Hexahydropyrano[3,4-<i>d</i>][1,3]thiazin-2-amine compounds

摘要

The present invention provides compounds of Formula I, and the tautomers thereof, and the pharmaceutically acceptable salts of the compounds and tautomers, wherein the compounds have the structure;
wherein the variables R1, R2, R3, R4 and x are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

主权项

1. A method of treating Alzheimer's disease in a patient, the method comprising administering a therapeutically effective amount of a compound of Formula I,Wherein
R1 is hydrogen or methyl, wherein said methyl is optionally substituted with one to three substituents independently selected from halogen or methoxy; R2 is C1-6 alkyl, —(C(R5)2)m—(C3-6 cycloalkyl), —(C(R5)2)m—(C6-10 aryl), —(C(R5)2)m-(5- to 10-membered heteroaryl) or —(C(R5)2)t—OR6; wherein said alkyl, cycloalkyl, aryl or heteroaryl moieties are optionally substituted with one to three substituents independently selected from halogen, C1-6 alkyl, —CH2F, —CHF2, —CF3, —CN or —OR7; R3 is —(C(R5)2)m—(CN) or —(C(R5)2)n—(NHR7); R4 is independently selected from halogen, C1-6 alkyl or C1-6 alkoxy; wherein said alkyl or alkoxy is optionally substituted with one to three fluoro; R5 at each occurrence is independently selected from hydrogen or C1-3 alkyl, wherein said alkyl is optionally substituted with one to three halogen; R6 is hydrogen, C1-6 alkyl or —(C(R5)2)n—(C6-10 aryl), wherein said alkyl and aryl are optionally substituted with one to three substituents independently selected from halogen, C1-3 alkyl, —CH2F, —CHF2, —CF3, —CN or —OH; R7 for each occurrence is hydrogen or C1-6 alkyl, wherein said alkyl is optionally substituted with one to three substituents independently selected from halogen or C1-6 alkoxy; m at each occurrence is independently 0, 1 or 2; n at each occurrence is independently is 1 or 2; t is 1 or 2; and x is 0, 1, 2 or 3; or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer;to a patient in need of treatment thereof.