2-Amino-6-Methyl-4,4a,5,6-Tetrahydropyrano[3,4-d][1,3]Thiazin-8a(8H)-yl-1,3-Thiazol-4-yl Amides

摘要

The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula I,;;and the variable R1 is as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

主权项

1. A compound of Formula Iwherein
R1 is selected from the group consisting of:phenyl optionally substituted with one to three R2;C3-9cycloalkyl optionally substituted with one to three R2; anda 5- to 10-membered heteroaryl, having one to four heteroatoms independently selected from N, O or S, wherein at least one of the heteroatoms is N and wherein said N is optionally substituted with R3; and wherein said 5- to 10-membered heteroaryl is optionally substituted on carbon with one to three R2;
R2 at each occurrence is independently selected from the group consisting of halogen, hydroxy, cyano, C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C1-6alkoxy, C3-6alkenyl, C3-6alkenyloxy, C3-6alkynyl, C3-6alkynyloxy, C1-6alkoxy-C1-6alkyl, C3-6cycloalkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C3-6cycloalkyl-C1-6alkoxy, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted with one to three substituents independently selected from fluoro, chloro, hydroxy, cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy; or two R2 groups taken together can be a C3-5alkylene; R3 is hydrogen, C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl; wherein said C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, 4- to 6-membered heterocycloalkyl and 4- to 6-membered heterocycloalkyl-C1-6alkyl are each optionally substituted with one to three substituents independently selected from fluoro, chloro, hydroxy, cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy and trifluoromethoxy; or R3 and R2 taken together can be a C3-5alkylene;or a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.