CAS 173334-58-2|(2E)-but-2-enedioic acid; bis((2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide)|A...

基本信息

化学结构

分子式

C₆₄H₁₁₀N₆O₁₆

分子量

1219.5888

精确质量

1218.79783147

电荷

InChI

InChI=1S/2C30H53N3O6.C4H4O4/c2*1-19(2)22(14-21-10-11-26(38-8)27(15-21)39-13-9-12-37-7)16-24(31)25(34)17-23(20(3)4)28(35)33-18-30(5,6)29(32)36;5-3(6)1-2-4(7)8/h2*10-11,15,19-20,22-25,34H,9,12-14,16-18,31H2,1-8H3,(H2,32,36)(H,33,35);1-2H,(H,5,6)(H,7,8)/b;;2-1+/t2*22-,23-,24-,25-;/m00./s1

InChIKey

KLRSDBSKUSSCGU-KRQUFFFQSA-N

Canonic Smiles

OC(=O)/C=C/C(=O)O.COCCCOc1cc(ccc1OC)C[C@H](C(C)C)C[C@@H]([C@H](C[C@H](C(=O)NCC(C(=O)N)(C)C)C(C)C)O)N.COCCCOc1cc(ccc1OC)C[C@H](C(C)C)C[C@@H]([C@H](C[C@H](C(=O)NCC(C(=O)N)(C)C)C(C)C)O)N

Isomeric Smiles

c1(c(cc(cc1)C[C@@H](C[C@@H]([C@H](C[C@H](C(=O)NCC(C(=O)N)(C)C)C(C)C)O)N)C(C)C)OCCCOC)OC.c1(c(cc(cc1)C[C@@H](C[C@@H]([C@H](C[C@H](C(=O)NCC(C(=O)N)(C)C)C(C)C)O)N)C(C)C)OCCCOC)OC.C(=O)(/C=C/C(=O)O)O

计算属性

JChem

LogD (pH = 7.4)

1.00

LogD (pH = 5.5)

0.13

Log P

3.12

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

false

Acid pKa

9.57

极化表面积

146.13

极化性

63.30

摩尔折射率

154.32

LOG S

-5.18

数据来源

产品目录

学术数据

数据来源

名称和标识

别名

Aliskiren hemifumaratebis((2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide); but-2-enedioic acidAliskiren hemifumaratealiskiren fumarate

IUPAC传统名

fumaric acid; bis(tekturna) bis(aliskiren); butenedioic acid aliskiren hemifumarate

IUPAC标准名

(2E)-but-2-enedioic acid; bis((2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide) bis((2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide); but-2-enedioic acid

名称和标识

数据登录号

MDL号

CAS号

PubChem CID

PubChem SID

DrugBank ID

SureChEMBL数据库

KEGG DRUG Database

ACToR数据库

CHEBI ID

CHEMBL

Beilstein号

数据登录号

化合物性质

产品相关信息

成盐信息

fumarate

纯度

95%

药理学性质

作用靶点

Renin

安全信息

保存条件

-20°C

理化性质

3.514

化合物性质

分子相关蛋白质

暂无数据

点击上传数据

分子图谱

暂无数据

点击上传数据

描述信息

Selleck Chemicals

S2199

Research Area

Description

Cardiovascular Disease

Biological Activity

Description

Aliskiren hemifumarate is a direct renin inhibitor with IC50 of 1.5 nM.

Targets

Renin

IC₅₀

1.5 nM ^[1]

In Vitro

Aliskiren hemifumarate appears to bind to both the hydrophobic S1/S3-binding pocket and to a large, distinct subpocket that extends from the S3-binding site towards the hydrophobic core of renin. Oral bioavailability of Aliskiren hemifumarate is 2.4% in rats, 16% in marmosets and about 2.5% in humans. ^[2]

In Vivo

Aliskiren hemifumarate (< 10="" mg/kg,="" oral)="" inhibits="" plasma="" renin="" activity="" and="" lowers="" blood="" pressure="" in="" sodium-depleted="" marmosets.="">^[3] Once-daily oral treatment with Aliskiren hemifumarate lowers blood pressure effectively, with a safety and tolerability profile, in patients with mild-to-moderate hypertension. ^[4]

Clinical Trials

Aliskiren hemifumarate is in Phase IV clinical trial of patients with hypertension.

Features

Combination Therapy

Description

The combination of Aliskiren hemifumarate (300 mg) and Valsartan (320 mg) lower mean sitting diastolic blood pressure from baseline by 12? mm Hg, significantly more than either monotherapy. ^[5]

Protocol

Kinase Assay ^[1]

Enzyme inhibition assay

All reactions are carried out in a flat bottom black opaque microtiter plate. Aliskiren hemifumarate in DMSO (2 μL) are mixed with 100 μL of the assay buffer (50 mM Tris-HCl (pH7.9), 100 mM NaCl) containing 5 μL of trypsin-activated recombinant human renin (final enzyme concentration of 50 μM), and the solution is pre-incubated at room temperature for 10 min. Next, 2 μM of the substrate (Arg-Glu(EDANS)-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Thr-Lys(DABCYL)-Arg) in 100 μL of the assay buffer is added, and the resulting mixture is incubated at 37 °C for 90 min. After completion of incubation, the concentration of generated angiotensin I is measured by fluorescence at 492 nm (excitation at 340 nm) using a multilabel reader.