Substituted phenylcarbamoyl alkylamino arene compounds and N,N′-BIS-arylurea compounds

摘要

Substituted phenylcarbamoyl alkylamino arenes; substituted phenylthiocarbamyl alkylamino arenes; substituted phenylcarbamoyl alkylamino heteroarenes; substituted phenylthiocarbamyl alkylamino heteroarenes; N-substituted aryl, N′-substituted aryl urea compounds; N-substituted aryl, N′-substituted heteroaryl urea compounds; N-substituted aryl, N′-substituted aryl thiourea compounds and N-substituted aryl, N′-substituted heteroaryl thiourea compounds are provided and may find use as androgen receptor modulators. The compounds may find particular use in treating prostate cancer, including castration-resistant prostate cancer and/or hormone-sensitive prostate cancer.

主权项

1. A compound of formula (II):or a pharmaceutically acceptable salt thereof, wherein:
W1 is CN, NO2 or SO2R4; W2 is hydrogen, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl; Z is S, 0 or NR5; Y1 and Y2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl or Y1 and Y2 are taken together with the carbon to which they are attached to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl or substituted cycloalkyl; Y3 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, substituted heterocyclyl carboxyl, formyl, alkyl carbonyl, substituted alkyl carbonyl, alkenyl carbonyl, substituted alkenyl carbonyl, alkynyl carbonyl, substituted alkynyl carbonyl, aryl carbonyl, substituted aryl carbonyl, heteroaryl carbonyl, substituted heteroaryl carbonyl, arylalkyl carbonyl, arylalkenyl carbonyl, arylalkynyl carbonyl, heteroaralkyl carbonyl, heterocyclyl carbonyl, substituted heterocyclyl carbonyl, cyano, aminocarbonyl, N-alkyl aminocarbonyl, N,N-dialkyl aminocarbonyl, N-substituted alkyl aminocarbonyl, N,N-bis-substituted alkyl aminocarbonyl, alkoxy carbonyl, substituted alkoxy carbonyl, halocarbonyl, hydroxymethyl, alkoxymethyl, substituted alkoxymethyl, thiocarboxyl, thioformyl, alkyl thiocarbonyl, substituted alkyl thiocarbonyl, alkenyl thiocarbonyl, substituted alkenyl thiocarbonyl, alkynyl thiocarbonyl, substituted alkynyl thiocarbonyl, aryl thiocarbonyl, substituted aryl thiocarbonyl, heteroaryl thiocarbonyl, substituted heteroaryl thiocarbonyl, arylalkyl thiocarbonyl, arylalkenyl thiocarbonyl, arylalkynyl thiocarbonyl, heteroaralkyl thiocarbonyl, heterocyclyl thiocarbonyl, substituted heterocyclyl thiocarbonyl, thiocarbamyl, N-alkyl thiocarbamyl, N,N-dialkyl thiocarbamyl, N-substituted alkyl thiocarbamyl, N,N-bis-substituted alkyl thiocarbamyl, alkoxy thiocarbonyl, substituted alkoxy thiocarbonyl, halothiocarbonyl, mercaptomethyl, substituted alkylthiomethyl; T is carbon or nitrogen and can be at any position in the ring; R1 is C1-C8 alkyl-NRaRb, —O—C1-C8 alkyl-NRcRd or —C(O)NReRf, wherein:
Ra is a C1-C12 alkyl and Rb is H or a C1-C12 alkyl or Ra and Rb are taken together with the N to which they are attached to form a heterocyclic ring;Rc is a C1-C12 alkyl and Rd is H or a C1-C12 alkyl or Rc and Rd are taken together with the N to which they are attached to form a heterocyclic ring;Re is a C1-C12 alkyl and Rf is H or a C1-C12 alkyl, or Re and Rf are taken together with the N to which they are attached to form a heterocyclic ring; R2 is hydrogen, halo, nitro, alkyl or substituted alkyl; R4 and R5 are independently hydrogen, alkyl, substituted alkyl, aryl or substituted aryl; and if R1 and R2 are both hydrogen, T is nitrogen.