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362665-56-3

中文名稱 替洛利生
英文名稱 Piperidine, 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-
CAS 362665-56-3
分子式 C17H26ClNO
分子量 295.85
MOL 文件 362665-56-3.mol
更新日期 2024/12/24 13:20:21
362665-56-3 結(jié)構(gòu)式 362665-56-3 結(jié)構(gòu)式

基本信息

中文別名
替洛利生
1-[3-[3-(4-氯苯基)丙氧基]丙基]哌啶
英文別名
PITOLISANT
Tirolisant
Tiprolisant
Pitolisant (BF2.649)
Tiprolisant Pitolisant
TIPROLISANT
BF-2649
BF 2.649
3-(4-Chlorophenyl)propyl 3-piperidinopropyl ether
1-[3-[3-(4-Chlorophenyl)propoxy]propyl]piperidine
Piperidine, 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-

物理化學(xué)性質(zhì)

沸點(diǎn)398.7±32.0 °C(Predicted)
密度1.056
儲(chǔ)存條件Sealed in dry,Store in freezer, under -20°C
溶解度DMSO
酸度系數(shù)(pKa)9.41±0.10(Predicted)
形態(tài)粉末
顏色Colorless to light yellow

常見問題列表

治療發(fā)作性睡病藥
替洛利生是一種選擇性組胺H3受體反向激動(dòng)劑,在歐洲藥品管理局(EMA)和美國(guó)食品藥品監(jiān)督管理局(FDA)分別獲得了孤兒藥認(rèn)定,且被美國(guó)FDA認(rèn)定為突破性治療藥物。2023年6月30日,瑯鈺集團(tuán)宣布中國(guó)國(guó)家藥品監(jiān)督管理局(NMPA)正式批準(zhǔn)鹽酸替洛利生片(鏵可思?)用于治療發(fā)作性睡病(Narcolepsy)成人患者的日間過度嗜睡(EDS)或猝倒。
替洛利生
發(fā)作性睡病(Narcolepsy)是全球公認(rèn)的罕見病,是一種罕見的睡眠/覺醒障礙疾病,通常被認(rèn)為是終身性疾病,臨床上以日間過度嗜睡(excessivedaytimesleepiness,EDS)、猝倒(cataplexy)、入睡前幻覺、睡眠癱瘓和夜間睡眠紊亂為主要特征,對(duì)患者的生活質(zhì)量、工作或?qū)W習(xí)能力、以及身心健康往往造成嚴(yán)重的影響。
藥理作用
替洛利生(Pitolisant)由法國(guó)Bioprojet研發(fā),是一款first-in-class選擇性組胺3(H3)受體拮抗劑/反向激動(dòng)劑,通過一種全新的作用機(jī)制發(fā)揮作用,即通過增強(qiáng)組胺能神經(jīng)元活性,增加大腦中促進(jìn)覺醒的神經(jīng)遞質(zhì)組胺的合成和釋放,進(jìn)而提高患者的清醒度和警覺性。該藥于2019年8月獲FDA批準(zhǔn)上市,是第一個(gè)也是唯一一個(gè)不受美國(guó)緝毒局管制的治療發(fā)作性睡病藥物。2020年10月,瑯鏵醫(yī)藥與Bioprojet就Pitolisant膜包衣片(4.45mg和17.8mg)達(dá)成戰(zhàn)略合作和獨(dú)家授權(quán)協(xié)議,獲得中國(guó)的獨(dú)家開發(fā)、注冊(cè)、商業(yè)化和生產(chǎn)權(quán)益。2021年,Pitolisant用于發(fā)作性睡病成人患者的日間過度嗜睡或猝倒的上市申請(qǐng)獲藥監(jiān)局受理。
替洛利生是全球范圍內(nèi)唯一獲得發(fā)作性睡病適應(yīng)癥,并且同時(shí)被美國(guó)、歐洲和中國(guó)指南推薦的非精神管控類藥物。全球上市多年來(lái),替洛利生以出色的安全性和有效性而受到臨床的廣泛認(rèn)可。替洛利生在中國(guó)的上市意味著結(jié)束了我國(guó)發(fā)作性睡病患者“超說(shuō)明書”和“紅處方”用藥為主的困局,為我國(guó)患者提供安全、有效和便捷的治療新選擇。
生物活性
Pitolisant 是一種有效的選擇性的非咪唑類重組人組胺 H3 受體反相激動(dòng)劑,Ki 為 0.16 nM。
靶點(diǎn)

Ki: 0.16 nM (H3 receptor)
EC50: 1.5 nM (H3 receptor)

體外研究

On the stimulation of guanosine 5′-O-(3-[ 35 S]thio)triphosphate binding to this receptor, Pitolisant (BF2.649) behaves as a competitive antagonist with a K i value of 0.16 nM and as an inverse agonist with an EC 50 value of 1.5 nM and an intrinsic activity ~50% higher than that of ciproxifan. Pitolisant displaces [ 125 I]iodoproxyfan binding from mouse brain cortical membranes with an IC 50 value of 26.4±4.5 nM. Taking into account the K d value of the radioligand (161±9 pM), the deduced K i value for Pitolisant is 14±1 nM. Pitolisant displaces [ 125 I]iodoproxyfan binding from membranes of rat glioma C6 cells stably expressing the human H 3 receptor with an IC 50 value of 4.2±0.2 nM. Taking into account the K d value of the radioligand (50±4 pM), the deduced K i value for Pitolisant is 2.7±0.5 nM. Pitolisant progressively reverses this response with a Hill coefficient close to unity and an IC 50 value of 330±68 nM, leading to a K i value of 17±4 nM. Pitolisant elicits a dose-dependent decrease of the basal-specific [ 35 S]GTPγS binding to membranes with a maximal effect corresponding to 75±1% of the basal-specific binding and an EC 50 value of 1.5±0.1 nM.

體內(nèi)研究

The administration of Pitolisantat a single dose of 10 mg/kg 30 min before a single dose of Olanzapine (2 mg/kg b.w.) also significantly affects immobility time in the FST. Subsequent administration of the aforementioned drug sequence in mice statistically significantly increases the duration of immobility in comparison to the time determined in the control group in the FST. It decreased locomotor activity as well. In contrast, the results obtained in subchronic treatment after fifteen administrations of both drugs (Pitolisant 10 mg/kg b.w., and after 30 min Olanzapine 2 mg/kg b.w., and again after 4 h Olanzapine 2 mg/kg b.w.) show that the administration of Pitolisant followed by that of Olanzapine equalized the locomotor activity in mice; in comparison to the level of motility in the control group, to which only Pitolisant is administered. More importantly, this combination of drugs significantly reduces immobility time to the level obtained in the control group in the forced swim test in mice [one-way ANOVA; F (3,20) =4.226,P=0.0181]. Rats given Pitolisant (10 mg/kg) during the conditioning phase stayed 502±94 s on the paired texture, a value not statistically different from that of controls, indicating that Pitolisant did not support place preference.

替洛利生價(jià)格(試劑級(jí))
報(bào)價(jià)日期產(chǎn)品編號(hào)產(chǎn)品名稱CAS號(hào)包裝價(jià)格
2024/11/08HY-12199替洛利生
Pitolisant
362665-56-35mg500元
2024/11/08HY-12199替洛利生
Pitolisant
362665-56-310mM * 1mLin DMSO550元
2024/11/08HY-12199替洛利生
Pitolisant
362665-56-310mg800元
"362665-56-3" 相關(guān)產(chǎn)品信息