360-63-4

Basic information

• Product Name: 9-fluoro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-(hydrogen phosphonate)
• Synonyms: 9-fluoro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-(hydrogen phosphonate);Betamethasone phosphate;Betamethasone 21-(dihydrogen phosphate);Betamethasone 21-phosphate;Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17-dihydroxy-16-methyl-21-(phosphonooxy)-, (11β,16β)- (9CI);Pregna-1,4-diene-3,20-dione, 9-fluoro-11β,17,21-trihydroxy-16β-methyl-, 21-(dihydrogen phosphate) (7CI, 8CI);9-Fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 21-phosphate;9-Fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 21-phosphoric acid
• CAS NO: 360-63-4
• Molecular Formula: C₂₂H₃₀FO₈P
• Molecular Weight: 456.4415642
• EINECS: 206-636-7
• Mol File: 360-63-4.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 669.6°Cat760mmHg
• Flash Point: 358.7°C
• Appearance: /
• Density: 1.45g/cm³
• CAS DataBase Reference: 9-fluoro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-(hydrogen phosphonate)(CAS DataBase Reference)
• NIST Chemistry Reference: 9-fluoro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-(hydrogen phosphonate)(360-63-4)
• EPA Substance Registry System: 9-fluoro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-(hydrogen phosphonate)(360-63-4)

Safety Data

• Hazardous Substances Data: 360-63-4(Hazardous Substances Data)

Usage

Originator

Bentelan,Biofutura

Uses

Glucocorticoid.

Manufacturing Process

A solution of bistriethylamine phosphate was prepared by slowly adding 2.36 ml of 85% phosphoric acid to 20 ml of acetonitrile containing 9.9 ml, of triethylamine at 20°C. This solution was added to a stirred mixture of 4.70 g of 9α-fluoro-11β,17α,21-trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione 21-methanesulfonate and 20 ml of acetonitrile. The mixture was heated under reflux for 4 h and then evaporated under reduced pressure to a volume of 12 ml. This mixture was a concentrated solution of 9α-fluoro-11β,17α,21- trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione 21-phosphate triethylamine salt with some inorganic phosphate. The salt of 9α-fluoro-11β,17α,21-trihydroxy-16α-methyl-1,4-pregnadiene- 3,20-dione 21-phosphate may be converted to 9α-fluoro-11β,17α,21- trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione 21-phosphate by treatment with acid (for example HCl).

Therapeutic Function

Glucocorticoid

Upstream product

• 1177-87-3 betamethasone 
• 2884-51-7 17α,21-dihydroxy-9β,11β-epoxy-16α-methylpregna-1,4-diene-3,20-dione 21-acetate 
• 50-02-2 dexamethasone 

Downstream Products

• 50-02-2 dexamethasone 

Relevant articles and documents

TARGETED STEROID CONJUGATES

A compound of the formula (I): G1-L-G2, or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein G1 is a folate radical, an antifolate radical, or a folate analog radical; L is a linker; and G2 is a radical of a steroid; compositions comprising such compounds; and the use of such compounds and compositions to treat, for example, inflammation associated with a disease or disorder.

A kind of improved dexamethasone sodium phosphate intermediates

The invention provides an improved preparation method of a dexamethasone sodium phosphate intermediate. The improved preparation method of the dexamethasone sodium phosphate intermediate comprises the following steps: (a) in tetrahydrofuran, with dexamethasone and pyrophosphoryl chloride as raw materials, carrying out a reaction at the temperature ranging from minus 35 DEG C to minus 45 DEG C, so that dexamethasone phosphate is obtained; (b) adding purified water, carrying out hydraulic analysis after a termination reaction is finished, and then adding sodium hydrogen carbonate for salifying; (c) filtering, and carrying out reduced pressure concentration at the temperature of 30-45 DEG C until tetrahydrofuran is not contained in filtrate; (d) adding an organic solvent for extraction; and (e) filtering, carrying out reduced pressure concentration at the temperature of 30-45 DEG C until the organic solvent is not contained in the filtrate, adding acid for acidification, stirring for 6-8 hours, filtering, and carrying out vacuum drying, so that dexamethasone phosphate is obtained. The improved preparation method of the dexamethasone sodium phosphate intermediate has the advantages that utilization rate of raw materials and purity and yield of a product are improved, so that production cost is reduced; and the improved preparation method of the dexamethasone sodium phosphate intermediate has a wide industrial application prospect.

Discovery of Pyrophosphate Diesters as Tunable, Soluble, and Bioorthogonal Linkers for Site-Specific Antibody-Drug Conjugates

As part of an effort to examine the utility of antibody-drug conjugates (ADCs) beyond oncology indications, a novel pyrophosphate ester linker was discovered to enable the targeted delivery of glucocorticoids. As small molecules, these highly soluble phosphate ester drug linkers were found to have ideal orthogonal properties: robust plasma stability coupled with rapid release of payload in a lysosomal environment. Building upon these findings, site-specific ADCs were made between this drug linker combination and an antibody against human CD70, a receptor specifically expressed in immune cells but also found aberrantly expressed in multiple human carcinomas. Full characterization of these ADCs enabled procession to in vitro proof of concept, wherein ADCs 1-22 and 1-37 were demonstrated to afford potent, targeted delivery of glucocorticoids to a representative cell line, as measured by changes in glucocorticoid receptor-mediated gene mRNA levels. These activities were found to be antibody-, linker-, and payload-dependent. Preliminary mechanistic studies support the notion that lysosomal trafficking and enzymatic linker cleavage are required for activity and that the utility for the pyrophosphate linker may be general for internalizing ADCs as well as other targeted delivery platforms.