130523-30-7Relevant articles and documents
INHIBITORS OF KRAS G12C PROTEIN AND USES THEREOF
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Paragraph 00222; 00223, (2021/12/28)
Provided are novel compounds useful as inhibitors of the KRAS protein, as well as pharmaceutical compositions comprising these compounds and methods of treatment by administration of these compounds or the pharmaceutical compositions.
Cobalt-catalysed C–H methylation for late-stage drug diversification
Ackermann, Lutz,Friis, Stig D.,Johansson, Magnus J.
, p. 511 - 519 (2020/06/05)
The magic methyl effect is well acknowledged in medicinal chemistry, but despite its significance, accessing such analogues via derivatization at a late stage remains a pivotal challenge. In an effort to mitigate this major limitation, we here present a strategy for the cobalt-catalysed late-stage C–H methylation of structurally complex drug molecules. Enabling broad applicability, the transformation relies on a boron-based methyl source and takes advantage of inherently present functional groups to guide the C–H activation. The relative reactivity observed for distinct classes of functionalities were determined and the sensitivity of the transformation towards a panel of common functional motifs was tested under various reaction conditions. Without the need for prefunctionalization or postdeprotection, a diverse array of marketed drug molecules and natural products could be methylated in a predictable manner. Subsequent physicochemical and biological testing confirmed the magnitude with which this seemingly minor structural change can affect important drug properties. [Figure not available: see fulltext.]
Conformational Studies by Dynamic NMR. 40. Conformational Atropoisomerism in Highly Hindered Naphthylamines
Davalli, S.,Lunazzi, L.,Macciantelli, D.
, p. 1739 - 1747 (2007/10/02)
N,N-Dialkyl-1-naphthylamines substituted by alkyl groups R (R=Me, Et, i-Pr, t-Bu) in position 2 display anisochronous NMR signals owing to their twisted conformational arrangement.These conformers are enantiomerically related (conformational atropoisomers), and variable temperature NMR measurements allowed the enantiomerization barriers to be determined.The barriers increase with the increasing dimension of the substituents (covering the range 15.7-23.0 kcal mol-1), and the observed trend was reproduced by Molecular Mechanics calculations.The calculations also gaveindications upon the structure of the conformers that correspond to energy minima.The final choice among the possible conformations could be achieved by comparing the computed interprotonic distances with the results of NOE experiments.
