CN104024228A - 咪唑二酮类化合物及其用途 - Google Patents
咪唑二酮类化合物及其用途 Download PDFInfo
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- CN104024228A CN104024228A CN201280052853.9A CN201280052853A CN104024228A CN 104024228 A CN104024228 A CN 104024228A CN 201280052853 A CN201280052853 A CN 201280052853A CN 104024228 A CN104024228 A CN 104024228A
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- Prior art keywords
- compound
- deuterated
- deuterium
- methyl
- pharmaceutically acceptable
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/28—Antiandrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin
Abstract
Description
Claims (1)
- 权 利 要 求1.一种式 (I)所示的咪唑二酮类化合物、 或其晶型、 药学上可接受的盐、 水合物或溶 剂合物,(I)其中,R1和 R2是各自独立选自于氢、 氘、 甲基或一次或多次氘代的或全氘代的 C C4烷 基;R3是氢、 氘、 或卤素;R4、 R5、 R6、 R9、 R1Q、 R12是氢、 氘、 或卤素;R7和 R8是各自独立选自于甲基或一次或多次氘代的或全氘代的 d-C4烷基、 或者 R7和 R8连接形成的 C3-C6环烷基;R11是未氘代的、 一次或多次氘代的或全氘代的 C C4烷基, 或者部分或全部卤素 取代的 d-C4烷基;X 是 S或者 0;附加条件是 (l)Ri、 R2、 R3、 R4、 R5、 R6、 R7、 R8、 R9、 R10 Ru、 R12中至少一个 是氘代的或氘, 或者 (2)当 R1和 R2都为甲基时, R3、 R4、 R5、 R6、 R7、 R8、 R9、 R1Q、 Ru、 R12中任一基团可以是氘或氘代的, 也可以是氢或非氘代的。2. 如权利要求 1所述的化合物, 其特征在于, R1和 R2分别独立地选自: 氢, 氘代 的甲基、 或氘代的乙基。3. 如权利要求 1所述的化合物, 其特征在于, 当 R1是氢时, R2选自下组: 一氘甲 基、 二氘甲基、 三氘甲基、 一氘乙基、 二氘乙基、 三氘乙基、 四氘乙基、 和五氘乙基。4. 如权利要求 1所述的化合物, 其特征在于, 当 R1是氢时, R2是三氘甲基。5. 如权利要求 1所述的化合物, 其特征在于, 所述化合物选自下组:6. 如权利要求 1所述的化合物, 其特征在于, 所述化合物选自下组:7.一种药物组合物的制备方法,其特征在于,将权利要求 1-6中任一所述的化合物、 或其晶型、 药学上可接受的盐、 水合物、 或溶剂合物和药学上可接受的载体进行混合, 从而形成药物组合物。8. 一种药物组合物, 其特征在于, 含有 (1)权利要求 1-6中任一所述的化合物、 或其 晶型、 药学上可接受的盐、 水合物或溶剂合物; 和 (2)药学上可接受的载体。9. 如权利要求 8所述药物组合物,其特征在于, 它还含有另外的治疗药物;较佳地, 所述的另外的治疗药物为治疗脱发、 再生发、 暗疮、 青春痘、 或前列腺癌的药物。10. 一种如权利要求 1-6 中任一所述的化合物, 或其晶型、 药学上可接受的盐、 水 合物或溶剂合物的用途, 其特征在于, 用作雄性激素受体拮抗剂, 或用于制备治疗和预 防雄性激素受体活性相关疾病的药物。11. 如权利要求 10所述的用途, 其特征在于, 所述疾病选自下组: 脱发、 再生发、 暗疮、 青春痘、 或前列腺癌。12. 一种治疗方法, 其特征在于, 包括步骤: 给需要治疗的对象, 施用权利要求 1-6 中任一所述的化合物, 或其晶型、 药学上可接受的盐、 水合物或溶剂合物, 或权利要求 8所述的药物组合物。13. 一种如权利要求 1所述的式 (I)化合物的制备方法, 其特征在于, 包括步骤: (1) 于酸性溶剂中, 在氰化物存在下, 将化合物 5a和 R7C(0)R8反应, 从而形成化 合物 6a,Η2Ν6a其中, 所述氰化物为 TMSCN、 氰化纳或氰化钾;(2) 于非质子溶剂溶剂中, 在酸性条件下, 将化合物 2a和化合物 6a反应, 从而形 成式 (I)化合物,上述各式中 R R2、 R3、 R4、 R5、 R6、 R7、 R8、 R9、 R10、 Ru、 R12或 X 的定义 同权利要求 1。14. 如权利要求 13 所述的制备方法, 其特征在于, 所述步骤 ( 之前还包括以下步 骤:(1 - 1) 于惰性溶剂中, 将化合物 3a与 NHR R2反应, 从而形成化合物 4a; 以及NHR,R2 \.-Ί 0關, R2 R5 4a(1 -2) 于惰性溶剂中, 将化合物 4a还原为化合物 5a上述各式中, R R2、 R3、 R4、 R5、 R6 的定义同权利要求 1 ,
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CN107954936B (zh) * | 2016-10-17 | 2021-03-19 | 海创药业股份有限公司 | 一种制备氘代咪唑二酮类化合物的方法 |
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JP2023517393A (ja) * | 2020-03-17 | 2023-04-25 | メッドシャイン ディスカバリー インコーポレイテッド | タンパク質分解調整剤およびその使用方法 |
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