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A new series of benzene-sulfonamide derivatives 3a-i was designed and synthesized via the reaction of N-(pyrimidin-2-yl)cyanamides 1a-i with sulfamethazine sodium salt 2 as dual Src/Abl inhibitors. Spectral data IR, 1 H-, 13 C- NMR and elemental analyses were used to confirm the structures of all the newly synthesized compounds 3a-i and 4a-i. Crucially, we screened all the synthesized compounds 3a-i against NCI 60 cancer cell lines. Among all, compound 3b was the most potent, with IC 50 of 0.018 μM for normoxia, and 0.001 μM for hypoxia, compared to staurosporine against HL-60 leukemia cell line. To verify the selectivity of this derivative, it was assessed against a panel of tyrosine kinase EGFR, VEGFR-2, B-raf, ERK, CK1, p38-MAPK, Src and Abl enzymes. Results revealed that compound 3b can effectively and selectively inhibit Src/Abl with IC 50 0.25 μM and Abl inhibitory activity with IC 50 0.08 μM, respectively, and was found to be more potent on these enzymes than other kinases that showed the following results: EGFR IC 50 0.31 μM, VEGFR-2 IC 50 0.68 μM, B-raf IC 50 0.33 μM, ERK IC 50 1.41 μM, CK1 IC 50 0.29 μM and p38-MAPK IC 50 0.38 μM. Moreover, cell cycle analysis and apoptosis performed to compound 3b against HL-60 suggesting its antiproliferative activity through Src/Abl inhibition. Finally, molecular docking studies and physicochemical properties prediction for compounds 3b, 3c, and 3 h were carried out to investigate their biological activities and clarify their bioavailability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Continuous reaction networks, which do not rely on purification or timely additions of reagents, serve as models for chemical evolution and have been demonstrated for compounds thought to have played important roles for the origins of life such as amino acids, hydroxy acids, and sugars. Step-by-step chemical protocols for ribonucleotide synthesis are known, but demonstrating their synthesis in the context of continuous reaction networks remains a major challenge. Herein, compounds proposed to be important for prebiotic RNA synthesis, including glycolaldehyde, cyanamide, 2-aminooxazole, and 2-aminoimidazole, are generated from a continuous reaction network, starting from an aqueous mixture of NaCl, NH 4 Cl, phosphate, and HCN as the only carbon source. No well-timed addition of any other reagents is required. The reaction network is driven by a combination of γ radiolysis and dry-down. γ Radiolysis results in a complex mixture of organics, including the glycolaldehyde-derived glyceronitrile and cyanamide. This mixture is then dried down, generating free glycolaldehyde that then reacts with cyanamide/NH 3 to furnish a combination of 2-aminooxazole and 2-aminoimidazole. This continuous reaction network models how precursors for generating RNA and other classes of compounds may arise spontaneously from a complex mixture that originates from simple reagents., Competing Interests: The authors declare no competing interest.

Nineteen new compounds containing tetrazole and/or cyanamide moiety have been designed and synthesised. Their structures were confirmed using spectroscopic methods and elemental analyses. Anti-inflammatory activity for all the synthesised compounds was evaluated in vivo. The most active compounds 4c, 5a, 5d-f, 8a and b and 9a and b were further investigated for their ulcerogenic liability and analgesic activity. Pyrazoline derivatives 9b and 8b bearing trimethoxyphenyl part and SO 2 NH 2 or SO 2 Me pharmacophore showed equal or nearly the same ulcerogenic liability (UI: 0.5, 0.75, respectively), to celecoxib (UI: 0.50). Most of tested compounds showed potent central and/or peripheral analgesic activities. Histopathological investigations were done to evaluate test compounds effect on rat's gastric tissue. The obtained results were in consistent with the in vitro data on COX evaluation. Docking study was also done for all the target compounds inside COX-2-active site.

The application of alkyl and aryl substituted cyanamides in synthetic chemistry has diversified multi-fold in recent years. In this review, we discuss recent advances (since 2012) in the chemistry of cyanamides and detail their application in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic cyanide-transfer agents and their unique radical and coordination chemistry.

4-dimethylamino-2-glycosylaminoquinazoline derivatives were synthesized by cyclodesulfurization of N-aryl-N'-glycosyl thioureas with dimethylcyanamide in the presence of silver triflate in good yields.