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 the formula:
or a pharmaceutically acceptable salt thereof; wherein:
R 1 and R 2 are independently hydrogen, halogen, (C 1 -C 4 )hydrocarbyl, (C 1 -C 4 )alkoxy, trifluoromethyl, trifluoromethoxy, cyano, or nitro;
R 3 is (C 1 -C 10 )hydrocarbyl, (C 1 -C 6 )oxaalkyl, or heterocyclylalkyl;
R 4 is hydrogen, methyl, halomethyl, dihalomethyl, or trihalomethyl; and
A is a 5- or 6-membered aromatic heterocycle.
2. The compound according to claim 1 , wherein A is pyrrolidine, furan, thiophene, or pyridine.
3. The compound according to claim 2 , wherein A is pyridine.
4. The compound according to claim 1 , wherein R 1 is hydrogen or methyl; and R 2 is hydrogen, methyl, methoxy, chloro, or fluoro.
5. The compound according to claim 4 , wherein R 1 is hydrogen; and R 2 is methyl.
6. The compound according to claim 4 , wherein R 1 is hydrogen; and R 2 is hydrogen.
7. The compound according to claim 1 , wherein Ring A is a 6-membered aromatic heterocycle; and R 1 is meta relative to the point of attachment of Ring A to the thieno[3,2-c]pyridine, wherein R 1 is halogen, (C 1 -C 4 )hydrocarbyl, (C 1 -C 4 )alkoxy, trifluoromethyl, trifluoromethoxy, cyano, or nitro.
8. The compound according to claim 7 , wherein R 1 is halogen.
9. The compound according to claim 8 , wherein R 2 is hydrogen, methyl, methoxy, chloro, or fluoro.
10. The compound according to claim 7 , wherein R 1 is methyl.
11. The compound according to claim 8 , wherein R 2 is hydrogen, methyl, methoxy, chloro, or fluoro.
12. The compound according to claim 1 , wherein R 3 is (C 1 -C 10 )alkyl.
13. The compound according to claim 12 , wherein R 3 is (C 3 -C 6 )alkyl.
14. The compound according to claim 1 , wherein R 3 is (C 3 -C 6 )alkyl, (C 3 -C 6 )alkenyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )oxaalkyl, furanyl(C 1 -C 4 )alkyl, thienyl(C 1 -C 4 )alkyl, pyrrolyl(C 1 -C 4 )alkyl, pyrrolidinyl(C 1 -C 4 )alkyl, or tetrahydrofuranyl(C 1 -C 4 )alkyl.
15. The compound according to claim 1 , wherein R 3 is methoxyethyl, methoxypropyl, ethoxypropyl, isopropyl, cyclopropyl, allyl or furanylmethyl.
16. The compound according to claim 1 , wherein R 3 is of the formula:
17. The compound according to claim 1 , wherein R 4 is hydrogen.
18. The compound according claim 1 , of the formula:
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition comprising a compound of claim 18 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.