25122-46-7

Basic information

• Product Name: Clobetasol propionate
• Synonyms: 17-propionate;cgp9555;clobesol;pregna-1,4-diene-3,20-dione,21-chloro-9-fluoro-11-beta,17-dihydroxy-16-beta-me;CLOBESTASOL PROPIONATE;CLOBETASOL-17-PROPIONATE;CLOBETASOLE PROPIONATE;CLOBETASOL PROPIONATE
• CAS NO: 25122-46-7
• Molecular Formula: C₂₅H₃₂ClFO₅
• Molecular Weight: 466.97
• EINECS: 246-634-3
• Product Categories: TORADOL;Hormone Drugs;Halogenated Heterocycles ,Pyrazines ,Pyrans;Organics;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Pharmaceutical intermediate
• Mol File: 25122-46-7.mol

Chemical Properties

• Melting Point: 195.5-1970C
• Boiling Point: 569 °C at 760 mmHg
• Flash Point: 297.9 °C
• Appearance: White crystalline powder
• Density: 1.1653 (estimate)
• Vapor Pressure: 2.58E-15mmHg at 25°C
• Refractive Index: 1.56
• Storage Temp.: -20°C Freezer
• Solubility: Practically insoluble in water, freely soluble in acetone, sparingly soluble in ethanol (96 per cent).
• PKA: 12.88±0.70(Predicted)
• CAS DataBase Reference: Clobetasol propionate(CAS DataBase Reference)
• NIST Chemistry Reference: Clobetasol propionate(25122-46-7)
• EPA Substance Registry System: Clobetasol propionate(25122-46-7)

Safety Data

• Hazard Codes: Xi,T
• Statements: 36/37/38-62-53-48/20/21-61
• Safety Statements: 26-36-45-36/37-53
• WGK Germany: 2
• RTECS: TU3725000
• Hazardous Substances Data: 25122-46-7(Hazardous Substances Data)

Usage

Uses

Used in Dermatology:
Clobetasol propionate is used as a topical corticosteroid for the short-term treatment of inflammatory or hyperplastic disorders. It is particularly effective in treating moderate to severe corticosteroid-responsive dermatoses of the scalp, such as eczema and psoriasis. Due to its potent nature, it may cause a more rapid or prolonged response compared to other topical corticosteroids.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, clobetasol propionate is utilized as an active ingredient in various formulations, such as creams, ointments, and lotions. These formulations are designed to provide targeted relief for skin conditions that require potent anti-inflammatory action.
Safety Precautions:
It is recommended that the maximum application of clobetasol propionate should not exceed 60 g/week and should be used for no longer than 14 days without occlusion. Additionally, it should not be used in children below the age of 12 due to potential side effects and risks associated with its potent nature.

Mechanism of Action

Clobetasol Propionate is the propionate salt form of clobetasol, a topical synthetic corticosteroid with anti-inflammatory, anti-pruritic, and vasoconstrictive properties. Clobetasol propionate exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in the synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. Specifically, clobetasol propionate appears to induce phospholipase A2 inhibitory proteins, thereby controlling the release of the inflammatory precursor arachidonic acid from membrane phospholipids by phospholipase A2.

Indications

Clobetasol propionate is the 17-O-propionate ester of clobetasol and it derives from a clobetasol and a propionic acid. A potent corticosteroid, it is used to treat various skin disorders, including exzema and psoriasis. Clobetasol propionate was patented in 1968 and came into medical use in 1978. It is available as a generic medication. Clobetasol propionate is used for the treatment of various skin disorders including eczema, herpes labialis, psoriasis, and lichen sclerosus. It is also used to treat several auto-immune diseases, including alopecia areata, lichen planus (auto immune skin nodules), and mycosis fungoides (T-cell skin lymphoma). It is used as first-line treatment for both acute and chronic GVHD of the skin.

Indications

Clobetasol propionate (Cormax, Temovate, Embeline, Olux) is one of the most potent of the currently available agents and is indicated for short-term treatment of inflammatory or hyperplastic disorders. It is a synthetic fluorinated corticosteroid. It may cause a more rapid or prolonged response than other topical corticosteroids. It is recommended that clobetasol have a maximum application of 60 g/week for no longer than 14 days without occlusion and that it should not be used in children below age 12.

