Heterocyclic amides compounds which are HDAC6 inhibitors and used as anti-tumoral agents

摘要

The present document describes compounds of Formula I, pharmaceutical compositions comprising the same as well as methods of treating diseases such as a cancer, neurological disease, neurodegenerative disorder, stroke, traumatic brain injury, parasitic infection, inflammation or an autoimmune disease with said compounds.;

主权项

1. A compound of Formula I or a pharmaceutically acceptable salt thereof, wherein: L and L′ are selected from a nitrogen atom or carbon atom with the proviso that L and L′ are a different atom; X is O, S, CH2, C(O), or a bond with the proviso that X is different than O and S when L is a nitrogen atom; Y is a bond, an aryl, or a heteroaryl which is unsubstituted or substituted; Z is a bond or selected from the groups consisting of C1-8alkylene, NRa, C(O)C1-8alkylene, C1-8alkyleneNRa, C1-6alkylenearyleneC1-6alkylene, C2-8alkenylene, C1-6alkylenearylene, C1-6alkyleneheteroarylene, C2-6alkenylenearyleneC1-6alkylene; any one of these groups being unsubstituted or substituted with one or more Ra; M is selected from —NHOH, CH2SH, CH2SC(O)C1-8alkyl, CH2SC(O)aryl, CH2SC(O)heteroaryl, CH2SC(O)C1-8alkylenearyl, CH2SC(O)C1-8alkylenheteroaryl or wherein is selected from the following heterocyclic moieties: whereinis selected from the following heterocyclic moieties: wherein each of A′, B′, D and E is independently selected from N, and C(Ra); wherein, in B ring is a 5 to 7-membered carbocyclic ring or a 5 to 7-membered carbocyclic ring in which one or more of the carbon atoms is replaced with C(O), O, S, NRc, wherein Rc is selected from hydrogen, C1-C6alkyl, C1-C6cycloalkyl, SO2Re, C(O)Re, wherein Re is C1-C6alkyl, C1-C6cycloalkyl, aryl, heterocycle, heteroaryl, with the proviso that there are no N—O or N—S bonds in B ring; wherein is selected from the following heterocyclic moieties: wherein each of A′, B′, D and E is independently selected from N, and C(Ra) with the proviso that at least one of A′, B′, C and D is N, wherein is a 5 to 7 membered carbocyclic ring or a 5 to 7 membered carbocyclic ring in which one or more of the carbon atoms is replaced with C(O), O, S, NRc wherein Rc is selected from hydrogen, C1-C6alkyl, C1-C6cycloalkyl, aryl, heteroaryl, C1-C6alkylenearyl, C1-C6alkyleneheteroaryl, SO2Re, C(O)Re, wherein Re is C1-C6alkyl, C1-C6cycloalkyl, aryl, heterocycle, heteroaryl, C1-C6alkylenearyl, C1-C6alkyleneheteroaryl; wherein is selected from the following heterocyclic moieties: wherein is selected from the following: which are optionally substituted with one or more Ra and Rb; Ra and Rb are independently selected from hydrogen, aliphatic, alicyclic, heteroaliphatic, eterocyclic, aromatic, heteroaromatic, aryl, heteroaryl, alkylaryl, heteroalkylaryl, alkylheteroaryl, eteroalkylheteroaryl, alkoxy, aryloxy, heteroalkoxy, heteroaryloxy, alkylthio, arylthio, eteroalkylthio, heteroarylthio, F, Cl, Br, I, —OH, —NO2, —CN, —CF3, —CH2CF3, —CHCl2, —CH2OH, —H2CH2OH, —CH2NH2, —CH2SO2CH3, —C(O)Rx, —CO2(Rx), —CON(Rx)2, —OC(O)Rx, —OCO2Rx, —CON(Rx)2, —N(Rx)2, —SF5, —S(O)Rx, —S(O)2Rx, —NRx(CO)Rx, wherein each occurrence of Rx independently includes aliphatic, alicyclic, heteroaliphatic, eterocyclic, aromatic, heteroaromatic, aryl, heteroaryl, alkylaryl, alkylheteroaryl, heteroalkylaryl r heteroalkylheteroaryl, wherein any one of the aliphatic, alicyclic, heteroaliphatic, heterocyclic, lkylaryl, or alkylheteroaryl substituents are substituted or unsubstituted, branched or unbranched, aturated or unsaturated, and wherein any one of the aromatic, heteroaromatic, aryl, heteroaryl, -alkyl)aryl or -(alkyl)heteroaryl substituents are substituted or unsubstituted; wherein two adjacent Ra or Ra and Rb can form a 5- to 7-membered carbocyclic ring or a 5- to 7-membered heterocyclic ring in which one or two carbon atoms are replaced by one or two S, O or NRc.