Aminotetrahydropyrans as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes

A compound of structural formula I:

• or a pharmaceutically acceptable salt thereof;
• wherein
• each n is independently 0, 1, 2 or 3;
• each m is independently 0, 1, or 2;
• each p is independently 0 or 1;
• V is selected from the group consisting of:
• Ar is phenyl optionally substituted with one to five R1 substituents;
• each R1 is independently selected from the group consisting of
• halogen,
• cyano,
• hydroxy,
• C1-6 alkyl, optionally substituted with one to five fluorines,
• C1-6 alkoxy, optionally substituted with one to five fluorines;
• each R2 is independently selected from the group consisting of
• hydrogen,
• hydroxy,
• halogen,
• cyano,
• C1-10 alkoxy, wherein alkoxy is optionally substituted with one to five substituents independently selected from fluorine and hydroxy,
• C1-10 alkyl, wherein alkyl is optionally substituted with one to five substituents independently selected from fluorine and hydroxy,
• C2-10 alkenyl, wherein alkenyl is optionally substituted with one to five substituents independently selected from fluorine and hydroxy,
• (CH2)n-aryl, wherein aryl is optionally substituted with one to five substituents independently selected hydroxy, halogen, cyano, nitro, CO2H, C1-6 alkyloxycarbonyl, C1-6 alkyl, and C1-6 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines,
• (CH2)n-heteroaryl, wherein heteroaryl is optionally substituted with one to three substituents independently selected from hydroxy, halogen, cyano, nitro, CO2H, C1-6 alkyloxycarbonyl, C1-6 alkyl, and C1-6 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines,
• (CH2)n-heterocyclyl, wherein heterocyclyl is optionally substituted with one to three substituents independently selected from oxo, hydroxy, halogen, cyano, nitro, CO2H, C1-6 alkyloxycarbonyl, C1-6 alkyl, and C1-6 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines,
• (CH2)n—C3-6 cycloalkyl, wherein cycloalkyl is optionally substituted with one to three substituents independently selected from halogen, hydroxy, cyano, nitro, CO2H, C1-6 alkyloxycarbonyl, C1-6 alkyl, and C1-6 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines,
• (CH2)n—COOH,
• (CH2)n—COOC1-6 alkyl,
• (CH2)n—NR4R5,
• (CH2)n—CONR4R5,
• (CH2)n—OCONR4R5,
• (CH2)n—SO2NR4R5,
• (CH2)n—SO2R6,
• (CH2)n—NR7SO2R6,
• (CH2)n—NR7CONR4R5,
• (CH2)n—NR7COR7, and
• (CH2)n—NR7CO2R6;
• wherein any individual methylene (CH2) carbon atom in (CH2)n is optionally substituted with one to two substituents independently selected from fluorine, hydroxy, C1-4 alkyl, and C1-4 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines;
• R3a and R3b are each independently hydrogen or C1-4 alkyl optionally substituted with one to five fluorines;
• R4 and R5 are each independently selected from the group consisting of
• hydrogen,
• (CH2)m-phenyl,
• (CH2)m—C3-6 cycloalkyl, and
• C1-6 alkyl, wherein alkyl is optionally substituted with one to five substituents independently selected from fluorine and hydroxy and wherein phenyl and cycloalkyl are optionally substituted with one to five substituents independently selected from halogen, hydroxy, C1-6 alkyl, and C1-6 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines;
• or R4 and R5 together with the nitrogen atom to which they are attached form a heterocyclic ring selected from azetidine, pyrrolidine, piperidine, piperazine, and morpholine wherein said heterocyclic ring is optionally substituted with one to three substituents independently selected from halogen, hydroxy, C1-6 alkyl, and C1-6 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines;
• each R6 is independently C1-6 alkyl, wherein alkyl is optionally substituted with one to five substituents independently selected from fluorine and hydroxyl;
• R7 is hydrogen or R6;
• and
• R8 is selected from the group consisting of
• hydrogen,
• (CH2)p-phenyl,
• (CH2)p—C3-6 cycloalkyl, and
• C1-6 alkyl, wherein alkyl is optionally substituted with one to five substituents independently selected from fluorine and hydroxy and wherein phenyl and cycloalkyl are optionally substituted with one to five substituents independently selected from halogen, hydroxy, C1-6 alkyl, and C1-6 alkoxy, wherein alkyl and alkoxy are optionally substituted with one to five fluorines.