3-Aryl-hydroxybenzoxazines and 3, 4-dihydro-3-aryl-hydroxybenzoxazines as selective estrogen receptor beta modulators
AssigneeBristol-Myers Squibb Company
InventorsJohn K. Dickson, Timur Gungor, Wu Yang
Life of this patent
Estimating the term…
Abstract
Substituted benzoxazine and 3,4-dihydrobenzoxazine derivatives possessing activity as estrogen receptor beta (ERβ) modulators are provided which have the structure of formula I 1 wherein the substitutents are as described herein. In addition, a method is provided for preventing, inhibiting or treating the progression or onset of pathological conditions associated with the estrogen receptor and to pharmaceutical compositions containing such compounds.
Claims14
A compound of the formula I
- 33
- wherein
- R1 and R2 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted arylalkyl and hydroxyalkyl, or R2 together with R4 may independently be cyclized to form —(CH2)n— where n=1, 2, or 3;
- R3 is selected from the group consisting of hydrogen, OH, halo, CF3, CN, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl and alkoxy;
- R4 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, halo, OH and alkoxy;
- Z is hydrogen, or Y and Z can together form a bond;
- Y, where Z is H, is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, COR5, CSR5, SO2R5, CONR6R7, COOR8 and COSR9, or Y together with R3 may form a six membered heterocyclic ring containing —OCH2CH2— or —OCH2CO—;
- R5 is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
- R6 and R7 are each independently hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
- and
- R8 and R9 are each independently substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
- including all prodrug esters, pharmaceutically acceptable salts and stereoisomers thereof.
A pharmaceutical composition capable of modulating the function of an estrogen receptor beta (ERβ), comprising a compound of formula I
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- wherein
- R1 and R2 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted arylalkyl and hydroxyalkyl, or R2 together with R4 may independently be cyclized to form —(CH2)n—where n=1, 2, or 3;
- R3 is selected from the group consisting of hydrogen, OH, halo, CF3, CN, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl and alkoxy;
- R4 is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, halo, OH and alkoxy;
- Z is hydrogen, or Y and Z can together form a bond;
- Y, where Z is H, is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, COR5, CSR5, SO2R5, CONR6R7, COOR8 and COSR9, or Y together with R3 may form a six membered heterocyclic ring containing —OCH2CH2— or —OCH2CO—;
- R5 is hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
- R6 and R7 are each independently hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
- and
- R8 and R9 are each independently substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
- including all prodrug esters, pharmaceutically acceptable salts and stereoisomers thereof;
- and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.