CN1273121C - 阻断雄激素受体的化合物 - Google Patents

阻断雄激素受体的化合物 Download PDF

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CN1273121C
CN1273121C CNB038020432A CN03802043A CN1273121C CN 1273121 C CN1273121 C CN 1273121C CN B038020432 A CNB038020432 A CN B038020432A CN 03802043 A CN03802043 A CN 03802043A CN 1273121 C CN1273121 C CN 1273121C
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J·P·马马纳
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Abstract

本发明描述用于阻断非必需雄激素受体的化合物。特别是，含有烷基的环己烯酮化合物可通过阻断非必需雄激素受体来治疗雄激素介导的疾病，例如痤疮、雄性斑秃、瘢痕疙瘩、皮肤起皱、以及骨关节炎。该环己烯酮化合物可经口、局部或体内给药。

Description

阻断雄激素受体的化合物
技术领域
本发明涉及用于通过阻断患者体内非必需的雄激素受体来治疗雄激素介导的疾病的化合物。
发明背景
我们都知道雄激素在引起例如痤疮和雄性斑秃等众多疾病方面起重要作用。其他与雄激素相关的疾病包括瘢痕疙瘩、粘连、弹性蛋白生成、起皱、以及骨关节炎。
用于治疗由雄激素介导或与雄激素有关的疾病的方法包括阻断相关的雄激素受体。雄激素受体有不同的类型而且它们可大体上分成两个基本的类型，必需的雄激素受体以及非必需的雄激素受体。通常，把有效阻断雄激素受体的化合物称作抗雄激素化合物或者雄激素阻断剂。
阻断非必需受体的化合物特别重要，因为这些化合物在治疗由雄激素介导的疾病中往往是有效的而不会产生抗雄激素样的反应，例如影响性能力或***。
发明概述
本发明涉及可被用于阻断患者体内雄激素受体的环己烯酮化合物。该化合物室温下稳定而且可以在用于局部应用、口服、或体内给药的各种组合物内使用。
发明详述
一些用于阻断雄激素受***点的化合物含有单环以及二环烷酮环，该烷酮环带有烷基部分侧链。这些化合物中的某些化合物，其烷基部分和环被碳-碳双键分开。通常，这些化合物制备困难而且在室温以及光照时不稳定。这些性质使其无法应用于商业化的组合物以及治疗方法。
与此不同，本发明的化合物在环境条件下是稳定的，可在室温下储藏，而且光照下是稳定的。本发明的化合物通常被称作是环己烯酮化合物。特别重要的化合物是3-(5-甲氧基庚基)-2-环己烯酮和3-(5-乙氧基庚基)-2-环己烯酮。这些化合物包含带有一个烷基部分的环己烯酮基团，其通常如结构1所示。
结构1.
环己烯酮基上的烷基部分有一个由OR表示的烷氧基部分，其中R是烷基。在-优选的方案中，R是甲基或乙基。
本说明书中的化学术语以及命名所提到和包含的化合物均在有机化学标准应用的术语和命名定义的范围之内。本发明的化合物可有一个或多个手性中心而且可以对映异构体和非对映异构体形式存在。本发明的范围包括这类化合物的所有形式。
本发明的化合物可以用已知方法按照本领域技术人员已知的一般有机化学合成步骤和途径进行制备。通常烷基可单独制备，然后如下面的反应方案1所示与环状试剂化合并制备出环己烯酮化合物。该化合物也可从营养制品原料如维生素H以及β-胡萝卜素进行制备。
反应方案1
本发明的化合物具有所希望的抗雄激素活性，因为该化合物可通过阻断雄激素受体来有效地治疗雄激素介导的疾病。这些疾病包括，但不限于，寻常痤疮、雄性脱发或者雄性斑秃、骨关节炎、抑制植入***的外来物体周围的乳腺囊的生成、瘢痕疙瘩、粘连、以及皮肤起皱。另外，通过主要作用于非必需的雄激素受体，本发明的化合物大体上是选择性的。
