Thyrotropin-releasing hormone analogues and their therapeutic applications

A pharmaceutical composition comprising a compound having the following structure

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• R1 is selected from the group consisting of H, alkyl, aryl, heterocycle, heteroaryl, hydroxyalkyl, alkylaryl, substituted aryl, COX, and COOX, wherein X is selected from the group consisting of alkyl, amine, alkylamino, aryl, substituted aryl, arylalkyl, and acyloxyalkyl;
• R3 is 3-(R1-)aminocarbonyl-pyridinium-1-yl, where carbon marker 2, 4, 5, or 6 of the pyridinium ring is independently and optionally attached to hydrogen, halogen, isopropyl, alkyl, alkenyl, alkynyl, carbocycle, aryl, heterocycle, heteroaryl, alkylamino, hydroxyalkyl, alkoxyalkyl, amide, CN, or a linear or branched hydrocarbon from 1–15 atoms carbon atoms in length, that can optionally include one or more heteroatoms in the chain;
• R5 is selected from the group consisting of alkyl, 1-Z, and 1H-imidazol-4-ylmethyl (or its tautomeric 1H-imidazol-5-ylmethyl), where Z is selected from the group consisting of H, alkyl, alkyloxycarbonyl, aryl, substituted aryl, arylalkyl, COX, or COOX;
• L is selected from the group consisting of alkyl including (CH2)n, aryl, heterocycle, or heteroaryl, where n is an integer from 0 to 10;
• and
• a pharmaceutically acceptable carrier or diluent.