3093-35-4

Usage

Uses

Used in Pharmaceutical Industry:
Halcinonide is used as a topical medication for the treatment of various skin conditions, such as psoriasis and eczema dermatitis. Its potent anti-inflammatory and immunosuppressive effects make it an effective treatment for these conditions.
Used in Cortical Hormone Drug Synthesis:
Halcinonide is utilized in the synthesis of 4-Fluorotriamcinolone Acetonide (F598640), an analog of Fluocinolone Acetonide (F455800), which is a glucocorticoid and anti-inflammatory agent. This by-product plays a significant role in the development of new medications with improved efficacy and reduced side effects.
Used in Anti-inflammatory Applications (Topical):
Halcinonide is used as a potent anti-inflammatory agent in topical formulations. Its ability to reduce inflammation, swelling, and itching makes it a popular choice for treating various skin conditions that require localized anti-inflammatory action.

Outline

Halcinonide is an efficient synthetic fluorine and chlorine corticosteroid, the effect of it is similar to fludrocortisone . It has strong anti-inflammatory, anti-allergic, anti-itching, inhibiting proliferation of immune effects, topical application can reduce the permeability of the capillary wall and cell membrane,and reduce the inflammatory exudate, and inhibit histamine and other inflammatory mediators formation and release.it is clinically used for subacute or chronic non-infectious skin diseases such as psoriasis, eczema, neurodermatitis, contact dermatitis, seborrheic dermatitis (non-face), atopic dermatitis, flat moss and discoid lupus erythematosus and the like which are hormone therapy ineffective .

Physical and Chemical Properties

White or off-white crystalline powder, odorless. Almost insoluble in water, slightly soluble in ethanol or methanol, soluble in acetone and chloroform. Sealed.

Pharmacological effects

This drug is a potent synthetic glucocorticoid ,its action is similar to fludrocortisone. It has strong anti-inflammatory, anti-allergic, anti-itching, inhibit proliferation of immune and other effects, topical application are unlikely to cause systemic adverse reactions. The drug has the same effect of inhibiting the proliferation of granulation tissue as dexamethasone ,it is stronger than hydrocortisone. The drug is not substantially absorbed in external skin, it has no irritating effect on the body. The extent of absorption of topical application is hugely different among anatomic sites: forearm 1%, 4% of the scalp, forehead, 7%, 36% of the scrotum, the greatest penetration is in the groin, armpits and face. The drug is mainly metabolized in the liver, it is mostly excreted by the kidneys, and less by biliary excretion. The above information is edited by the lookchem of Tian Ye.

Indications

The drug is suitable for treatment of contact dermatitis, atopic dermatitis, lichen,the small size of psoriasis, lichen, heat rash, genital atrophic lichen sclerosus, non-parasitic prurigo, ring granuloma, discoid lupus erythematosus, non-facial seborrheic dermatitis, mycosis fungoides pruritus symptomatic .It is also used for the treatment of insect bites, parasitic prurigo through specific treatment. It has a good effect on the treatment of psoriasis .

Indications

Halcinonide (Halog, Halog-E) is a synthetic fluorinated corticosteroid.

Adverse reactions

1. There are a small number of patients whose applicator parts of the skin occurs burning, stinging, itching temporary, long-term use can occur telangiectasia skin (especially face), skin atrophy, stretch marks (teenagers prone), fragile skin, hirsutism, folliculitis, milia, skin bleaching, delayed ulcer healing, packet method in skin folds easily causes fungal infection. 2. When it is much absorbed through the skin, it can cause systemic adverse reactions.

Contraindications

1.Patients who are allergic to this drug and adrenal corticosteroids are banned. 2. The primary skin diseases , exudative dermatitis, ulcerative lesions, acne, rosacea caused by bacteria, fungi, viruses and parasites are banned. 3. It is forbidden using in the eyelid portion (cause a risk of glaucoma).

Precautions

1. The large area of large quantities of drugs or medication packet mode allow more amount of the drug being absorbed through the skin, which causes systemic reactions, especially in young children and infants, it can cause reversible Cushing's syndrome and growth retardation, sudden withdrawal can cause acute adrenal insufficiency. 2. When the local intolerance phenomena occurs,the drug should be stopped and the reason should be found. 3. It should be paid attention that drug staying in the skin folds and diaper can be absorbed into the body.

Specification

Ointments, creams, solutions: 0.1%.