InChI:InChI=1/C25H32ClFO5/c1-5-21(31)32-25(20(30)13-26)14(2)10-18-17-7-6-15-11-16(28)8-9-22(15,3)24(17,27)19(29)12-23(18,25)4/h8-9,11,14,17-19,29H,5-7,10,12-13H2,1-4H3/t14-,17?,18?,19-,22-,23-,24-,25-/m0/s1

Synthetic route

C25H31ClO5 → clobetasol-17-propionate (25122-46-7)

Conditions	Yield
With hydrogen fluoride; potassium hydroxide In water; acetone at -40 - -30℃; for 6h; Temperature;	95%

C25H31ClO5 → clobetasol-17-propionate (25122-46-7)

Conditions	Yield
With hydrogen fluoride In tetrahydrofuran; water at -5 - 0℃; Solvent;	94.3%
With hydrogen fluoride In chloroform; water at -40℃;	84%

Betamethasone 17α,21-ethyl orthopropanoate (1062-09-5) → clobetasol-17-propionate (25122-46-7)

Conditions	Yield
With chloro-trimethyl-silane In N,N-dimethyl-formamide

C22H26O2 → clobetasol-17-propionate (25122-46-7)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: sodium hydroxide / -5 - 5 °C 1.2: 20 °C / Darkness 1.3: 20 °C 2.1: toluene-4-sulfonic acid / dichloromethane / 20 °C 3.1: tert.-butylhydroperoxide; N-benzyl-trimethylammonium hydroxide / tetrahydrofuran / 20 °C 4.1: hydrogen bromide / dichloromethane / 20 °C 4.2: Raney nickel / 20 °C 5.1: triethylamine; dmap / chloroform / 50 °C 6.1: 5,5-dibromohydantoin; perchloric acid / acetone / -5 - 5 °C 7.1: hydrogen fluoride / chloroform; water / -40 °C View Scheme

C24H31ClO3 → clobetasol-17-propionate (25122-46-7)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: toluene-4-sulfonic acid / dichloromethane / 20 °C 2.1: tert.-butylhydroperoxide; N-benzyl-trimethylammonium hydroxide / tetrahydrofuran / 20 °C 3.1: hydrogen bromide / dichloromethane / 20 °C 3.2: Raney nickel / 20 °C 4.1: triethylamine; dmap / chloroform / 50 °C 5.1: 5,5-dibromohydantoin; perchloric acid / acetone / -5 - 5 °C 6.1: hydrogen fluoride / chloroform; water / -40 °C View Scheme

C22H25ClO2 → clobetasol-17-propionate (25122-46-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: tert.-butylhydroperoxide; N-benzyl-trimethylammonium hydroxide / tetrahydrofuran / 20 °C 2.1: hydrogen bromide / dichloromethane / 20 °C 2.2: Raney nickel / 20 °C 3.1: triethylamine; dmap / chloroform / 50 °C 4.1: 5,5-dibromohydantoin; perchloric acid / acetone / -5 - 5 °C 5.1: hydrogen fluoride / chloroform; water / -40 °C View Scheme

C22H25ClO3 → clobetasol-17-propionate (25122-46-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogen bromide / dichloromethane / 20 °C 1.2: Raney nickel / 20 °C 2.1: triethylamine; dmap / chloroform / 50 °C 3.1: 5,5-dibromohydantoin; perchloric acid / acetone / -5 - 5 °C 4.1: hydrogen fluoride / chloroform; water / -40 °C View Scheme

21-Chloro-17α-hydroxy-16β-methylpregna-1,4,9(11)-triene-3,20-dione (116846-77-6) → clobetasol-17-propionate (25122-46-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; dmap / chloroform / 50 °C 2: 5,5-dibromohydantoin; perchloric acid / acetone / -5 - 5 °C 3: hydrogen fluoride / chloroform; water / -40 °C View Scheme

clobetasol-17-propionate (25122-46-7) → 21-chloro-9α-fluoro-16β-methyl-11β,17α-dihydroxy-5β-pregnane-3,20-dione 17-propionate (80042-35-9)

Conditions	Yield
palladium In 4,4-dichlorobutan-2-one; ethyl acetate
palladium In 4,4-dichlorobutan-2-one; ethyl acetate

Upstream product

• 116846-77-6 21-Chloro-17α-hydroxy-16β-methylpregna-1,4,9(11)-triene-3,20-dione 
• 1062-09-5 Betamethasone 17α,21-ethyl orthopropanoate 

Relevant articles and documents

Clobetasol propionate intermediate and preparation method thereof

The invention provides a clobetasol propionate intermediate and a preparation method thereof. The preparation method of clobetasol propionate comprises the following steps: A) in a protective atmosphere, reacting a compound DB11 with a chlorination reagent in an organic solution in the presence of a first catalyst to obtain a system containing an intermediate shown as a formula V; b) adding a second catalyst into the system containing the intermediate shown in the formula V, and continuously reacting to obtain a system containing an intermediate shown in a formula VI; c) adding an organic basecatalyst and a propionylation reagent into the system containing the intermediate shown in the formula VI, continuously reacting, performing standing for layering after the reaction is finished, extracting, concentrating and filtering to obtain an intermediate shown in a formula VII; and d) slowly adding the intermediate shown in the formula VII into a solvent for reaction, and crystallizing thereaction solution to obtain a clobetasol propionate crude product. The reaction route is as follows. The preparation method disclosed by the invention is efficient, green and environment-friendly, andthe purity and yield of the clobetasol propionate product are high.

