494861-72-2Relevant academic research and scientific papers
Discovery and synthesis of tetrahydropyrimidinedione-4-carboxamides as endothelial lipase inhibitors
Hu, Carol H.,Wang, Tammy C.,Qiao, Jennifer X.,Haque, Lauren,Chen, Alice Y.A.,Taylor, David S.,Ying, Xiaohong,Onorato, Joelle M.,Galella, Michael,Shen, Hong,Huang, Christine S.,Toussaint, Nathalie,Li, Yi-Xin,Abell, Lynn,Adam, Leonard P.,Gordon, David,Wexler, Ruth R.,Finlay, Heather J.
, p. 3721 - 3725 (2018/10/24)
Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahydropyrimidinedione (THP) EL inhibitors. Synthesis and SAR studies including modification of the amide group, together with changes on the pyrimidinone core led to a series of arylcycloalkyl, indanyl, and tetralinyl substituted 5-amino or 5-hydroxypyrimidinedione-4-carboxamides. Several compounds were advanced to PK evaluation. Among them, compound 4a was one of the most potent with measurable ELHDL hSerum potency and compound 3g demonstrated the best overall pharmacokinetic parameters.
TRIAZOLOPYRIDINE INHIBITORS OF MYELOPEROXIDASE
-
Page/Page column 68, (2017/10/18)
The present invention provides compounds of Formula (I). wherein A and Z are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and may be useful for for the treatment and/or prophylaxis of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.
Discovery of novel orally active ureido NPY Y5 receptor antagonists
Li, Guoqing,Stamford, Andrew W.,Huang, Ying,Cheng, Kuo-Chi,Cook, John,Farley, Constance,Gao, Jun,Ghibaudi, Lorraine,Greenlee, William J.,Guzzi, Mario,van Heek, Margaret,Hwa, Joyce J.,Kelly, Joe,Mullins, Deborra,Parker, Eric M.,Wainhaus, Sam,Zhang, Xiaoping
, p. 1146 - 1150 (2008/09/18)
We have derived a novel series of neuropeptide Y (NPY) Y5 receptor antagonists from the biphenylurea 3. Cyclohexylurea 21c, a member of the series, is a potent NPY Y5 receptor antagonist that exhibits excellent pharmacokinetic parameters in rats and dogs. On chronic oral administration to diet-induced obese rats, 21c displayed an anti-obesity profile, causing a modest reduction in food intake, a significant decrease in body weight gain, a decrease in adipose mass, and an increase in lean tissue mass.
