18446-90-7Relevant academic research and scientific papers
Discovery of MK-4688: An Efficient Inhibitor of the HDM2-p53 Protein-Protein Interaction
Altman, Michael D.,Bogen, Stephane,Cai, Mingmei,Cammarano, Carolyn,Chen, Dapeng,Christopher, Matthew,Cryan, John,Daublain, Pierre,Dussault, Isabelle,Fradera, Xavier,Geda, Prasanthi,Goldenblatt, Peter,Hill, Armetta D.,Kemper, Raymond A.,Kutilek, Victoria,Li, Chaomin,Machacek, Michelle R.,Marshall, C. Gary,Martinez, Michelle,McCoy, Mark,Nair, Latha,Pan, Weidong,Reutershan, Michael H.,Scapin, Giovanna,Shizuka, Manami,Spatz, Marianne L.,Steinhuebel, Dietrich,Sun, Binyuan,Thompson, Christopher F.,Trotter, B. Wesley,Voss, Matthew E.,Wang, Xiao,Yang, Liping,Yeh, Tammie C.
, p. 16213 - 16241 (2021/11/16)
Identification of low-dose, low-molecular-weight, drug-like inhibitors of protein-protein interactions (PPIs) is a challenging area of research. Despite the challenges, the therapeutic potential of PPI inhibition has driven significant efforts toward this goal. Adding to recent success in this area, we describe herein our efforts to optimize a novel purine carboxylic acid-derived inhibitor of the HDM2-p53 PPI into a series of low-projected dose inhibitors with overall favorable pharmacokinetic and physical properties. Ultimately, a strategy focused on leveraging known binding hot spots coupled with biostructural information to guide the design of conformationally constrained analogs and a focus on efficiency metrics led to the discovery of MK-4688 (compound 56), a highly potent, selective, and low-molecular-weight inhibitor suitable for clinical investigation.
Substituted Imidazopyridines as HDM2 Inhibitors
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Paragraph 0916, (2014/07/08)
The present invention provides substituted imidazopyridines as described herein or a pharmaceutically acceptable salt or solvate thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.
2,6,7 SUBSTITUTED PURINES AS HDM2 INHIBITORS
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Page/Page column 98, (2014/08/20)
The present invention provides 2,6,7 substituted purines as described herein or a pharmaceutically acceptable salt thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.
METHOD FOR PRODUCING CYCLOHEXYL ALKYL KETONES
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Page/Page column 6, (2012/07/27)
Provided is an industrially superior method for producing cyclohexyl alkyl ketones, which solves the problems in process reduction and in disposal of wastes such as metals. An aromatic ketone represented by a formula (1) is nuclear-hydrogenated with pressurized hydrogen and in the presence of a solvent at a temperature of from 20 to 120° C., in the presence of a catalyst that carries from 0.1 to 20% by weight of a ruthenium atom on the carrier, thereby producing a cyclohexyl alkyl ketone represented by a formula (2): provided that, in the formula (2), n indicates an integer of from 1 to 3; R represents a hydroxyl group, a cyclohexyl group, an alkyl group having from 1 to 4 carbon atoms, or an acyl group having from 1 to 4 carbon atoms
SUBSTITUTED AMINOTHIAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE
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Page/Page column 49-50, (2010/04/06)
Substituted aminothiazole derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted aminothiazole, and methods of use in treating human or animal disorders. The compounds may be useful as inhibitors of action of AgRP on a melanocortin receptor and thus may be useful for the management, treatment, control, or the adjunct treatment of diseases which may be responsive to the modulation of melanocortin receptors including obesity-related disorders.
Asymmetric synthesis of α,α-dibranched propargylamines by acetylide additions to N-tert-butanesulfinyl ketimines
Patterson, Andrew W.,Ellman, Jonathan A.
, p. 7110 - 7112 (2007/10/03)
Addition of lithium acetylides prepared from 1-pentyne, phenylacetylene, and trimethylsilylacetylene to diverse N-tert-butanesulfinyl ketimines affords a range of α,α-dibranched propargyl sulfinamides in generally good yields (up to 87%) and with high dia
Directing Effects in Homogeneous Hydrogenation with PF6
Crabtree, Robert H.,Davis, Mark W.
, p. 2655 - 2661 (2007/10/02)
The presence of a ligating group, e.g., OH, CO2Me, C=O, or OMe, on an olefinic substrate is shown to direct the attack of the hydrogenation catalyst PF6/H2/CH2Cl2 from the face of the molecule containing the directing group.Isomerization is a minor side reaction in the cases studied.The origin of this effect is discussed and a model intermediate isolated.
