73870-22-1Relevant articles and documents
CYCLOBUTYL AMIDE MONOACYLGLYCEROL LIPASE MODULATORS
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Paragraph 0277; 0326; 0327; 0340; 0341, (2022/03/31)
Compounds of Formula (I), and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to depression, major depressive disorder, treatment resistant depression, anxious depression, autism spectrum disorders, Asperger syndrome, and bipolar disorder), cancers and eye conditions: wherein R1, , R3, and L are as defined herein.
FUMAGILLOL HETEROCYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME
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Paragraph 00287, (2017/03/08)
Disclosed herein, in part, are fumagillol compounds and methods of use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making fumagillol compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL
Bruncko, Milan,Oost, Thorsten K.,Belli, Barbara A.,Ding, Hong,Joseph, Mary K.,Kunzer, Aaron,Martineau, Darlene,McClellan, William J.,Mitten, Michael,Ng, Shi-Chung,Nimmer, Paul M.,Oltersdorf, Tilman,Park, Cheol-Min,Petros, Andrew M.,Shoemaker, Alexander R.,Song, Xiaohong,Wang, Xilu,Wendt, Michael D.,Zhang, Haichao,Fesik, Stephen W.,Rosenberg, Saul H.,Elmore, Steven W.
, p. 641 - 662 (2007/10/03)
Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.
