Department of Medicinal Chemistry, School of Pharmacy, Box 980540, Virginia Commonwealth University, Richmond, VA 23298-0540,USA.
Curr Top Med Chem. 2010;10(5):579-95. doi: 10.2174/156802610791111542.
Arylsulfonyl analogs of aminopyrimidines (e.g. Ro 04-6790; 2), aminopyridines (e.g. Ro 63-0563; 3), 1-phenylpiperazines (e.g. SB-271046; 4), and tryptamines (e.g. MS-245; 5) were described as the first examples of selective 5-HT(6) receptor antagonists only ten years ago. Today, hundreds of compounds of seemingly diverse structure have been reported. The early antagonists featured an arylsulfonyl group leading to the wide notspread assumption that an arylsulfonyl moiety might be critical for binding and antagonist action. With respect to the arylsulfonyltryptamines, it seems that neither the "arylsulfonyl" nor the "tryptamine" portion of these compounds is essential for binding or for antagonist action, and some such derivatives even display agonist action. The present review describes many of the currently available 5-HT(6) receptor ligands and, unlike prior reviews, provides a narrative of the thinking (where possible) that led to their design, synthesis, and evaluation. The arylsulfonyltryptamines are also used as the structural basis of attempts to relate various structure-types to one another to afford a better understanding of the overall structural requirements for 5-HT(6) receptor binding.
10 年前，芳基磺酰基氨基嘧啶类（例如 Ro 04-6790；2）、氨基吡啶类（例如 Ro 63-0563；3）、1-苯基哌嗪类（例如 SB-271046；4）和色胺类（例如 MS-245；5）被描述为首个选择性 5-HT（6）受体拮抗剂。如今，已经报道了数百种结构似乎不同的化合物。早期的拮抗剂具有芳基磺酰基，这导致了广泛的假设，即芳基磺酰基部分可能对结合和拮抗作用至关重要。对于芳基磺酰基色胺类化合物，这些化合物的“芳基磺酰基”部分和“色胺”部分似乎都不是结合或拮抗作用所必需的，并且一些此类衍生物甚至具有激动剂作用。本综述描述了许多当前可用的 5-HT（6）受体配体，与之前的综述不同，它提供了对导致它们设计、合成和评估的思路（在可能的情况下）的叙述。芳基磺酰基色胺类化合物也被用作尝试将各种结构类型相互关联的结构基础，以更好地理解 5-HT（6）受体结合的整体结构要求。
