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Expert Opinion on Therapeutic Patents Volume 26, 2016 - Issue 1
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Patent Evaluations

Novel functionalized 5-(phenoxymethyl)-1,3-dioxane analogs exhibiting cytochrome P450 inhibition: a patent evaluation WO2015048311 (A1)

Richard L SchroederDepartment of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA
,
Phan TramDepartment of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA
,
Jiawang LiuDepartment of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA
,
Maryam ForoozeshDepartment of Chemistry, Xavier University of Louisiana, New Orleans, LA, USA
&
Jayalakshmi SridharDepartment of Chemistry, Xavier University of Louisiana, New Orleans, LA, USACorrespondence[email protected]
Pages 139-147 | Published online: 29 Oct 2015

References

  • Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.
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• Demonstrates the direct association between cortisol levels, insulin resistance and complications in type 2 diabetic subjects. Hypothalmic-pituitary-adrenal (HPA) activity was shown to be enhanced only in diabetic patients with chronic complications.

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• This review gives an extensive overview of the patient studies that link high cortisol levels after stroke that is associated with dependency, morbidity and mortality.

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• Analyzed the role of the A2 variant of CYP17 with incidence of advanced breast cancer. The study was conducted in 483 homogenous Finnish origin breast cancer patients and compared to earlier studies.

• This review takes an in-depth look into the role of cortisol in the pathophysiology of metabolic syndrome and Cushing’s disease suggesting that reducing cortisol levels will positively influence the outcome of type 2 diabetes and cardiovascular disease.

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•• Describes the development of chiral etomidate derivatives as CYP11B1 selective inhibitors for the treatment of cortisol-dependent diseases such as Cushing’s syndrome and related disease.

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•• Outlines the synthesis of a series of steroidal inhibitors of CYP17 that decreased the plasma testosterone concentration in rats by 81 – 84% after 2h.

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•• An exhaustive review on the development of abiraterone and other CYP17 inhibitors for treatment of metastatic prostate cancer. The clinical parameters of abiraterone administration and the results of post-translational studies are described.

  • Vasaitis T, Belosay A, Schayowitz A, et al. Androgen receptor inactivation contributes to antitumor efficacy of 17α-hydroxylase/17,20-lyase inhibitor 3β-hydroxy-17-(1H-benzimidazole-1-Yl)androsta-5,16-diene in prostate cancer. Mol Cancer Ther. 2008;7(8):2348–2357.
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•• The efficacy of abiraterone acetate in the treatment of castration-resistant prostate cancer is evaluated. The studies have shown successful reversal of resistance to abiraterone acetate using low-dose dexamethasone in some patients.

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•• Treatment of patients with endogenous Cushing’s syndrome with metyrapone and/or aminoglutethimide is reported. The report shows marked clinical improvement for a majority of the patients.

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