Pyrimido-pyridazinone compounds and methods of use thereof

A pharmaceutical composition comprising a compound of Formula (I):

• wherein:
• R1 is NR4R5, optionally substituted C1 to C6 alkoxy, optionally substituted C6 to C14 aryl, optionally substituted heteroaryl, optionally substituted 3-10 membered monocyclic or bicyclic cycloalkyl, or optionally substituted 3-10 membered monocyclic or bicyclic heterocyclyl,
• wherein:
• (i) 3-4 membered cycloalkyl and heterocyclyl are saturated;
• (ii) hydrogen atoms on the same carbon atom of said cycloalkyl or heterocyclyl are optionally replaced with an optionally substituted 3-6 membered cycloalkyl or heterocyclyl to form a spirocycloalkyl or spiroheterocyclyl;
• and
• (iii) hydrogen atoms on the same atom of said cycloalkyl or heterocyclyl are optionally replaced with 0 to form an oxo substituent;
• R2 is optionally substituted phenyl, —O—(C1 to C6 alkyl)-optionally substituted phenyl, or optionally substituted 5-6 membered heteroaryl, with the proviso that when R2 is 4-pyridyl, the 4-pyridyl lacks a carbonyl substituent at the 2nd position;
• R4 and R5 are:
• (a) independently selected from the group consisting of H, C1 to C6 alkyl, C1 to C6 hydroxyalkyl, C3 to C8 cycloalkyl, and —(C1 to C6 alkyl)N(C1 to C6 alkyl)(C1 to C6 alkyl);
• (b) joined to form an optionally substituted 3-8 membered heterocyclyl,
• wherein;
• (bi) hydrogen atoms on the same carbon atom of said heterocyclyl are optionally replaced with an optionally substituted 3-6 membered cycloalkyl or heterocyclyl to form a spirocycloalkyl or spiroheterocyclyl;
• and
• (bii) hydrogen atoms on the same atom of said heterocyclyl (b), cycloalkyl (bi), or heterocyclyl (bi), are optionally replaced with 0 to form an oxo substituent;
• or a pharmaceutically acceptable salt or ester thereof,
• a pharmaceutically acceptable carrier, and
• one or more excipients.