Inhibitors of protein arginine deiminases (PADs) and methods of preparation and use thereof

A compound having the structural formula (I),

• wherein
• each of Ra and Rb is independently selected from the group consisting of H, D and F;
• L is a bivalent hydrocarbyl linker, optionally with one or more carbon atoms replaced by a heteroatom selected from the group consisting of O, S and N;
• X is a halogen atom;
• Y is N, O or S;
• provided that when Y is S or O, its bonding to the adjacent carbons are single bonds;
• Z is N—R1, O or S;
• R1 is selected from the group consisting of:
• H, a C1-6 alkyl, OH, a C1-3 alkoxy, CF3, COCH3, or COCF3 groups;
• each of R2, R3, R4 and R5 is independently selected from the group consisting of:
• H, hydroxyl, halogen atom, C1-6 alkyl, C1-6 alkoxy, alkynyl, CF2Rc, or OCF2Rc groups, where Rc is H, F or alkyl;
• and
• R6 is a group selected from the group consisting of:
• wherein
• R7 is independently selected from the group consisting of H, C1-6 alkyl, C1-6 alkoxy, hydroxyl, halogen atoms, aryl, —COOR8, ethynyl, alkynyl, CF2Rc, and OCF2Rc, where Rc is H, F or alkyl;
• R8 is independently selected from the group consisting of H and C1-6 alkyl;
• and
• R9 is CH2, O, NH2 or S,
• or a pharmaceutically acceptable form thereof.