24150-24-1

Basic information

• Product Name: EM-1421
• Synonyms: EM-1421;M4N;TETRAMEPROCOL;TETRAMETHYL NDGA;TETRAMETHYL NORDIHYDROGUAIARETIC ACID;TMNDGA;Butane, 1,4-bis(3,4-dimethoxyphenyl)-2,3-dimethyl-, meso-;Meso-tetramethoxy-4,4'-(2,3-dimethyltetramethylene)dipyrocatechol
• CAS NO: 24150-24-1
• Molecular Formula: C₂₂H₃₀O₄
• Molecular Weight: 358.475
• Mol File: 24150-24-1.mol

Chemical Properties

• Melting Point: 101-102 °C
• Boiling Point: 458.5±40.0 °C(Predicted)
• Appearance: white to off-white/
• Density: 1.036±0.06 g/cm3(Predicted)
• Storage Temp.: ?20°C
• Solubility: DMSO: ≥10mg/mL
• CAS DataBase Reference: EM-1421(CAS DataBase Reference)
• NIST Chemistry Reference: EM-1421(24150-24-1)
• EPA Substance Registry System: EM-1421(24150-24-1)

Safety Data

• Hazard Codes: N
• Statements: 50/53
• Safety Statements: 60-61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 24150-24-1(Hazardous Substances Data)

Usage

Uses

Terameprocol is a synthetic derivative of NDGA and non-selective lipoxygenase inhibitor.

Biological Activity

tetramethyl nordihydroguaiaretic acid (tmndga) is a synthetic derivative of ndga (nordihydroguaiaretic acid), a non-selective lipoxygenase inhibitor. tmndga showed the strongest anti-hiv activity.

in vitro

in vero cells, tmndga inhibited sp1 transcription factor binding at the hiv long terminal repeat promoter and at the α-icp4 promoter with ic50 values of 11 and 43.5 μm, respectively. the ic50 of tmndga varied between 11.7 and 4 μm in 10 passages of hsv-1 and 4 passages of hsv-2 [2]. tmndga inhibited sp1-dependent cdc2 gene expression. in m4n-treated transformed c3 cells, tmndga induced growth arrest and apoptosis by suppressing sp1-dependent cdc2 and survivin gene expression giving rise to its antitumorigenic activity [3]. tmndga treatment suppressed expression of the sp1-dependent survivin gene. in transiently and stably survivin-transfected c3 cells, tmndga reduced caspase-3 activation by 50% and 75%, respectively [3]. tmndga inhibited the growth of a number of tumor cell lines by inducing apoptosis in a non-schedule-dependent manner [4]. tmndga inhibited the synthesis of dna by melanoma cells and causes cell cycle arrest in g0/g1 and g2/m phases of the cell cycle [4].

in vivo

tmndga effectively inhibited the growth of human tumors in nude mice [5]. tmndga inhibited the growth of both murine and human melanomas and human colon cancer without apparent hepatic or renal toxicity [4]. in nude (nu/nu) mice bearing xenografts of human tumor types (hep 3b, lncap, ht-29, mcf7, and k-562), treatment with tmndga (i.v. or i.p.) down-regulated cdc2 and survivin genes expression [5].

references

[1] hwu j r, tseng w n, gnabre j, et al. antiviral activities of methylated nordihydroguaiaretic acids. 1. synthesis, structure identification, and inhibition of tat-regulated hiv transactivation[j]. journal of medicinal chemistry, 1998, 41(16): 2994-3000.[2] chen h, teng l, li j n, et al. antiviral activities of methylated nordihydroguaiaretic acids. 2. targeting herpes simplex virus replication by the mutation insensitive transcription inhibitor tetra-o-methyl-ndga[j]. journal of medicinal chemistry, 1998, 41(16): 3001-3007.[3] chang c c, heller j d, kuo j, et al. tetra-o-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting cdc2 and survivin expression[j]. proceedings of the national academy of sciences of the united states of america, 2004, 101(36): 13239-13244.[4] lambert j d, meyers r o, timmermann b n, et al. tetra-o-methylnordihydroguaiaretic acid inhibits melanoma in vivo[j]. cancer letters, 2001, 171(1): 47-56.[5] park r, chang c c, liang y c, et al. systemic treatment with tetra-o-methyl nordihydroguaiaretic acid suppresses the growth of human xenograft tumors[j]. clinical cancer research, 2005, 11(12): 4601-4609.

Upstream product

• 103402-11-5 meso-1,4-bis-(toluene-4-sulfonyloxy)-2,3-diveratryl-butane 
• 4676-33-9 3,4-dimethyl-2,5-bis(3,4-dimethoxyphenyl)furan 
• 186581-53-3 diazomethane 
• 1050512-02-1 nordihydroguairetic acid 
• 77-78-1 dimethyl sulfate 
• 107534-93-0 macelignan 
• 156769-16-3 (2R*,3S*)-2,3-(methanesulfonyloxymethyl)-1,4-bis-(3,4-dimethoxyphenyl)butane 
• 36469-60-0 (8R,8'S)-dihydroguaiaretic acid 
• 278808-09-6 C₂₂H₂₈O₄ 
• 776-99-8 3,4-dimethoxyphenylacetone 
• 335327-93-0 1,4-bis(3,4-dimethoxyphenyl)-2,3-dimethyl-2,3-butanediol 
• 72430-92-3 4-[(3,4-dimethoxyphenyl)methyl]dihydrofuran-2-one 
• 156769-15-2 meso-2,3-bis[(3,4-dimethoxyphenyl)methyl]-butane-1,4-diol 
• 4773-01-7 (3S*,4R*)-3-(3,4-dimethoxybenzyl)-4-(3,4-dimethoxybenzyl)-4,5-dihydro-2(3H)-furanone 

