Abstract: Invented are compounds of Formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

Abstract: Invented are compounds of Formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

Abstract: The present invention relates to a process for preparing aminocyclohexyl ether compounds of Formula I: or the pharmaceutically acceptable salts and esters thereof. In particular, the instant invention is directed towards a process for preparing (1R,2R)-2-[(3R)-Hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane as well as various intermediates.

Abstract: The present invention relates to a process for preparing aminocyclohexyl ether compounds of Formula I: or the pharmaceutically acceptable salts and esters thereof. In particular, the instant invention is directed towards a process for preparing (1R,2R)-2-[(3R)-Hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane as well as various intermediates.

Abstract: The disclosure provides transaminase polypeptides capable of converting the substrate, 2-(3,4-dimethoxyphenethoxy)cyclohexanone to the trans diastereomer product (1R,2R)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine in at least a 2:1 diastereomeric ratio relative to the cis diastereomer (1R,2S)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine. The disclosure also provides polynucleotides, vectors, host cells, and methods of making and using the transaminase polypeptides in processes for preparing (1R,2R)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine and its analogs, which can product compounds can be further used to prepare the aminocyclohexylether compound, (3R)-1-[(1R,2R)-2-[2-(3,4-dimethoxyphenyl)ethoxy]cyclohexyl]pyrrolidin-3-ol, which is an ion channel blocker.

Abstract: The present invention relates to a process for preparing aminocyclohexyl ether compounds of Formula I: or the pharmaceutically acceptable salts and esters thereof. In particular, the instant invention is directed towards a process for preparing (1R,2R)-2-[(3R)-Hydroxypyrrolidinyl]-1-(3,4-dimethoxyphenethoxy)-cyclohexane as well as various intermediates.