Patent ID: 6265377
Filing Date: 2001-07-24
Classification: A61K,A61P,C07K

Abstract:
An ApoA-I agonist compound comprising:a 15 to 22-residue peptide or peptide analogue which forms an amphipathic .alpha.-helix in the presence of lipids and which comprises formula (I):Z.sub.1 -X.sub.1 -X.sub.2 -X.sub.3 -X.sub.4 -X.sub.5 -X.sub.6 -X.sub.7 -X.sub.8 -X.sub.9 -X.sub.10 -X.sub.11 -X.sub.12 -X.sub.13 -X.sub.14 -X.sub.15 -X.sub.16 -X.sub.17 -X.sub.18 -Z.sub.2 (I)or a pharmaceutically acceptable salt thereof, wherein:X.sub.1 is Pro (P), Ala (A), Gly (G), Asn (N), Gln (Q) or D-Pro (p);X.sub.2 is an aliphatic amino acid;X.sub.3 is Leu (L);X.sub.4 is an acidic amino acid;X.sub.5 is Leu (L) or Phe (F);X.sub.6 is Leu (L) or Phe (F);X.sub.7 is a basic amino acid;X.sub.8 is an acidic amino acid;X.sub.9 is Leu (L) or Trp (W);X.sub.10 is Leu (L) or Trp (W);X.sub.11 is an acidic amino acid or Asn (N);X.sub.12 is an acidic amino acid;X.sub.13 is Leu (L), Trp (W) or Phe (F);X.sub.14 is a basic amino acid or Leu (L);X.sub.15 is Gln (Q) or Asn (N);X.sub.16 is a basic amino acid;X.sub.17 is Leu (L);X.sub.18 is a basic amino acid;Z.sub.1 is H.sub.2 N-- or RC(O)NH--;Z.sub.2 is --C(O)NRR, --C(O)OR or --C(O)OH or a salt thereof;each R is independently --H, (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) alkenyl, (C.sub.1 -C.sub.6) alkynyl, (C.sub.5 -C.sub.20) aryl, (C.sub.6 -C.sub.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.sub.1 through X.sub.18 independently designates an amide linkage, a substituted amide linkage, an isostere of an amide or an amide mimetic; andup to eight of residues X.sub.1, X.sub.2, X.sub.3, X.sub.4, X.sub.5, X.sub.6, X.sub.7, X.sub.8, X.sub.9, X.sub.10, X.sub.11, X.sub.12, X.sub.13, X.sub.14, X.sub.15, X.sub.16, X.sub.17 and X.sub.18 are optionally deleted.