Anti tubercular drug: compositions and methods

A method of preparing a substituted ethylene diamine compound of the formula

• wherein R4 is selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkynyl, cycloalkyl, cycloalkenyl;
• and wherein R1, R2 and R3 are independently selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroaryl, halide, alkoxy, aryloxy, alkylthio, arylthio, silyl, siloxy, amino;
• or
• wherein R1 is selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroaryl, halide, alkoxy, aryloxy, alkylthio, arylthio, silyl, siloxy, amino, and NR2R2 is derived from a cyclic secondary amine;
• comprising activating a solid-support resin containing hydroxyl groups with a halo-donating reagent in the presence of base to produce a solid-support resin containing halo groups;
• displacing the halo groups with an initial primary amine to produce a solid-support resin containing amine groups;
• acylating the amine groups with a halo-acylhalide in the presence of a basic compound, or with a halo-acylacid in the presence of base, to produce a solid-support resin containing α-haloacetyl amide groups;
• displacing α-halo groups of the α-haloacetyl amides with a secondary or subsequent primary amine to produce a solid-support resin containing α-amine imide groups;
• reducing the carbonyl moiety on the α-amine imide groups with a reducing agent to produce a solid-support resin containing two amine groups separated by two carbon atoms;
• cleaving the amine groups separated by two carbon atoms from the solid support resin in the presence of acid to produce the substituted ethylene diamine compound.

A method of treating disease caused by an infectious agent comprising administering an effective amount of a substituted ethylene diamine compound of the formula:

• wherein R4 is selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkynyl, cycloalkyl, cycloalkenyl;
• and wherein R1, R2 and R3 are independently selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroaryl, halide, alkoxy, aryloxy, alkylthio, arylthio, silyl, siloxy, amino;
• or
• wherein R1 is selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroaryl, halide, alkoxy, aryloxy, alkylthio, arylthio, silyl, siloxy, amino, and NR2R2 is derived from a cyclic secondary amine.

A method of preparing a substituted ethylene diamine compound of the formula

• wherein R4 is selected from H, alkyl, aryl, heteroatom substituted alkyl and aryl, alkenyl, alkynyl, aralkyl, aralkynyl, cycloalkyl, cycloalkenyl;
• and wherein R1, R2 and R3 are independently selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroaryl, halide, alkoxy, aryloxy, alkylthio, arylthio, silyl, siloxy, amino;
• comprising activating a solid-support resin containing hydroxyl groups with a halo-donating reagent in the presence of base to produce a solid-support resin containing halo groups;
• displacing the halo groups with an initial primary amine to produce a solid-support resin containing amine groups;
• acylating the amine groups with a FMOC protected amino acid in the presence of a coupling reagent and a base, followed by removal of FMOC protecting group to produce a solid-support resin containing α-amino acetamide groups;
• modification of α-amino groups of the α-amino acetamide groups with a carbonyl compound to produce a solid-support resin containing corresponding derivative of α-amino acetamide groups;
• reducing the carbonyl moiety on the amide groups with a reducing agent to produce a solid-support resin containing two amine groups separated by two carbon atoms;
• and
• cleaving the amine groups separated by two carbon atoms from the solid support resin in the presence of acid to produce the substituted ethylene diamine compound.

A composition comprising a symmetrical substituted ethylene diamine compound of the formula

• wherein R4 is selected from H, alkyl, aryl, heteroatom substituted alkyl and aryl, alkenyl, alkynyl, aralkyl, aralkynyl, cycloalkyl, cycloalkenyl;
• and wherein R1, R2 and R3 are independently selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroaryl, halide, alkoxy, aryloxy, alkylthio, arylthio, silyl, siloxy, amino;
• or
• wherein R1 is selected from H, alkyl, aryl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkenyl, heteroalkyl, heteroaryl, halide, alkoxy, aryloxy, alkylthio, arylthio, silyl, siloxy, amino, and NR2R2 is derived from a cyclic secondary amine.