Answer Happy

го UMTUU ΤατυΙΙαΙΙ. UT - AVC Wu.j. Realny (0) Define the undecided tem (ii) Explain what type of physicochemical parameter is represented by the symbols, Op, Om, T and Es. Describe what is represented by the data, n, 12. SE and F listed under Equation 1. (iv) Write a short paragraph describing the structure of the hit compound. Include in your answer the functional groups and ring systems in the structure, and the manner in wbich they are connected relative to each other. Ensure you use appropriate chemical terminology and nomenclature in your answer Question A research group wished to develop and bring to market a novel kinase inhibitor for the treatment of advanced renal cell carcinoma. Their target was the inhibition of vascular endothelial growth factor receptor (VEGFR). After an initial screening, the researchers discovered the hit compound below where X = Y = H. They synthesised a series of analogues of the hit compound by varying both the substituents at positions X and Y simultaneously in order to find a potential lead compound with higher VEGFR potency and selectivity relative to their hit compound. (v) Dees Equation 1 gbex the Jopliss-castello rule? Explain your answer (vi) Which of the descriptors, o, o Es, do you think is, the most dominant physicochemical property of X and Y that influences the biological activity to the greatest extent of compounds in the dataset? Explain your answer (vii) What are the advantages and disadvantages of combining the physicochemical descriptors, for X and Y as single descriptor terms in Equation 1? After biologically determining the IC50 values of their dataset against in vitro inhibition of the VEGFR protein, they performed a Hansch. analysis in order to predict the optimal physicochemical properties of X and Y that maximise potency and inhibition of VEGFR. The Hansch equation they developed is displayed below as Equation 1, where descriptors Es and I represent the combined physicochemical properties of X and Y for those descriptors. (viii) Bx analysing. Equation 1. predict three substituents, fer X and Y that the equatico is predicting should provide patent activity as VEGFR inbibitors. Explain your answer (ix) ooo What does the statistical data tell you about (a) the spread of data points about the regression line of equation 1 when plotted and (b) the reliability/robustness, of the equation to predict bioactivities of analogues of the hit compound? X NH Log (1/1C50) = 2.34 (20 380 +0.89(+0 100m - 0.347(+0,018) Es - 0.146(+0.1511 + 1.29 Accoccihili 'Focus