6809-52-5

Usage

Uses

Used in Pharmaceutical Industry:
Teprenone is used as an anti-ulcerative agent for its ability to enhance gastric mucosal glycoprotein secretion, providing protection to the stomach lining.
Used in Medical Research:
Teprenone is used as an inducer of heat shock protein 70 (HSP70) to analyze its protective effects against various conditions, such as cerebral ischemia/reperfusion (I/R), inflammatory bowel disease, hypoxic/ischemic brain injury, and spinal and bulbar muscular atrophy. It exhibits cytoprotective and anti-inflammatory effects by inducing the expression of HSP70, HSPB8, and HSPB1.
Used in Neuroprotection:
Teprenone is used for its neuroprotective effects, as it has been shown to protect against cerebral ischemia/reperfusion injuries by inducing HSP70 expression, which helps in maintaining cellular homeostasis and protecting against neuronal damage.
Used in Amyloidosis Research:
Teprenone has been studied for its ability to induce the expression of HSPB8 and HSPB1, which can reduce the formation of amyloid oligomers and insoluble aggregates in certain mouse models, potentially offering therapeutic benefits in conditions associated with amyloid protein misfolding and aggregation.

Biochem/physiol Actions

Geranylgeranylacetone can induce expression of HSP70, HSPB8, and HSPB1. Induction of HSP70 expression is protective against the development of various diseases, such as inflammatory bowel disease, hypoxic/ischemic brain injury and spinal and bulbar muscular atrophy (cytoprotective and anti-inflammatory effects). Reports indicate that GGA protects against NSAID-induced gastric and intestinal lesions by induction of HSP70 expression. Other studies have shown that GGA induces expression of HSPB8 and HSPB1 and reduces the formation of amyloid oligomers as well as insoluble aggregates in HSPB5 R120G TG mice.

References

1) Kamal and Omran (2013) The role of heat shock protein 70 induced by geranylgeranylacetone in carbon tetrachloride-exposed adult rat testes; Pathophysiology, 20 139 2) Lennikov et al. (2013) Induction of heat chock protein 70 ameliorates ultraviolet-induced photokeratitis in mice; Int. J. Mol. Sci., 14 2175 3) Adache et al. (2010) An acyclic polyisoprenoid derivative, geranylgeranylacetone, protects against visceral adiposity and insulin resistance in high fat fed mice; Am. J. Physiol. Endocrinol. Metab., 299 E764 4) Marunouchi et al. (2014) Protective effect of geranylgeranylacetone via enhanced induction of HSPB1 and HSPB8 in mitochondria of the failing heart following myocardial infarction in rats; Eur. J. Pharmacol. 730 140

InChI:InChI=1/C23H38O/c1-19(2)11-7-12-20(3)13-8-14-21(4)15-9-16-22(5)17-10-18-23(6)24/h11,13,15,17H,7-10,12,14,16,18H2,1-6H3/b20-13+,21-15+,22-17+

Upstream product

• 1117-52-8 6,10,14-trimethyl-5,9,13-pentadecatriene-2-on 
• 1066-26-8 sodium acetylide 
• 71668-81-0 (4E,8E,12E)-ethyl 2-acetyl-5,9,13,17-tetramethyloctadeca-4,8,12,16-tetraenoate 
• 1113-21-9 (6E,10E)-geranyllinalool 
• 141-97-9 ethyl acetoacetate 
• 50848-64-1 2E,6E,10E-geranylgeranyl bromide 
• 689-67-8 pseudo-ionone 
• 24034-73-9 Geranylgeraniol 
• 42207-88-5 (2E,6E,10E)-methyl 3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenoate 
• 3796-70-1 trans geranyl acetone 
• 24035-35-6 (2E,6E,10E)-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenoic acid ethyl ester 
• 1007476-32-5 sodium ethyl acetylacetate enolate 
• 68931-30-6 1,6,10,14-hexadecatetraen-3-ol, 3,7,11,15-tetramethyl- 
• 141-52-6 sodium ethanolate 

Downstream Products

• 64284-92-0 (E,E,E,E)-geranylfarnesoic acid 
• 22488-05-7 geranylfarnesol 
• 1182-68-9 2-Methyl-3-<3,7,11,15,19-pentamethyl-eicosapentaen-(2,6,10,14,18)-yl-(1)>-naphthochinon-(1,4) 

Relevant academic research and scientific papers

Synthesis method of teprenone and intermediate thereof

The invention relates to synthesis methods of teprenone and an intermediate thereof. The synthesis of the intermediate all-trans (5E,9E)-farnesyl acetone comprises: 1) in the presence of a catalyst, carrying out a carroll rearrangement reaction on the mixture of 5E-nerolidol and 5Z-nerolidol and hydrocarbonyl acetoacetate to obtain the isomer mixture of (5Z,9Z)-farnesyl acetone, (5Z,9E)-farnesyl acetone, (5E,9Z)-farnesyl acetone, and (5E,9E)-farnesyl acetone, wherein the content of (5E,9E)-farnesyl acetone in the isomer mixture is controlled at more than 18%; and 2) carrying out low-temperature crystallization separation on the isomer mixture in a moderately polar solvent to obtain the all-trans (5E,9E)-farnesyl acetone. According to the present invention, the high-purity all-trans (5E,9E)-farnesyl acetone is obtained by using the mixture of 5E-nerolidol and 5Z-nerolidol as the raw material through the low-temperature crystallization separation, such that the teprenone with the qualified quality can be conveniently obtained.

