Patent ID: 7157425

Claim:
An Apo A-I agonist compound comprising: (i) a 22 to 29-residue D-enantiomeric peptide or peptide analogue which forms an amphipathic α-helix in the presence of lipids and which 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 -X 19 -X 20 -X 21 -X 22 -X 23 -Z 2 or a pharmaceutically acceptable salt thereof, wherein: X, is D-Ala (a), Gly (G), D-Gln (q), D-Asn (n) D-Asp (d) or D-Pro (p); X 2 is a D-enantiomeric aliphatic residue; X 3 is D-Leu (l) or D-Phe (f); X 4 is D-Glu (e); X 5 is a D-enantiomeric aliphatic residue; X 6 is D-Leu (l) or D-Phe (f); X 7 is D-Glu (e) or D-Leu (l); X 8 is D-Asn (n) or D-Gln (q); X 9 is D-Leu (l); X 10 is D-Leu (l), D-Trp (w) or Gly (G); X 11 is a D-enantiomeric acidic residue; X 12 is D-Arg (r); X 13 is D-Leu (l) or Gly (G); X 14 is D-Leu (l), D-Phe (f) or GLy (G); X 15 is D-Asp (d); X 16 is D-Ala(a); X 17 is D-Leu (l); X 15 is D-Asn (a) or D-Gln (q); X 19 is a D-enantiomeric basic residue; X 20 is a D-enantiomeric basic residue; X 21 is D-Leu (l); X 22 is a D-enantiomeric basic residue; X 23 is absent or a D-enantiomeric basic residue; Z 1 is R 2 N— or RC(O)NR—; Z 2 is —C(O)NRR, —C(O)OR or —C(O)OH or a salt thereof; each R is independently —H, (C 1 –C 6 ) alkyl, (C 1 –C 6 ) alkenyl, (C 1 –C 6 ) alkynyl, (C 5 –C 20 ) aryl, (C 6 –C 26 ) alkaryl, 5–20 membered heteroaryl, 6–26 membered alkheteroaryl or a 1 to 7-residue peptide or peptide analogue in which one or more bonds between residues 1 through 7 are independently a substituted amide, an isostere of an amide or an amide mimetic; and each “-” between residues X 1 , through X 23 independently designates an amide linkage, a substituted amide linkage, an isostere of an amide or an amide mimetic; or (ii) a 14 to 28-residue deleted D-enantiomeric peptide or peptide analogue 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 , X 18 , X 19 , X 20 , X 21 , X 22 , and X 23 are optionally deleted; or (iii) a 22 to 29-residue altered D-enantiomeric peptide or peptide analogue according to formula (I) in which at least one 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 , X 18 , X 19 , X 20 , X 21 , X 22 , and X 23 is conservatively substituted with another D-enantiomeric residue.