Patent ID: 6900177

Claim:
An ApoA-I agonist compound comprising: (i) a 15 to 26-residue peptide or peptide analogue according to formula (I) which forms an amphipathic α-helix in the presence of lipids and exhibits at least about 38% LCAT activation activity as compared with human ApoA-I wherein one or two helical turns are deleted from formula (I), wherein a helical turn consists of 3 to 4 consecutive residues selected from residues X 1 to X 23 of 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 1 is Pro (P), Ala (A), Gly (G), Gln (Q), Asn (N), Asp (D) or D-Pro (p); X 2 is an aliphatic residue; X 3 is a Leu (L) or Phe (F); X 4 is Glu (E) X 5 is an aliphatic residue; X 6 is Leu (L) or Phe (F); X 7 is Glu (E) or Leu (L); X 8 is Asn (N) or Gln (Q); X 9 is Leu (L); X 10 is Leu (L), Trp (W) or Gly (G); X 11 is an acidic residue; X 12 is Arg (R); X 13 is Leu (L) or Gly (G); X 14 is Leu (L), Phe (F) or Gly (G); X 15 is Asp (D); X 16 is Ala (A); X 17 is Leu (L); X 18 is Asn (N) or Gln (Q); X 19 is a basic residue; X 20 is a basic residue; X 21 is Leu (L); X 22 is a basic residue; X 23 is absent or a basic residue; Z 1 is H 2 N—; Z 2 is —C(O)NRR or —C(O)OR; 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 or 6-26 membered alkheteroaryl or a 1 to 7-residue peptide or peptide analogue in which one more bonds between residues 1-7 are independently a substituted amide, an isostere of an amide or an amide mimetic; and each “-” between residues X 1 to X 23 and between residues of the peptide to Z 2 independently designates an amide linkage, 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).