3-(4'-Bromobenzylindenyl)-2-indolinone and analogues thereof for the treatment of disease

A compound having the formula:

• ##STR12## or a pharmaceutically acceptable salt thereof, wherein:
• R.sub.1 is H or alkyl;
• R.sub.2 is O or S;
• R.sub.3 is hydrogen;
• R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• R.sub.3 ' and R.sub.5 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• R.sub.2 ' and R.sub.6 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2),CO.sub.2 R, and CONRR';
• n is 0-3;
• Z is Br, Cl, F, I, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, or tert-butyl;
• R is H, alkyl or aryl;
• R' is H, alkyl or aryl;
• and
• with the provisos that:
• (i) when Z is Cl, R.sub.3 ' is not halogen;
• (ii) when Z is Br, Cl, F or methyl, at least one of R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.2 ', R.sub.3 ', R.sub.5 ', or R.sub.6 ' is independently selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2),CO.sub.2 R, and CONRR';
• (iii) when Z is Cl or F, R.sub.1 is not alkyl;
• (iv) when Z is Br or Cl, R.sub.6 is not trihalomethyl;
• (v) when Z is Cl, R.sub.4 is not halogen, and
• (vi) when Z is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, or tert-butyl, R.sub.5 is not hydrogen or halogen.

A compound having the formula:

• ##STR13## or a pharmaceutically acceptable salt thereof, wherein:
• R.sub.1 is H or alkyl;
• R.sub.2 is O or S;
• R.sub.3 is hydrogen;
• R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• R.sub.3 ' and R.sub.5 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• R.sub.2 ' and R.sub.6 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NR.sub.2, OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• n is 0-3;
• Z is I;
• R is H, alkyl or aryl;
• and
• R' is H, alkyl or aryl.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a compound having the formula:

• ##STR14## or a pharmaceutically acceptable salt thereof, wherein:
• R.sub.1 is H or alkyl;
• R.sub.2 is O or S,
• R.sub.3 is hydrogen;
• R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SONRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH),CO.sub.2 R, and CONRR';
• R.sub.2 ', R.sub.3 ', R.sub.4 ', and R.sub.6 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• n is 0-3;
• Z is Br, Cl, F, I, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, or tert-butyl;
• R is E, alkyl or aryl;
• R' is H, alkyl or aryl;
• and
• with the provisos that:
• (i) when Z is Cl, R.sub.3 ' is not Cl;
• (ii) when Z is F, at least one of R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.2 ', R.sub.2 ', R.sub.3 ', R.sub.5 ', or R.sub.6 ' is independently selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 RR', SO.sub.3 R, SR, NO.sub.2, OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• (iii) when Z is Br or Cl, R.sub.6 is not trihalomethyl, and
• (iv) if one or both of R.sub.2 ' and R.sub.6 ' are NRR', then R and R' are not alkyl substituted with N(CH.sub.3).sub.2 or amino.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a compound having the formula:

• ##STR15## or a pharmaceutically acceptable salt thereof, wherein:
• R.sub.1 is H or alkyl;
• R.sub.2 is O or S;
• R.sub.3 is hydrogen;
• R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• R.sub.3 ' and R.sub.5 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• R.sub.2 ' and R.sub.6 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• n is 0-3;
• Z is Br, Cl, F, I, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, or tert-butyl;
• R is H, alkyl or aryl;
• R.sub.1 is alkyl or aryl;
• and
• with the provisos that:
• (i) when Z is Cl, R.sub.3 ' is not halogen;
• (ii) when Z is Br, Cl, F or methyl, at least one of R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.2 ', R.sub.3 ', R.sub.5 ', or R.sub.6 ' is independently selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, N.sub.2 O, OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• (iii) when Z is Cl or F, R, is not alkyl;
• (iv) when Z is Br or Cl, R.sub.6 is not trihalomethyl;
• and
• (v) when Z is Cl, R.sub.4 is not halogen.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a compound having the formula having the formula:

• ##STR16## or a pharmaceutically acceptable salt thereof, wherein:
• R.sub.1 is H or alkyl;
• R.sub.2 is O or S;
• R.sub.3 is hydrogen;
• R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR, OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2),CO.sub.2 R, and CONRR';
• R.sub.3 ' and R.sub.5 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, NRR', OH, CN, C(O)R, OC(O)R, NHC(O)R, (CH.sub.2),CO.sub.2 R, and CONRR';
• R.sub.2 ' and R.sub.6 ' are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, aryloxy, alkaryl, alkaryloxy, halogen, trihalomethyl, S(O)R, SO.sub.2 NRR', SO.sub.3 R, SR, NO.sub.2, OH, CN, C(O)R, OC(O)R, OC(O)R, NHC(O)R, (CH.sub.2).sub.n CO.sub.2 R, and CONRR';
• n is 0-3;
• Z is I, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, or tert-butyl;
• R is H, alkyl or aryl;
• and
• R' is H, alkyl or aryl.