R4β, R5β or R6β is a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl, only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;
• and
• wherein when one of R2β, R3β, R4β, R5β or R6β is a carbon-carbon linked optionally substituted saturated or unsaturated thienyl or benzothienyl, only one of R2β, R3β, R4β, R5β or R6β can be —OCH3;
• with the proviso that R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together, or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a heterocyclic or heteroaryl optionally substituted by one or more alkoxycarbonylalkyl, carboxyalkyl, hydroxyalkyl or aminoalkyl and optionally substituted with one or more selected from the group consisting of hydroxy, alkyl, carboxy, hydroxyalkyl, carboxyalkyl, amino, cyano, alkoxy, alkoxycarbonyl, acyl, oxo, —NR7R8, and halo;
• or
• R2α and R3α taken together or R3α and R4α taken together or R4α and R5α taken together or R2β and R3β taken together or R3β and R4β taken together or R4β and R5β taken together form a 5- or 6-membered ring containing one sulfur, which may optionally be substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2;
• provided that R2α, R3α, R4α, R5α, R6α, R2β, R3β, R4β, R5β and R6β cannot be —OC(R1)2C(O)OH;
• or
• at least one of R2α, R3α, R4α, R5α, R6α or one of R2β, R3β, R4β, R5β, R6β must be selected from the group consisting of cyano, tetrazol-5-yl, carboxy, —C(O)OR2, —C(O)NH2, —C(O)NHR2, —C(O)N(R2)2, —C(O)NR7R8, —C(O)NHC(O)NHR2, —C(O)NHC(O)N(R2)2, —C(O)NHC(O)NR7R8, —C(O)NHSO2NHR2, —C(O)NHSO2N(R2), —C(O)NHSO2NR7R8, —C(O)NHC(O)R2, —C(O)NHSO2R2, —C(CH3)2C(O)OH, (CH2)yC(O)OH, wherein is 1, 2, 3, 4, 5, or 6, thiol, —SC(R1)2C(O)OH, —SC(R1)2C(O)OR2, —SCH2C(O)OH, —SCF2C(O)OH, —SO2NH2, —SO2NHR2, —SO2N(R2)2, SO2NR7R8, —SO2NHC(O)R2, —SR2, —SO2NHC(O)NHR2, —SO2NHC(O)N(R2)2, —SO2NHC(O)NR7R8, —OC(R1)2C(O)OH, —OC(R1)2C(O)OR2, —OC(R1)2C(O)NH2, —OC(R1)2C(O)NHR2, —OC(R1)2C(O)N(R2)2, —OC(R1)2C(O)NR7R8, amino, —NHR2, N(R2)2, NR7R8, —NHC(R1)2C(O)OH, —NHC(R1)2C(O)OR2, —NHC(O)R2, —N(R2)C(O)R2, —NHC(O)OR2, —NHC(O)SR2, —NHSO2NHR2, —NHSO2R2, —NHSO2NR7R8, —N(C(O)NHR2)2, —NR2SO2R2, —NHC(O)NHR2, —NHC(O)NR7R8, and —NHC(O)N(R2)2;
• wherein all R1, R2, R7, and R8 substituents can be optionally substituted with one or more selected from the group consisting of halo, alkyl, lower alkyl, alkenyl, cycloalkyl, acyl, hydroxy, hydroxyalkyl, heterocyclic, amino, aminoalkyl, —NR7R8, alkoxy, oxo, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, —C(O)NR7R8, and —C(O)N(R2)2.