Generating Multibillion Chemical Space of Readily Accessible Screening Compounds.
iScience
; 23(11): 101681, 2020 Nov 20.
Article
en En
| MEDLINE
| ID: mdl-33145486
ABSTRACT
An approach to the generation of ultra-large chemical libraries of readily accessible ("REAL") compounds is described. The strategy is based on the use of two- or three-step three-component reaction sequences and available starting materials with pre-validated chemical reactivity. After the preliminary parallel experiments, the methods with at least â¼80% synthesis success rate (such as acylation - deprotection - acylation of monoprotected diamines or amide formation - click reaction with functionalized azides) can be selected and used to generate the target chemical space. It is shown that by using only on the two aforementioned reaction sequences, a nearly 29-billion compound library is easily obtained. According to the predicted physico-chemical descriptor values, the generated chemical space contains large fractions of both drug-like and "beyond rule-of-five" members, whereas the strictest lead-likeness criteria (the so-called Churcher's rules) are met by the lesser part, which still exceeds 22 million.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Idioma:
En
Revista:
IScience
Año:
2020
Tipo del documento:
Article
País de afiliación:
Ucrania