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173334-58-2 molecular structure
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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

ChemBase ID: 72892
Molecular Formular: C64H110N6O16
Molecular Mass: 1219.5888
Monoisotopic Mass: 1218.79783147
SMILES and InChIs

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
Canonical 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
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

Cite this record

CBID:72892 http://www.chembase.cn/molecule-72892.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
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
(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)
IUPAC Traditional name
bis(aliskiren); butenedioic acid
fumaric acid; bis(tekturna)
Synonyms
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
Aliskiren hemifumarate
CAS Number
173334-58-2
MDL Number
MFCD10566724
PubChem SID
162037813
PubChem CID
6918427

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID
PubChem 6918427 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 14.557217  H Acceptors
H Donor LogD (pH = 5.5) 0.12925176 
LogD (pH = 7.4) 1.0046214  Log P 3.1245122 
Molar Refractivity 154.3183 cm3 Polarizability 61.064808 Å3
Polar Surface Area 146.13 Å2 Rotatable Bonds 40 
Lipinski's Rule of Five false 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Hydrophobicity(logP)
3.514 expand Show data source
Storage Condition
-20°C expand Show data source
Target
Renin expand Show data source
Purity
95% expand Show data source
Salt Data
fumarate expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S2199 external link
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.
References
[1] Nakamura Y, et al. ACS Med Chem Lett, 2012, 3(9), 754–758.
[2] Buczko W, et al. Pharmacol Rep, 2008, 60(5), 623-631.
[3] Wood JM, et al. Biochem Biophys Res Commun, 2003, 308(4), 698-705.
[4] Gradman AH, et al. Circulation, 2005, 111(8), 1012-1018.
[5] Oparil S, et al. Lancet, 2007, 370(9583), 221-229.

PATENTS

PATENTS

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INTERNET

INTERNET

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