Imidazole compounds as inhibitors of ENPP1
AssigneeStingray Therapeutics, Inc.
InventorsSrinivas Rao Kasibhatla, Sunil Sharma, Mohan Kaadige, Alexis Weston, Trason Thode
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Abstract
Compounds having activity as inhibitors of ENPP1 are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, stereoisomer, or prodrug thereof, wherein L, R1, R2a, R2b, R2c, R2d, R2e and n are as defined herein. This disclosure provides methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds, and methods for treating disorders associated with ENPP1, including uncontrolled cellular proliferation, cancer and viral or bacterial infections in a mammal.
Claims20
A compound having the following structure (I):
- or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein:
- L is S(O)z;
- R1 is CN, C(═O)R1a, C(═O)NHSO2R1b, C(═NR1d)NR1cR1e, OR1e, NHR1e, NHS(O)2R1b, S(O)2NR1bR1e, PO3HR1e, SO3H or 5-membered heteroaryl;
- R1a is OR1e or NR1cR1e,
- R1b is C1-C6 alkyl or C6-C10 aryl;
- R1c is H, C1-C6 alkyl or C6-C10 aryl;
- R1d is H, OH or C1-C6 alkyl;
- R1e is H, C1-C6 alkyl, C1-C6 hydroxylalkyl, C1-C6 aminoalkyl, C1-C6 alkylaminylalkyl or C6-C10 aryl;
- R2a, R2b, R2c, R2d and R2e are each independently H, amino, halo, hydroxyl, nitro, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C6-C10 aryloxy or 3-8-membered heterocyclyl;
- n is 0 or 1;
- and
- z is 0, 1 or 2;
- wherein each C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryloxy, 3-8-membered heterocyclyl and 5-membered heteroaryl are independently optionally substituted, and provided that when R1 is C(═O)OCH3 or C(═O)OCH2CH3, then R2c is C1-C6 alkoxy, and at least one of R2b and R2d is C1-C6 alkoxy.
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound having the following structure (I):
- or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein:
- L is S(O)z;
- R1 is CN, C(═O)R1a, C(═O)NHSO2R1b, C(═NR1d)NR1cR1e, OR1e, NHR1e, NHS(O)2R1b, S(O)2NR1bR1e, PO3HR1e, SO3H or 5-membered heteroaryl;
- R1a is OR1e or NR1cR1e,
- R1b is C1-C6 alkyl or C6-C10 aryl;
- R1c is H, C1-C6 alkyl or C6-C10 aryl;
- R1d is H, OH or C1-C6 alkyl;
- R1e is H, C1-C6 alkyl, C1-C6 hydroxylalkyl, C1-C6 aminoalkyl, C1-C6 alkylaminylalkyl or C6-C10 aryl;
- R2a, R2b, R2c, R2d and R2e are each independently H, amino, halo, hydroxyl, nitro, CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C6-C10 aryloxy or 3-8-membered heterocyclyl;
- n is 0 or 1;
- and
- z is 0, 1 or 2;
- wherein each C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryl, C6-C10 aryloxy, 3-8-membered heterocyclyl and 5-membered heteroaryl are independently optionally substituted.
Dependencies are inferred from the claim text.