Dihydronaphthyridinyl(organo)methanone analogs as positive allosteric mGluR5 modulators

A compound having a structure represented by a formula:

• wherein one of Y1 and Y2 is N, and the other is C—R3a;
• wherein Y3 is O, N—R7, or a covalent bond;
• wherein one of L1 and L2 is —O—, and the other is —C(R1a, R1b)—;
• provided that when Y1 is N, L1 is —O— and L2 is —C(R1aR1b)—;
• wherein Ar1 is phenyl with 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, and C1-C4 alkyloxy, or Ar1 is monocyclic heteroaryl having 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, and C1-C4 alkyloxy;
• wherein each of R1a and R1b is independently selected from hydrogen and C1-C4 alkyl;
• wherein R2 is selected from hydrogen;
• C1-C6 alkyl;
• (C1-C6 alkyloxy) C1-C6 alkyl;
• C3-C8 cycloalkyl;
• (C3-C8 cycloalkyl) C1-C6 alkyl;
• C2-C5 heterocyclyl;
• phenyl with 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, and C1-C4 alkyloxy;
• and monocyclic heteroaryl having 0-3 substituents selected from halogen, cyano, C1-C4 alkyl, and C1-C4 alkyloxy;
• wherein R3a is selected from hydrogen, halogen, cyano, and C1-C4 alkyl;
• wherein R3b is selected from hydrogen, halogen, cyano, and C1-C4 alkyl, or R3a and R3b are substituted on adjacent carbons and are covalently bonded and, together with the intermediate carbons, comprise an optionally substituted fused ring selected from 4- to 7-membered cycloalkenyl, 5- to 7-membered heteroaryl, and 6-membered aryl;
• wherein R4a and R4b are independently selected from hydrogen and C1-C4 alkyl, or R4a and R4b are covalently bonded and, together with the intermediate carbon, comprise an optionally substituted 3- to 7-membered spirocycloalkyl;
• wherein R5a and R5b are independently selected from hydrogen and C1-C4 alkyl;
• or R5a and R5b are covalently bonded and, together with the intermediate carbon, comprise an optionally substituted 3- to 7-membered spirocycloalkyl;
• or R4a and R5a are optionally covalently bonded and, together with the intermediate atoms, comprise an optionally substituted 3- to 7-membered fused cycloalkyl;
• wherein R6a and R6b are independently selected from hydrogen and C1-C4 alkyl, or R6a and R6b together comprise an exocyclic double bond, or R6a and R6b arecovalently bonded and, together with the intermediate carbon, comprise cyclopropyl;
• and
• wherein R7 is selected from hydrogen and C1-C6 alkyl;
• and
• or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof.