Discovery of Potent Deuterated Compounds as Potential KRAS G12D Inhibitors in Cancer Therapy

Abstract

The disclosure in this Patent Highlight describes a new class of deuterated compounds that bind directly to KRASG12D and block its activity. These exemplary deuterated compounds are potentially useful as pharmaceuticals that may possess desirable properties, including bioavailability, stability, and therapeutic index. This may have significant influence in drugs absorption, distribution, metabolism, excretion, and half-life when administered to a human or animal. The replacement of C–H with C–D increases the kinetic isotope effect, which makes the C–D bond up to ∼10 times stronger than the C–H bond.