Downstream Products

• 115647-98-8 (6R,7S)-2,3,10,11-Tetramethoxy-6,7-dimethyl-5,6,7,8-tetrahydro-dibenzo[a,c]cyclooctene 
• 521-54-0 (±)-isogalbulin 
• 27686-84-6 C₁₈H₂₂O₄ 
• 36287-35-1 meso-1,4-bis-(2-bromo-4,5-dimethoxy-phenyl)-2,3-dimethyl-butane 
• 1050512-02-1 nordihydroguairetic acid 

Relevant articles and documents

Inhibitors of adenosine 3',5'-cyclic monophosphate phosphodiesterase from Schisandra chinensis and the structure activity relationship of lignans

The structure activity relationship was studied in analogous lignans from Schisandra chinensis and their derivatives. These compounds were tested for cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase inhibition. An inhibitor, nordihydroguaiaretic acid (13), was isolated from this plant, so we discussed this compound and a derivative, nordihydroguaiaretic acid tetramethyl ether, using molecular mechanics involving three-dimensional modeling and minimization of the structure using the MM2PP program. As a result, it was found that the structure of nordihydroguaiaretic acid tetramethyl ether and papaverine (30) (positive control) shared a similar low energy conformation. This fact suggested that these compounds inhihited cAMP phosphodiesterase by a similar mechanism.

THE STRUCTURE OF MACELIGNAN FROM MYRISTICA FRAGRANS

A new lignan, macelignan, isolated from the arils of Myristica fragrans, is shown to have the structure (2R,3S)-1-(3,4-methylenedioxyphenyl)-2,3-dimethyl-4-(4-hydroxy-3-methoxyphenyl)-butane by spectral analysis, chemical conversion and X-ray crystallographic analysis. - Key Word Index: Myristica fragrans; Myristicaceae; lignans; macelignan.

A sterically encumbered photoredox catalyst enables the unified synthesis of the classical lignan family of natural products

Herein, we detail a unified synthetic approach to the classical lignan family of natural products that hinges on divergence from a common intermediate that was strategically identified from nature's biosynthetic blueprints. Efforts toward accessing the common intermediate through a convergent and modular approach resulted in the discovery of a sterically encumbered photoredox catalyst that can selectively generate carbonyl ylides from electron-rich epoxides. These can undergo concerted [3 + 2] dipolar cycloadditions to afford tetrahydrofurans, which were advanced (2-4 steps) to at least one representative natural product or natural product scaffold within all six subtypes in classical lignans. The application of those synthetic blueprints to the synthesis of heterolignans bearing unnatural functionality was demonstrated, which establishes the potential of this strategy to accelerate structure-activity-relationship studies of these natural product frameworks and their rich biological activity.

meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity

Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50 μg/mL. Seven meso-DGA derivatives bearing amino-ethers (26–31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25 μg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies.

Synthesis of nordihydroguaiaretic acid derivatives and their bioactivities on S. pombe and K562 cell lines

Nordihydroguaiaretic acid (NDGA) and its synthetic analogues are potentially useful in treating diseases related to cancers, diabetes, viral and bacterial infections, and inflammation. In this paper, we report the optimal synthetic methods and the bioactivity study of terameprocol 2, NDGA derivative 3, and its cyclized analogue 4. The IC50 of these three compounds 2, 3 and 4 on the growth metabolism of Schizosacchromyces pombe and K562 cell lines were determined by microcalorimetry. The preliminary results showed that the compounds 2, 3 and 4 possessed good inhibition activities on S. pombe and K562 cell lines, and exhibited bidirectional biological effect and Hormesis effect. In particular, terameprocol 2 was found to possess the most potent inhibitory effect on K562 cell lines.

Larrealignans A and B, novel lignan glycosides from the aerial parts of Larrea tridentata

Two new lignan glycosides, named larrealignans A (1) and B (2), and a known lignan (3) were isolated from the aerial parts of Larrea tridentata (Zygophyllaceae). The structures of 1 and 2 were determined on the basis of spectroscopic analysis and the results of hydrolytic cleavage. The isolated compounds (1-3) and aglycones (1a, 2a) of 1 and 2 were evaluated for their cytotoxic activities against HL-60 human leukemia cells.

SCALABLE SYNTHETIC PROCESS FOR MAKING TERAMEPROCOL

A manufacturing process for making terameprocol (1) which includes the following reaction scheme, wherein a first general reaction is the formation of a furan intermediate (39) and a second general reaction is the ring-reduction and ring-opening of the furan intermediate (39) to form the terameprocol (1)

Synthesis, characterization, and anti-melanoma activity of tetra-O-substituted analogs of nordihydroguaiaretic acid

Synthesis of seven semi-synthetic analogs of NDGA is described. An approach to NDGA derivatization is described in which the ortho-phenolic groups are tethered together by one atom, forming a 5-membered heterocyclic ring. The analogs were evaluated for cy

ORAL FORMULATIONS FOR DELIVERY OF CATECHOLIC BUTANES INCLUDING NDGA COMPOUNDS

The present invention provides for compositions, kits and methods for treatment of diseases, where the compositions contain catecholic butanes, including NDGA compounds, such as NDGA derivatives, for example tetra-O-methyl NDGA. The present invention also

A short synthetic route to nordihydroguaiaretic acid (NDGA) and its stereoisomer using Ti-induced carbonyl-coupling reaction

A rapid synthetic approach to natural meso-nordihydroguaiaretic acid (NDGA) and its non-meso isomer is described from (3,4-dimethoxyphenyl)acetone using as a key step the low-valent Ti-induced carbonyl-coupling reaction of the ketone. The method involves