Originator

Halog,Squibb,US,1974

Manufacturing Process

(A) 16α-Hydroxy-9α-fluorohydrocortisone acetonide 27-mesylate: To a solution of 1.5 g of 16α-hydroxy-9α-fluorohydroortisone acetonide in 15 ml of dry pyridine is added at 0°C. 1.5 ml of methane-sulfonyl chloride. After standing in the refrigerator for 2,5 hours, excess methanesulfonyl chloride is destroyed by the addition of a small amount of ice, after which ice-water is added slowly to precipitate the reaction product. After ? hour in the refrigerator the material is filtered off, washed thoroughly with water and dried in vacuo. The resulting crude material after recrystallization from acetone-hexane gives the pure 21-mesylate of the following properties: melting point about 225°C to 227°C (decomposition); [α]D23+112° (c, 0.5 in chloroform). (B) 21-Chloro-9α-fluoro-δ4-pregnene-11β,16α,17α-triol-3,20-dione16,17- acetonide : A solution of 200 mg of the acetonide 21-mesylate from part (A) and 900 mg of lithium chloride in 25 ml of dimethylformamide is kept at 100°C for 24 hours. The mixture is poured on ice, extracted with chloroform and the chloroform extract washed with water and dried over sodium sulfate. Evaporation of the solvent in vacuo furnishes the crystalline chloride, which after recrystallization from acetone-ethanol has a melting point about 276°C to 277°C.

Therapeutic Function

Topical corticosteroid

InChI:InChI=1/C24H32ClFO5/c1-20(2)30-19-10-16-15-6-5-13-9-14(27)7-8-21(13,3)23(15,26)17(28)11-22(16,4)24(19,31-20)18(29)12-25/h9,15-17,19,28H,5-8,10-12H2,1-4H3/t15?,16?,17?,19-,21?,22?,23?,24-/m1/s1

Upstream product

• 91160-87-1 9α-bromo-11β,16α,17α,21-tetrahydroxypregn-4-en-3,20-dione 21-acetate 
• 74220-43-2 21-Acetoxy-16α,17α-dihydroxy-4,9(11)-pregnadien-3,20-dion 
• 23460-76-6 21-acetoxy-pregna-4,9⁽¹¹⁾,16-triene-3,20-dinone 
• 1524-86-3 16α-17-[(1-methylethylidene)bis(oxy)]-11β,21-dihydroxy-9-fluoro-4-ene-pregna-3,20-dione 
• 982-91-2 21-chloro-9α-fluoro-11β,16α,17α-trihydroxy-4-pregnen-3,20-dione 
• 67-64-1 acetone 
• 82427-95-0 9-Brom-21-chlor-11β-hydroxy-16α,17-isopropylidendioxy-4-pregnen-3,20-dion 
• 82427-96-1 21-Chlor-9,11β-epoxy-16α,17-isopropylidendioxy-4-pregnen-3,20-dion 

Relevant academic research and scientific papers

Preparation method of

The invention provides a preparation method of and an intermediate thereof. The preparation method comprises the following steps: carrying out chlorination reaction on the compound of the formula N - 7 N - 3 with a chlorination reagent, then carrying out a fluorine reaction with the fluorine-containing reagent, and reacting the compound as follows. Of these, the chlorinating agent is selected from the sulfonyl chlorides of aromatic hydrocarbons, in particular benzenesulfonyl chloride. At least one of p-toluenesulfonyl chloride and p-chlorobenzoyl chloride, wherein the fluorine-containing agent is hydrofluoric acid. The preparation method is efficient, green and environment-friendly, shortens the production cycle, reduces a large amount of wastewater, improves the yield, reduces the production cost, realizes clean production, HPLC content of the product is less than 99.0%, and the yield reaches 0.10% 100% or more.

Synthesis method and application of 9-fluorosteroid compound

The invention provides a synthesis method and application of a 9-fluorosteroid compound, and relates to the technical field of chemical synthesis. The synthesis method of the 9-fluorosteroid compoundcomprises the following step: reacting a compound II in an ionic liquid containing hydrogen fluoride salt to obtain a 9-fluorosteroid compound III. According to the synthesis method of the 9-fluorosteroid compound, the ionic liquid containing the hydrogen fluoride salt is used as a fluorinating agent to replace a traditional hydrogen fluoride aqueous solution, volatilization of hydrogen fluoride gas is avoided, corrosivity is small, toxicity is greatly reduced, reaction conditions are mild, reaction can be completed at the room temperature, operability is high, the safety coefficient is high,and production applicability is improved. The synthesis method of the 9-fluorosteroid compound is used for preparing corticosteroid drugs, highly toxic chemical reagents are not used in the synthesisroute, the operability is high, the safety coefficient is high, and the production applicability is improved.