Novel intermediate for synthesizing teprenone and application of novel intermediate

The invention discloses a novel intermediate for synthesizing teprenone. The novel intermediate is a compound shown as a formula 5. The novel intermediate has the advantages that process routes for synthesizing the teprenone by the compound shown as the formula 5 are simple, raw materials are easily available, reaction conditions are mild, side reaction rarely can be carried out, and accordingly the novel intermediate is favorable for industrial production; the high-purity teprenone can be obtained by the aid of the process routes without rectification, and the requirements on ratios of isomermono-cis-form (5Z, 9E and 13E) to all-trans-forms (5E, 9E and 13E) of the teprenone can be met.

Process for synthesizing teprenone

The invention discloses a process for synthesizing teprenone.According to the process for synthesizing teprenone, nerolidol is adopted as an initial raw material and subjected to selenium dioxide and tert-butyl hydroperoxide oxidizing in sequence, nerolidol and dihydropyran are subjected to acid catalysis to form acetal, acetal reacts with a Grignard reagent on the presence of copper salt and reacts with methyl acetoacetate on the presence of aluminum salt, and the teprenone product consistent with the configuration of products sold on the market is obtained through four steps of reactions.According to a preparation method of teprenone, the raw material is cheap and easy to obtain, operation is easy and convenient, the reaction conditions are mild, and industrial production is expected to be achieved.

A process for the preparation of Teprenone

The invention discloses a method for preparing teprenone. The method comprises the following steps: (a) mixing geranyl linalool, acetyl Meldrum's acid and aluminum isopropoxide according to a molar ratio of 1: (1.2-1.5): (0.02-0.1), dissolving the mixture in a paraxylene solvent, heating up to 50-160 DEG C, refluxing for 6-10 hours, cooling and removing the solvent to obtain a teprenone mixture; (b) washing and extracting the teprenone mixture, mixing organic layers, and drying to obtain a crude product of teprenone; (c) carrying out molecular distillation, impurity removal, decompression rectifying and impurity removal on the crude product of teprenone to obtain a teprenone product. The method is simple and easy to control, the conversion rate of the product is high, and the prepared product is high in purity, stable in quality and high in safety, thereby being convenient to promote and use in clinical and industrial production.

GGA DERIVATIVES

This invention relates to geranylgeranyl acetone (GGA) derivatives, pharmaceutical compositions comprising GGA derivatives and the use of GGA derivatives.

METHODS FOR TREATING NEURON DAMAGE

This invention relates to the use of geranylgeranyl acetone (GGA), its isomers, and GGA derivatives in a method for for treating a disease in a subject mediated in part by miRNA-378 or miRNA-711 increased activity comprising administering to the subject a therapeutically effective amount of 5-trans-GGA or a derivative thereof.

GGA AND GGA DERIVATIVES COMPOSITIONS THEREOF AND METHODS FOR TREATING NEURODEGENERATIVE DISEASES INCLUDING PARALYSIS INCLUDING THEM

This invention relates to geranylgeranyl acetone (GGA) derivatives and the use of GGA, its isomers, and GGA derivatives in methods for inhibiting neural death, increasing neural activity, increasing axon growth and cell viability, and increasing the survival rate of subjects administered the GGA or GGA derivatives.

GGA AND GGA DERIVATIVES, COMPOSITIONS THEREOF AND METHODS FOR TREATING NEURODEGENERATIVE DISEASES INCLUDING PARALYSIS INCLUDING THEM

This invention relates to geranylgeranyl acetone (GGA) derivatives and the use of GGA, its isomers, and GGA derivatives in methods for inhibiting neural death, increasing neural activity, increasing axon growth and cell viability, and increasing the survival rate of subjects administered the GGA or GGA derivatives.

GERANYLGERANYLACETONE DERIVATIVES

Provided herein are geranylgeranylacetone derivatives and methods of using them.

METHODS FOR TREATING NEURODEGENERATIVE DISEASES

This invention relates to the 5-cis and 5-trans isomers of geranylgeranyl acetone, preferably such synthetic isomers, and pharmaceutical compositions containing such isomers. Other aspects of this invention relate to the use of geranylgeranyl acetone and its isomers in methods for inhibiting neural death, increasing neural activity, and increasing axon growth and cell viability. Geranylgeranyl acetone is a known anti-ulcer drug used commercially and in clinical situations. GGA has also been shown to exert cytoprotective effects on a variety of organs, such as the eye, brain, and heart.