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AssigneePraecis Pharmaceuticals, Inc.
InventorsMark A. Findeis, Howard Benjamin, Marc B. Garnick, Malcolm L. Gefter, Arvind Hundal, Laura Kasman, Gary Musso, Ethan R. Signer, James Wakefield, Michael J. Reed
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Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural β amyloid peptides (β-AP). In a preferred embodiment, the β amyloid modulator compounds of the invention are comprised of an Aβ aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural β amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural β-AP aggregation when the natural β-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
An amyloid modulator compound having the structure:
An amyloid modulator compound having the structure:
A compound comprising an amyloidogenic peptide comprising at least one D-amino acid and having a modifying group attached to the peptide, wherein said modifying group is not a n acetyl or amide group and comprises a cyclic, heterocyclic, or polycyclic group having 4 to 10 carbon atoms, or other moiety having similar steric bulk, and wherein the compound inhibits aggregation of natural amyloidogenic proteins or peptides when contacted with the natural amyloidogenic proteins or peptides, provided that said peptide is not calcitonin.
A compound comprising a retro-inverso isomer of an amyloidogenic peptide, and having a modifying group attached to said isomer, wherein said modifying group is not an acetyl or amide group and comprises a cyclic, heterocyclic, or polycyclic group having 4 to 10 carbon atoms, or other moiety having similar steric bulk, and wherein the compound inhibits aggregation of natural amyloidogenic proteins or peptides when contacted with the natural amyloidogenic proteins or peptides.
A pharmaceutical composition comprising a compound comprising an amyloidogenic peptide, and a pharmaceutically acceptable carrier, said amyloidogenic peptide comprising at least one D-amino acid, wherein said peptide inhibits aggregation of natural amyloidogenic proteins or peptides when contacted with natural amyloidogenic proteins or peptides, provided that said peptide is not calcitonin.
A pharmaceutical composition comprising a compound comprising a retro-inverso isomer of an amyloidogenic peptide, and a pharmaceutically acceptable carrier, wherein the retro-inverso isomer inhibits aggregation of natural amyloidogenic proteins or peptides when contacted with natural amyloidogenic proteins or peptides.
A compound comprising an amyloidogenic peptide comprising at least one D-amino acid and having a modifying group attached to the peptide, wherein said modifying group comprises a cyclic, heterocyclic, or polycyclic group having 4 to 10 carbon atoms, or other moiety having similar steric bulk, and wherein the compound inhibits aggregation of natural amyloidogenic proteins or peptides when contacted with the natural amyloidogenic proteins or peptides, provided that said peptide is not calcitonin or atrial natriuretic factor.
A compound comprising a retro-inverso isomer of an amyloidogenic peptide, and having a modifying group attached to said isomer, wherein said modifying group comprises a cyclic, heterocyclic, or polycyclic group having 4 to 10 carbon atoms, or other moiety having similar steric bulk, and wherein the compound inhibits aggregation of natural amyloidogenic proteins or peptides when contacted with the natural amyloidogenic proteins or peptides, provided that said peptide is not atrial natriuretic factor.
Dependencies are inferred from the claim text.