Pyrrolopyrimidine compounds, use as inhibitors of the kinase LRRK2, and methods for preparation thereof

A method for the treatment of a disorder associated with LRRK2 kinase dysfunction in a mammal having the disorder, the method comprising the step of administering to the mammal an effective amount of at least one compound having a structure represented by a formula:

• wherein Z is selected from N and CR20;
• wherein each occurrence of R20, when present, is independently selected from hydrogen, —CN, —F, —Cl, —CF3, and C1-C4 alkyl;
• wherein R1 is selected from Cy1, Ar2, —CR21aR21bCy2, and —CR21aR21bAr2;
• wherein each of R21a and R21b, when present, are independently selected from hydrogen and C1-C4 alkyl;
• wherein Cy1, when present, is selected from C3-C5 cycloalkyl and 2,3-dihydroindene and is substituted with 0, 1, or 2 groups independently selected from halogen, C1-C4 alkyl, C1-C4 monohaloalkyl, and C1-C4 polyhaloalkyl;
• wherein Cy2, when present, is selected from C3-C6 cycloalkyl, C2-C5 heterocycloalkyl, and 2,3-dihydroindene and is substituted with 0, 1, or 2 groups independently selected from halogen, C1-C4 alkyl, C1-C4 monohaloalkyl, and C1-C4 polyhaloalkyl;
• wherein Ar2, when present, is selected from C5-C6 aryl and C4-C5 heteroaryl and is substituted with 0, 1, or 2 groups independently selected from halogen, C1-C4 alkyl, C1-C4 monohaloalkyl, and C1-C4 polyhaloalkyl;
• and
• wherein each of R2, R3, and R4 are independently selected from hydrogen and C1-C4 alkyl;
• wherein Ar1 is a structure selected from:
• wherein A is selected from NR22 and CR23aR23b;
• wherein R22, when present, is selected from hydrogen, halogen, C1-C8 alkyl, C1-C8 monohaloalkyl, C1-C8 polyhaloalkyl, C1-C8 hydroxyalkyl, C1-C8 alkoxyalkyl, —(C1-C8 alkyl)NH2, —(C1-C8 alkyl)NH(C1-C8alkyl), —(C1-C8 alkyl)N(C1-C8 alkyl)(C1-C8 alkyl), C1-C8 alkylacid, —(C1-C4 alkyl)CONH2, —(C1-C4 alkyl)CONH(C1-C4 alkyl), —(C1-C4 alkyl)CON(C1-C4 alkyl)(C1-C4 alkyl), —(C1-C4 alkyl)(C═O)Cy3, and Cy3;
• wherein each occurrence of Cy3, when present, is independently selected from C3-C6 cycloalkyl and C2-C5 heterocycloalkyl and is substituted with 0, 1, or 2 groups independently selected from halogen, C1-C4 alkyl, C1-C4 monohaloalkyl, and C1-C4 polyhaloalkyl;
• wherein each of R23a and R23b, when present, is independently selected from hydrogen, halogen, C1-C8 alkyl, C1-C8 monohaloalkyl, C1-C8 polyhaloalkyl, C1-C8 hydroxyalkyl, C1-C8 alkoxyalkyl, C1-C8 alkylacid, —(C1-C4 alkyl)(C═O)Cy1, —(C1-C4 alkyl)CONH2, —(C1-C4 alkyl)CONH(C1-C4 alkyl), —(C1-C4 alkyl)CON(C1-C4 alkyl)(C1-C4 alkyl), and Cy3;
• wherein each of Q1, Q2, and Q3 is independently selected from N and CR24;
• and
• wherein each occurrence of R24, when present, is independently selected from hydrogen, halogen, C1-C8 alkyl, C1-C8 monohaloalkyl, C1-C8 polyhaloalkyl, C1-C8 alkoxyalkyl, —(C1-C4 alkyl)CONH2, —(C1-C4 alkyl)CONH(C1-C4 alkyl), —(C1-C4 alkyl)CON(C1-C4 alkyl)(C1-C4 alkyl),
• provided that two or three of A, Q1, Q2, and Q3 are N, or a pharmaceutically acceptable salt thereof,
• wherein the disorder is selected from a neurodegenerative disorder and leprosy.