22033-87-0

Basic information

• Product Name: Olesoxime
• Synonyms: (NE)-N-[10,13-dimethyl-17-(6-methylheptan-2-yl)-1,2,6,7,8,9,11,12,14,1 5,16,17-dodecahydrocyclopenta[a]phenanthren-3-ylidene]hydroxylamine;olesoxime;Cholest-4-en-3-one, oxime, NSC 21311;TRO 19622;Cholest-4-en-3-one oxime;NSC 21311;TRO19266
• CAS NO: 22033-87-0
• Molecular Formula: C₂₇H₄₅NO
• Molecular Weight: 399.65
• Mol File: 22033-87-0.mol
• Article Data: 2

Chemical Properties

• Melting Point: 145-148 ºC
• Boiling Point: 510 °C at 760 mmHg
• Flash Point: 341 °C
• Appearance: white/
• Density: 1.10
• Vapor Pressure: 1.56E-12mmHg at 25°C
• Refractive Index: 1.583
• Storage Temp.: −20°C
• Solubility: DMSO: >10mg/mL
• PKA: 12.27±0.70(Predicted)
• Stability: Stable for 1 year as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: Olesoxime(CAS DataBase Reference)
• NIST Chemistry Reference: Olesoxime(22033-87-0)
• EPA Substance Registry System: Olesoxime(22033-87-0)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 22033-87-0(Hazardous Substances Data)

Usage

Description

Olesoxime, also known as TRO19622, is a neuroregenerative and neuroprotective agent that acts on components of the mitochondrial permeability transition pore (MPTP). It is a promising pharmaceutical candidate for the treatment of neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS). Olesoxime has been shown to promote neuron survival under stress conditions, reduce reactive oxygen species (ROS) and NLRP3 inflammasome activation, inhibit MPTP opening, and protect neurons from apoptosis.

Uses

Used in Neuroscience:
Olesoxime is used as a neuroregenerative and neuroprotective agent for promoting neuron survival under stress conditions and treating amyotrophic lateral sclerosis (ALS). It acts on components of the mitochondrial permeability transition pore (MPTP), rescuing motor neurons from axotomy-induced cell death and promoting nerve regeneration following sciatic nerve crush in mice.
Used in Neurodegenerative Disease Treatment:
Olesoxime is used as a potential drug for treating neurodegenerative diseases, particularly ALS, due to its ability to reduce ROS and NLRP3 inflammasome activation in a mouse model of intracerebral hemorrhage.
Used in Neuroprotection:
Olesoxime is used as a mitochondrial permeability transition pore inhibitor in mouse neurons, inhibiting MPTP opening and protecting neurons from apoptosis.
Used in Myelin Repair:
Olesoxime is used to stimulate myelin repair in rat models of demyelination, promoting oligodendrocyte maturation in culture and myelin regeneration in vivo in a rodent model.

Biological Activity

Neuroprotective and neuroregenerative compound. Rescues motor neurons from axotomy-induced cell death and promotes nerve regeneration following sciatic nerve crush in vivo . Binds directly to two components of the mitochondrial permeability pore, the voltage-dependent anion channel (VDAC) and translocator protein.

Biochem/physiol Actions

TRO 19622 can decrease axonal degradation and enhance the rescue of motor nerve conduction in peripheral neuropathy. Furthermore, TRO 19622 can reverse neuropathic pain and tactile allodynia in rat models of diabetes and chemotherapy-induced neuropathic pain4.

References

1) Bordet?et al.?(2007),?Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis; J. Pharmacol. Exp. Ther.,?322?709 2) Ma?et al.?(2014),?NLRP3 inflammasome contributes to inflammation after intracerebral hemorrhage; Ann. Neurol.,?75?209 3) Martin?et al.?(2011),?The mitochondrial permeability transition pore regulates nitric oxide-mediated apoptosis of neurons induced by target deprivation; J. Neurosci.,?31?359 4) Magalon?et al. (2016),?Olesoxime favors oligodendrocyte differentiation through a functional interplay between mitochondria and microtubules; Neuropharmacology,?111?293

InChI:InChI=1/C27H45NO/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28-29)13-15-26(20,4)25(22)14-16-27(23,24)5/h17-19,22-25,29H,6-16H2,1-5H3/b28-21+

