5767-35-1Relevant articles and documents
Novel pyrimidine derivatives as potential anticancer agents: Synthesis, biological evaluation and molecular docking study
Tylińska, Beata,Wiatrak, Benita,Czy?nikowska, ?aneta,Cie?la-Niechwiadowicz, Aneta,G?barowska, El?bieta,Janicka-K?os, Anna
, (2021)
In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitu-mor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.
In silico and in vitro Antitubercular Studies for Nitrogen Rich Hybrids of homopiperazine-pyrimidine-Pyrazole Adducts
Marvaniya, Vanita,Pansuriya, Vrajlal,Patel, Popatbhai,Patel, Shivani,Vavaiya, Bhavinkumar
, p. 562 - 568 (2022/02/22)
Novel homopiperazine-pyrimidine-pyrazole hybrids (3a-j) were synthesized using ethyl 2-cyanoacetate and 4,6-dichloropyrimidine as starting materials by a multi-step process to afford ethyl 5-amino-1-(6-chloropyrimidin-4-yl)-1H-pyrazole-4-carboxylate in good yields using polar protic media. The intermediate 1, in two steps, chloroamine condensation followed by acid amine coupling, furnished the title compounds ethyl 5-amino-1-(6-(4-substituted aryl-1,4-diazepan-1-yl)pyrimidin-4-yl)-1H-pyrazole-4-carboxylate (3a-j). The synthesized compounds were docked in the crystal structure of Mycobacterium tuberculosis (PDB ID: 4TRO) to get insights into structural requirements for antitubercular activity. In vitro antitubercular activity against M. tuberculosis H37Rv strains showed that compounds 3a, 3d, 3e and 3g were found to be the most potent (Docking score: > -21; MIC = 1.6 μg/mL) among the synthesized molecules. All the synthesized compounds showed acceptable drug-like properties which make them suitable for further lead modification using in silico design approaches.
GPR52 MODULATOR COMPOUNDS
-
Paragraph 73-74, (2021/05/15)
The disclosures herein relate to novel compounds of Formula (1): (1) and salts thereof, wherein R1, Q, X, Y and Z are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with GPR52 receptors.