- Expedient synthesis of 17α,21-dihydroxy-9β,11β-epoxy- 16αmethylpregna- 1,4-diene-3,20-dione 21-acetate from prednisolone utilising a novel Mattox rearrangement
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A six step transformation of prednisolone to 17a,21-dihydroxy-9b,11b-epoxy- 16a-amethylpregna-1,4- diene-3,20-dione 21-acetate has been achieved in 13% unoptimised yield. Novel conditions for effecting a Mattox rearrangement and double dehydration of prednisolone were identified. Enhanced knowledge on the oxidation of silyl D19,20-enol ethers and structural factors that impact the success of the oxidation are also presented.
- Hulcoop, David G.,Shapland, Peter D.P.
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Read Online
- AQUEOUS ORAL PHARMACEUTICAL SUSPENSION COMPOSITIONS
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Provided is an aqueous oral pharmaceutical suspension composition comprising vamorolone Form I. Also provided are methods for its preparation and its use.
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Paragraph 0124; 0130
(2020/09/22)
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- Improvements in corticosteroid 21-acetoxy-17α-hydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione synthesis and its use as common intermediate in the synthesis of some impurities related to dexamethasone and mometasone
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There are quite substantial number of impurities related to dexamethasone or mometasone which cannot be made from respective Active Pharmaceutical Ingredients but from common intermediate 21-acetoxy-17α-hydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione (12). As such, a robust and economical synthesis of this key intermediate is important for delivering a resilient and economically viable supply chain for these impurities. Therefore, it is critical to have a robust and economically viable process to synthesize the intermediate 12 in good yield and quality. We report here an improved synthesis of 12 and eight impurities related to dexamethasone and mometasone from this common intermediate.
- Das, Saibal Kumar,Dubey, Manoj Kumar,Buchhikonda, Ravinder
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- Non-hormonal steroid modulators of NF-κβ for treatment of disease
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The present invention relates to compounds and methods which may be useful as treatments of diseases.
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Page/Page column 43-44
(2019/11/18)
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- Synthesis method of 17-site side chain of steroidal drug
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The invention provides a synthesis method of 17-site side chain of a steroidal drug. The method is characterized in that a compound I is taken as a starting material, and the 17-site side chain of thesteroidal drug is synthesized by means of reactions such as a nucleophilic reaction, an esterification reaction, an elimination reaction and an oxidation reaction; compared with the traditional technology, the method adopts 3-hydroxypropionitrile and a cyano group, and does not use a material such as acetone nitrile alcohol or sodium cyanide with violent toxicity, thus being safer and higher in environmental protection property; furthermore, all the steps of reactions are relatively easy to implement; the method is high in yield and purity as well as more economical and safe in production, thus being more suitable for industrial production.
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- NON-HORMONAL STEROID MODULATORS OF NF-KAPPA BETA FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of diseases.
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Paragraph 0240-0242
(2017/01/19)
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- NON-HORMONAL STEROID MODULATORS OF NF-KB FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-κB for the treatment or prevention of muscular wasting disease, including muscular dystrophy.
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Paragraph 0165; 0166
(2015/09/23)
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- VBP15: Preclinical characterization of a novel anti-inflammatory delta 9,11 steroid
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Δ9,11 modifications of glucocorticoids (21-aminosteroids) have been developed as drugs for protection against cell damage (lipid peroxidation; lazaroids) and inhibition of neovascularization (anecortave). Part of the rationale for developing these compounds has been the loss of glucocorticoid receptor binding due to the Δ9,11 modification, thus avoiding many immunosuppressive activities and deleterious side effect profiles associated with binding to glucocorticoid and mineralocorticoid receptors. We recently demonstrated that anecortave acetate and its 21-hydroxy analog (VBP1) do, in fact, show glucocorticoid and mineralocorticoid receptor binding activities, with potent translocation of the glucocorticoid receptor to the cell nucleus. We concluded that Δ9,11 steroids showed novel anti-inflammatory properties, retaining NF-κB inhibition, but losing deleterious glucocorticoid side effect profiles. Evidence for this was developed in pre-clinical trials of chronic muscle inflammation. Here, we describe a drug development program aimed at optimizing the Δ9,11 chemistry. Twenty Δ9,11 derivatives were tested in in vitro screens for NF-κB inhibition and GR translocation to the nucleus, and low cell toxicity. VBP15 was selected as the lead compound due to potent NF-κB inhibition and GR translocation similar to prednisone and dexamethasone, lack of transactivation properties, and good bioavailability. Phamacokinetics were similar to traditional glucocorticoid drugs with terminal half-life of 0.35 h (mice), 0.58 h (rats), 5.42 h (dogs), and bioavailability of 74.5% (mice), and 53.2% (dogs). Metabolic stability showed ≥80% remaining at 1 h of VBP6 and VBP15 in human, dog, and monkey liver microsomes. Solubility, permeability and plasma protein binding were within acceptable limits. VBP15 moderately induced CYP3A4 across the three human hepatocyte donors (24-42%), similar to other steroids. VBP15 is currently under development for treatment of Duchenne muscular dystrophy.
- Reeves, Erica K.M.,Hoffman, Eric P.,Nagaraju, Kanneboyina,Damsker, Jesse M.,McCall, John M.
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p. 2241 - 2249
(2013/05/22)
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- NON-HORMONAL STEROID MODULATORS OF NF-KB FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of diseases.
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Paragraph 0207
(2013/06/27)
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- NON-HORMONAL STEROID MODULATORS OF NF-?B FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-?Β for the treatment or prevention of muscular wasting disease, including muscular dystrophy.
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Page/Page column 54-55
(2011/10/31)
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- 16α-methylation process
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Disclosed is a process for the production of a Δ17(20) -steroid of the formula STR1 which comprises starting with a 16-unsaturated corticoid of the formula STR2 and contacting the 16-unsaturated corticoid (I) with a methylating agent in the presence of a copper catalyst and a silylating agent.
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- 16α-methylatedΔ17(20)-corticoids
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C16 -unsaturated corticoids are readily transformed to the corresponding 16α-methyl-17α-hydroxy corticoids by use of a Δ17 (20)-20-silyl ether.
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- Process for preparation of 16 α-methyl corticoids from Δ16 -steroids
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This invention discloses a general process for the production of corticoids from respective steroid-type compounds having a double bond from C-16 to C-17. The invention provides a viable alternative synthesis of 17α-hydroxy-progesterones and like corticoids.
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