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.

类固醇激素的合成对人体生理至关重要，对这些关键分子的合成或相关受体的激活进行不适当的调节会导致疾病。这引起了对开发能够调节类固醇激素合成的化合物的浓厚兴趣。能够抑制雌激素合成中关键酶Cyp19（芳香酶）的化合物已成功地用作乳腺癌治疗，而Cyp17（17α-羟化酶-17,20-裂合酶）抑制剂是合成雌激素的关键酶。糖皮质激素，盐皮质激素和甾体性激素是前列腺癌治疗的关键组成部分。CYP17的抑制也被认为是治疗库兴综合征和代谢综合征的可能靶标。我们已经鉴定了两个新的基于的CYP17抑制剂系列，并证明了这些系列中的示例性化合物具有与口服药物一致的药代动力学特性。这些发现表明，这些类别的化合物可用于治疗与糖皮质激素合成和糖皮质激素受体活化的不当调节有关的疾病和状况。