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57943-82-5 molecular structure
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(2E)-but-2-enedioic acid; (2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine

ChemBase ID: 72811
Molecular Formular: C25H30ClNO5
Molecular Mass: 459.9624
Monoisotopic Mass: 459.18125075
SMILES and InChIs

SMILES:
c1c(ccc(c1)Cl)C(OCC[C@@H]1N(CCC1)C)(c1ccccc1)C.OC(=O)/C=C/C(=O)O
Canonical SMILES:
Clc1ccc(cc1)C(c1ccccc1)(OCC[C@H]1CCCN1C)C.OC(=O)/C=C/C(=O)O
InChI:
InChI=1S/C21H26ClNO.C4H4O4/c1-21(17-7-4-3-5-8-17,18-10-12-19(22)13-11-18)24-16-14-20-9-6-15-23(20)2;5-3(6)1-2-4(7)8/h3-5,7-8,10-13,20H,6,9,14-16H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t20-,21-;/m1./s1
InChIKey:
PMGQWSIVQFOFOQ-YKVZVUFRSA-N

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CBID:72811 http://www.chembase.cn/molecule-72811.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
(2E)-but-2-enedioic acid; (2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
IUPAC Traditional name
clemastine; fumaric acid
Synonyms
(2R,3Z,5R)-3-(2-Hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid Methyl Ester
[2R-(2α,3Z,5α)]- 3-(2-Hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic Acid Methyl Ester
Methyl Clavulanate
Clavulanic Acid Methyl Ester
Tavist
Xolamin
Agasten
Aloginan
Clemastine fumarate
CAS Number
57943-82-5
14976-57-9
PubChem SID
162037732
PubChem CID
5281069

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID
PubChem 5281069 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
H Acceptors H Donor
LogD (pH = 5.5) 1.5297673  LogD (pH = 7.4) 2.7880056 
Log P 4.923333  Molar Refractivity 101.6476 cm3
Polarizability 39.855114 Å3 Polar Surface Area 12.47 Å2
Rotatable Bonds Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

Physical Property Safety Information Product Information Bioassay(PubChem)
Solubility
DMSO expand Show data source
Storage Condition
-20°C expand Show data source
MSDS Link
Download expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
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DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals TRC TRC
Selleck Chemicals - S1847 external link
Research Area
Description Immunology
Biological Activity
Description Clemastine Fumarate (Clemastine) is a selective histamine H1 receptor antagonist with IC50 of 3 nM.
Targets Histamine H1 receptor
IC50 3 nM [1]
In Vitro Clemastine Fumarate inhibits histamine induced rise in [Ca2+]i in HL-60 cells with an IC50 of 3 nM as compared with that of chlorpheniramine or diphenhydramine with IC50 values of 20 nM and 100 nM, respectively. [1] At concentrations of ≥25 μM, Clemastine Fumarate significantly blocks NK and ADCC reactions of lymphocytes against the human erythroleukemia cell line K562 and human B-lymphoblast cell line SB, respectively. [2] Clemastine Fumarate inhibits histamine-induced contraction of guinea pig ileum with an IC50 of 231 nM. [3] Clemastine Fumarate potently inhibits the HERG K+ channel in a concentration-dependent manner in HEK 293 cells stably expressing HERG channels with an IC50 of 12 nM, which can be attenuated by the Y652A or F656A mutation of HERG. [4] Clemastine Fumarate significantly potentiates ATP-induced increase in [Ca2+]i in HEKhP2X7 cells not relying on histamine receptor blockage but on sensitizing P2X7 receptor in a concentration-dependent manner with an EC50 of 10 μM, and increases the IL-1β release from LPS-induced human macrophages. [5]
In Vivo Administration of Clemastine Fumarate (5-20 mg/kg) displays significantly inhibitory effect on simultaneously induced zymosan paw oedema and croton oil ear oedema in rats in a dose-dependent manner, with the inhibition of 53.6% and 46.8%, respectively, at the dose of 20 mg/kg, and with ID50 values of 18.0 mg/kg and 20.5 mg/kg, respectively. [6] Clemastine Fumarate treatment strongly reduces innate immune responses to Listeria monocytogenes in mice by interfering with the extracellular signal-regulated kinase (ERK)-mediated production of proinflammatory cytokines such as TNF-α and IL-6 surprisingly not dependent on blocking the histamine H1 receptor, leading to significantly higher mortality. [7]
Clinical Trials Currently under Phase III study to evaluate the effectiveness of Clemastine Fumarate 1.0 mg/g + dexamethasone 0.5 mg/g compared to dexchlorpheniramine maleate 10 mg/g in eczema treatment
Features
Protocol
Kinase Assay [1]
Inhibition of [Ca2+]i HL-60 cells are suspended at 1×107 cells/mL in a buffer consisting of 138 mM NaCl, 6 mM KC1, 1 mM MgSO4, 1 mM Na2HPO4, 5 mM NaHCO3, 5.5 mM glucose, and 20 mM HEPES-NaOH, pH 7.4, supplemented with 0.1% (w/v) bovine serum albumin. The dye fura-2/AM is added at a concentration of 4 μM, and cells are incubated for 10 minutes at 37 °C. Thereafter, cells are diluted with the aforementioned buffer to a concentration of 5×106 cells/mL and incubated for 45 minutes at 37 °C. Subsequently, cells are diluted with the aforementioned buffer to a final concentration of 0.5 × 106 cells/mL and centrifuged at 250 g for 10 minutes at 20 °C. Cells are suspended at 1.0 × 106 cells/mL in the aforementioned buffer and kept at 20 °C until measurement. HL-60 cells are used for up to 4 hours after loading with fura-2/AM, and suspended in 2 mL of the aforementioned buffer, using acryl fluorescence cuvettes. HL-60 cells are incubated for 3 minutes at 37 °C, in the presence of 1 mM Ca2+ and various concentrations of Clemastine Fumarate, before the addition of histamine (100 μM). Fluorescence is determined at 37 °C, with constant stirring of the cells at 1×103 rpm, using a Ratio II spectrofluorometer. The basal fluorescence (basal [Ca2+]i) is measured for 1 minute. The basal [Ca2+]i values are subtracted from the corresponding peak [Ca2+]i values, to calculate the increase in [Ca2+]i. The excitation and emission wavelengths are 340 and 500 nm, respectively. The IC50 value is assessed from competitive curve.
Animal Study [6]
Animal Models Male Wistar rats with paw oedema induced by subplantar injection of zymosan and ear oedema induced by croton oil
Formulation Dissolved in saline
Doses 5-20 mg/kg
Administration Intraperitoneally
References
[1] Seifert R, et al. Mol Pharmacol, 1992, 42(2), 227-234.
[2] Nair MP, et al. Cell Immunol, 1983, 81(1), 45-60.
[3] Merlos M, et al. J Pharmacol Exp Ther, 1997, 280(1), 114-121.
[4] Ridley JM, et al. J Mol Cell Cardiol, 2006, 40(1), 107-118.
[5] Nörenberg W, et al. J Biol Chem, 2011, 286(13), 11067-11081.
[6] Blazsó G, et al. Pharmacol Res, 1997, 35(1), 65-71.
Toronto Research Chemicals - C563770 external link
Clavulanic Acid Methyl Ester is a substituted Clavulanic acid (C563750) as β-lactamase inhibitor.

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