Identification | Back Directory | [Name]
Lu AE 58054 Hydrochloride | [CAS]
467458-02-2 | [Synonyms]
CS-1517 IdalopirdineHCl Lu AE58054(HCl) Lu AE58054 HCl salt Lu AE 58054 Hydrochloride Lu AE58054 (Hydrochloride) Idalopirdine Hydrochloride LU AE58054; LU AE-58054; LU AE 58054; IDALOPIRDINE HYDROCHLORIDE; LU AE 58054 HYDROCHLORIDE 6-fluoro-N-[[3-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]-1H-Indole-3-ethanamine hydrochloride N-[2-(6-Fluoro-1H-indol-3-yl)ethyl]-3-(2,2,3,3-tetrafluoropropoxy)benzylamine monohydrochloride 2-(6-Fluoro-1H-indol-3-yl)-N-[3-(2,2,3,3-tetrafluoropropoxy)benzyl]ethanamine hydrochloride (1:1) | [Molecular Formula]
C20H20ClF5N2O | [MDL Number]
MFCD25372046 | [MOL File]
467458-02-2.mol | [Molecular Weight]
434.831 |
Hazard Information | Back Directory | [Uses]
Idalopirdine hydrochloride (Lu AE58054 hydrochloride) is a potent, selective 5-HT6 receptor antagonist with a Ki value of 0.83 nM. Idalopirdine hydrochloride may be used in studies of Alzheimer's disease and schizophrenia, among other related disorders[1][2]. | [Synthesis]
The general procedure for the synthesis of N-(2-(6-fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropoxy)benzylamine hydrochloride using 6-fluorotryptophan and 3-(2,2,3,3-tetrafluoropropoxy)benzaldehyde was as follows: a mixture of 6-fluorotryptophan (11.0 g, 62 mmol) and 3-(2,2,3,3-tetrafluoropropoxy)benzaldehyde Formaldehyde (14.4 g, 59 mmol) were dissolved in toluene (120 mL) and isopropanol (96 mL), and the reaction was heated at 75°C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature and 3% Pt/C catalyst (Evonik Noblyst P8080 type, 61.2% w/w water content, 3.06 g, 0.183 mmol) was added. The hydrogenation reaction was carried out at 70-75 °C and 5 bar pressure for 6 hours. At the end of the reaction, the mixture was cooled, the catalyst was removed by filtration, and the filtrate was concentrated to dryness to afford the crude product N-(2-(6-fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropoxy)benzylamine (25.7 g). The crude product (24.7 g, 1 g was retained for analysis) was dissolved in toluene (205 mL) and washed sequentially twice with 2% sodium hydroxide solution (79 mL) and then with a mixture of 3% ammonium chloride solution (74 mL) and water (74 mL). A dilute hydrochloric acid solution (10 mL) prepared from 6.4 mL of 37% w/w aqueous hydrochloric acid and 21.3 mL of water was slowly added, followed by the addition of acetonitrile (20 mL) and the mixture was heated to 50 °C. At this point, the target compound precipitated as hydrochloride (1:1), which was separated by filtration and washed with a mixture of toluene/acetonitrile, dilute hydrochloric acid and water. The wet product was dried in vacuum at 65 °C overnight to afford dry N-(2-(6-fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropoxy)benzylamine hydrochloride (20.4 g, 47 mmol, corrected yield 83%), which was analyzed by HPLC and showed a UV purity of 99.1%. | [in vivo]
Idalopirdine (intraperitoneal injection, 5?mg/kg, daily, 28 days) hydrochloride can reduce food intake and body weight in over-eating rat models[1].
Idalopirdine (1 or 2?mg/kg, i.v) hydrochloride can dose-dependently increase the gamma power during nPO electrical stimulation, enhance effect of donepezil on cortical gamma oscillations but no alteration of sleep-wake patterns in rats[2].
Animal Model: | Male Wistar rats[1] | Dosage: | 5?mg/kg | Administration: | intraperitoneal injection, daily, 28 days | Result: | Significantly reduced the amount of calories consumed by animals in a palatable diet and significantly reduced plasma levels of glucose, triglycerides and cholesterol. |
Animal Model: | Male Sprague-Dawley rats[2] | Dosage: | 1 or 2?mg/kg | Administration: | i.v. | Result: | No significant increase in the gamma power at 1 mg/kg and significantly increased the gamma power at 2 mg/kg.
Significantly enhanced and/or prolonged effect of low-dose donepezil (0.3 mg/kg) on gamma power during 60-minute nPO stimulation after donepezil administration. |
| [IC 50]
5-HT6 Receptor: 0.83 nM (Ki) | [storage]
Store at -20°C | [References]
[1] Magdalena Kotańska, et al. Idalopirdine, a selective 5-HT6?receptor antagonist, reduces food intake and body weight in a model of excessive eating. Metab Brain Dis. 2018 Jun;33(3):733-740. DOI:10.1007/s11011-017-0175-1 [2] Maria Amat-Foraster, et al. The 5-HT6?receptor antagonist idalopirdine potentiates the effects of donepezil on gamma oscillations in the frontal cortex of anesthetized and awake rats without affecting sleep-wake architecture. Neuropharmacology. 2017 Feb;113(Pt A):45-59. DOI:10.1016/j.neuropharm.2016.09.017 |
|
|