Therapeutic agents and methods of use thereof for the modulation of angiogenesis
AssigneePraecis Pharmaceuticals, Inc.
InventorsGary Olson, Christopher Self, Lily Lee, Charles Cook, Jens Birktoft, Barry Morgan, Christopher Arico-Muendel
Life of this patent
Estimating the term…
Abstract
The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.
Claims22
A compound of Formula I,
- wherein
- A is a Met-AP2 inhibitory core;
- W is O or NR2;
- R1 and R2 are each, independently, hydrogen or alkyl;
- X is alkylene or substituted alkylene;
- n is 0 or 1;
- R3 and R4 are each, independently, hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
- or R3 and R4, together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic group;
- or R3 and R4 together form an alkylene group;
- Z is —C(O)— or alkylene-C(O)—;
- and
- P is a peptide comprising from 1 to about 100 amino acid residues attached at its amino terminus to Z or a group OR5 or N(R6)R7, wherein
- R5, R6 and R7 are each, independently, hydrogen, alkyl, substituted alkyl, azacycloalkyl or substituted azacycloalkyl;
- or R6 and R7, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocyclic ring structure;
- or
- Z is —O—, —NR8—, alkylene-O— or alkylene-NR8—, where R8 is hydrogen or alkyl;
- and
- P is hydrogen, alkyl or a peptide consisting of from 1 to about 100 amino acid residues attached at its carboxy terminus to Z.
-61. (canceled)
A method of treating an angiogenic disease in a subject, comprising administering to the subject a therapeutically effective amount of an angiogenesis inhibitor compound comprising the structure
- wherein
- A is a Met-AP2 inhibitory core;
- W is O or NR2;
- R1 and R2 are each, independently, hydrogen or alkyl;
- X is alkylene or substituted alkylene;
- n is 0 or 1;
- R3 and R4 are each, independently, hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
- or R3 and R4, together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic group;
- or R3 and R4 together form an alkylene group;
- Z is —C(O)— or alkylene-C(O)—;
- and
- P is a peptide comprising from 1 to about 100 amino acid residues attached at its amino terminus to Z or a group OR5 or N(R6)R7, wherein
- R5, R6 and R7 are each, independently, hydrogen, alkyl, substituted alkyl, azacycloalkyl or substituted azacycloalkyl;
- or R6 and R7, together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocyclic ring structure;
- or
- Z is —O—, —NR8—, alkylene-O— or alkylene-NR8—, where R8 is hydrogen or alkyl;
- and
- P is hydrogen, alkyl or a peptide consisting of from 1 to about 100 amino acid residues attached at its carboxy terminus to Z.
-65. (canceled)
Dependencies are inferred from the claim text.