681136-29-8
中文名稱(chēng)
N/A
英文名稱(chēng)
JNJ 1661010
CAS
681136-29-8
分子式
C19H19N5OS
分子量
365.459
MOL 文件
681136-29-8.mol
更新日期
2024/06/12 17:31:27
681136-29-8 結(jié)構(gòu)式
基本信息
中文別名
化合物JNJ-1661010JNJ-1661010游離態(tài)
N-苯基-4-(3-苯基-1,2,4-噻二唑-5-基)哌嗪-1-酰胺
N-苯基-4-(3-苯基-1,2,4-噻二唑-5-基)-1-哌嗪甲酰胺
英文別名
1-Piperazinecarboxamide, N-phenyl-4-(3-phenyl-1,2,4-thiadiazol-5-yl)-CS-1527
Takeda-25
JNJ 1661010
JNJ 1661010, >=98%
JNJ 1661010 USP/EP/BP
TAKEDA-25
JNJ-1661010
JNJ 1661010
N-Phenyl-4-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine-1-carboxamide
N-Phenyl-4-(3-phenyl-1,2,4-thiadiazol-5-yl)-1-piperazinecarboxamide
所屬類(lèi)別
生物化工：FAAH 抑制劑物理化學(xué)性質(zhì)
密度1.340±0.06 g/cm3(Predicted)
儲(chǔ)存條件Sealed in dry,2-8°C
儲(chǔ)存條件Store at +4°C
溶解度在DMSO中的溶解度≥28mg/mL
酸度系數(shù)(pKa)13.94±0.70(Predicted)
形態(tài)固體
顏色米白色
穩(wěn)定性從購(gòu)買(mǎi)之日起 2 年內(nèi)保持穩(wěn)定。 DMSO 或乙醇溶液可在 -20℃ 下保存長(zhǎng)達(dá) 3 個(gè)月。
常見(jiàn)問(wèn)題列表
生物活性
JNJ-1661010是一種有效的，選擇性的FAAH抑制劑，IC50分別為10 nM(大鼠)和12 nM (人類(lèi))，作用于FAAH-1比作用于FAAH-2選擇性高100倍以上。體外研究
FAAH preincubated with JNJ-1661010 suggests a slow reversibility of the interaction between the JNJ-1661010 and the active site, which is accelerated at higher temperatures. JNJ-1661010 is a covalent, mechanism-based substrate inhibitor as examined by LC-ESI-MS. JNJ-1661010 docks with the phenylthiadiazole in the hydrophobic tunnel and the phenylurea in the hydrophilic pocket of FAAH.體內(nèi)研究
JNJ-1661010 (20 mg/kg i.p.) inhibits FAAH by at least 85% for up to 4 h after dosing, resulting accumulation of lipid ethanolamides in rat brain. JNJ-1661010 dose-dependently reverses the tactile allodynia with a maximum efficacy of approximately 90% at 30 min postdose in both Mild Thermal Injury (MTI) mice and rat model. JNJ-1661010 (20 mg/kg) reverses tactile allodynia by 60.8% at 30 min in rat spinal nerve ligation injury model. JNJ-1661010 (50 mg/kg i.p.) shows a significant attenuation of the hyperalgesia at 30 min postdose in rat carrageenan model of inflammatory pain. Rats dosed with JNJ-1661010 (20 mg/kg i.p.) has a plasma Cmax of 26.9 μM at the Tmax of 0.75 h and a Cmax in the brain of 6.04 μM at the Tmax of 2 h. JNJ-1661010 (20 mg/kg i.p.) inhibits brain FAAH and elevates AEA level in brain tissue in rat.生物活性
JNJ-1661010 (Takeda-25)是一種有效的，選擇性的FAAH抑制劑，IC50分別為10 nM(大鼠)和12 nM (人類(lèi))，作用于FAAH-1比作用于FAAH-2選擇性高100倍以上。靶點(diǎn)
| Target | Value |
| FAAH (rat) | 10 nM |
| FAAH (human) | 12 nM |
體外研究
FAAH與JNJ-1661010預(yù)培養(yǎng)表明，JNJ-1661010和活性部位相互作用具有緩慢可逆性，并且在高溫下會(huì)加速。 LC-ESI-MS檢測(cè)表明，JNJ-1661010是一種共價(jià)的，基于機(jī)制的底物抑制劑。JNJ-1661010與苯基噻二唑在疏水性通道中對(duì)接，與苯脲在FAAH的親水性口袋中對(duì)接。
體內(nèi)研究
JNJ-1661010(20 mg/kg i.p.)至少抑制85%的FAAH，給藥后作用能維持4小時(shí)以上，導(dǎo)致大鼠大腦中脂質(zhì)乙醇酰胺積累。溫和熱損傷的(MTI)小鼠和大鼠模型中，JNJ-1661010劑量依賴(lài)性逆轉(zhuǎn)觸覺(jué)異常疼痛，最大效能在給藥30分鐘后大約為90%。在大鼠脊髓神經(jīng)結(jié)扎損傷模型中，JNJ-1661010 (20 mg/kg)給藥30分鐘時(shí)逆轉(zhuǎn)60.8%觸覺(jué)異常疼痛。在大鼠角叉菜膠炎性疼痛模型中，JNJ-1661010 (50 mg/kg i.p.)給藥30分鐘后顯著減弱痛覺(jué)過(guò)敏。大鼠以JNJ-1661010 (20 mg/kg i.p.)給藥，Tmax為0.75 h時(shí)，血漿Cmax為26.9 μM，Tmax為2 h時(shí)，大腦中Cmax為6.04 μM。JNJ-1661010 (20 mg/kg i.p.)抑制大鼠大腦中FAAH，并提高腦組織中AEA水平。