您当前所在的位置:首页 > 产品中心 > 产品详细信息
957116-20-0 分子结构
点击图片或这里关闭

2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-6-yl]acetamide hydrochloride

ChemBase编号:72734
分子式:C31H30ClF2N5O3
平均质量:594.0514064
单一同位素质量:593.20052397
SMILES和InChIs

SMILES:
c1c(cc2c(c1)C[C@@]1(C2)c2c(NC1=O)nccc2)NC(=O)CN1C(=O)C2(NC[C@H]1c1cc(cc(c1)F)F)CCCC2.Cl
Canonical SMILES:
O=C(CN1[C@@H](CNC2(C1=O)CCCC2)c1cc(F)cc(c1)F)Nc1ccc2c(c1)C[C@@]1(C2)C(=O)Nc2c1cccn2.Cl
InChI:
InChI=1S/C31H29F2N5O3.ClH/c32-21-10-19(11-22(33)13-21)25-16-35-31(7-1-2-8-31)29(41)38(25)17-26(39)36-23-6-5-18-14-30(15-20(18)12-23)24-4-3-9-34-27(24)37-28(30)40;/h3-6,9-13,25,35H,1-2,7-8,14-17H2,(H,36,39)(H,34,37,40);1H/t25-,30+;/m0./s1
InChIKey:
VWKNXYACOMQRBX-KZCKSIIFSA-N

引用这个纪录

CBID:72734 http://www.chembase.cn/molecule-72734.html

Collapse All Expand All

名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-6-yl]acetamide hydrochloride
IUPAC传统名
2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2'-oxo-1,3-dihydro-1'H-spiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-6-yl]acetamide hydrochloride
别名
MK 3207 hydrochloride
CAS号
957116-20-0
PubChem SID
162037655
PubChem CID
49867927

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID 价格
Selleck Chemicals
S1542 external link 加入购物车 请登录
数据来源 数据ID
PubChem 49867927 external link

理论计算性质

理论计算性质

JChem
Acid pKa 11.737793  质子受体
质子供体 LogD (pH = 5.5) 2.8627436 
LogD (pH = 7.4) 4.000662  Log P 4.076857 
摩尔折射率 150.0481 cm3 极化性 55.98474 Å3
极化表面积 103.43 Å2 可自由旋转的化学键
里宾斯基五规则 false 

分子性质

分子性质

安全信息 药理学性质 产品相关信息 生物活性(PubChem)
保存条件
-20°C expand 查看数据来源
作用靶点
CGRP expand 查看数据来源
成盐信息
hydrochloride expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals
Selleck Chemicals -  S1542 external link
Research Area
Description Cancer
Biological Activity
Description MK 3207 is a potent CGRP receptor antagonist with IC50 of 0.12 nM.
Targets CGRP
IC50 0.12 nM [1]
In Vitro MK 3207 exhibits significantly higher affinity for both native and recombinant human CGRP receptor, as well as rhesus monkey CGRP receptor with Ki of 24 pM, ~24 pM and 22 pM, respectively, as compared to CGRP receptors from other species, including canine and rodent (Ki values of ~10 nM). Although has affinity for AMY1 (CTR/RAMP1) receptor with a Ki value of 0.75 nM, MK 3207 displays marked selectivity for human CGRP receptor versus related human AM1 (CLR/RAMP2) receptor, AM2 (CLR/RAMP3) receptor, AMY3 (CTR/RAMP3) receptor, and CTR with Ki values of 16.5 μM, 0.156 μM, 0.128 μM and 1.9 μM, respectively. MK 3207 potently inhibits human α-CGRP-induced cAMP production in HEK293 cells stably expressing human CLR/RAMP1 with an IC50 of 0.12 nM, and maintains similar potency in the presence of 50% human serum with an IC50 of 0.17 nM, indicating that the activity of MK 3207 would not be dramatically affected by plasma protein binding in vivo. MK 3207 exhibits approximately 65-fold more potent in the human serum-shifted in vitro functional assay than telcagepant with an IC50 of 10.9 nM. [1]
In Vivo Administration of MK 3207 produces a concentration-dependent inhibition of capsaicin-induced dermal vasodilation in rhesus monkeys, blocking the blood flow increase with an EC50 of 0.8 nM and an EC90 of 7 nM, respectively. MK 3207 displays approximately 100-fold more potent in the rhesus monkey CIDV assay versus telcagepant with an EC90 of 994 nM. [1]
Clinical Trials A Phase II study to demonstrate the effectiveness and appropriate dosage level of MK 3207 in the treatment of acute migraine has been completed.
Features MK 3207 is the most potent orally active CGRP receptor antagonist described to date.
Protocol
Kinase Assay [1]
In Vitro Functional Study HEK293 cells stably expressing the human CGRP receptor are preincubated with various concentrations of MK 3207 in the presence or absence of 50% human serum for 30 minutes at 37 °C. Isobutyl-methylxanthine (300 μM) is added to the cells, and then they are incubated for 30 minutes at 37 °C followed by stimulation with 0.3 nM α-CGRP for 5 minutes at 37 °C. After agonist stimulation cells are washed with PBS and the intracellular cAMP concentration is measured using the cAMP SPA Biotrak direct screening assay. Dose-response curve is plotted, and IC50 value is determined.
Animal Study [1]
Animal Models Adult rhesus monkeys (either sex) with capsaicin-induced dermal vasodilation
Formulation Dissolved in DMSO
Doses ~123.1 μg/kg
Administration Intravenous bolus followed by 25 minutes continuous intravenous infusion
References
[1] Salvatore CA, et al. J Pharmacol Exp Ther, 2010, 333(1), 152-160.

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
正在搜索,请耐心等待...(如果遇到网页错误或者长时间没有结果,请刷新页面[F5])

专利

专利

PubChem iconPubChem Patent Google Patent Search IconGoogle Patent

互联网资源

互联网资源

百度图标百度 google iconGoogle