本发明的环己烯酮化合物较长时期置于室温以及光照下是稳定的。这种稳定性使其可以较好地在组合物中使用以通过阻断雄激素受体治疗由雄激素介导的疾病。
可施用本发明的化合物以阻断非必需雄激素受体。通常，对于哺乳动物中任何由雄激素或雄激素受体介导的疾病或症状的治疗可通过给予治疗有效剂量的一种或多种本发明的环己烯酮化合物来完成。治疗有效量是足以阻断患者体内雄激素受体以使病情得以减轻所需的化合物的量，患者可以是动物或人类。化合物的量视疾病的类型、病情轻重、以及本领域专业人士已知的与患者有关的情况而定。环己烯酮化合物可口服、局部、或体内给药。对大多数患者来说口服剂量范围为约0.0001mg至约30mg，该剂量范围对于阻断雄激素受体以减轻正在治疗的疾病是有效的。优选地，口服剂量范围为约0.01至约5mg。当用于口服时，该环己烯酮化合物可制备成片剂、胶囊、混悬剂、溶液、或其他适合于口服的形式。
在一个优选的实施方案中，含有本发明的环己烯酮化合物的局部用组合物在患者身上的预定区域局部使用。局部用组合物可以软膏、霜、香波、与化合物混合的溶液成分等形式使用。环己烯酮化合物当作为局部用组合物的一部分时，其优选的浓度按重量计为局部用组合物重量的约0.001％至约10％，更优选约0.05％至约5％。
该局部用组合物可包括各种添加剂。实际上可使用任何添加剂，只要该添加剂不在化学上改变化合物或者妨碍该化合物阻断雄激素受体。一些添加剂包括，但不限于，填充剂、防晒剂、润湿剂、以及色料成分。
本发明的化合物可通过注射剂体内或静脉内给药。当体内或静脉内给药时，环己烯酮化合物应当溶于或混悬于适合于注射或静脉给药的溶液中。这类溶液包括，但不限于生理盐水溶液、乳酸林格溶液、水、以及其他类似的溶液。
另外，其他有助于治疗该疾病的化合物均可与本发明的化合物联合应用。例如，用于治疗痤疮的局部用组合物可包括本发明的化合物以及与其合用的过氧化苯甲酰、维A酸、维生素E润肤剂、或者这些成分的混合物。这样，就可以使用能控制与疾病相关的其他变量的组分治疗疾病。
虽然本发明已按照其优选的实施方案作了描述，但是本领域的专业技术人员会认识到，在所附权利要求的精神和范围之内，实施本发明时可以进行改动。

Claims (10)

1.具有下式的化合物：
Figure C038020430002C1
其中R选自氢和烷基。
2.如权利要求1的化合物，其中R是CH3。
3.含有3-(5-甲氧基庚基)-2-环己烯酮的组合物在制备阻断哺乳动物体内雄激素受***点的药物中的用途。
4.如权利要求3的用途，其中组合物适合于局部给药而且是局部给药。
5.如权利要求3的用途，其中组合物是口服给药。
6.如权利要求3的用途，其中组合物是体内给药。
7.如权利要求3的用途，其中组合物是施用给患有痤疮的哺乳动物。
8.如权利要求3的用途，其中组合物是施用给患有瘢痕疙瘩的哺乳动物。
9.如权利要求3的用途，其中组合物是施用给患有雄性斑秃的哺乳动物。
10.用于哺乳动物给药的含有3-(5-甲氧基庚基)-2-环己烯酮的局部用或口服组合物。
CNB038020432A 2002-01-09 2003-01-09 阻断雄激素受体的化合物 Expired - Fee Related CN1273121C (zh)

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US20060263452A1 (en) * 2005-05-17 2006-11-23 Alwyn Dowell Topical composition containing essential oils
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