Substituted 2,3-dihydrobenzofuranyl compounds and uses thereof
View Patent ↗The invention generally relates to substituted 2,3-dihydrobenzofuranyl compounds, and more particularly to a compound represented by Structural Formula I: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of cancer (e.g., mantle cell lymphoma), and other diseases and disorders.
1. A compound represented by Structural Formula IXa or Xa:
or a pharmaceutically acceptable salt thereof, wherein:
R 1a is selected from halo, hydroxyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy; and
R 11a is phenyl or a 5-6-membered heteroaryl having 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulfur optionally and is independently substituted with 1, 2 or 3 optional substituents.
2. The compound of claim 1 , wherein R 1a is selected from halogen and halo(C 1 -C 4 )alkyl.
3. The compound of claim 1 , wherein R 1a is selected from fluoro, chloro, —CF 3 and —CHF 2 .
4. The compound of claim 1 , wherein R 11a is substituted with one substituent selected from halogen; (C 1 -C 4 )alkyl optionally substituted with hydroxyl; (C 2 -C 4 )alkenyl; (C 1 -C 4 )haloalkyl; —C(O)(C 1 -C 4 )alkyl; —C(O)O(C 1 -C 4 )alkyl; —C(O)(CH 2 ) 0-1 (C 3 -C 7 )carbocyclyl; phenyl; —C(O)(CH 2 ) 0-1 NR 12 R 13 , wherein R 12 and R 13 are each methyl, or R 12 and R 13 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted saturated (C 3 -C 7 )heterocyclyl; and —S(O) 2 NR 12 R 13 , wherein R 12 and R 13 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted saturated (C 3 -C 7 )heterocyclyl.
5. The compound of claim 1 , wherein R 11a is substituted with a first substituent selected from halogen; (C 1 -C 4 )alkyl optionally substituted with hydroxyl; (C 2 -C 4 )alkenyl; (C 1 -C 4 )haloalkyl; —C(O)(C 1 -C 4 )alkyl; —C(O)O(C 1 -C 4 )alkyl; —C(O)(CH 2 ) 0-1 (C 3 -C 7 )carbocyclyl; phenyl; —C(O)(CH 2 ) 0-1 NR 12 R 13 , wherein R 12 and R 13 are each methyl, or R 12 and R 13 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted saturated (C 3 -C 7 )heterocyclyl; and —S(O) 2 NR 12 R 13 , wherein R 12 and R 13 are taken together with the nitrogen atom to which they are commonly attached to form an optionally substituted saturated (C 3 -C 7 )heterocyclyl, and a second substituent selected from halogen, (C 1 -C 4 )alkyl and (C 1 -C 4 )haloalkyl.
6. The compound of claim 1 , wherein R 11a is selected from phenyl, thiophenyl, pyridinyl, pyrimidinyl, isoxazolyl, furanyl, pyridazinyl and oxadiazolyl, and is substituted with 1, 2 or 3 independently selected substituents.
7. The compound of claim 1 , wherein the saturated heterocyclyl formed by R 12 and R 13 together with the nitrogen atom to which they are attached is optionally substituted with 1 or 2 substituents independently selected from halogen, (C 1 -C 4 )alkyl and (C 1 -C 4 )haloalkyl.
8. A compound selected from:
or a pharmaceutically acceptable salt thereof.
9. A compound selected from one of the following:
or a pharmaceutically acceptable salt thereof.
10. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.
11. A method of treating lymphoma in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
12. The method of claim 11 , wherein the lymphoma is mantle cell lymphoma.