Steroid 21-hydroxyl chlorination or bromination method

The invention discloses a steroid 21-hydroxyl chlorination or bromination method. A compound shown as formula A is adopted as the start material, and in the presence of SO2, reaction with a chlorination or bromination reagent is carried out to prepare a compound shown as formula B. The method provided by the invention has the characteristics of mild process conditions, environmental friendliness,easily available reagents, easy operation, low cost and high yield, and is suitable for industrial mass production.

Preparation method of halcinonide

The invention provides a preparation method of halcinonide. The method includes: (1) chlorination reaction: in the presence of SO2, reacting a compound 1 with a chlorination reagent to generate a compound 2, with the chlorination reagent being selected from one or more of acetyl chloride, propionyl chloride, benzoyl chloride, lithium chloride, carbon tetrachloride, chlorosuccinimide and dichloro dimethylhydantoin; and (2) ring-opening reaction: reacting the compound 2 with hydrogen fluoride to obtain halcinonide. The method provided by the invention has the beneficial effects of mild reactionconditions, friendly environment, easy operation and low cost, has industrialization value, can effectively control side reaction, and improve the reaction yield and quality; the process design does not involve high-risk reaction, and is easy to realize industrialization; high-pollution reaction does not exist, thus easing the pressure of environmental protection treatment.

Pregnane derivatives 16, 17 - acetal (ketone) preparation method

Disclosed is a method for preparing a pregnane derivative 16,17-acetal (ketal) compound shown in the general formula I, the method comprising the step of reacting a compound of a general formula II with a compound of a general formula III or a general formula IV in the presence of boron trifluoride, wherein the dotted line between site 1 and site 2 denotes a saturated or unsaturated bond; R is hydroxyl, halogen or -OCOR7, wherein R7 is a C1-C12 linear chain or branched alkyl, a C3-C10 cycloalkyl, a C2-C8 alkenyl or a C2-C8 alkynyl; R1 and R2 are each hydrogen, a C1-C12 linear chain or branched alkyl, a C3-C10 cycloalkyl, a C2-C8 alkenyl or a C2-C8 alkynyl, or R1, R2 and the carbon to which they are connected form a C3-C10 cycloalkyl together, with the provision that R1 and R2 are not hydrogen simultaneously; R3 is hydrogen or -OCOR8, wherein R8 is a C1-C12 linear chain or branched alkyl, or a C3-C10 cycloalkyl; R4 is hydrogen, fluorine or chlorine; R5 is hydrogen, fluorine, chlorine or methyl; and R6 is a C1-C12 linear chain or branched alkyl. Compared with current processes, the method causes little pollution to the environment, has relatively mild reaction conditions, ease of control, reduced energy consumption and low production costs.

Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor

Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.

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.

Mucosal adhesive device for long-acting delivery of pharmaceutical combinations in oral cavity

Mucosal adhesive devices are provided for use in the oral cavity for therapy against infections. The devices are dosage units which comprise a combination of antimicrobial agents such as antifungal agents and anti-inflammatory agents, optionally also a local anesthetic. The dosage units yield a gradual and relatively constant release of the pharmaceuticals over at least a 12-hour period.

A New Method of Transforming 11β,17α,21-Trihydroxy-20-oxo Steroids into the 21-Chloro-20-oxo-Δ9(11),16 Derivatives

Reaction of the 17α nitrates 1a,b with lithium chloride in hexamethylphosphoric triamide or N-methylpyrrolidone results in formation of the Δ16 steroids 2a,b by elimination of the 17α nitrooxy group.The corresponding 21 mesylates 1c,d are transformed into the 21-chloro-Δ16 steroids 2b,c under the same conditions.When the reaction was carried out with the 11β,17α-dinitrooxy-21-mesyloxy derivatives 4, the 21-chloro-Δ9(11),16 steroids 5 were obtained. 5a is a suitable intermediate for a short synthesis of 10, a topical anti-inflammatory corticosteroid.