Thienoisoquinoline-phenylsulfonamides and their use as ER-NFκB inhibitors
This invention provides estrogen receptor modulators having the structure: wherein R 1 to R 7 are as defined in the specification; or a pharmaceutically acceptable salt thereof.
1. A compound of the formula:
or pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen, alkyl, halogen, aryl, thienyl, furanyl, or pyrrolyl;
R 2 , R 3 , R 5 , and R 6 are, independently, hydrogen, hydroxy, lower alkyl, alkoxy, or halogen;
R 4 is alkyl;
R 7 is hydrogen, methyl, —(C═O)R 16 , —S(O) 2 R 17 , or —S(O) 2 N(R 18 )(R 19 );
R 16 is alkyl;
R 17 is alkyl, alkenyl or alkynyl; and
R 18 and R 19 are, independently, hydrogen, alkyl, alkenyl, or alkynyl.
2. The compound of claim 1 or pharmaceutically acceptable salt thereof wherein R 5 and R 6 are H.
3. The compound of claim 1 having the formula:
or pharmaceutically acceptable salt thereof.
4. The compound of claim 1 or pharmaceutically acceptable salt thereof wherein R 1 is methyl, ethyl, halogen, phenyl, or thienyl.
5. The compound of claim 4 or pharmaceutically acceptable salt thereof wherein R 1 is methyl, ethyl, bromo, phenyl, or thienyl.
6. The compound of claim 1 or pharmaceutically acceptable salt thereof wherein R 2 is H or Br.
7. The compound of claim 1 or pharmaceutically acceptable salt thereof wherein R 3 is H or Br.
8. The compound of claim 1 or pharmaceutically acceptable salt thereof wherein R 2 and R 3 are each, independently, H or Br.
9. The compound of claim 1 or pharmaceutically acceptable salt thereof wherein R 4 is methyl or ethyl.
10. The compound of claim 1 or pharmaceutically acceptable salt thereof wherein R 7 is H or methyl.
11. A compound of that is:
4-[(5-Methylthieno[3,2-c]isoquinolin-4(5H)-yl)sulfonyl]phenol,
4-[(5-Ethylthieno[3,2-c]isoquinolin-4(5H)-yl)sulfonyl]phenol,
4-[(2-Bromo-5-methylthieno[3,2-c]isoquinolin-4(5H) yl)sulfonyl]phenol,
4-{[(5R)-2-bromo-5-methylthieno[3,2-c]isoquinolin-4-(5H)-yl]sulfonyl}phenol,
4-{[(5S)-2-bromo-5-methylthieno[3,2-c]isoquinolin-4-(5H)-yl]sulfonyl}phenol,
4-[(2-Bromo-5-ethylthieno[3,2-c]isoquinolin-4(5H)-yl)sulfonyl]phenol,
4-[(5-Ethyl-2-thien-3-ylthieno[3,2-c]isoquinolin-4(5H)-yl)sulfonyl]phenol,
4-[(5-Ethyl-2-phenylthieno[3,2-c]isoquinolin-4(5H)-yl)sulfonyl]phenol,
2-Bromo-4-[(2-bromo-5-methylthieno[3,2-c]isoquinolin-4(5H)-yl)sulfonyl]phenol,
2,6-Dibromo-4-[(2-bromo-5-methylthieno[3,2-c]isoquinolin-4(5H)-yl)sulfonyl]phenol, or
4-[(2,5-Diethylthieno[3,2-c]isoquinolin-4(5H)-yl )sulfonyl]phenol, or pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising a compound of claim 1 or pharmaceutically acceptable salt thereof and a pharmaceutical carrier.