Day: November 24, 2022

Sekigawa, Masayuki published the artcileComprehensive screening of human genes with inhibitory effects on yeast growth and validation of a yeast cell-based system for screening chemicals, Name: SU6656, the publication is Journal of Biomolecular Screening (2010), 15(4), 368-378, database is CAplus and MEDLINE.

To evaluate yeast as a high-throughput cell-based system for screening chems. that may lead to drug development, 10,302 full-length human cDNAs (鈭?0% of the total cDNAs) were introduced into yeast. Approx. 5.6% (583 clones) of the cDNAs repressed the growth of yeast. Notably, 鈭?5% of the repressive cDNAs encoded uncharacterized proteins. Small chems. can be readily surveyed by monitoring their restorative effects on the growth of yeast. The authors focused on protein kinases because protein kinases are involved in various diseases. Among 263 protein kinase cDNAs (鈭?0% of the total) expressed in yeast, 60 cDNAs (鈭?3%), including c-Yes, a member of the Src tyrosine kinase family, inhibited the growth of yeast. Known inhibitors for protein kinases were examined for whether they reversed the c-Yes-induced inhibition of the yeast growth. Among 85 inhibitors tested, 6 compounds (PP2, PP1, SU6656, purvalanol, radicicol, and geldanamycin) reversed the inhibition, indicating a high specificity sufficient for validating this screening system. Human c-Yes was found to interact with Hsc82, one of the yeast chaperones. Radicicol and geldanamycin probably exerted their actions through interactions with Hsc82. These results indicate that when human proteins requiring mol. chaperones for their activities are subjected to the yeast screening system, 2 groups of chems. may be found. The actions of one group are exerted through direct interactions with the human proteins, whereas those of the other group are mediated through interactions with chaperones.

Journal of Biomolecular Screening published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C22H12F6O6S2, Name: SU6656.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Blackwell, J. Henry published the artcileVisible-Light-Mediated Carbonyl Alkylative Amination to All-Alkyl 伪-Tertiary Amino Acid Derivatives, Name: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Journal of the American Chemical Society (2021), 143(3), 1598-1609, database is CAplus and MEDLINE.

The all-alkyl 伪-tertiary amino acid scaffold represents an important structural feature in many biol. and pharmaceutically relevant mols. Syntheses of this class of mol., however, often involve multiple steps and require activating auxiliary groups on the nitrogen atom or tailored building blocks. A straightforward, single-step, and modular methodol. for the synthesis of all-alkyl 伪-tertiary amino esters was reported. This new strategy uses visible light and a silane reductant to bring about a carbonyl alkylative amination reaction that combines a wide range of primary amines, 伪-ketoesters, and alkyl iodides to form functionally diverse all-alkyl 伪-tertiary amino esters. Bronsted acid-mediated in situ condensation of primary amine and 伪-ketoester delivers the corresponding ketiminium species, which undergoes rapid 1,2-addition of an alkyl radical (generated from an alkyl iodide by the action of visible light and silane reductant) to form an aminium radical cation. Upon a polarity-matched and irreversible hydrogen atom transfer from electron rich silane, the electrophilic aminium radical cation is converted to an all-alkyl 伪-tertiary amino ester product. The benign nature of this process allows for broad scope in all three components and generates structurally and functionally diverse suite of 伪-tertiary amino esters that will likely have widespread use in academic and industrial settings.

Journal of the American Chemical Society published new progress about 167015-84-1. 167015-84-1 belongs to indole-building-block, auxiliary class Indols, name is tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, and the molecular formula is C15H20N2O2, Name: tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles