Molecules specific for NPFF receptors and uses thereof

A method of treating pain in a subject in need of such treatment comprising administering to the subject an effective amount of a compound having the structure:

• 91
• wherein R1 is straight chained or branched C1-C7 alkyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, or polyfluorocycloalkyl;
• C5-C7 cycloalkenyl;
• naphthyl;
• arylalkyl, heteroarylalkyl, phenyl or heteroaryl,
• wherein the arylalkyl, heteroarylalkyl, phenyl or heteroaryl is unsubstituted or substituted with one or more of the following substituents:
• halogen, hydroxy, C1-C6 alkoxy, aryloxy, straight chained or branched C2-C6 alkyl, aryl, heteroaryl, nitro, cyano, C1-C6 alkylthio, substituted or unsubstituted arylalkyl or heteroarylalkyl, —C(═Y)R7, —C(═Y)OR7, —N(R7)2, —C(═Y)NR7, —NR7C(═Y)R7 or —N(R7)C(═Y)N(R7)2,
• wherein Y is O or S;
• wherein R7 is independently H, straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, or polyfluorocycloalkyl;
• C5-C7 cycloalkenyl;
• wherein R2 is —(CH2)n—NH—C(═NH)—NH2;
• —(CH2)n—C(═NH)—NH2;
• —(CH2)n—N(R7)2;
• or -J;
• wherein n is an integer between 1 and 6, and wherein J is any of the following structures:
• 92
• wherein each of R3 and R4 is independently H, straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, or polyfluorocycloalkyl;
• or C5-C7 cycloalkenyl;
• wherein R5 is —OR8 or —N(R8)2;
• wherein each R8 is independently H, straight chained or branched C1-C7 alkyl, alkoxyalkyl, alkylthioalkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl;
• or C5-C7 cycloalkenyl;
• wherein R6 is arylalkyl, heteroarylalkyl, aryl or heteroaryl, each optionally substituted with one or more of the following substituents:
• halogen, hydroxy, C1-C6 alkoxy, aryloxy, straight chained or branched C1-C6 alkyl, aryl, heteroaryl, nitro, cyano, C1-C6 alkylthio, substituted or unsubstituted arylalkyl or heteroarylalkyl, —C(═Y)R7, —C(═Y)OR7, —N(R7)2, —C(═Y)NR7, —NR7C(═Y)R7 or —N(R7)C(═Y)N(R7)2,
• or a pharmaceutically acceptable salt thereof,
• to thus treat the pain in the subject.

A method of treating a lower urinary tract disorder in a subject in need of such treatment comprising administering to the subject an effective amount of a compound having the structure:

• 94
• wherein R1 is straight chained or branched C1-C7 alkyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, or polyfluorocycloalkyl;
• C5-C7 cycloalkenyl;
• naphthyl;
• arylalkyl, heteroarylalkyl, phenyl or heteroaryl,
• wherein the arylalkyl, heteroarylalkyl, phenyl or heteroaryl is unsubstituted or substituted with one or more of the following substituents:
• halogen, hydroxy, C1-C6 alkoxy, aryloxy, straight chained or branched C2-C6 alkyl, aryl, heteroaryl, nitro, cyano, C1-C6 alkylthio, substituted or unsubstituted arylalkyl or heteroarylalkyl, —C(═Y)R7, —C(═Y)OR7, —N(R7)21—C(═Y)NR7, —NR7C(═Y)R7 or —N(R7)C(═Y)N(R7)2,
• wherein Y is O or S;
• wherein R7 is independently H, straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, or polyfluorocycloalkyl;
• C5-C7 cycloalkenyl;
• wherein R2 is —(CH2)n—NH—C(═NH)—NH2;
• —(CH2)n—C(═NH)—NH2;
• —(CH2)n—N(R7)2;
• or J;
• wherein n is an integer between 1 and 6, and wherein J is any of the following structures:
• 95
• wherein each of R3 and R4 is independently H, straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, or polyfluorocycloalkyl;
• or C5-C7 cycloalkenyl;
• wherein R5 is —OR8 or —N(R8)2;
• wherein each R8 is independently H, straight chained or branched C1-C7 alkyl, alkoxyalkyl, alkylthioalkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, or polyfluorocycloalkyl;
• C5-C7 cycloalkenyl;
• wherein R6 is naphthyl, arylalkyl, heteroarylalkyl, phenyl or heteroaryl, each optionally substituted with one or more of the following substituents:
• halogen, hydroxy, C1-C6 alkoxy, aryloxy, straight chained or branched C1-C6 alkyl, aryl, heteroaryl, nitro, cyano, C1-C6 alkylthio, substituted or unsubstituted arylalkyl or heteroarylalkyl, —C(═Y)R7, —C(═Y)OR7, —N(R7)2—C(═Y)NR7, —NR7C(═Y)R7 or —N(R7)C(═Y)N(R7)2,
• or a pharmaceutically acceptable salt thereof,
• to thus treat the lower urinary tract disorder in the subject.