Androgen receptor suppressors in the therapy and diagnosis of prostate cancer, alopecia and other hyper-androgenic syndromes
AssigneeBiophysica, Inc.
InventorsMilos Sovak, Allen L. Seligson, James Gordon Douglas, III, Brian Campion, Jason W. Brown
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Abstract
Substituted phenylalanines are provided comprising an hydantoin, urea or 2-hydroxyl, 2-methylpropionyl group, dimers thereof and alkyl, polyfluoroamido and haloarylamino derivatives thereof, as well as radiolabeled derivatives thereof. The compounds bind specifically to the androgen receptor and find use in indications associated with the androgen receptor, such as cell hyperplasia dependent on androgens, hirsutism, acne and androgenetic alopecia.
Claims35
A compound of the formula:
- wherein:
- X is nitro, cyano or halogen;
- V is CF3, halogen or H;
- W is OH when T is H and is methyl when T and T1 are taken together to form a C═Z bridge;
- U is N when T and T1 are taken together to form a C═Z bridge or is taken together with T1 to form a bond or O or N;
- Q is a chalcogen;
- n is 1 or 2and d is 0 or 1;
- when d is 0, T and T1 are hydrogen;
- when d is 1, then:
- when n is 1, Y is a bond or linking group of from 1 to 10 carbon atoms and from 0 to 6 heteroatoms in the chain, where the heteroatoms are N, O, or S;
- Z, when other than taken together with Y, is an aliphatic group of from 1 to 6 carbon atoms, a polyfluoroacylamido group of from 2 to 8, carbon atoms and having at least 2 fluorines and not more than 2m−1 fluorines, wherein m is the number of carbon atoms, or haloanilino, where halo is of atomic number 9 to 80;
- and
- when n is 2, Y and Z are taken together to form a bond or a linking group of from 1 to 10 carbon atoms and from 0 to 6 heteroatoms, with from 0 to 4 heteroatoms in the chain, where the heteroatoms are N, O, and S.
A compound of the formula:
- wherein:
- X1 is nitro or cyano;
- V1 is CF3;
- A1 is a chalcogen other than S;
- Y1 is alkylene of from 2 to 8 carbon atoms;
- Z1 is a polyfluoroacylamido of from 2 to 8 and having at least 2m−2 fluoro groups,
- wherein m is the number of carbon atoms, or substituted arylamino of from 6 to 10 carbon atoms, and halogen of atomic number from 9 to 80.
A compound of the formula:
- wherein:
- X3 is cyano;
- V3 is CF3;
- n3 is 1 or 2;
- Q3 is a chalcogen;
- when n is 1, Y3 is a bond or linking group of a total of from 1 to 6 atoms, which are C, N, O, and S;
- Z3 is alkyl of from 1 to 6 carbon atoms, polyfluoroacylamido of from 2 to 6 carbon atoms and at least 2m−2 fluorine atoms, wherein m is the number of carbon atoms, or haloanilino, where halo is of atomic number from 9 to 80;
- and
- when n is 2, Y3 and Z3 are taken together to form a linking group of a total of 1 to 10 C, N, O, and S atoms.
A compound of the formula:
- wherein:
- X2 is nitro or cyano;
- V2 is CF3;
- n2 is 1 or 2;
- U2 is a bond, N or chalcogen;
- when n is 1, Y2 is a bond or linking group of a total of from 1 to 6 atoms, which are C, N, O, and S;
- with the proviso that when U2 is a bond, Y2 is also a bond;
- and
- Z2 is polyfluoroacylamido of from 2 to 6 carbon atoms and at least 2m−2 fluorine atoms, wherein m is the number of carbon atoms, an aliphatic group of from 1 to 6 carbon atoms substituted with a radioisotope or haloanilino, where halo is of atomic number 9 to 80;
- and
- when n is 2, Y2 and Z2 are taken together to form a linking group of a total of 1 to 10 C, N, O, and S atoms.
A compound of the formula N-(3-trifluoromethyl-4-cyanophenyl), N′-propyl thiourea.
Dependencies are inferred from the claim text.