881401-74-7Relevant academic research and scientific papers
Thrombopoietin Receptor Agonists
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Page/Page column 20, (2010/11/30)
A compound of the formula (I) useful as promoters of thrombopoiesis and megakaryocytopoiesis, wherein A, B, D, E, W, X, Y, Z, R1 and R2 are defined as above.
Pyrimidine benzamide-based thrombopoietin receptor agonists
Reiter, Lawrence A.,Subramanyam, Chakrapani,Mangual, Emilio J.,Jones, Christopher S.,Smeets, Marc I.,Brissette, William H.,McCurdy, Sandra P.,Lira, Paul D.,Linde, Robert G.,Li, Qifang,Zhang, Fangning,Antipas, Amy S.,Blumberg, Laura C.,Doty, Jonathan L.,Driscoll, James P.,Munchhof, Michael J.,Ripp, Sharon L.,Shavnya, Andrei,Shepard, Richard M.,Sperger, Diana,Thomasco, Lisa M.,Trevena, Kristen A.,Wolf-Gouveia, Lilli A.,Zhang, Liling
, p. 5447 - 5454 (2008/03/11)
A series of pyrimidine benzamide-based thrombopoietin receptor agonists is described. The lead molecule contains a 2-amino-5-unsubstituted thiazole, a group that has been associated with idiosyncratic toxicity. The potential for metabolic oxidation at C-5 of the thiazole, the likely source of toxic metabolites, was removed by substitution at C-5 or by replacing the thiazole with a thiadiazole. Potency in the series was improved by modifying the substituents on the pyrimidine and/or on the thiazole or thiadiazole pendant aryl ring. In vivo examination revealed that compounds from the series are not highly bioavailable. This is attributed to low solubility and poor permeability.