A clobetasol propionate preparation method (by machine translation)

The invention relates to a method for the preparation of steroid compounds, in particular to the preparation of clobetasol propionate. The invention formula 1 compound as the initiator and, sequentially through chlorination reaction, esterification reaction, ring-opening reaction, [...] times he cable. The invention new process more industrialization value, can effectively control the secondary reaction, improves the reaction yield and quality; in process design does not involve high-risk reaction, is easy to realize industrial; not the existence of high pollution response, the processing pressure of environmental protection. (by machine translation)

Preparation method of clobetasol propionate

The invention provides a brand new synthesis route for preparation of clobetasol propionate; adopted raw materials are cheaper and are easier to obtain, reactive raw materials are hydroxylated and then chloridized, carbonyl protection groups are removed, five-membered ring double bonds are subjected to selective oxidation and reduction, after esterification, six-membered ring double bonds are subjected to epoxidation, and then fluorination ring opening is performed to obtain the clobetasol propionate product. The reaction process is easy to operate, the yield of each step is relatively high, the purity of the obtained product is higher, the formation of by-products is effectively avoided, the production cost is reduced and industrialized production is facilitated.

Cosmetic use of microorganism(s) for the treatment of scalp disorders

The present invention relates to a use of an effective amount of at least one probiotic microorganism and/or a fraction thereof and/or a metabolite thereof for preventing and/or treating dandruff disorders of the scalp, as well as a cosmetic process for preventing and/or treating a dandruff condition including the administration a first cosmetic active agent and of at least a second cosmetic active agent, topically, the said first and second cosmetic active agents being formulated in separate compositions, the first cosmetic active agent being chosen from probiotic microorganisms, and mixtures thereof, and the second cosmetic active agent being chosen from antidandruff active agents.

Composition for the topical treatment of poison ivy and other forms of contact dermatitis

Composition for topical administration comprising (a) a corticosteroid, and (b) a drying agent.

Novel process for the preparation of steroidal esters

A process for the preparation of corticosteriod esters of the formula STR1 in which ---- signifies that a double bond can be present; X is hydrogen, chlorine or fluorine; R1 is hydrogen, fluorine, chlorine or methyl, which may be either α or β; R2 is halogen, oxo or hydroxyl; or R3 is hydrogen, α-methyl or β-methyl; or R2 and X jointly form an epoxide group; R4 is an acyl group of the formula RCO, in which R is one of the following (i) an alkyl group containing 1 to 16 carbon atoms, whether straight-chained, branched or cyclic; (ii) an aralkyl group of 7 to 8 carbon atoms; (iii) a phenyl group; R5 is hydroxyl or R6 ; where R6 is hydrogen, one or two halogen atom substituents or OR7, where R7 is an acyl group of the formula R'CO in which R', which can be identical or different to R in the same molecule, is one of the following: (i) an alkyl group of 1 to 16 carbon atoms, whether straight-chained, branched or cyclic; (ii) an aralkyl group of 7 to 8 carbon atoms; or (iii) a phenyl group. which comprises esterifying a compound of the formula STR2 wherein X, R1, R3 and R5 are as defined above, and R8 is trihaloacetate, halogen or oxo, or jointly forms an epoxide group with X; at the 17-position only, or at the 17- and 21-positions when R5 in formula III is hydroxyl, the said esterification being carried out with the anhydride of the acid containing the group desired.

Process for the preparation of 21-halogeno-21-desoxy-17α-acyloxy-20-keto-pregnenes

21-Halogeno-17α-acyloxy-20-keto-4-pregnenes having physiological properties are prepared by the reaction of a 17α,21-dihydroxy-20-keto-4-pregnene 17α,21-orthoester with a halide reagent selected from the group consisting of triarylsilyl halides and tri-lower alkylsilyl halides in an organic solvent, said halide being chloride or bromide. Preferred reagents are tri-lower alkylsilyl halides, particularly trimethylsilyl chloride.