BIOMAT Database Logo BIOMAT Database Logo

4-Substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives: design, synthesis, antitumor and EGFR tyrosine kinase inhibitory activity. 2015

Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt.

Four series of some 4-substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives 5a-f, 6a-f, 8a-f, and 9a-f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF-7) and lung (A-549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR-TK inhibitory activity where they revealed 41-91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP-binding site of EGFR-TK demonstrated their binding mode where H-bonding interaction with Met793 through N(1) of pyrimidine or N(2) of pyrazole was observed.

UI MeSH Term Description Entries
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006860 Hydrogen Bonding A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
RETRACTED: Design, synthesis, structure-activity relationship and kinase inhibitory activity of substituted 3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ones.
July 2016, Bioorganic & medicinal chemistry letters,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
Synthesis, EGFR Inhibition and Anti-cancer Activity of New 3,6-dimethyl-1-phenyl-4-(substituted-methoxy)pyrazolo[3,4-d] pyrimidine Derivatives.
January 2017, Anti-cancer agents in medicinal chemistry,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
[Studies on pyrazolo(3,4-d)pyrimidine derivatives. XI. On 1-phenyl-1H-pyrazolo(3,4-d)pyrimidine-4-carbonitrile (author's transl)].
July 1978, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
Design, synthesis and antitumor activity of novel pyrazolo[3,4-d]pyrimidine derivatives as EGFR-TK inhibitors.
June 2016, Bioorganic chemistry,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
[Studies on pyrazolo[3,4-d]pyrimidine derivatives. IX. On 4-(p-tolylsulfonyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine (author's transl)].
January 1978, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
[Studies on pyrazolo[3,4-d]pyrimidine derivatives. XII. On 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4-carboxylic acid (author's transl)].
September 1978, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors.
November 2023, Bioorganic chemistry,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
Design, Synthesis, and Antitumor Evaluation of Novel Pyrazolo[3,4-d]pyrimidine Derivatives.
January 2012, Scientia pharmaceutica,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
Synthesis and antitumor properties of pyrazolo [3,4-D] pyrimidine derivatives.
January 1987, Polish journal of pharmacology and pharmacy,
Safinaz E-S Abbas, and Enayat I Aly, and Fadi M Awadallah, and Walaa R Mahmoud
[Studies on pyrazolo(3,4-d)pyrimidine derivatives. III. On the reaction of 1-methyl- and 1-phenyl-4-chloro-1H-pyrazolo(3,4-d)-pyrimidine with carbanion (author's transl)].
November 1976, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,
Copied contents to your clipboard!