Ann M Rowley, Gang Yao, Logan Andrews, Aaron Bedermann, Ross Biddulph, Ryan Bingham, Jennifer J Brady, Rachel Buxton, Ted Cecconie, Rona Cooper, Adam Csakai, Enoch N Gao, Melissa C Grenier-Davies, Meghan Lawler, Yiqian Lian, Justyna Macina, Colin Macphee, Lisa Marcaurelle, John Martin, Patricia McCormick, Rekha Pindoria, Martin Rauch, Warren Rocque, Yingnian Shen, Lisa M Shewchuk, Michael Squire, Will Stebbeds, Westley Tear, Xin Wang, Paris Ward, Shouhua Xiao
Human genetic evidence shows that PDE3B is associated with metabolic and dyslipidemia phenotypes. A number of PDE3 family selective inhibitors have been approved by the FDA for various indications; however, given the undesirable proarrhythmic effects in the heart, selectivity for PDE3B inhibition over closely related family members (such as PDE3A; 48% identity) is a critical consideration for development of PDE3B therapeutics. Selectivity for PDE3B over PDE3A may be achieved in a variety of ways, including properties intrinsic to the compound or tissue-selective targeting...
January 29, 2024: Journal of Medicinal Chemistry