Heterocyclic spiro compounds and methods of use

A compound of Formula I

• or a pharmaceutically acceptable salt thereof, wherein
• R1 at each occurrence independently is H, 2H, C1-4haloalkyl, C1-4alkoxy, —CH2OH, —(CH2)O(C1-4alkyl), —(CH2)O(C1-4haloalkyl), —(CH2)-C1-4dialkylamino, aziridin-1-yl-methyl, azetidin-1-yl-methyl, pyrrolidine-1-yl-methyl, piperidin-1-yl-methyl, or morpholin-1-yl-methyl;
• R2 is H, 2H, halogen, —CN, C1-4alkyl, C1-4haloalkyl, —CH2CN, —CH2OH, C1-4alkoxy, or C1-4haloalkoxy;
• wherein, optionally, one R1 and R2 together with the carbon atoms to which they are attached form a
• group;
• R3 at each occurrence independently is H, halogen, CN, OH, C1-4alkyl, C1-4haloalkyl, —CH2CN, —CH2OH, C1-4alkoxy, or C1-4haloalkoxy, wherein two substituents R3 attached to the same carbon atom optionally form together with said carbon atom a C3-6cycloalkyl or a carbonyl group;
• A at each occurrence independently is CR3R3 or absent;
• R4 is 1,2,3,4-tetrahydro-8-quinolinyl, 6 or 10 membered aryl, or 5 to 10 membered heteroaryl,
• wherein the aryl or heteroaryl is optionally substituted with 1 to 5 substituents independently selected from OH, halogen, —CN, NH2, C1-4alkyl, C1-4deuteroalkyl, C1-4haloalkyl, C1-4alkoxy, C1-4haloalkoxy, —SO2NH2, and —NHSO2CH3,
• wherein the C1-4alkyl is optionally substituted with OH;
• X1 is CR5 or N;
• X2 is CH, CF, or N;
• X3 is C or N;
• X4 is C or N;
• R5 is H, halogen, CN, —COO(C1-4alkyl), C1-4alkyl, C2-4alkenyl, C1-4haloalkyl, —(CH2)m(C1-4alkoxy), —(CH2)m(C1-4haloalkoxy), C3-5cycloalkyl, C3-5cyclohaloalkyl, or C3-5heterocycloalkyl;
• B together with the atoms to which it is attached forms a 4 to 7 membered fully saturated, fully unsaturated, or partially unsaturated carbocyclic or heterocyclic ring system,
• wherein the heterocyclic ring system comprises 1 to 5 heteroatoms independently selected from N, O, and S,
• wherein the ring system is optionally substituted with 1 to 5 substituents R6;
• R6 at each occurrence independently is halogen, OH, —CN, —NH2, C1-6alkyl, C1-6haloalkyl, C1-4alkoxy, C1-4haloalkoxy, —C(═O)C1-6alkyl, —R7-(C3-5cycloalkyl), —R7-(C3 5cyclohaloalkyl), —R7-(C3-6heterocycloalkyl), —R7-(phenyl), or —R7-(5 to 6 membered heteroaryl),
• wherein the C1-6alkyl is optionally substituted with C1-4alkoxy, C1-4alkylamino, C1-4dialkylamino, —CO(C1-4alkylamino) or —CO(C1-4dialkylamino),
• wherein the C1-6haloalkyl is optionally substituted with a OH,
• wherein the C3-6heterocycloalkyl is optionally substituted with 1 to 3 substituents independently selected from (=O) and C1-6alkyl,
• wherein the phenyl is optionally substituted with 1 to 3 substituents independently selected from halogen and C1-4alkoxy,
• wherein the heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halogen, —(CH2)1-3OH, (CH2)1-3O (C1-4alkyl), —(CH2)1-3O (C1-4haloalkyl), C1-4alkyl, and C1-4haloalkyl,
• wherein two substituents R6 together optionally form a —(CH2)n— group creating a ring together with the ring atom or ring atoms to which the two substituents R6 are attached,
• wherein the —(CH2)n— group optionally has one —CH2— group substituted with one heteroatom selected from N, O, and S, and
• wherein the —(CH2)n— group is optionally substituted with 1 to 3 substituents independently selected from halogen and C1-6alkyl;
• R7 is (CH2) m or CO;
• n is 1, 2, 3, 4, 5 or 6;
• and
• m is 0 or 1.