2,19-methyleneoxy and 2,19-methylenethio bridged steroids as aromatase, 19-hydroxylaser inhibitors and methods of their use in the treatment of estrogen mediated disorders
AssigneeMerrell Dow Pharmaceuticals Inc.
InventorsNorton P. Peet, J. O'Neal Johnston, Joseph P. Burkhart
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Abstract
The present invention is directed to a method of using a certain compounds which are 2,19-methyleneoxy or 2,19 methylenethio bridged steroids, and related steroidal compounds as inhibitors of the enzyme steroid aromarase, 19-hydroxylase and as treatment for various estrogen dependent/mediated disorders including hormonal dependent breast cancer.
Claims25
A method of inhibiting aromatase activity which comprises contacting an effective aromarase-inhibiting amount of a compound of the formula:
- wherein:
- ----- represents a single or double bond,
- A is O, S, SO, or SO.sub.2,
- R is H, .dbd.CH.sub.2, .dbd.O, or --OH,
- R.sup.1 is H or C.sub.1-4 alkyl,
- R.sup.2 is .dbd.O, --OH, or --O--(C.sub.1-4 alkanoyl),
- X is .dbd.O, .dbd.CH.sub.2, --OH, or --O--(C.sub.1-4 alkanoyl), and
- Y is H, --OH, or --O--(C.sub.1-4 alkanoyl), and when Y.dbd.H, --OH, or --O--(C.sub.1-4 alkanoyl), X may not include --OH, and R may not include .dbd.O or --OH.
- with an aromatase enzyme.
A method of treating hyperestrogenemia, which comprises administering to a patient having said condition an effective aromatase-inhibiting amount of a compound of the formula:
- ##STR20## wherein:
- ----- represents a single or double bond,
- A is O, S, SO, or SO.sub.2,
- R is H, .dbd.CH.sub.2, .dbd.O, or --OH,
- R.sup.1 is H or C.sub.1-4 alkyl,
- R.sup.2 is .dbd.O, --OH, or --O--(C.sub.1-4 alkanoyl), and
- X is .dbd.O, .dbd.CH.sub.2, --OH, or --O--(C.sub.1-4 alkanoyl), and
- Y is H, --OH, or --O--(C.sub.1-4 alkanoyl), and when Y.dbd.H, --OH, or --O--(C.sub.1-4 alkanoyl), X may not include --OH, and R may not include .dbd.O or --OH.
A method of treating estrogen-induced or estrogen-stimulated disorders, which comprises administering to a patient having said condition an effective aromatase-inhibiting amount of a compound of the formula:
- ##STR26## wherein:
- ----- represents a single or double bond,
- A is O, S, SO, or SO.sub.2,
- R is H, .dbd.CH.sub.2, .dbd.O, or --OH,
- R.sup.1 is H or C.sub.1-4 alkyl,
- R.sup.2 is .dbd.O, --OH, or --O--(C.sub.1-4 alkanoyl),
- X is .dbd.O, .dbd.CH.sub.2, --OH, or --O--(C.sub.1-4 alkanoyl), and
- Y is H, --OH, or --O--(C.sub.1-4 alkanoyl), and when Y.dbd.H, --OH, or -O-(C.sub.1-4 alkanoyl), X may not include --OH, and R may not include =0 or --OH.
A method of treating hypertensive or edemous conditions, which comprises administering to a patient in need thereof an effective aromatase inhibiting amount of a compound of the formula:
- ##STR32## wherein:
- ----- represents a single or double bond,
- A is O, S, SO, or SO.sub.2,
- R is H, .dbd.CH.sub.2, .dbd.O, or --OH,
- R.sup.1 is H or C.sub.1-4 alkyl,
- R.sup.2 is .dbd.O, --OH, or --O--(C.sub.1-4 alkanoyl),
- X is .dbd.O, .dbd.CH.sub.2, --OH, or --O--(C.sub.1-4 alkanoyl), and
- Y is H, --OH, or --O--(C.sub.1-4 alkanoyl), and when Y.dbd.H, --OH, or --O--(C.sub.1-4 alkanoyl), X may not include --OH, and R may not include .dbd.O or --OH.
Dependencies are inferred from the claim text.