Anti-bacterial stilbene derivatives and methods of use

A method of making a compound of Formula Ia, the method comprising:

• contacting a compound of Formula IV, or a salt, solvate, tautomer, enantiomer, or geometric isomer thereof:
• with a medium comprising an organism and at least one metal salt, to yield a compound of Formula Ia, or a salt, solvate, tautomer, enantiomer, or geometric isomer thereof:
• wherein:
• at each occurrence R2, R3, A1, A2, A3, A4, and A5, is independently selected from hydrogen, F, Cl, Br, I, OR, OC(O)N(R)2, CN, NO, NO2, ONO2, azido, CF3, OCF3, R, methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, SO2R, SO2N(R)2, SO3R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)0-2N(R)C(O)R, (CH2)0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R;
• and
• at each occurrence R is independently hydrogen, (C1-C100) hydrocarbyl, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, or heteroarylalkyl.

A method of killing or disinfecting bacteria, the method comprising:

• contacting a bacterial population with a compound of Formula I, or a salt, solvate, tautomer, enantiomer, or geometric isomer thereof:
• wherein:
• at each occurrence R1, R2, R3, R4, R5, A1, A2, A3, A4, A5, A1′, A2′, A3′, A4′, and A5′ is independently selected from hydrogen, F, Cl, Br, I, OR, OC(O)N(R)2, CN, NO, NO2, ONO2, azido, CF3, OCF3, R, methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, SO2R, SO2N(R)2, SO3R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)0-2N(R)C(O)R, (CH2)0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R;
• at each occurrence R6 is independently selected from hydrogen, CF3, R, methylenedioxy, ethylenedioxy, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)1-2N(R)C(O)R, (CH2)1-2N(R)N(R)2, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R;
• and
• at each occurrence R is independently hydrogen, (C1-C100) hydrocarbyl, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, or heteroarylalkyl;
• wherein the bacterial population is killed or disinfected after coming into contact with the compound of Formula I, or salt, solvate, tautomer, enantiomer, or geometric isomer thereof.

A method of treating a bacterial infection in a subject, the method comprising:

• administering to the subject a therapeutically effective amount of a composition comprising at least one pharmaceutically acceptable excipient and a compound of Formula I, or a salt, solvate, tautomer, enantiomer, or geometric isomer thereof:
• wherein:
• at each occurrence R1, R2, R3, R4, R5, A1, A2, A3, A4, A5, A1′, A2′, A3′, A4′, and A5′ is independently selected from hydrogen, F, Cl, Br, I, OR, OC(O)N(R)2, CN, NO, NO2, ONO2, azido, CF3, OCF3, R, methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, SO2R, SO2N(R)2, SO3R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)0-2N(R)C(O)R, (CH2)0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R;
• at each occurrence R6 is independently selected from hydrogen, CF3, R, methylenedioxy, ethylenedioxy, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)1-2N(R)C(O)R, (CH2)1-2N(R)N(R)2, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R;
• and
• at each occurrence R is independently hydrogen, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, or heteroarylalkyl.

A method of treating or ameliorating psoriasis or atopic dermatitis, the method comprising:

• contacting the skin of a subject with a composition comprising the compound of Formula I, or a salt, solvate, tautomer, enantiomer, or geometric isomer thereof:
• wherein:
• at each occurrence R1, R2, R3, R4, R5, A1, A2, A3, A4, A5, A1′, A2′, A3′, A4′, and A5′ is independently selected from hydrogen, F, Cl, Br, I, OR, OC(O)N(R)2, CN, NO, NO2, ONO2, azido, CF3, OCF3, R, methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, SO2R, SO2N(R)2, SO3R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)0-2N(R)C(O)R, (CH2)0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R;
• at each occurrence R6 is independently selected from hydrogen, CF3, R, methylenedioxy, ethylenedioxy, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2)1-2N(R)C(O)R, (CH2)1-2N(R)N(R)2, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R;
• and
• at each occurrence R is independently hydrogen, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, or heteroarylalkyl.