4-phenylpiperidines, their preparation and use

A method for treating a disease characterized by excessive lipofuscin accumulation in the retina in a mammal afflicted therewith comprising administering to the mammal an effective amount of a compound having the structure:

• R1, R2, R3, and R4, are each independently H, halogen, CF3 or C1-C4 alkyl, and wherein R5 is CF3;
• R6 is H, OH, or halogen;
• B is a substituted or unsubstituted pyridazine, pyrimidine, pyrazine, or B has the structure:
• wherein
• n is 1;
• R7 is H, C1-C4 alkyl, or oxetane;
• Y1 and Y4 are each CH2;
• and
• one of Y2 or Y3 is CH2 and the other of Y2 or Y3 is O, SO2, or N—R10,
• wherein
• R10 is H, C1-C4 alkyl, C1-C4 cycloalkyl, (C1-C4 alkyl)-CF3, (C1-C4 alkyl)-OCH3, (C1-C4 alkyl)-halogen, SO2—(C1-C4 alkyl), SO2—(C1-C4 alkyl)-CF3, SO2—(C1-C4 alkyl)-OCH3, SO2—(C1-C4 alkyl)-halogen, C(O)—(C1-C4 alkyl), C(O)—(C1-C4 alkyl)-CF3, C(O)—(C1-C4 alkyl)-OCH3, C(O)—(C1-C4 alkyl)-halogen, C(O)—NH—(C1-C4 alkyl), C(O)—N(C1-C4 alkyl)2, C1-C4 alkyl)-C(O)OH, or oxetane;
• or B has the structure:
• wherein
• R7 is H, C1-C4 alkyl, or oxetane;
• and
• Y1, Y2, Y3 and Y4 are each independently CR8 or N,
• wherein each R8 is independently H, halogen, C1-C4 alkyl, C1-C4 cycloalkyl, O—(C1-C4 alkyl), C(O)OH, C(O)—NH2, C(O)—N(CH3)2, C(O)—NHCH3, NHC(O)—N(CH3)2, CN, or CF3;
• or B has the structure:
• wherein
• Y1, Y2, Y3 and Y4 are each independently CR8 or N,
• wherein each R8 is independently H, halogen, C1-C4 alkyl, C1-C4 cycloalkyl, O—(C1-C4 alkyl), C(O)OH, C(O)—NH2, C(O)—N(CH3)2, C(O)—NHCH3NHC(O)—N(CH3)2, CN, or CF3;
• and
• wherein the disease characterized by excessive lipofuscin accumulation in the retina is Age-Related Macular Degeneration, dry Age-Related Macular Degeneration, Geographic atrophy, Stargardt Disease, Best disease, adult vitelliform maculopathy, or Stargardt-like macular dystrophy;
• or a pharmaceutically acceptable salt thereof.