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Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17).

Abstract：

:The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones. Compounds capable of inhibiting Cyp19 (Aromatase), a key enzyme in the synthesis of estrogens, have been successfully employed as breast cancer therapies, while inhibitors of Cyp17 (17α-hydroxylase-17,20-lyase), a key enzyme in the synthesis of glucocorticoids, mineralocorticoids and steroidal sex hormones, are a key component of prostate cancer therapy. Inhibition of CYP17 has also been suggested as a possible target for the treatment of Cushing Syndrome and Metabolic Syndrome. We have identified two novel series of stilbene based CYP17 inhibitors and demonstrated that exemplary compounds in these series have pharmacokinetic properties consistent with orally delivered drugs. These findings suggest that compounds in these classes may be useful for the treatment of diseases and conditions associated with improper regulation of glucocorticoids synthesis and glucocorticoids receptor activation.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Blass BE,Iyer P,Abou-Gharbia M,Childers WE,Gordon JC,Ramanjulu M,Morton G,Arumugam P,Boruwa J,Ellingboe J,Mitra S,Reddy Nimmareddy R,Paliwal S,Rajasekhar J,Shivakumar S,Srivastava P,Tangirala RS,Venkataramanaiah K,Bob

doi

10.1016/j.bmcl.2018.05.040

subject

Has Abstract

pub_date

2018-07-15 00:00:00

pages

2270-2274

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30441-4

journal_volume

28

pub_type

杂志文章

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