(R)-69

(R)-69
	File:(R)-69.svg
临床资料
其他名称	R-69; 3IQ
药物类别	Non-hallucinogenic Serotonin 5-HT2A receptor agonist
识别信息
	IUPAC命名法 3-[(5R)-5-methyl-1,2,5,6-tetrahydropyridin-3-yl]-1H-pyrrolo[2,3-b]pyridine; ;
CAS号	2765652-48-8 check
PubChem CID	164513426;
ChemSpider	129875387;
UNII	L3MT297ZZJ;
ChEMBL	ChEMBL5399968;
PDB配体ID	3IQ (PDBe, RCSB PDB);
E编码	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}Module:EditAtWikidata第29行Lua错误：attempt to index field 'wikibase' (a nil value);
ECHA InfoCard	{{#property:P2566}}Module:EditAtWikidata第29行Lua错误：attempt to index field 'wikibase' (a nil value)
化学信息
化学式	C13H15N3
摩尔质量	213.28 g·mol−1
3D模型（JSmol）	交互式图像;
	SMILES C[C@@H]1C=C(CNC1)c1c[NH]c2ncccc12;
	InChI InChI=1S/C13H15N3/c1-9-5-10(7-14-6-9)12-8-16-13-11(12)3-2-4-15-13/h2-5,8-9,14H,6-7H2,1H3,(H,15,16)/t9-/m1/s1; Key:HNDPIXZRQWKEFZ-SECBINFHSA-N;

(R)-69也称为3IQ是一种含氮有机化合物，分子式C
13H
15N
3，属于色胺的类似物，由布莱恩·L·罗斯（英语：Bryan Roth）及其同事在2022年为5-HT_2A受体的激动剂研发，可作为迷幻药物^[1]^[2]。

参考文献[编辑]

^ Duan W, Cao D, Wang S, Cheng J. Serotonin 2A Receptor (5-HT_2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants. Chemical Reviews. January 2024, 124 (1): 124–163. PMID 38033123. doi:10.1021/acs.chemrev.3c00375. Very recently, the docking of a bespoke tetrahydropyridines (THPs) library combined with a structure-based optimization approach by Kaplan et al. led to the discovery of novel 5-HT2AR agonists with antidepressant activity in mouse models.202 The docking of a virtual library of 75 million THP compounds against the model of 5-HT2AR yielded 17 initial hits, among which 4 compounds showed low-micromolar activities at either 5-HT2AR or 5-HT2BR. Further modifications afforded [...] compounds (R)-69 (170) and (R)-70 (171) as agonists (Ki = 680 and 880 nM; EC50 = 41 nM (90.1%) and 110 nM (73.3%) in the calcium flux assay, respectively) (Figure 14D). Both compounds showed moderate binding selectivity against the 5-HT2BR and 5-HT2CR, and overall better selectivity profiles than those of classic psychedelic 5-HT2AR agonists. Interestingly, compounds (R)-69 and (R)-70 were pharmacologically profiled as G protein-biased 5-HT2AR agonists and were demonstrated as nonhallucinogenic in the HTR test and could block LSD-induced HTR effects. Very importantly, the compounds exhibited both acute and lasting (at least over 24 h) antidepressant effects in several mouse behavioral models.202
^ Kaplan AL, Confair DN, Kim K, Barros-Álvarez X, Rodriguiz RM, Yang Y, Kweon OS, Che T, McCorvy JD, Kamber DN, Phelan JP, Martins LC, Pogorelov VM, DiBerto JF, Slocum ST, Huang XP, Kumar JM, Robertson MJ, Panova O, Seven AB, Wetsel AQ, Wetsel WC, Irwin JJ, Skiniotis G, Shoichet BK, Roth BL, Ellman JA. Bespoke library docking for 5-HT_2A receptor agonists with antidepressant activity. Nature. October 2022, 610 (7932): 582–591. Bibcode:2022Natur.610..582K. PMC 9996387 可免费查阅. PMID 36171289. S2CID 252598838. doi:10.1038/s41586-022-05258-z.

外部链接[编辑]

- (R)-69 - Isomer Design

[Duan_2024-1] Duan W, Cao D, Wang S, Cheng J. Serotonin 2A Receptor (5-HT_2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants. Chemical Reviews. January 2024, 124 (1): 124–163. PMID 38033123. doi:10.1021/acs.chemrev.3c00375. Very recently, the docking of a bespoke tetrahydropyridines (THPs) library combined with a structure-based optimization approach by Kaplan et al. led to the discovery of novel 5-HT2AR agonists with antidepressant activity in mouse models.202 The docking of a virtual library of 75 million THP compounds against the model of 5-HT2AR yielded 17 initial hits, among which 4 compounds showed low-micromolar activities at either 5-HT2AR or 5-HT2BR. Further modifications afforded [...] compounds (R)-69 (170) and (R)-70 (171) as agonists (Ki = 680 and 880 nM; EC50 = 41 nM (90.1%) and 110 nM (73.3%) in the calcium flux assay, respectively) (Figure 14D). Both compounds showed moderate binding selectivity against the 5-HT2BR and 5-HT2CR, and overall better selectivity profiles than those of classic psychedelic 5-HT2AR agonists. Interestingly, compounds (R)-69 and (R)-70 were pharmacologically profiled as G protein-biased 5-HT2AR agonists and were demonstrated as nonhallucinogenic in the HTR test and could block LSD-induced HTR effects. Very importantly, the compounds exhibited both acute and lasting (at least over 24 h) antidepressant effects in several mouse behavioral models.202

[Kaplan_2022-2] Kaplan AL, Confair DN, Kim K, Barros-Álvarez X, Rodriguiz RM, Yang Y, Kweon OS, Che T, McCorvy JD, Kamber DN, Phelan JP, Martins LC, Pogorelov VM, DiBerto JF, Slocum ST, Huang XP, Kumar JM, Robertson MJ, Panova O, Seven AB, Wetsel AQ, Wetsel WC, Irwin JJ, Skiniotis G, Shoichet BK, Roth BL, Ellman JA. Bespoke library docking for 5-HT_2A receptor agonists with antidepressant activity. Nature. October 2022, 610 (7932): 582–591. Bibcode:2022Natur.610..582K. PMC 9996387 可免费查阅. PMID 36171289. S2CID 252598838. doi:10.1038/s41586-022-05258-z.

[1]

[2]

(R)-69

参考文献[编辑]

外部链接[编辑]

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