165949-85-9Relevant articles and documents
COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
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Page/Page column 73-74, (2011/12/02)
The present invention relates to pyrazine and pyridine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I wherein the variables are as defined herein.
PYRROLO- PYRAZINE DERIVATIVES USEFUL AS INHIBITORS OF ATR KINASE
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Page/Page column 66, (2012/01/14)
The present invention relates to pyrrolopyrazines compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various disea
Template-constrained cyclic peptides: Design of high-affinity ligands for GPIIb/IIIa
Jackson, Sharon,DeGrado, William,Dwivedi, Anil,Parthasarathy, Anju,Higley, Anne,Krywko, James,Rockwell, Arlene,Markwalder, Jay,Wells, Greg,Wexler, Ruth,Mousa, Shaker,Harlow, Richard
, p. 3220 - 3230 (2007/10/02)
Although peptides adopt a large ensemble of conformations in aqueous solution, they are generally believed to bind to a receptor in a unique conformation. Thus, there is considerable interest in devising methods to restrict the conformational freedom of peptides. One such approach involves tying the amino and carboxy terminal ends of the peptide onto a semirigid template that will lock the intervening peptide backbone into a single conformer or a family of related conformers. This general strategy has been tested using the tripeptide sequence Arg-Gly-Asp (RGD), which binds with low affinity to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa or α(IIb)β3). Mimics of RGD are of interest as antithrombotics because of their ability to inhibit the aggregation of platelets. Prior to this study, other workers (Samanen et al. J. Med. Chem. 1991, 34, 3114-3125) prepared a disulfide- containing cyclic pentapeptide that bound to GPIIb/IIIa with an affinity of approximately 0.1 μM. NMR analysis of the solution conformation of this peptide suggested that replacing the disulfide-containing portion of the cycle with the amino acid m-(aminomethyl)benzoic acid would lead to a more rigid structure. Indeed, introduction of this template into a cyclic RGD- containing peptide resulted in compounds with high affinity for the receptor. Further, systematic inclusion of additional conformational constraints in the form of N(α)- and C(α)-alkyl groups led to a peptide with an affinity of approximately 100 pM for binding to the receptor. This peptide also showed good activity in the platelet aggregation assay at oral doses as low as 0.1 mg/kg.
