Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications.

Pyrido[2,3-d]pyrimidines (1) are a type of privileged heterocyclic scaffolds capable of providing ligands for several receptors in the body. Among such structures, our group and others have been particularly interested in pyrido[2,3-d]pyrimidine-7(8H)-ones (2) due to the similitude with nitrogen bases present in DNA and RNA. Currently there are more than 20,000 structures 2 described which correspond to around 2900 references (half of them being patents). Furthermore, the number of references containing compounds of general structure 2 have increased almost exponentially in the last 10 years. The present review covers the synthetic methods used for the synthesis of pyrido[2,3-d]pyrimidine-7(8H)-ones (2), both starting from a preformed pyrimidine ring or a pyridine ring, and the biomedical applications of such compounds.

Tyrosine kinase inhibition effects of novel Pyrazolo[1,5-a]pyrimidines and Pyrido[2,3-d]pyrimidines ligand: Synthesis, biological screening and molecular modeling studies.

Tyrosine kinases are one of the most critical mediators in the signaling path way. Late studies have proved the part of tyrosine kinases in the pathophysiology of cancer diseases. This current research paper has focused on investigating the novel Pyrazolo[1,5-a]pyrimidines and Pyrido[2,3-d]pyrimidines as a small molecules that can inhibit tyrosine kinase in cancer cells. NCI protocol was applied to test the antitumor activity of such compounds. Leukemia and renal cancer cell lines proved to be sensitive to some derivatives such as 6b-d, 9a and 11 with GI% values ranging from 30.4 to 41.3%. In addition, compound 11 proved to be the most active against MCF-7 with GI% 62.5. The synthesized compounds were also evaluated for their inhibitory effects against EGFR kinase enzyme. Compound 9b proved to be the most active one among the synthesized series with inhibition % value of 81.72 at 25 nM concentration and IC50 8.4 nM which is very close to the reference drug Sorafenib. In vitro cytotoxicity test was also performed using the MCF-7 breast cell line. Computer modeling using the active site of tyrosine kinase as a template and the most active tyrosine kinase inhibitors were calculated. Docking studies of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results.

Poly(acrylic acid)/Fe3O4 supported on MIL-100(Cr) MOF as a novel and magnetic nanocatalyst for the synthesis of Pyrido[2,3-d]Pyrimidines.

In the current work, a convenient and simple approach for preparing poly (acrylic acid)/Fe3O4 supported on MIL-100(Cr) for the synthesis of pyrido [2,3-d]pyrimidine derivatives via the three-component one-pot reaction of 1,3-indandione, 6-amino uracil, and aromatic aldehydes is reported. The effectiveness of this new magnetic nanocatalyst was proved. The results showed this nanocatalyst's moderate to high yield under reflux conditions. SEM, TEM, IR, EDX, XRD, BET, and TGA were used to characterize the structure of the synthesized nanocatalyst. This synthetic protocol offers various advantages, including cost-saving, excellent yields in short reaction times (67-98%), low catalyst loading, and catalyst reusability.

Expanding the Diversity at the C-4 Position of Pyrido[2,3-d]pyrimidin-7(8H)-ones to Achieve Biological Activity against ZAP-70.

Pyrido[2,3-d]pyrimidin-7(8H)-ones have attracted widespread interest due to their similarity 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 reactions, 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.

An overview on synthetic and pharmaceutical prospective of pyrido[2,3-d]pyrimidines scaffold.

Pyrido[2,3-d]pyrimidine, a fused hetero-bicyclic nucleus containing pyridine and pyrimidine rings has attained the momentary attention in the sphere of multicomponent synthetic protocol and medicinal chemist. Pyrido[2,3-d]pyrimidine derived drugs have manifested diverse pharmacological activities, particularly, anti-inflammatory, cytotoxic, antimicrobial, phosphodiesterase inhibitors and cytokine inhibitors etc. The present review illustrates various modern synthetic strategies adopted, the structure-activity relationship (SAR) aspects and discloses the extensive crucial biological properties (anticancer, anti-infectious, anti-diabetics and CNS agents) of pyrido[2,3-d]pyrimidines.

Synthesis of some novel annulated pyrido[2,3-d]pyrimidines via stereoselective intramolecular hetero Diels-Alder reactions of 1-oxa-1,3-butadienes.

Some novel annulated pyrido[2,3-d]pyrimidines 6 and 7 were synthesized stereoselectively by intramolecular hetero Diels-Alder reactions involving 1-oxa-1,3-butadienes.