上海交通大学：《药物化学》课程教学资源（课后题库）Chapter 2 Receptors

1.Indicate what drug-receptor interactions are involved at every arrow shown.More than one kind of interaction is possible for each letter. Asn Ser OH Glu HO OH /al NH3 Lys 9 b c d 2.A receptor has lysine and histidine residues important to binding that do not interact with each other.The pKa of the lysine residue is 6.4(pKa in solution is 10.5),and the pKa of the histidine residue is 9.4 (pKa in solution is 6.5).Based on the discussion in Chapter 2 about pKa variabilities as a result of the environment,what can you say about possible other residues in the binding site to rationalize these observations? 3.A.What problems are associated with administration of racemates? B.How can you increase the eudismic ratio? 4.Design confomationally rigid analogs for: OH HO NHCH3 HN√COO HO A C A.4-aminobutyric acid(GABA) B.Epinephrine C.Nicotine 5.Based on generalizations about ring topology discussed in the chapter,would you expect the compound below to be a tranquilizer, have both antidepressant and tranquilizing properties,or be an antidepressant agent?Why?

1. Indicate what drug–receptor interactions are involved at every arrow shown. More than one kind of interaction is possible for each letter. H3N S Val OH OH Ser HO H2N Asn O COO Glu NH3 Lys a b c d e a b c d e 2. A receptor has lysine and histidine residues important to binding that do not interact with each other. The pKa of the lysine residue is 6.4 (pKa in solution is 10.5), and the pKa of the histidine residue is 9.4 (pKa in solution is 6.5). Based on the discussion in Chapter 2 about pKa variabilities as a result of the environment, what can you say about possible other residues in the binding site to rationalize these observations? 3. A. What problems are associated with administration of racemates? B. How can you increase the eudismic ratio? 4. Design confomationally rigid analogs for: HN COO HO HO NHCH3 OH N N CH3 A B C A. 4-aminobutyric acid (GABA) B. Epinephrine C. Nicotine 5. Based on generalizations about ring topology discussed in the chapter, would you expect the compound below to be a tranquilizer, have both antidepressant and tranquilizing properties, or be an antidepressant agent? Why?

HC 6.An isosteric series of compounds shown below,where X=CH2, NH,O,S,was synthesized.The order of potency was X=NH>O> S>CH2.How can you rationalize these results (you need to consider the three-dimensional structure)? CH: H 7.Tyramine binds to a receptor that triggers the release of norepinephrine,which can raise the blood pressure.If the tyramine receptor were isolated,and you wanted to design a new antihypertensive agent,discuss what you would do in terms of lead discovery and modification. HO -NH2

S Cl CH3 H3C 6. An isosteric series of compounds shown below, where X = CH2, NH, O, S, was synthesized. The order of potency was X= NH > O > S > CH2 . How can you rationalize these results (you need to consider the three-dimensional structure)? X CH3 H 7. Tyramine binds to a receptor that triggers the release of norepinephrine, which can raise the blood pressure. If the tyramine receptor were isolated, and you wanted to design a new antihypertensive agent, discuss what you would do in terms of lead discovery and modification. HO NH2