Bermudez J, Dabbs S, Joiner K A, King F D
Beecham Pharmaceuticals Research Division, Harlow, Essex, England.
J Med Chem. 1990 Jul;33(7):1929-32. doi: 10.1021/jm00169a017.
Indazole 1 has previously been shown to be a potent and selective 5-HT3 receptor antagonist. A novel series of potent 5-HT3 receptor antagonists, 1-indolinecarboxamides 2a-q and 1-indolecarboxamides 3b,i,j,k, is described. The activity of the indolines suggests that aromaticity of the 5-membered ring is not an essential requirement for potency provided that an "in plane" orientation of the carbonyl group is favored. Upon the basis of this hypothesis indene 9 was prepared in which the "in plane" orientation of the carbonyl group is maintained by conjugation with the aromatic ring through the sp2 hybridized carbon. It was also found to be a potent 5-HT3 receptor antagonist.
吲唑1此前已被证明是一种强效且选择性的5-羟色胺3（5-HT3）受体拮抗剂。本文描述了一系列新型强效5-HT3受体拮抗剂，即1-吲哚啉甲酰胺2a-q和1-吲哚甲酰胺3b、i、j、k。吲哚啉的活性表明，只要羰基的“平面内”取向有利，五元环的芳香性并非活性的必要条件。基于这一假设，制备了茚9，其中羰基通过sp2杂化碳与芳环共轭来维持“平面内”取向。它也被发现是一种强效5-HT3受体拮抗剂。
