Novel urea compounds, compositions and methods of use and preparation

A compound of Formula (Ia):

• 95
• wherein:
• R1 is selected from the group consisting of hydrogen, Rs, and —Rt—O—Rs where Rs is selected from the group consisting of —(C1-C12) alkyl, —(C1-C12) alkenyl, or —(C1-C12) alkynyl;
• and Rt is selected from the group consisting of —(C1-C12) alkylene, —(C1-C12) alkenylene, or —(C1-C12) alkynylene;
• R5 is selected from the group consisting of hydrogen, —(C1-C12) alkyl, substituted alkyl, or heteroalkyl, —(C1-C12) alkenyl, substituted alkenyl, or heteroalkenyl, —(C1-C12) alkynyl, substituted alkynyl, or heteroalkynyl, or —(C0-C12 alkylene or substituted alkylene)-(C3-C12 arylene or heteroarylene)-(C0-C12 alkyl or substituted alkyl);
• n is an integer from 1 to 5;
• zero or one Y is selected from the group consisting of —O—, —NRa—, and —S—, and all remaining Y are —CR6R7—;
• and where R6 and R7 are each independently hydrogen, Rc, —OH, —ORc, —SH, —SRc, —NH2, —NHRc, —NRcRd, —C(═O)Rc, —C(═O)NRcRd, —(═O)ORc, —C(═O)SRc, —C(═O)CRcRdRe, —C(═O)OCRcRdRe, —S(═O)2NRcRd, —N(Rc)C(═O)Rd, —N(Rc)C(═O)ORd, —N(Rc)S(═O)2Rd, or —N(Rc)S(═O)2ORd, or where two vicinal R6 or R7 groups combine to form a substituted or unsubstituted C4-C10 cyclic alkyl, cyclic heteroalkyl, aryl or heteroaryl group;
• where Rc, Rd and Re are each independently hydrogen, —(C1-C12) alkyl, substituted alkyl, or heteroalkyl, —(C1-C12) alkenyl, substituted alkenyl, or heteroalkenyl, —(C1-C12) alkynyl, substituted alkynyl, or heteroalkynyl, or —(C0-C8 alkylene or substituted alkylene)-(C3-C12 arylene or heteroarylene)-(C0-C8 alkyl or substituted alkyl), or where, when two or three of Rc, Rd and Re are attached to the same atom, two or three of Rc, Rd and Re can combine to form a substituted or unsubstituted —(C4-C10) cyclic alkyl, cyclic heteroalkyl, aryl or heteroaryl group;
• or a pharmaceutically acceptable salt thereof.

A compound of the Formula (Ib):

