Patent NZ-505279-A (NZ)
Title: Substituted diphenyl indanone, indane and indole compounds and analogues thereof useful for the treatment or prevention of diseases characterized by abnormal cell proliferation
Inventor: KELLEHER EUGENE W
IPC: A61K31/22
Filed: 1998-11-20
Abstract: The compound of formula (I) is described wherein: - - - is a single or double bond; m is 0, 1, 2, 3 or 4; each n is 0, 1, 2, 3, 4 or 5; Y is absent, (C1-C6)alkyl, (C1-C6)alkenyl or (C1-C6)alkynyl; R1 is H, -OR, -SR, -O- C(O)R, -S-C(O)R, -O-C(S)R, -S-C(S)R, or when taken together with R2 is a =O, =S, =N-OR, a 3-8 membered heterocycloalkyl or a substituted 3-8 membered heterocycloalkyl; R2 is absent or -H; R3 is absent or -H; R4 is -H, -OR', -SR', -NR'2, -CN, -NO2, (C3 -C8)cycloalkyl, 3-8 membered heterocycloalkyl, -C(O)R', -C(S)R', -C(O)OR', -C(S)OR', - C(O)SR', -C(S)SR', -C(O)NR'2 or -C(S)NR'2; each R5, R6 and R7 is independently selected from the group consisting of halogen, -R', -OR', -SR', -NR'2, -ONR'2, -SNR'2, -NO2, - CN, -C(O)R', -C(S)R', -C(O)OR', -C(O)SR', -C(S)OR', - CS(S)R', -C(O)NR'2, -C(S)NR'2, -C(O)NR'(OR'), - C(S)NR'(OR'); -C(O)NR'(SR'), -C(S)NR'(SR'), -CH(CN)2, - CH[C(O)R']2, -CH[C(S)R']2, -CH[C(O)OR']2, -CH[C(S)OR']2, - CH[C(O)SR']2 and -CH[C(S)SR']2 ; with the following exceptions: when --- is single bond, X is C, R1 is -OH, R2 is , R3 and R4 are H, Y is absent then at least one of R5, R6 and R7 are other than H or when --- is single bond , X is C, R1 and R2 taken together are =O, Y is absent, R3 and R4 are H , then at least one of R5, R6 and R7 are other than H ; or when --- is single bond, X is C, R1 and R2 taken together are -O, Y is absent, R3 and R4 are H, m=0, n=1 and R5 is H, then R6 is Br(para) or OME (para) or OH(para) or when --- is single bond, X is C, R1, R2, R3 and R4 are H, Y is absent then (a) at least one of R5 , R6 or R7 is other than H and (b) if m=0 and n=1, then R5 and R6 are not both NH2(para) or -OH(para); or when --- is double bond, X is C, R1 and R4 aer H, R2, R3 and Y are basent then (a) at least one of R5 , R6 or R7 is other than H and (b) if m=0 and n=1, and R5 is H then R6 is not OMe(para) or Br(para) or -CN(para); or when --- is single bond, X is C, R1 and R2 taken together are =O, Y is CH2, R3 and R4 are H, m=0, n=1 then R5 and R6 are not both -OH(para); or when --- is single bond, X is C, R1 and R2 taken together are =O, Y is CH2, R3 is H, R4 -C(O)OEt, m=0, n=1 and R5 is H, then R6 is not -OH(para); or when --- is single bond, X is C, R1 is -OH, R2 , R3 and R4 are H, Y is absent, m=0, n=1 and R5 is H, then R6 is not -Br at the para position; or when --- is single bond, X is C, R1 and R2 taken together are =N-OR, wherein R is H, and Y is absent and R3, R4, R5, R6 and R7 are H then the salt can not be hydrochloric; or when --- is single bond, X is N, R1, R3 and R4 are H, Y and R2 are absent then a) at least one of R5, R6 or R7 are other than H, and b) if n=0 and m is 2, then the R7 substituents are not both Br at the 5 and 7 positions of the indole moiety or when --- is single bond, X is N, R1, R3 and R4 are H, Y and R2 are absent, m=0, n=1 then R5 and R6 are not both NMe2(para) or Me(para); or when --- is double bond, X is N, R1, R2, R3 and Y are absent, R4 is H then a) at least one of R5, R6 or R7 are other than H, and b) if n=0 and m=2, then the R7 substituents are not both Br at the 5 and 7 positions of the indole moiety or when --- is double bond, X is N, R1, R2, R3 and Y are absent, R4 is H, m=0, n=1 then R5 and R6 are not both Me(para); or when --- is double bond, X is N, R1, R2, R3 and Y are absent, R4 is NH2 or OCH3 then at least one of R5, R6 or R7 are other than H; each R is independently selected from the group consisting of H, (C1-C6)alkyl, (C1-C6)alkenyl, (C1-C6)alkynyl, (C5- C20)aryl, substituted (C5-C20)aryl, (C6-C26)alkaryl and substituted (C6-C26)alkaryl; each R' is independently selected from the group consisting of -H, (C1-C6)alkyl, (C1- C6)alkenyl and (C1-C6)alkynyl. Pharmaceutical compositions comprising the compounds are useful treating or preventing a disorder characterized by abnormal cell proliferation, including cancer, a blood vessel proliferative disorder, a fibrotic disorder or an arteriosclerotic condition, Kaposi's sarcoma and dermatological diseases such as keloids, seborrheic dermatosis, papilloma virus infection and eczema,