Synthetic route

Cholest-4-en-3-one (601-57-0) → cholest-4-en-3-one oxime (22033-87-0)

Conditions	Yield
With hydroxylamine hydrochloride; sodium acetate In methanol; water at 60℃;	90%
With potassium dihydrogenphosphate; hydroxylamine hydrochloride In ethanol for 1h; Heating;

cholest-4-en-3-one oxime (22033-87-0) → Cholest-4-en-3-one (601-57-0)

Conditions	Yield
With benzeneseleninic anhydride In tetrahydrofuran	80%

cholest-4-en-3-one oxime (22033-87-0) + 2-chloroethanamine hydrochloride (870-24-6) → 3-(2'-aminoethoxyimino)-cholest-4-ene

Conditions	Yield
With sodium methylate In methanol	80%

cholest-4-en-3-one oxime (22033-87-0) → Cholest-4-en-3-one (601-57-0) + 4-aza-A-homocholest-4a-en-3-one (21002-96-0)

Conditions	Yield
In methanol for 7.5h; Product distribution; Irradiation; between conditions, investigation of steroidal α,β-unsaturated ketone oximes;	A 51% B 33%
In methanol for 7.5h; Irradiation;	A 51 % Turnov. B 33 % Turnov.

cholest-4-en-3-one oxime (22033-87-0) → 3α-Amino-cholesten-4 + 3β-Amino-cholesten-4

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether

cholest-4-en-3-one oxime (22033-87-0) + acetic anhydride (108-24-7) → N-acetyl-cholesta-3,5-dien-3-amine (56909-94-5)

Conditions	Yield
With pyridine
With pyridine for 18h; Heating;

cholest-4-en-3-one oxime (22033-87-0) + acetic anhydride (108-24-7) → 3-Diacetylaminocholesta-3,5-dien

Conditions	Yield
With pyridine

cholest-4-en-3-one oxime (22033-87-0) → (5aR,5bS,7aR,8R,10aS,10bS)-5a,7a-dimethyl-8-((R)-6-methylheptan-2-yl)-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12-tetradecahydrocyclopenta[5,6]naphtho[1,2-d]azepin-2(3H)-one (10062-39-2)

Conditions	Yield
With thionyl chloride In 1,4-dioxane for 0.333333h; Ambient temperature;	46 % Turnov.

cholest-4-en-3-one oxime (22033-87-0) + chloro-diphenylphosphine (1079-66-9) → C39H54NOP (215456-23-8)

Conditions	Yield
With triethylamine In dichloromethane; Petroleum ether at -40℃; for 1.75h;

cholest-4-en-3-one oxime (22033-87-0) → C39H56NOP

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2; petroleum ether / 1.75 h / -40 °C 2: 9-borobicyclo<3.3.1>nonane / tetrahydrofuran / 40 h / Ambient temperature View Scheme

cholest-4-en-3-one oxime (22033-87-0) → N-(diphenylphosphinyl)-4-cholesten-3β-amine

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N / CH2Cl2; petroleum ether / 1.75 h / -40 °C 2: 9-borobicyclo<3.3.1>nonane / tetrahydrofuran / 40 h / Ambient temperature View Scheme

Upstream product

• 601-57-0 Cholest-4-en-3-one 

Downstream Products

• 601-57-0 Cholest-4-en-3-one 
• 21002-96-0 4-aza-A-homocholest-4a-en-3-one 
• 10062-39-2 (5aR,5bS,7aR,8R,10aS,10bS)-5a,7a-dimethyl-8-((R)-6-methylheptan-2-yl)-4,5,5a,5b,6,7,7a,8,9,10,10a,10b,11,12-tetradecahydrocyclopenta[5,6]naphtho[1,2-d]azepin-2(3H)-one 
• 215456-23-8 C₃₉H₅₄NOP 

Relevant articles and documents

Convenient preparation of A-ring fused pyridines from steroidal enamides

A facile strategy for the preparation of A-ring fused pyridosteroids has been accomplished in high yields by the reaction of Vilsmeier reagent (chloromethyleneiminium salt) with steroidal A-ring enamides (2- and 3-ene) under thermal conditions. The structure of 6′-chloro-5α-cholest [3,2-b]pyridine was determined by X-ray analysis.