J. Thomas Leonard et. al (Bioorganic & Medicinal Chemistry Letters 16 (2006) 4467-4474) investigated the CCR5 receptor b

[answerhappygod]

J Thomas Leonard Et Al Bioorganic Medicinal Chemistry Letters 16 2006 4467 4474 Investigated The Ccr5 Receptor B 1 (190.24 KiB) Viewed 21 times

J. Thomas Leonard et. al (Bioorganic & Medicinal Chemistry Letters 16 (2006) 4467-4474) investigated the CCR5 receptor binding affinity of substituted 1-(3,3-diphenylpropyl)-piperidinyl ureas (1). Equation 1 can explain 77.9% of the variance of the CCR5 binding affinity data. hossa. i) ii) in) iv) v) vi) log(1/ICso) = 4.794logP-0.430logp² +1.013GR +0.579LR-0.050LR² +1.416MRx-0.071MRX² - 11.609. ....(Equation 1) n=79; r² = 0.810; s = 0.403; F = 25.9 What does "ICso" mean and why is it expressed as "log(1/1Cso)" in Equation 1? (3 marks) What type of group (electron donating or electron withdrawing) is best for R and what is the optimal value? Explain your reasoning. (2 marks) Considering ONLY your answer to part ii) what effect does R have on the acidity of the urea? What does this suggest about the active site of CCRS? (2 marks) What is the optimal value of L for the R group? Show your working in full. What type of parameter is L? What does it measure? (3 marks) (2 marks) From your value for L calculated in part iv), what are the functional groups that are +0.50 from this optimum value in the QSAR Table on Page 14? (2 marks) vii) Draw a Craig plot of LR VS GR for all the groups from part vi) and decide which group would be best according to Equation 1 (3 marks) viii) From the QSAR Table on Page 14, what would be the best group for the X-position on 1? (3 marks) Show your working.