Patent ID: 6060477
Filing Date: 2000-05-09
Classification: A61K

Abstract:
A method of treating a patient having precancerous lesions sensitive to the compounds below in need of treatment, comprising administering to the patient a pharmacologically effective amount of a compound of the formula: ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 may be located at any of the available positions on the phenyl ring, each of R.sup.1, R.sup.2 and R.sup.3 may be independently selected from hydrogen, halogen, a lower alkyl group, such as having 1 to 6 carbon atoms, a lower alkoxy, a lower alkenyl, a lower alkenoxy, a lower alkyl thio, a lower alkylamino, a di(lower)alkylamino, a cyano, an acylamino, a carboxyl, a carboalkoxy, a lower alkoxycarbonyl, a lower alkylcarbonyl, a cyclo(lower)alkoxy and cyclo(lower)alkyl (lower)alkoxy in which the ring contains 3 to 8 carbon atoms, preferably 3-6 carbon atoms, a phenyl(lower) alkoxy a nitrogen containing ring, a lower alkyl-carbamoyloxy, or a halogen substituted lower alkyloxy group;and further, R.sup.3 may be --SO--NHR.sup.12 R.sup.3, NO.sub.2, NH.sub.2, NHCOR.sup.14, NHSO.sub.2 R.sup.14, SO.sub.2 NR.sup.12 R.sup.13, or N (SO.sub.2 R.sup.14).sub.2 ; wherein R.sup.12 and R.sup.13 are each independently selected from H and C.sub.1 -C.sub.4 alkyl optionally substituted with CO.sub.2 R.sup.5, OH, pryridyl, 5-isoxazolin-3-onyl, morpholino or 1-imidazolidin-2-onyl; or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, morpholino, 1-pyrazolyl or 4-(NR.sup.15)-1-piperazinyl group wherein any of said groups may optionally be substituted with one or two substitutents selected from C.sub.1 -C.sub.4 alkyl, CO.sub.2 R.sup.9, NH.sub.2 and OH; R.sup.14 is C.sub.1 -C.sub.4 alkyl or pyridyl; and R.sup.15 is H, C.sub.1 -C.sub.4 alkyl or (hydroxy) C.sub.2 -C.sub.3 alkyl;R.sup.4 may be a hydrogen, lower alkyl, a lower alkoxy, a phenyl, a hydroxy, a halogen, --NHCOR.sup.5, --NHCONHR.sup.6, 5-tetrazolyl, --CO.sub.2 R.sup.7, a cyano, --CONR.sup.8 R.sup.9, or --NR.sup.10 R.sup.11, wherein R.sup.5 to R.sup.9 are independently hydrogen or lower alkyl or R.sup.9 may be 5-tetrazolyl, and R.sup.10 and R.sup.11 are independently hydrogen or lower alkyl optionally substituted by hydroxy provided that the carbon atom adjacent to the nitrogen atom is not substituted by hydroxy; andX.sup.1, X.sup.2, X.sup.3 and X.sup.4 may be independently nitrogen or carbon with the proviso that: at least one of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 must be nitrogen and at least one of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 must be carbon; any two of X.sup.1, X.sup.2, X.sup.3 and X.sup.4 may be nitrogen; when X.sup.2 and X.sup.4 are nitrogen, X.sup.3 must be carbon; and, when X.sup.1 and X.sup.3 are nitrogen, X.sup.2 must be carbon.