3,4,6-triaryl-(1,3)-oxazine-2-ketone compound as well as preparation method and application thereof

Abstract

The invention belongs to the field of pharmaceutical chemistry and relates to a 3,4,6-triaryl-(1,3)-oxazine-2-ketone compound, a preparation method thereof and also a drug composition containing the compound in a formula (I). The 3,4,6-triaryl-(1,3)-oxazine-2-ketone compound and the drug composition are used as an androgen receptor antagonist and can be used for preparing a non-steroidal drug for preventing and / or treating prostatic hyperplasia, prostate cancers, hirsutism, severe androgen-dependent alopecia or acne symptoms or diseases, associated with androgen receptors.

Description

Technical field The invention belongs to the field of medicinal chemistry, and relates to 3,4,6-triaryl-[1,3]-oxazin-2-one compound (I) and its preparation method, pharmaceutical composition and preparation for prevention or / and treatment Androgen receptor-related prostate hyperplasia, prostate cancer, women's hirsutism, severe androgen-dependent alopecia or acne symptoms or diseases in non-steroidal drugs. Where R 1 , R 2 , R 3 , R 4 Represents H, halogen, C 1 ~C 12 Alkyl, C 1 ~C 12 Alkoxy, nitro, cyano, carboxyl, hydroxyl, CF 3 , NR 6 R 7 ; R 6 , R 7 Represents H, C 1 ~C 12 Alkyl, C 6 ~C 12 Aryl; R 1 , R 2 , R 3 , R 4 Can be in any possible position of the benzene ring, R 1 , R 2 , R 3 , R 4 They may be the same or different; Ar represents an aryl group or a substituted aryl group. Background technique Androgen (Androgen) is a general term for hormones such as testosterone, dihydrotestosterone, and adrenal androsterone. It is mainly secreted by the interstitial cells of the ...

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Problems solved by technology

However, it has been found in clinical use that both steroidal and non-steroidal AR antagonists have certain side effects, including estrogen and androgen metabolic disorders, gynecomastia and liver toxicity; Side effects such as gastrointestinal discomfort, nausea, vomiting, insomnia, fatigue, headache, anxiety, blurred vision, and loss of libido may occur with hetamine or bicalutamide; secondly, patients with benign prostatic hyperplasia / prostate cancer take a single antiandrogen drug Later, "Antiandrogen Withdrawal Syndrome" (AWS) will appear, which is manifested by the rapid increase of the suppressed prostate-specific antigen (Prostate-specific Antigen, PSA) level and tumor volume after a period of medication , can only stop taking the drug or switch to other anti-androgen drugs

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