501951-42-4
中文名稱
SB-705498
英文名稱
SB-705498
CAS
501951-42-4
分子式
C17H16BrF3N4O
分子量
429.234
MOL 文件
501951-42-4.mol
更新日期
2024/12/24 19:29:59
501951-42-4 結構式
基本信息
中文別名
(R)-1-(2-溴苯基)-3-(1-(5-(三氟甲基)吡啶-2-基)吡咯烷-3-基)脲N-(2-溴苯基)-N'-[(3R)-1-[5-(三氟甲基)-2-吡啶基]-3-吡咯烷基]脲
英文別名
CS-279SB-705498
SB 705498
SB705498
1-(2-Bromophenyl)-3-[(3R)-1-[5-(trifluoromethyl)-2-pyridyl]pyrrolidin-3-yl]urea
(R)-1-(2-bromophenyl)-3-(1-(5-(trifluoromethyl)pyridin-2-yl)pyrrolidin-3-yl)urea
N-(2-Bromophenyl)-N'-[(3R)-1-[5-(trifluoromethyl)-2-pyridinyl]-3-pyrrolidinyl]urea
Urea, N-(2-bromophenyl)-N'-[(3R)-1-[5-(trifluoromethyl)-2-pyridinyl]-3-pyrrolidinyl]-
所屬類別
生物化工：激動劑抑制劑物理化學性質(zhì)
沸點506.9±50.0 °C(Predicted)
密度1.59
儲存條件-20°C
溶解度溶于DMSO(>25mg/ml)
酸度系數(shù)(pKa)13.00±0.20(Predicted)
形態(tài)固體
顏色白色
穩(wěn)定性Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
常見問題列表
生物活性
SB705498是一種hTRPV1拮抗劑，抑制TRPV1的Capsaicin，酸和熱激活，IC50分別為3 nM， 0.1 nM和6 nM，該作用具有一定的電壓依賴性，作用于TRPV1比作用于TRPM8選擇性高100倍以上。Phase 2。體外研究
SB705498 (0.3 nM-1 μM) potently inhibits capsaicin-induced activation of human TRPV1 expressed in 1321N1 cells or HEK293 cells with apparent pKi of 7.5 or 7.6, respectively. Coapplication of 100 nM SB705498 rapidly, completely and reversibly inhibits hTRPV1 expressed in HEK293 cells. SB705498 has no significant effect on endogenous [Ca2+] responses in HEK293 cells produced by muscarinic acetylcholine receptor activation with carbachol or store-operated channel-mediated Ca2+ entry after depletion of intracellular stores with the Ca2+ pump inhibitor thapsigargin. SB705498 (10 pM-1 μM) also has no significant antagonist effect versus the close TRPV1 receptor paralog TRPV4 transiently expressed in HEK293 cells and activated using the synthetic ligand 4α-phorbol-12,13-didecanoate (10 μM). SB705498 reveals good antagonist potency against both the rat and guinea pig TRPV1. SB705498 antagonizes rat and guinea pig TRPV1 with pKi of 7.5 and 7.3, respectively. Coapplication of 100 nM to 10 μM SB705498 to the steady state of a maintained capsaicin response leads to rapid and complete inhibition of hTRPV1 at -70 mV. SB705498 inhibits capsaicin-mediated activation of hTRPV1 with IC50 of 3 nM and 17 nM at positive and negative holding potentials (-70 mV and + 70 mV), respectively. Coapplication of 1 μM SB705498 to the plateau period of the response produces complete and reversible inhibition of the TRPV1-mediated conductance. SB705498 shows approximately equal activity versus multiple and diverse chemical and physical modes of TRPV1 receptor activation. SB705498 shows little or no activity versus a wide range of ion channels, receptors and enzymes. SB705498 produces full blockade of heat as well as pH activation of hTRPV1.體內(nèi)研究
SB705498 exhibits potent and reversible blockade against the multiple modes of TRPV1 activation, namely the vanilloid (capsaicin), heat- and acid-mediated activation of the receptor. SB705498 displays excellent activity at 10 and 30 mg/kg po with good reversal of allodynia. SB705498 is also shown to give 80% reversal of allodynia in the guinea pig FCA model at 10 mg/kg p.o..靶點
| Target | Value |
|
hTRPV1
() | 7.6(pKi) |
|
hTRPV1
() | 7.1(pIC50) |
體外研究
SB705498(0.3 nM-1 μM)有效抑制辣椒素誘導的在1321N1細胞或HEK293細胞中表達的人TRPV1的活化，表觀pK i 分別為7.5或7.6。100 nM SB705498快速，完全且可逆地抑制HEK293細胞中表達的hTRPV1。SB705498對毒蕈堿乙酰膽堿受體激活產(chǎn)生的HEK293細胞中內(nèi)源性[Ca SB705498對TRPV1受體激活的多重不同的化學和物理模式表現(xiàn)出近似相等的活性。SB705498對hTRPV1的高溫和pH激活產(chǎn)生完全的阻斷。
體內(nèi)研究
SB705498對TRPV1激活的多重模式，即辣椒素，熱-和酸-介導的受體激活表現(xiàn)出有效可逆的阻斷。SB705498以10和30 mg/kg的劑量口服給藥表現(xiàn)出良好的活性，并逆轉(zhuǎn)痛覺超敏。SB705498以10 mg/kg的劑量口服給藥，在豚鼠FCA模型中逆轉(zhuǎn)80%的痛覺超敏。