Discovery of a lead series of potent benzodiazepine 5-HT2C receptor agonists with high selectivity in functional and binding assays

Ren, Albert; Zhu, Xiuwen; Feichtinger, Konrad; Lehman, Juerg; Kasem, Michelle; Schrader, Thomas O.; Wong, Amy; Dang, Huong; Le, Minh; Frazer, John; Unett, David J.; Grottick, Andrew J.; Whelan, Kevin; Morgan, Michael; Sage, Carleton R.; Semple, Graeme

doi:10.1016/j.bmcl.2019.126929

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…The usage of spirocyclic derivatives to improve the selectivity profile was also evaluated by Ren et al for the discovery of 5-hydroxytryptamine receptor (5-HT 2C R) agonists. 129 On the basis of the vabicaserin scaffold, they synthesized derivatives and evaluated the substitution pattern of the five-membered ring (compounds 198 and 199, Figure 14). Introduction of a dimethyl group gave a modest improvement in 5-HT 2C R activity but increased the selectivity.…”

Section: ■ Influence On Selectivitymentioning

confidence: 99%

Spirocyclic Scaffolds in Medicinal Chemistry

et al. 2020

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Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to obtain spirocyclic systems. The impact of spirocycles on potency and selectivity, including the aspect of stereochemistry, is discussed. Furthermore, we examine the changes in physicochemical properties as well as in in vitro and in vivo ADME using selected studies that compare spirocyclic compounds to their nonspirocyclic counterparts. In conclusion, the value of spirocyclic scaffolds in medicinal chemistry is discussed.

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Section: ■ Influence On Selectivitymentioning

confidence: 99%

Spirocyclic Scaffolds in Medicinal Chemistry

et al. 2020

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“…Indolines are classical privileged scaffolds that exist widely in natural products and drug molecules, 1 among which fused indolines with a seven-membered ring and alkylated indolines have attracted more attention because of their various pharmacological activities (Fig. 1), such as anti-inflammatory 2 and anti-tumor activities, 3 regulation of appetite and feeding, 4 treatment of aldosteronism 5 and metabolic disorders, 6 and neuroprotection. 7 However, only a limited number of synthetic methods have been reported for these intriguing seven-membered 1,7-fused indoline backbones.…”

Section: Introductionmentioning

confidence: 99%