TY - JOUR
T1 - Expanding the diversity at the C-4 position of pyrido[2,3-d]pyrimidin-7(8H)-ones to achieve biological activity against ZAP-70
AU - Masip, Victor
AU - Lirio, Ángel
AU - Sánchez-López, Albert
AU - Cuenca, Ana B.
AU - Puig de la Bellacasa, Raimon
AU - Abrisqueta, Pau
AU - Teixidó, Jordi
AU - Borrell, José I.
AU - Gibert, Albert
AU - Estrada-Tejedor, Roger
N1 - Funding Information:
Funding: This research has been funded by Instituto de Salud Carlos III through the project “PI18/01392” (Co-funded by European Regional Development Fund “A way to make Europe”).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Pyrido[2,3-d]pyrimidin-7(8H)-ones have attracted widespread interest due to their similar-ity with nitrogenous bases found in DNA and RNA and their potential applicability as tyrosine kinase inhibitors. Such structures, presenting up to five diversity centers, have allowed the synthesis of a wide range of differently substituted compounds; however, the diversity at the C4 position has mostly been limited to a few substituents. In this paper, a general synthetic methodology for the synthesis of 4-substituted-2-(phenylamino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones is described. By using cross-coupling reactions, such as Ullmann, Buchwald–Hartwig, Suzuki–Miyaura, or Sonogashira re-actions, catalyzed by Cu or Pd, we were able to describe new potential biologically active compounds. The resulting pyrido[2,3-d]pyrimidin-7(8H)-ones include N-alkyl, N-aryl, O-aryl, S-aryl, aryl, and arylethynyl substituents at C4, which have never been explored in connection with the biological activity of such heterocycles as tyrosine kinase inhibitors, in particular as ZAP-70 inhibitors.
AB - Pyrido[2,3-d]pyrimidin-7(8H)-ones have attracted widespread interest due to their similar-ity with nitrogenous bases found in DNA and RNA and their potential applicability as tyrosine kinase inhibitors. Such structures, presenting up to five diversity centers, have allowed the synthesis of a wide range of differently substituted compounds; however, the diversity at the C4 position has mostly been limited to a few substituents. In this paper, a general synthetic methodology for the synthesis of 4-substituted-2-(phenylamino)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones is described. By using cross-coupling reactions, such as Ullmann, Buchwald–Hartwig, Suzuki–Miyaura, or Sonogashira re-actions, catalyzed by Cu or Pd, we were able to describe new potential biologically active compounds. The resulting pyrido[2,3-d]pyrimidin-7(8H)-ones include N-alkyl, N-aryl, O-aryl, S-aryl, aryl, and arylethynyl substituents at C4, which have never been explored in connection with the biological activity of such heterocycles as tyrosine kinase inhibitors, in particular as ZAP-70 inhibitors.
KW - Cross-coupling
KW - Pyrido[2,3-d]pyrimidines
KW - Tyrosine kinase inhibitors
KW - ZAP-70
UR - http://www.scopus.com/inward/record.url?scp=85124767201&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000748871700001&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.3390/PH14121311
DO - 10.3390/PH14121311
M3 - Article
C2 - 34959711
AN - SCOPUS:85124767201
SN - 1424-8247
VL - 14
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 12
M1 - 1311
ER -