Steriod inhibitors of estrone sulfatase and associated pharmaceutical compositions and methods of use
AssigneeSRI International
InventorsMasato Tanabe, Richard H. Peters, Wan-Ru Chao, Kazuhiko Shigeno
Life of this patent
Estimating the term…
Abstract
Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) ##STR1## wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.
Claims13
A compound having the structural formula (I) ##STR21## wherein:
- n is 1;
- R.sup.1 and R.sup.2 are different, and are selected from the group consisting of hydrogen, lower alkyl, lower alkynyl, and OR.sup.6 where R.sup.6 is hydrogen, lower alkyl or --(CO)--R.sup.7 where R.sup.7 is lower alkyl, or wherein R.sup.1 and R.sup.2 together form .dbd.O, .dbd.S, or .dbd.C(R.sup.8 R.sup.9) in which R.sup.8 and R.sup.9 are independently selected from the group consisting of hydrogen, --CHO, lower alkyl, and cyano, or together form a .dbd.CH.sub.2 substituent;
- R.sup.3 is hydrogen, halogen or lower alkyl, or, when the dotted line at q.sub.1 indicates the presence of a double bond, is CH.sub.2 ;
- R.sup.4 is selected from the group consisting of hydrogen and lower alkyl;
- R.sup.5 is selected from the group consisting of hydrogen, hydroxyl, lower alkyl, lower alkenyl, lower alkoxy, and aryl, or when the dotted line at q.sub.2 indicates the presence of a double bond, is CH.sub.2 ;
- and
- X and Y are linked to form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, if dihydro-oxathiazine, having a substituent R.sup.10 on the carbon atom adjacent to the A ring, wherein R.sup.10 is hydrogen, lower alkyl, lower alkynyl or monocyclic aryl, and Z is hydrogen,
- and pharmaceutically acceptable salts and esters thereof.
A method for inhibiting the enzymatic activity of estrone sulfatase comprising contacting the enzyme with an effective estrone sulfatase inhibiting amount of a compound having the structural formula (I) ##STR22## wherein:
- n is 1;
- R.sup.1 and R.sup.2 are different, and are selected from the group consisting of hydrogen, lower alkyl, lower alkynyl, and OR.sup.6 where R.sup.6 is hydrogen, lower alkyl or --(CO)--R.sup.7 where R.sup.7 is lower alkyl, or wherein R.sup.1 and R.sup.2 together form .dbd.O, .dbd.S, or .dbd.C(R.sup.8 R.sup.9) in which R.sup.8 and R.sup.9 are independently selected from the group consisting of hydrogen, --CHO, lower alkyl, and cyano, or together form a .dbd.CH.sub.2 substituent;
- R.sup.3 is hydrogen, halogen or lower alkyl, or, when the dotted line at q.sub.1 indicates the presence of a double bond, is CH.sub.2 ;
- R.sup.4 is selected from the group consisting of hydrogen and lower alkyl;
- R.sup.5 is selected from the group consisting of hydrogen, hydroxyl, lower alkyl, lower alkenyl, lower alkoxy, and aryl, or when the dotted line at q.sub.2 indicates the presence of a double bond, is CH.sub.2 ;
- and
- X and Y are linked to form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, if dihydro-oxathiazine, having a substituent R.sup.10 on the carbon atom adjacent to the A ring, wherein R.sup.10 is hydrogen, lower alkyl, lower alkynyl or monocyclic aryl, and Z is hydrogen,
- or with a pharmaceutically acceptable salt or ester thereof.
Dependencies are inferred from the claim text.