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US 11,766,480 B2Granted
Multivalent peptoid oligomers, pharmaceutical compositions and methods of using same
AssigneeNew York University
InventorsKent Kirshenbaum, Paul Michael Levine, Michael John Garabedian, Justin M. Holub
Life of this patent
Estimating the term…
Abstract
Novel peptoid oligomers are disclosed that have a formula represented by the following formula Ia or Ib: The peptoid oligomers are prepared as modulators of androgen receptor (AR), and may be prepared as pharmaceutical compositions and used for the prevention or treatment of a variety of conditions in mammals, including humans, associated with unwanted or aberrant AR activity. The present peptoid oligomers are particularly valuable for the treatment of subjects with cancer.
Claims20
An antagonist of an androgen receptor, wherein the antagonist is a synthetic oligomer according to formula Ia or Ib:
- or a pharmaceutically acceptable salt thereof;
- and stereoisomers, isotopic variants and tautomers thereof;
- wherein
- each R1 is independently a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
- a substituted or unsubstituted cycloalkylalkyl, a substituted or unsubstituted heterocycloalkylalkyl, a substituted or unsubstituted aralkyl, or a substituted or unsubstituted heteroarylalkyl;
- each R2 is independently hydrogen, or a substituted or unsubstituted alkyl;
- n is an integer between 2-45, when the synthetic oligomer is of formula Ia;
- and n is an integer between 4-45, when the synthetic oligomer is of formula Ib;
- and
- X is H, or a substituted or unsubstituted acyl;
- Y is NH2, OH, an acylamino, or acyloxy;
- provided that two monomers up to 40 monomers comprise an androgen receptor modulator moiety;
- wherein the monomers comprising an androgen receptor modulator moiety are according to formula II:
- wherein
- L1 is —(CH2)-m1 wherein the subscript m1 is an integer between 1-10;
- L2 is a single bond or —(CH2)-m2 wherein the subscript m2 is an integer between 1-10;
- Q1 is N, and Q2 is C;
- or Q1 is C, and Q2 is N;
- one of the dotted bonds is a single bond and the other is a double bond;
- AR is
- Z is O or N—O—R3a;
- R3a is H or substituted or unsubstituted alkyl;
- R4 is H or acyl;
- R5 is substituted or unsubstituted alkyl;
- each R6 and R7 is independently H or substituted or unsubstituted alkyl;
- and * denotes the attachment point;
- and
- provided that the oligomer is other than
- wherein t is 2 or 3.
26 more elements
An antagonist of an androgen receptor, wherein the antagonist is a synthetic oligomer according to formula VII:
- wherein
- each R1 is independently a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
- a substituted or unsubstituted cycloalkylalkyl, a substituted or unsubstituted heterocycloalkylalkyl, a substituted or unsubstituted aralkyl, or a substituted or unsubstituted heteroarylalkl;
- X is H, or a substituted or unsubstituted acyl;
- Y is NH2, OH, an acylamino, or acyloxy;
- the subscript t is an integer between 1 to 15;
- the subscript n1 is an integer between 1-10;
- each R3 is
- wherein Z is O or N—O—R3a;
- R3a is H or substituted or unsubstituted alkyl;
- R4 is H or acyl;
- R5 is substituted or unsubstituted alkyl;
- each R6 and R7 is independently H or substituted or unsubstituted alkyl;
- and the subscript m1 is an integer between 1-10;
- and the subscript m2 is an integer between 0-10 and * denotes the attachment point;
- or a pharmaceutically acceptable salt thereof;
- and stereoisomers, isotopic variants and tautomers thereof.
14 more elements
An antagonist of an androgen receipt, wherein the antagonist is a synthetic oligomer according to formula VIII:
- wherein
- each R1 is independently a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
- a substituted or unsubstituted cycloalkylalkyl, a substituted or unsubstituted heterocycloalkylalkyl, a substituted or unsubstituted aralkyl, or a substituted or unsubstituted heteroarylalkyl;
- X is H, or a substituted or unsubstituted acyl;
- Y is NH2, OH, an acylamino, or acyloxy;
- the subscript u is an integer between 0 to 15;
- each of the subscripts p, q, and y is an integer between 1-10;
- each R3 is
- wherein Z is O or N—O—R3a;
- R3a is H or substituted or unsubstituted alkyl;
- R4 is H or acyl;
- R5 is substituted or unsubstituted alkyl;
- each R6 and R7 is independently H or substituted or unsubstituted alkyl;
- and the subscript m1 is an integer between 1-10;
- and the subscript m2 is an integer between 0-10 and * denotes the attachment point;
- or a pharmaceutically acceptable salt thereof;
- and stereoisomers, isotopic variants and tautomers thereof.
14 more elements
An antagonist of an androgen receptor, wherein the antagonist is a synthetic oligomer according to formula IX:
- wherein
- each R1 is independently a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
- a substituted or unsubstituted cycloalkylalkyl, a substituted or unsubstituted heterocycloalkylalkyl, a substituted or unsubstituted aralkyl, or a substituted or unsubstituted heteroarylalkyl;
- the subscript v is an integer between 1 to 15;
- the subscript z is an integer between 1-10;
- each R3 is
- wherein Z is O or N—O—R3a;
- R3a is H or substituted or unsubstituted alkyl;
- R4 is H or acyl;
- R5 is substituted or unsubstituted alkyl;
- each R6 and R7 is independently H or substituted or unsubstituted alkyl;
- and the subscript m1 is an integer between 1-10;
- and the subscript m2 is an integer between 0-10;
- and * denotes the attachment point;
- or a pharmaceutically acceptable salt thereof;
- and stereoisomers, isotopic variants and tautomers thereof.
13 more elements
An antagonist of an androgen receptor, wherein the antagonist is a synthetic oligomer according to formula X:
- wherein R3 is
- wherein Z is O or N—O—R3a;
- R3a is H or substituted or unsubstituted alkyl;
- R4 is H or acyl;
- R5 is substituted or unsubstituted alkyl;
- each R6 and R7 is independently H or substituted or unsubstituted alkyl;
- and the subscript m1 is an integer between 1-10;
- and the subscript m2 is an integer between 0-10;
- and * denotes the attachment point;
- each R1 is independently unsubstituted alkyl, substituted alkyl, cycloalkylalkyl, or N-containing heteroarylalkyl;
- the subscript v is an integer between 2 to 15;
- and the subscript z is an integer between 1-10;
- or a pharmaceutically acceptable salt thereof;
- and stereoisomers, isotopic variants and tautomers thereof.
11 more elements
Dependencies are inferred from the claim text.