The chemical properties of alicyclic heterocycles are similar to those of the corresponding chain compounds. Compound: 3-(Pyridin-4-yl)-1H-pyrazol-5-amine, is researched, Molecular C8H8N4, CAS is 91912-53-7, about Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine derivatives as potent inhibitors of Bloom helicase, the main research direction is pyridinylthiadiazolamine derivative preparation SAR Bloom helicase inhibitor; ADME; BLM; BS; Bloom helicase; Bloom syndrome; DMF; HR; HTS; Inhibitor; MLM; NADPH; PBS; PEPPSITM-IPr; SAR; SCE; Small molecule; [1,3-Bis(2,6-Diisopropylphenyl)imidazole-2-ylidene](3-chloropyridyl)palladium(II)chloride; absorption, distribution, metabolism and excretion; dimethylformamide; high throughput screen; homologous recombination; mouse liver microsomes; nicotinamide adenine dinucleotide phosphate; phosphate buffered saline; sister chromatid exchanges; structure activity relationship.Application In Synthesis of 3-(Pyridin-4-yl)-1H-pyrazol-5-amine.
Human cells utilize a variety of complex DNA repair mechanisms to combat constant mutagenic and cytotoxic threats from both exogenous and endogenous sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM), plays an important function in DNA repair by unwinding complementary strands of duplex DNA and atypical DNA structures such as Holliday junctions. Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive disorder associated with cancer predisposition. BLM-deficient cells exhibit increased sensitivity to DNA damaging agents indicating that a selective BLM inhibitor could be useful in potentiating the anticancer activity of these agents. In this work, we describe the medicinal chem. optimization of the hit mol. following a quant. high-throughput screen of >355,000 compounds These efforts lead to the identification of ML216 and related analogs, which possess potent BLM inhibition and exhibit selectivity over related helicases. Moreover, these compounds demonstrated cellular activity by inducing sister chromatid exchanges, a hallmark of Bloom syndrome.
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