Treatment of pancreatic and related cancers with 5-acyl-6,7-dihydrothieno[3,2-c]pyridines
Methods for inhibiting the growth of pancreatic cancer cells or other cancer cells driven by Sonic hedgehog are disclosed. The method involves exposing the cells to 5-acyl-6,7-dihydrothieno[3,2-c]pyridines of formula (I)
1. A compound of formula
or a pharmaceutically acceptable salt thereof;
wherein:
R 1 and R 2 are independently selected from hydrogen, halogen, (C 1 -C 4 )hydrocarbyl, (C 1 -C 4 )alkoxy, trifluoromethyl, trifluoromethoxy, cyano and nitro;
R 3 is
R 4 is selected from hydrogen, methyl, halomethyl, dihalomethyl, and trihalomethyl; and
A is phenyl.
2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 , wherein R 1 is hydrogen; and R 2 is hydrogen or methyl.
4. The compound according to claim 1 , wherein R 1 is ortho relative to the point of attachment of phenyl to the thieno[3,2-c]pyridine; and R 2 is para to the point of attachment of phenyl to the thieno[3,2-c]pyridine.
5. The compound according to claim 1 , wherein R 1 is hydrogen or methyl and R 2 is chosen from hydrogen, methyl, methoxy, chloro, and fluoro.
6. The compound according to claim 1 , wherein R 1 and R 2 are the same and are chosen from hydrogen and halogen.
7. The compound according to claim 1 , wherein R 4 is hydrogen.
8. The compound according to claim 1 , wherein R 1 is meta relative to the point of attachment of phenyl to the thieno[3,2-c]pyridine.
9. The compound according to claim 8 , wherein R 1 is methyl and R 2 is hydrogen.
10. The compound according to claim 1 of the formula:
or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 10 , or a pharmaceutically acceptable salt thereof.
12. The compound according to claim 1 , wherein each of R 1 , R 2 , and R 4 is hydrogen, or a pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 12 , or a pharmaceutically acceptable salt thereof.