Fused heterotricyclic organic compounds, pharmaceutical compositions, and medical uses thereof

A method selected from:

• (a) a method of reducing the amount of subcutaneous fat in a subject, comprising exposing subcutaneous fat in a subject to an effective amount of a compound of Formula I to reduce the amount of subcutaneous fat in said subject, wherein Formula I is represented by:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is phenyl, 5-6 membered heteroaryl, aralkyl, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, —(C1-C6)alkylene-OH, or —(C1-C6)alkylene-O—(C1-C6)alkyl, wherein said phenyl, 5-6 membered heteroaryl, aralkyl, and cycloalkyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, hydroxyl, —(C1-C6)alkoxy, and —N(R5)R6;
• R2 and R3 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or halogen;
• R4 is —C(O)N(R5)R6, —N(R5)C(O)R6, —CO2R6, —C(O)R6, —(C1-C6)alkylene-N(R5)R6, —(C1-C6)alkylene-OR6, or —(C1-C6)alkoxy;
• R5 and R6 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or —(C3-C6)cycloalkyl;
• or when R5 and Re are attached to the same nitrogen atom, then R5 and R6 may be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocycle;
• and
• n and m each represent independently 1 or 2;
• b) a method for inducing retraction of dermal tissue in a subject, comprising administering an effective amount of a compound of Formula I to dermal tissue of a subject to induce retraction of dermal tissue, wherein Formula I is represented by:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is phenyl, 5-6 membered heteroaryl, aralkyl, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, —(C1-C6)alkylene-OH, or —(C1-C6)alkylene-O—(C1-C6)alkyl, wherein said phenyl, 5-6 membered heteroaryl, aralkyl, and cycloalkyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, hydroxyl, —(C1-C6)alkoxy, and —N(R5)R6;
• R2 and R3 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or halogen;
• R4 is —C(O)N(R5)R6, —N(R5)C(O)R6, —CO2R6, —C(O)R6, —(C1-C6)alkylene-N(R5)R6, —(C1-C6)alkylene-OR6, or —(C1-C6)alkoxy;
• R5 and R6 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or —(C3-C6)cycloalkyl;
• or when R5 and R6 are attached to the same nitrogen atom, then R5 and R6 may be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocycle;
• and
• n and m each represent independently 1 or 2;
• (c) a method for inducing retraction of subcutaneous tissue in a subject, comprising administering an effective amount of a compound of Formula I to subcutaneous tissue of a subject to induce retraction of subcutaneous tissue, wherein Formula I is represented by:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is phenyl, 5-6 membered heteroaryl, aralkyl, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, —(C1-C6)alkylene-OH, or —(C1-C6)alkylene-O—(C1-C6)alkyl, wherein said phenyl, 5-6 membered heteroaryl, aralkyl, and cycloalkyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, hydroxyl, —(C1-C6)alkoxy, and —N(R5)R6;
• R2 and R3 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or halogen;
• R4 is —C(O)N(R5)R6, —N(R5)C(O)R6, —CO2R6, —C(O)R6, —(C1-C6)alkylene-N(R5)R6, —(C1-C6)alkylene-OR6, or —(C1-C6)alkoxy;
• R5 and R6 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or —(C3-C6)cycloalkyl;
• or when R5 and R6 are attached to the same nitrogen atom, then R5 and R6 may be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocycle;
• and
• n and m each represent independently 1 or 2;
• (d) a method of treating a disorder selected from the group consisting of an adipose tissue tumor, fat embolism, dyslipidemia, and or fatty liver disease due to alcohol-induced liver cirrhosis in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I to treat the disorder, wherein Formula I is represented by:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is phenyl, 5-6 membered heteroaryl, aralkyl, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, —(C1-C6)alkylene-OH, or —(C1-C6)alkylene-O—(C1-C6)alkyl, wherein said phenyl, 5-6 membered heteroaryl, aralkyl, and cycloalkyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, hydroxyl, —(C1-C6)alkoxy, and —N(R5)R6;
• R2 and R3 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or halogen;
• R4 is —C(O)N(R5)R6, —N(R5)C(O)R6, —CO2R6, —C(O)R6, —(C1-C6)alkylene-N(R5)R6, —(C1-C6)alkylene-OR6, or —(C1-C6)alkoxy;
• R5 and R6 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or —(C3-C6)cycloalkyl;
• or when R5 and Re are attached to the same nitrogen atom, then R5 and R6 may be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocycle;
• and
• n and m each represent independently 1 or 2;
• (e) a method of reducing the amount of fat or cholesterol in a subject, comprising administering to a subject in need thereof an effective amount of a compound of Formula I to reduce the amount of fat or cholesterol in the subject, wherein Formula I is represented by:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is phenyl, 5-6 membered heteroaryl, aralkyl, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, —(C1-C6)alkylene-OH, or —(C1-C6)alkylene-O—(C1-C6)alkyl, wherein said phenyl, 5-6 membered heteroaryl, aralkyl, and cycloalkyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, hydroxyl, —(C1-C6)alkoxy, and —N(R5)R6, R2 and R3 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or halogen;
• R4 is —C(O)N(R5)R6, —N(R5)C(O)R6, —CO2R6, —C(O)R6, —(C1-C6)alkylene-N(R5)R6, —(C1-C6)alkylene-OR6, or —(C1-C6)alkoxy;
• R5 and R6 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or —(C3-C6)cycloalkyl;
• or when R5 and Re are attached to the same nitrogen atom, then R5 and R6 may be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocycle;
• and
• n and m each represent independently 1 or 2;
• and
• (f) a method of reducing the amount of mesenchymal pre-adipocyte stem cell precursors in a subject, comprising administering to a subject in need thereof an effective amount of a compound of Formula I to reduce the amount of mesenchymal pre-adipocyte stem cell precursors in the subject, wherein Formula I is represented by:
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is phenyl, 5-6 membered heteroaryl, aralkyl, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, —(C1-C6)alkylene-OH, or —(C1-C6)alkylene-O—(C1-C6)alkyl, wherein said phenyl, 5-6 membered heteroaryl, aralkyl, and cycloalkyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, —(C1-C6)alkyl, —(C3-C6)cycloalkyl, hydroxyl, —(C1-C6)alkoxy, and —N(R5)R6;
• R2 and R3 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or halogen;
• R4 is —C(O)N(R5)R6, —N(R5)C(O)R6, —CO2R6, —C(O)R6, —(C1-C6)alkylene-N(R5)R6, —(C1-C6)alkylene-OR6, or —(C1-C6)alkoxy;
• R5 and R6 each represent independently for each occurrence hydrogen, —(C1-C6)alkyl, or —(C3-C6)cycloalkyl;
• or when R5 and R6 are attached to the same nitrogen atom, then R5 and R6 may be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocycle;
• and
• n and m each represent independently 1 or 2.