71441-28-6

Usage

Uses

Used in Research and Development:
TTNPB (Arotinoid Acid) is used as a research tool for studying the action of RAR in diverse processes such as epidermal cell proliferation, embryogenesis, and stem cell differentiation. Its potent and selective activation of RAR makes it an ideal candidate for understanding the molecular mechanisms underlying these processes and for the development of potential therapeutic strategies targeting RAR.
Used in Transcription Assays:
TTNPB (Arotinoid Acid) is utilized as a RAR-agonist in transcriptional assays conducted in 293T cells. These assays help researchers investigate the effects of RAR activation on gene expression and the subsequent cellular responses.
Used in Cell Culture Studies:
TTNPB has been employed as a RAR-agonist in cultured human cord blood CD34+CD38-lincells. This application allows researchers to study the effects of RAR activation on hematopoietic stem cells and progenitor cells, which are crucial for understanding the role of RAR in blood cell development and function.

Biochemical Actions

Selective and highly potent retinoic acid analog with affinity for retinoic acid receptors (RAR) α, β, and γ, which are nuclear transcription factors. Produces ligand-activated transcription of genes that possess retinoic acid responsive elements.

In vitro

TTNPB binds to nuclear retinoic acid receptors with high affinity, inhibits binding of [3H]tRA with IC50 of 3.8 nM, 4.0 nM, and 4.5 nM for mRARα, β, and γ, respectively. TTNPB increases transcriptional activation of Mouse RARs in JEG-3 cells after 72 h using conditioned media with EC50 of 2.0 nM, 1.1 nM and 0.8 nM for mRARα, β, and γ, respectively. TTNPB inhibits the growth of normal human mammary epithelial cells (HMECs) and estrogen receptor-positive (ER-positive) breast cancer cells by inducing G1 cell cycle blockade.? TTNPB causes a concentration-dependent decrease in ES-D3 cell differentiation.

In vivo

TTNPB (0.25 mg/kg) causes growth inhibition in both MXT-HS and MXT-HI models by inducing cell apoptosis.

DIFFERENTIATION

In combination with CHIR99021 or Activin A, induces intermediate mesoderm formation from human or mouse pluripotent stem cells, respectively (Araoka et al.; Oeda et al.). Promotes neuronal differentiation in cultured chick caudal neural plate explants (Diez del Corral et al.).

REPROGRAMMING

Enables chemical reprogramming (without genetic factors) of mouse embryonic fibroblasts to induced pluripotent stem (iPS) cells, in combination with CHIR99021, Tranylcypromine, Valproic Acid, 3-Deazaneplanocin A, and E-616452 (Hou et al.).

CANCER RESEARCH

Induces the in vitro growth and differentiation to granulocytes of myeloid progenitors isolated from myelodysplastic syndrome (MDS) patients (Fabian et al.).

Biological Activity

Extremely potent analog of retinoic acid, selective for the retinoic acid receptor (RAR) subtype.

Biochem/physiol Actions

Selective and highly potent retinoic acid analog with affinity for retinoic acid receptors (RAR) α, β, and γ, which are nuclear transcription factors. Produces ligand-activated transcription of genes that possess retinoic acid responsive elements.

Safety Profile

An experimental teratogen. Otherexperimental reproductive effects. When heated todecomposition it emits acrid smoke and irritating fumes.

references

[1] pignatello m a, kauffman f c, levin a a. multiple factors contribute to the toxicity of the aromatic retinoid, ttnpb (ro 13-7410): binding affinities and disposition. toxicology and applied pharmacology, 1997, 142(2): 319-327.

InChI:InChI=1/C24H28O2/c1-16(14-17-6-8-18(9-7-17)22(25)26)19-10-11-20-21(15-19)24(4,5)13-12-23(20,2)3/h6-11,14-15H,12-13H2,1-5H3,(H,25,26)/b16-14+

Upstream product

• 140-67-0 Estragole 
• 108-95-2 phenol 
• 6223-78-5 2,5-dichloro-2,5-dimethyl hexane 
• 102389-53-7 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]benzoic acid methyl ester 
• 71441-51-5 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]benzoic acid benzyl ester 
• 78767-55-2 benzyl 4-formylbenzoate 
• 69251-24-7 [1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-ethyl]-triphenylphosphonium bromide 
• 619-58-9 4-iodobenzoic acid 
• 6287-86-1 p-ethoxycarbonylbenzaldehyde 
• 6683-46-1 1,1,4,4-Tetramethyl-1,2,3,4-tetrahydro-naphthalene 
• 69251-25-8 5,6,7,8-tetrahydro-α,5,5,8,8-pentamethyl-2-naphthalene methanol 
• 69251-26-9 2-(bromoethyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene 
• 17610-21-8 1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)ethanone 
• 71441-09-3 AGN 190316 

Downstream Products

• 71489-76-4 4-nitrobenzyl p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoate 
• 71441-29-7 p-<(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl>-benzoic acid monoethylamide 
• 71441-52-6 2-hydroxyethyl p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoate 
• 71441-36-6 p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid diethylamide 
• 71441-51-5 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]benzoic acid benzyl ester 
• 75078-92-1 p-<(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl>-benzoic acid tert. butyl ester 
• 71441-37-7 4-{4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-propenyl]-benzoyl}-morpholine 
• 71441-38-8 p-<(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl>-benzoic acid isopropyl ester 
• 78315-04-5 (E)-4-<2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-methylethenyl>benzoyl chloride 
• 71441-39-9 p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-benzoic acid 2-diethylamino-ethyl ester 