• 96
• wherein:
• R1 is selected from the group consisting of hydrogen, Ra, —Rb—OH, and —Rb—O—Ra where Ra is selected from the group consisting of —(C1-C12) alkyl, substituted alkyl, or heteroalkyl, —(C1-C12) alkenyl, substituted alkenyl, or heteroalkenyl, —(C1-C12) alkynyl, substituted alkynyl, or heteroalkynyl, or —(C0-C8 alkyl or substituted alkyl)-(C3-C12 aryl or heteroaryl)-(C0-C8 alkyl or substituted alkyl);
• and Rb is selected from the group consisting of —(C1-C12) alkylene, substituted alkylene, or heteroalkylene, —(C1-C12) alkenylene, substituted alkenylene, or heteroalkenylene, —(C1-C12) alkynylene, substituted alkynylene, or heteroalkynylene, or —(C0-C8 alkylene or substituted alkylene)-(C3-C12 arylene or heteroarylene)-(C0-C8 alkyl or substituted alkyl);
• R5 is selected from the group consisting of hydrogen, —(C1-C12) alkyl, substituted alkyl, or heteroalkyl, —(C1-C12) alkenyl, substituted alkenyl, or heteroalkenyl, —(C1-C12) alkynyl, substituted alkynyl, or heteroalkynyl, or —(C0-C12 alkyl or substituted alkyl)-(C3-C12 aryl or heteroaryl)-(C0-C12 alkyl or substituted alkyl);
• n is an integer from 1 to 5;
• zero or one Y is selected from the group consisting of —O—, NRa, and —S—, and all remaining Y are —CR6R7—;
• and R6 and R7 are each independently —H, —Rh, —OH, —ORh, —SH, —SRh, —NH2, —NHRh, —NRhRi, —C(═O)H, —C(═O)Rh, —C(═O)NH2, —C(═O)NHRh, —C(═O)NRhRi, —C(═O)OH, —C(═O)ORh, —C(═O)SH, —C(═O)SRh, —C(═O)CH3, —C(═O)CH2Rh, —C(═O)CHRhRi, —C(═O)CRhRlRj, —C(═O)OCH3, —C(═O)OCH2Rh, —C(═O)OCHRhRl, —C(═O)OCRhRlRj, —S(═O)2NH2, —S(═O)2NHRh, —S(═O)2NRhRi, —NHC(═O)H, —N(Rh)C(═O)H, —NHC(═O)Ri, —NHC(═O)ORi, —N(Rh)C(═O)Ri, —N(Rh)C(═O)ORl, —NHS(═O)2H, —N(Rh)S(═O)2H, —NHS(═O)2ORi, —N(Rh)S(═O)2ORi, —N(H)S(═O)2Ri, or —N(Rh)S(═O)2Ri;
• where Rh, Ri and Rj are each independently —(C1-C12) alkyl, substituted alkyl, or heteroalkyl, —(C1-C12) alkenyl, substituted alkenyl, or heteroalkenyl, —(C1-C12) alkynyl, substituted alkynyl, or heteroalkynyl, or (C0-C8 alkylene or substituted alkylene)-(C3-C12 arylene or heteroarylene)-(C0-C8 alkyl or substituted alkyl) or a pharmaceutically acceptable salt thereof.

A compound selected from the group consisting of:

• N-hydroxy-2-[N-(3-methylbutyl)-N-(2-(S)-3-phenoxy-phenylaminocarbonyl)-pyrrolidin-1-carbonyl)amino]acetamide;
• N-hydroxy-2-[N-(2-cyclopentylethyl)-N-(2-(S)-2-methyl-1,3,4-thiadiazol-5-ylaminocarbonyl)pyrrolidin-1-carbonyl)amino]acetamide;
• N-hydroxy-2-[N-(2-cyclopentylethyl)-N-(2-(S)-thiazol-2-ylaminocarbonyl)-pyrrolidin-1-carbonyl)amino]acetamide;
• N-hydroxy-2-[N-(2-cyclopentylethyl)-N-(2-(S)-6-phenylimidazol-2-yl aminocarbonyl)-pyrrolidin-1-carbonyl)amino]acetamide;
• N-hydroxy-2-[N-(2-cyclopentylethyl)-N-(2-(S)-pyrazin-2-ylaminocarbonyl)-pyrrolidin-1-carbonyl)amino]acetamide;
• N-hydroxy-2-[N-(3-methylbutyl)-N-(2-(S)-3-methylbutylaminocarbonyl)-pyrrolidin-1-carbonyl) amino]acetamide;
• N-hydroxy-2-[N-(2-cyclopentylethyl)-N-(2-(S)-imidazol-2-ylaminocarbonyl)-pyrrolidin-1-carbonyl)amino]acetamide;
• N-hydroxy-2-[N-(2-cyclopentylethyl)-N-(2-(S)-4,5-dimethylthiazol-2-yl aminocarbonyl)-pyrrolidin-1-carbonyl)amino]acetamide;
• and
• N-hydroxy-2-[N-(3-methylbutyl)-N-(2-(S)-4,5-dimethylthiazol-2-yl aminocarbonyl)-pyrrolidin-1-carbonyl)amino]acetamide or a pharmaceutically acceptable salt thereof.