Chemistry is the experimental science by definition. We want to make observations to prove hypothesis. For this purpose, we perform experiments in the lab. , COA of Formula: C12H15NO4, 1676-73-9, Name is H-Glu(OBzl)-OH, molecular formula is C12H15NO4, belongs to phthalazine compound. In a document, author is Reilly, Sean W., introduce the new discover.
Examination of Diazaspiro Cores as Piperazine Bioisosteres in the Olaparib Framework Shows Reduced DNA Damage and Cytotoxicity
Development of poly(ADP-ribose) polymerase inhibitors (PARPi’s) continues to be an attractive area of research due to synthetic lethality in DNA repair deficient cancers; however, PARPi’s also have potential as therapeutics to prevent harmful inflammation. We investigated the pharmacological impact of incorporating spirodiamine motifs into the phthalazine architecture of FDA approved PARPi olaparib. Synthesized analogues were screened for PARP-1 affinity, enzyme specificity, catalytic inhibition, DNA damage, and cytotoxicity. This work led to the identification of 10e (12.6 +/- 1.1 nM), which did not induce DNA damage at similar drug concentrations as olaparib. Interestingly, several worst in class compounds with low PARP-1 affinity, including 15b (4397 +/- 1.1 nM), induced DNA damage at micromolar concentrations, which can explain the cytotoxicity observed in vitro. This work provides further evidence that high affinity PARPi’s can be developed without DNA damaging properties offering potential new drugs for treating inflammatory related diseases.
A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 1676-73-9. COA of Formula: C12H15NO4.
Reference:
Phthalazine – Wikipedia,
,Phthalazine | C8H6N2 – PubChem