Relevant academic research and scientific papers

Olefin functionalization/isomerization enables stereoselective alkene synthesis

Despite tremendous efforts aimed at devising methods for stereoselective alkene synthesis, critical challenges are yet to be addressed. Direct access to a diverse range of 1-aryl(boryl)-1-methyl-functionalized tri- and tetrasubstituted trans alkenes, entities that are prevalent in many important molecules, through a catalytic manifold from readily available α-olefin substrates remains elusive. Here, we demonstrate that catalytic amounts of a non-precious N-heterocyclic carbene–Ni(I) complex in conjunction with a sterically bulky base promote site- and trans-selective union of monosubstituted olefins with a wide array of electrophilic reagents to deliver tri- and tetrasubstituted alkenes in up to 92% yield and >98% regio- and stereoselectivity. The protocol is amenable to the preparation of carbon- and heteroatom-substituted C=C bonds, providing distinct advantages over existing transformations. Utility is highlighted through concise stereoselective synthesis of biologically active compounds. [Figure not available: see fulltext.].

A method for synthesizing substituted diphenyl derivatives

The invention relates to a synthesis method of a compound shown in Formula (I). A compound shown in Formula (III) is prepared via reaction of a compound shown in Formula (II) with a phase transfer catalyst, and the compound shown in Formula (I) is prepared via direct hydrolysis of the compound shown in Formula (III).

18-20 MEMBER BI-POLYCYCLIC COMPOUNDS

The invention relates to 18-20 member bi-polycyclic compounds, methods of making these compounds, and methods of using them in treating hyperproliferative disorders (e.g., cancer) and non-malignant tumors; promoting muscle formation; inhibiting muscle degeneration or the loss of muscle mass or muscle function; and myofibers ex vivo.

Synthesis of arotinoid acid and temarotene using mixed (Z)-1,2- bis(organylchalcogene)-1-alkene as precursor

An efficient and novel total synthesis of the two bioactive retinoids temarotene and arotinoid acid (TTNPB) is described. The key steps in this process include the regio and stereoselective hydrotelluration of thioacetylene 9 and Te/Li transmetalation of mixed (Z)-1,2-bis(organylchalcogene)-1-alkene (Z)-3. The subsequent reaction involving the β-phenylthio vinyl lithiated intermediate 10 with dimethyl sulfate gave the (E)-vinyl sulfide 11. The Ni +2 cross-coupling of 11 with the corresponding phenylzinc bromide and p-oxazoline phenylzinc bromide 12 afforded the respective temarotene 2 and retinoid-oxazoline substituted 13. Finally, compound 13 was deprotected with HCl to furnish arotinoid acid (TTNPB) 1.

Retinoid compounds and their use

The invention relates to retinoid compounds of the formula (I): wherein V is a hydrophobic group;W is a non-polyenic linker; andX is a polar group comprising a hydrogen bond donor; or a salt thereof, and to the use of such compounds in the control of cell differentiation.

A-[(E)-2-(5,6,7,8-TETRAHYDRO-5,5,8,8-TETRAMETHYL-2-NAPTHALENYL)-1-PROPENYL]BENZOIC ACID ANALOGS AND METHOD OF MANUFACTURE AND AND USE THEREOF

Analogs of 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)-1 - propenyl]benzoic acid and methods of manufacture and use thereof, such as for use in cancer prevention and treatment.

Programmed cell death (PCD) associated with the stilbene motif of arotinoids: Discovery of novel apoptosis inducer agents possessing activity on multidrug resistant tumor cells

Considering that the stereochemistry of the C9-C10 alkenyl portion of natural 9-cis-RA, as the one of the olefinic moiety of the previously described isoxazole retinoid 4, seems of particular importance for their apoptotic activity, we prepared a novel class of TTNPB analogues bearing both the cis or trans configuration of the alkenyl portion. The compounds were evaluated in vitro for their cytotoxic and apoptotic activities. We discovered that the cis-TTNPB 9c possesses apoptotic activity comparable with that of the retinoid 4. Moreover, the amino arotinoid 16c showed potent apoptotic activity in HL60 promyelocytic leukemia cells. Interestingly, 16c proved to be a particularly potent apoptosis-inducing agent active in multidrug resistant (MDR) cell lines. Therefore, to the best of our knowledge, 16c may represent the first known aminoarotinoid endowed with potent apoptotic activity in MDR cells. Taken together, these results seem to point out that the cis-stilbene motif of arotinoids may be at least an important feature in conferring cytotoxic and apoptotic activity to this class of compounds. (C) 2000 Elsevier Science Ltd.

Arotinoids, a new class of highly active retinoids

The synthesis and biological activity of new aromatic retinoids are reported. The most active ones belong to a chemical class of compounds, which we have termed 'arotinoids'. For the compound p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-propenyl)]-benzoic acid ethyl ester, a therapeutic potency in the antipapilloma test was found which exceeds that of retinoic acid by a factor of 8000, while the concurrently observed toxic hypervitaminosis A effects are only increased by a factor of 800. The structural relationship of the arotinoids with retinoic acid is demonstrated; the arotinoids contain the retinoic acid carbon skeleton in a fixed cisoid geometric conformation.