Patent ID: 7211565

Claim:
An ApoA-I agonist compound comprising: (i) a 18 to 22-residue peptide analogue that forms an amphipathic α-helix in the presence of lipids and that comprises formula (I): Z 1 -X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17 -X 18 -Z 2 or a pharmaceutically acceptable salt thereof, wherein X 1 is Pro (P), Ala (A), Gly (G), Asn (N), Gln (Q) or D-pro (p); X 2 is an aliphatic residue; X 3 is Leu (L); X 4 is an acidic residue; X 5 is Leu (L) or Phe (F); X 6 is Leu (L) or Phe (F); X 7 is a basic residue; X 8 is an acidic residue; X 9 is Leu (L) or Trp (W); X 10 is Leu (L) or Trp (W); X 11 is an acidic residue or Asn (N); X 12 is an acidic residue; X 13 is Leu (L), Trp (W) or Phe (F); X 14 is a basic residue or Leu (L); X 15 is Gln (Q) or Asn (N);X 16 is a basic residue; X 17 is Leu (L); X 18 is a basic residue; Z 1 is H 2 N—, or RC(O)NR—; Z 2 is —C(O)NRR, —C(O)OR or —C(O)OH; each R is independently —H, (C 1 –C 6 ) alkyl, (C 2 –C 6 ) alkenyl, (C 2 –C 6 ) alkynyl, (C 5 –C 20 ) aryl, (C 6 –C 26 ) alkaryl, 5–20 membered heteroaryl or 6–26 membered alkheteroaryl or a 1 to 4-residue peptide or peptide analogue; each “-” between residues X 1 through X 18 independently designates an amide linkage, a substituted amide linkage, an isostere of an amide or an amide mimetic, wherein at least one “-” is a substituted amide linkage, an isostere of an aniide or an amide mimetic; (ii) a 15 to 21-residue peptide analogue according to formula (I) in which at least one and up to eight of residues X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , X 16 , X 17 and X 18 are optionally deleted and wherein at least one “-” is a substituted amide linkage, an isostere of an amide or an amide mimetic; or (iii) an 18 to 22-residue altered peptide analogue according to formula (I) in which at least one of residues X 1 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , X 16 , X 17 and X 18 is conservatively substituted and wherein at least one is a substituted amide linkage, an isostere of an amide or an amide mimetic; or an N-terminally blocked form, a C-terminally blocked form or an N- and C-terminally blocked form of formula (I).