Inhibitors of cyclin-dependent kinase 7 (CDK7)
The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
1. A compound of formula
2. A pharmaceutically acceptable salt of a compound of formula
3. The pharmaceutically acceptable salt of claim 2 , wherein the salt is a hydrochloric acid salt.
4. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula
or a pharmaceutically acceptable salt thereof.
5. The pharmaceutical composition of claim 4 , wherein the composition comprises the pharmaceutically acceptable salt of the compound.
6. The pharmaceutical composition of claim 5 , wherein the pharmaceutically acceptable salt is a hydrochloric acid salt.
7. The pharmaceutical composition of claim 4 , wherein the composition is a lyophilized solid.
8. The pharmaceutical composition of claim 4 , wherein the composition is an aqueous solution.
9. The pharmaceutical composition of claim 4 , wherein the composition is formulated for parenteral administration.
10. The pharmaceutical composition of claim 9 , wherein the composition is formulated for infusion.
11. The pharmaceutical composition of claim 4 , wherein the composition is in a single unit dosage form.
12. The pharmaceutical composition of claim 5 , wherein the composition is an aqueous solution.
13. The pharmaceutical composition of claim 5 , wherein the composition is formulated for parenteral administration.
14. The pharmaceutical composition of claim 13 , wherein the composition is formulated for infusion.
15. The pharmaceutical composition of claim 5 , wherein the composition is in a single unit dosage form.
16. The pharmaceutical composition of claim 6 , wherein the composition is an aqueous solution.
17. The pharmaceutical composition of claim 6 , wherein the composition is formulated for parenteral administration.
18. The pharmaceutical composition of claim 17 , wherein the composition is formulated for infusion.
19. The pharmaceutical composition of claim 6 , wherein the composition is in a single unit dosage form.