Treatment and prevention of prostatic cancer metastasis

A method of treating or preventing the metastasis to bone of prostatic cancer in a patient in need of such treatment or prevention comprising administering to such patient an effective amount of a compound of the formula ##STR13## wherein R and R.sup.1 both represent hydrogen or combine to form a bond;

• R.sup.2 represents hydrogen or C.sub.1 -C.sub.3 alkyl;
• R.sup.3 represents hydrogen, methyl or ethyl;
• either R.sup.4 and X--R.sup.5 have the following definitions, (R.sup.6).sub.m is absent, and R.sup.3 does not represent hydrogen;
• or (R.sup.6).sub.m has the following definition, R.sup.4 and X--R.sup.5 are absent, and R.sup.3 does not represent ethyl;
• R.sup.4 and --X--R.sup.5 each occupies one of the 7-, 8- and 9-positions;
• R.sup.4 represents hydrogen, halo, methyl or ethyl;
• X represents C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, a bond, --SO--, --SO.sub.2 --, --CO--Y--(CH.sub.2).sub.n --, --Y--CO--(CH.sub.2).sub.n, --CO--, --Z--(CH.sub.2).sub.n --, or --SO.sub.3 --;
• wherein X groups which are not symmetrical may be in either orientation;
• Y represents --S--, --O--, or --NH--;
• Z represents --O-- or --S--;
• n represents 0-3;
• R.sup.5 represents phenyl, naphthalenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, anthracenyl, acenaphthalenyl, thiazolyl, benzimidazolyl, indazolyl, thiophenyl, phenanthrenyl, quinolinyl, fluorenyl, isoquinolinyl, indanyl, benzopyranyl, indolyl, benzisoquinolinyl, benzindolyl, benzothiazolyl, benzothiophenyl, quinoxalinyl, benzoxazolyl, tetrazolyl, naphthothiazolyl, quinazolinyl, thiazolopyridinyl, pyridazinoquinazolinyl, benzisothiazolyl, benzodioxolyl, benzodioxinyl, diphenylmethyl or triphenylmethyl;
• the above R.sup.5 groups are unsubstituted or substituted with 1-3 groups chosen from the group consisting of halo, trifluoromethyl, trifluoroethoxy, C.sub.1 -C.sub.4 alkyl, trifluoromethoxy, hydroxy, C.sub.1 -C.sub.3 alkoxy, nitro, C.sub.1 -C.sub.3 alkylthio, C.sub.1 -C.sub.6 alkanoyl, phenyl, oxo, phenoxy, phenylthio, C.sub.1 -C.sub.3 alkylsulfinyl, C.sub.1 -C.sub.3 alkylsulfonyl, cyano, amino, C.sub.1 -C.sub.3 alkylamino, diphenylmethylamino, triphenylmethylamino, benzyloxy, benzylthio, (mono-halo, nitro or CF.sub.3)benzyl(oxy or thio), di(C.sub.1 -C.sub.3 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or C.sub.4 -C.sub.8 cycloalkylalkyl)amino, (mono-C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo)-(phenyl, phenoxy, phenylthio, phenylsulfonyl or phenoxysulfonyl), C.sub.2 -C.sub.6 alkanoylamino, benzoylamino, diphenylmethylamino(C.sub.1 -C.sub.3 alkyl), aminocarbonyl, C.sub.1 -C.sub.3 alkylaminocarbonyl, di(C.sub.1 -C.sub.3 alkyl)aminocarbonyl, halo-C.sub.1 -C.sub.6 alkanoyl, aminosulfonyl, C.sub.1 -C.sub.3 alkylaminosulfonyl, di(C.sub.1 -C.sub.3 alkyl)aminosulfonyl, phenyl(oxy or thio)(C.sub.1 -C.sub.3 alkyl), (halo, C.sub.1 -C.sub.3 alkyl or C.sub.1 -C.sub.3 alkoxy)phenyl(oxy or thio)(C.sub.1 -C.sub.3 alkyl), benzoyl, or (amino, C.sub.1 -C.sub.3 alkylamino or di(C.sub.1 -C.sub.3 alkyl)amino)(C.sub.1 -C.sub.3 alkyl);
• or an above R.sup.5 group is substituted with a morpholino(C.sub.1 -C.sub.3 alkyl) group, a phenyl(C.sub.1 -C.sub.3 alkyl)piperidinyl group, a phenyl(C.sub.1 -C.sub.3 alkyl)piperidinylaminocarbonyl group, a C.sub.2 -C.sub.6 alkanoylaminothiophenyl group, or a (amino, C.sub.1 -C.sub.3 alkylamino or di(C.sub.1 -C.sub.3 alkyl)amino)naphthalenylsulfonylamino group;
• or R.sup.5 is a perhalophenyl group;
• m represents 1-2;
• R.sup.6 represents hydrogen, halogen, NO.sub.2, cyano, CF.sub.3, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, carboxy, C.sub.1 -C.sub.6 alkoxycarbonyl, amino, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, amido, C.sub.1 -C.sub.4 alkylamido, C.sub.1 -C.sub.4 dialkylamido, mercapto, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulfinyl, C.sub.1 -C.sub.6 alkylsulfonyl, or a group --A--R.sup.7 where A is C.sub.1 -C.sub.6 alkylene C.sub.2 -C.sub.6 alkenylene or C.sub.2 -C.sub.6 alkynylene;
• and R.sup.7 represents halogen, hydroxy, CF.sub.3, C.sub.1 -C.sub.6 alkoxy, carboxy, C.sub.1 -C.sub.6 alkoxycarbonyl, amino, C.sub.1 -C.sub.4 alkylamino, C.sub.1 -C.sub.4 dialkylamino, amido, C.sub.1 -C.sub.4 alkylamido, C.sub.1 -C.sub.4 dialkylamido, C.sub.1 -C.sub.4 alkylsulfonylamino, aminosulfonyl or C.sub.1 -C.sub.4 alkylaminosulfonyl;
• or a pharmaceutically acceptable salt thereof.