Substituted quinazolin-4(3H)-ones, pyrido[3,4-d]pyrimidin-4(3H)-ones, pyrido[3,2-d]pyrimidin-4(3H)-ones and pyrido[2,3-d]pyrimidin-4(3H)-ones as positive allosteric modulators of muscarinic acetycholine receptor M1

A compound having a structure represented by a formula:

• wherein:
• Q1 is selected from N and CR1a;
• Q2 is CR1b;
• Q3 is selected from N and CR1c;
• Q4 is selected from N and CR1d;
• provided that 0 or 1 of Q1, Q3, and Q4 is N;
• each of R1a, R1b, R1c, and R1d, when present, is independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl-oxy-C1-C6 alkyl, C1-C6 polyhaloalkyl-oxy-C1-C6 alkyl, and C1-C6 dialkylamino;
• Q5 is selected from N and CR2a;
• Q6 is selected from N and CR2b;
• Q7 is selected from N and CR2c;
• Q8 is selected from N and CR2d;
• provided that 0, 1 or 2 of Q5, Q6, Q7, and Q8 are N;
• each of R2a, R2b, R2c, and Rd, when present, is independently selected from hydrogen, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkylamino, C1-C6 haloalkyl-oxy C1-C6 alkyl, C1-C6 polyhaloalkyl-oxy-C1-C6 alkyl, C1-C6 dialkylamino, —C(OH)R20aR20b, and —SO2R30;
• each of R20a and R20b is independently selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 polyhaloalkyl;
• R30 is selected from C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 polyhaloalkyl;
• R3 is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 polyhaloalkyl, cyclopropyl, and Ar1;
• wherein Ar1 is selected from phenyl, indenyl, and naphthalenyl;
• wherein Ar1 is substituted with 0-3 substituents selected from halogen, hydroxyl, cyano, —NH2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkylamino, and C1-C6 dialkylamino;
• R4 is selected from Ar2, —L2—Ar2, and Cy1;
• L2 is selected from —CR8aR8b—, —O—, —NR9—, —S—, —(S═O)—, and —(SO2)—;
• each of R8a and R8b is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 polyhaloalkyl;
• R9 is selected from hydrogen and C1-C6 alkyl;
• Ar2 is selected from benzodioxolyl, benzofuranyl, benzoimidazolyl, benzoisoxazolyl, benzooxadiazolyl, benzooxazolyl, benzothiazolyl, benzothiophenyl, dihydrobenzodioxinyl, dihydrobenzofuranyl, dihydroisobenzofuranyl, furanyl, furopyridinyl, imidazolyl, imidazopyrazinyl, imidazopyridinyl, indazolyl, indolinyl, indolyl, isoindolinyl, isoquinolinyl, naphthyridinyl, oxadiazolyl, oxazolyl, oxoindolinyl, 2′-oxospiro[1,3]dioxolane-2,3′-indolinyl, pyrazinyl, pyridinyl, pyrimidinyl, pyrrolopyridinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydroquinolinyl, thiadiazolyl, thiazolyl, triazopyridinyl, and triazolyl;
• wherein Ar2 is substituted with 0-3 substituents selected from halogen, hydroxyl, cyano, —NH2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkylamino, and C1-C6 dialkylamino;
• or
• Ar2 is pyrazolyl substituted with 1-3 substituents selected from halogen, hydroxyl, cyano, —NH2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1-C6 alkylamino, and C1-C6 dialkylamino;
• Cy1 is C2-C5 heterocycloalkyl or C2-C5 heterocycloalkenyl;
• wherein Cy1 is substituted with 0-3 substituents selected from halogen, hydroxyl, cyano, —NH2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 polyhaloalkyl, C1C6 alkylamino, and C1-C6 dialkylamino, and wherein two of the substituents are optionally covalently bonded, and together with the intermediate atoms, comprise a 3- to 6-membered fused ring group;
• and each of R7a and R7b is independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 polyhaloalkyl;
• or a pharmaceutically acceptable salt, thereof.