Ortho-Aminothiophenol Compounds and Uses Thereof

A pharmaceutical composition for use in the treatment of a microbial infection in a subject in need thereof, the pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula Ia, a compound of Formula IIa, or one or two compounds independently selected from Formula Ia or Formula IIa complexed with a metal core, or a pharmaceutically acceptable salt, prodrug or hydrate thereof, or an antimicrobial composition comprising a therapeutically effective amount of a compound of Formula Ia, a compound of Formula IIa, a compound of Formula Ia or a compound of Formula IIa complexed with a metal core, or a pharmaceutically acceptable salt, prodrug or hydrate thereof, and a solvent or diluent

• wherein,
• R1 is C1-6 alkyl, C2-6 alkenyl, aryl, heteroaryl, C3-10 cycloaliphatic, or 5-10 membered heterocycloaliphatic having 1-3 heteroatoms independently selected from N, O, or S, any of which is optionally substituted;
• R2 is independently hydrogen, or each pair of R2 groups is —N═CR10R11, wherein one of R10 and R11 is hydrogen and the other is optionally substituted phenyl or an optionally substituted 5-6 membered heteroaryl having 1-2 heteroatoms independently selected from N, O, or S;
• R4 is —ZBR6, wherein each ZB is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZB are optionally and independently replaced by —CO—, —CS—, —CONRB—, —CO2—, —OCO—, —NRBCO2—, —O—, —NRBCONRB—, —OCONRB—, —NRBNRB—, —NRBCO—, —S—, —SO—, —SO2—, —NRB—, —SO2NRB—, —NRBSO2—, or —NRBSO2NRB—,
• R6 is independently RB, halo, —OH, —NH2, —NO2, —CN, —CF3, or —OCF3,
• RB is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl;
• or
• two R4 groups together with the carbon atoms to which they are attached form an optionally substituted 5-6 membered ring having 0-3 heteroatoms independently selected from N, O, or S;
• One of R10 and R11 is hydrogen and the other is optionally substituted phenyl or an optionally substituted 5-6 membered heteroaryl having 1-2 heteroatoms independently selected from N, O, and S;
• and
• R7 is an optionally substituted phenyl or an optionally substituted 6 membered heteroaryl having 1-2 heteroatoms independently selected from N, O, or S and
• Each of m, n, and p is independently 0 or a positive integer from 1-3, and a pharmaceutically acceptable excipient,
• wherein administration of said pharmaceutical composition to said subject provides for a minimum period of time of 6-12 hours a concentration in a target tissue of at least about 2-10 times the MIC of the bacteria.

A method for sterilizing a solid surface, the method comprising:

• contacting the surface, with a therapeutically effective amount of a compound of Formula Ia, a compound of Formula IIa, or one or two compounds independently selected from Formula Ia or Formula IIa complexed with a metal core, or a pharmaceutically acceptable salt, prodrug or hydrate thereof, or an antimicrobial composition comprising a therapeutically effective amount of a compound of Formula Ia, a compound of Formula IIa, a compound of Formula Ia or a compound of Formula IIa complexed with a metal core, or a pharmaceutically acceptable salt, prodrug or hydrate thereof, and a solvent or diluent
• wherein,
• R1 is C1-6 alkyl, C2-6 alkenyl, aryl, heteroaryl, C3-10 cycloaliphatic, or 5-10 membered heterocycloaliphatic having 1-3 heteroatoms independently selected from N, O, or S, any of which is optionally substituted;
• R2 is independently hydrogen, or each pair of R2 groups is —N═CR10R11, wherein one of R10 and R11 is hydrogen and the other is optionally substituted phenyl or an optionally substituted 5-6 membered heteroaryl having 1-2 heteroatoms independently selected from N, O, or S;
• R4 is —ZBR6, wherein each ZB is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZB are optionally and independently replaced by —CO—, —CS—, —CONRB—, —CO2—, —OCO—, —NRBCO2—, —O—, —NRBCONRB—, —OCONRB—, —NRBNRB—, —NRBCO—, —S—, —SO—, —SO2—, —NRB—, —SO2NRB—, —NRBSO2—, or —NRBSO2NRB—,
• R6 is independently RB, halo, —OH, —NH2, —NO2, —CN, —CF3, or —OCF3,
• RB is independently hydrogen, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl;
• or
• two R4 groups together with the carbon atoms to which they are attached form an optionally substituted 5-6 membered ring having 0-3 heteroatoms independently selected from N, O, or S;
• One of R10 and R11 is hydrogen and the other is optionally substituted phenyl or an optionally substituted 5-6 membered heteroaryl having 1-2 heteroatoms independently selected from N, O, and S;
• and
• R7 is an optionally substituted phenyl or an optionally substituted 6 membered heteroaryl having 1-2 heteroatoms independently selected from N, O, or S and
• Each of m, n, and p is independently 0 or a positive integer from 1-3.