Build-Couple-Transform: A Paradigm for Lead-like Library Synthesis with Scaffold Diversity was written by Uguen, Melanie;Davison, Gemma;Sprenger, Lukas J.;Hunter, James H.;Martin, Mathew P.;Turberville, Shannon;Watt, Jessica E.;Golding, Bernard T.;Noble, Martin E. M.;Stewart, Hannah L.;Waring, Michael J.. And the article was included in Journal of Medicinal Chemistry in 2022.Application In Synthesis of 2-Methoxyethylamine The following contents are mentioned in the article:
High-throughput screening provides one of the most common ways of finding hit compounds Lead-like libraries e.g., I, in particular, provide hits with compatible functional groups and vectors for structural elaboration and phys. properties suitable for optimization. Library synthesis approaches can lead to a lack of chem. diversity because they employ parallel derivatization of common building blocks using single reaction types. This problem through a “build-couple-transform” paradigm for the generation of lead-like libraries e.g., I with scaffold diversity was addressed. Nineteen transformations of 4-oxo-2-butenamides RC(O)CH=CHC(O)N(R1)R2 (R = Ph, 4-methoxyphenyl, tetrahydro-2H-pyran-4-yl, etc.; R1 = H; R2 = 2-methoxyethyl, Bn, 1-methyl-1H-pyrazol-3-yl; R1R2 = -(CH2)5-, -(CH2)2O(CH2)2-) scaffold template were optimized, including 1,4-cyclizations, 3,4-cyclizations, reductions, and 1,4-additions A pool-transformation approach efficiently explored the scope of these transformations for nine different building blocks and synthesized a >170-member library with enhanced chem. space coverage and favorable drug-like properties. Screening revealed hits against CDK2. This work establishes the build-couple-transform concept for the synthesis of lead-like libraries e.g., I and provides a differentiated approach to libraries with significantly enhanced scaffold diversity. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3Application In Synthesis of 2-Methoxyethylamine).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Application In Synthesis of 2-Methoxyethylamine
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem