CAS 173334-58-2|Aliskiren hemifumarate|fumaric acid; bis(tekturna)|(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)p...

General Information

Structure

Molecular Formula

C₆₄H₁₁₀N₆O₁₆

Molecular Mass

1219.5888

Exact Mass

1218.79783147

Charge

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

Calculated Properties

JChem

LogD (pH = 7.4)

1.00

LogD (pH = 5.5)

0.13

Log P

3.12

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

false

Acid pKa

9.57

Polar Surface Area

146.13

Polarizability

63.30

Molar Refractivity

154.32

LOG S

-5.18

Data Source

Commercial Catalog

Academic Data

Data Source

Names and Identifiers

Synonyms

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 Traditional name

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

IUPAC name

(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

Names and Identifiers

Registration numbers

MDL Number

CAS Number

PubChem CID

PubChem SID

KEGG DRUG Database

ACToR Database

DrugBank ID

SureChEMBL Database

Beilstein Number

CHEBI ID

CHEMBL

Registration numbers

Properties

Safety Information

Storage Condition

-20°C

Pharmacology Properties

Target

Renin

Product Information

Salt Data

fumarate

Purity

95%

Physical Property

Hydrophobicity(logP)

3.514

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

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.