CN1268887A - 治疗银屑病的新化合物 - Google Patents

治疗银屑病的新化合物 Download PDF

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CN1268887A
CN1268887A CN98808689A CN98808689A CN1268887A CN 1268887 A CN1268887 A CN 1268887A CN 98808689 A CN98808689 A CN 98808689A CN 98808689 A CN98808689 A CN 98808689A CN 1268887 A CN1268887 A CN 1268887A
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endipalene
psoriasis
lonapalene
treatment
application
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乔治·恩德里奇
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics

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Abstract

5－脂肪氧化酶的抑制与足以有效治疗银屑病的抗炎和免疫调节活性的关联在文献中已有报导。具体来说,使用氯萘帕林(6－氯－2,3－二甲氧基萘二酚二乙酸)似乎可以获得良好的结果。但是,氯萘帕林的临床应用并不成功,这很大程度上是因为多种副作用。有鉴于此,经过大量研究之后,我们鉴定到了一种分子,该分子似乎可以保证显著的疗效而没有副作用,我们已经将其以endipalene的名称要求专利保护。

Description

治疗银屑病的新化合物
技术领域
本发明涉及具有两个芳香稠环(萘环)的分子，其特征在于通过对花生四烯酸“下调”中一个或多个步骤的抑制作用而具有良好的抗炎活性。
背景技术
自九十年代以来，在医学文献中有大量关于专利化合物氯萘帕林(见图1)的研究报导，该分子具有强大的抗皮肤炎症的作用。氯萘帕林(6-氯-2，3-二甲氧基萘二酚二乙酸)降低类似于或等同于化学引诱物花生四烯酸5-脂肪氧化酶产物白三烯B4的物质的水平在统计学上是显著的(Black A.K.，LAMP RD.，Malled AT.，Cunningham FM.，Hofbauer M.，Greaves MW.；5-脂肪氧化酶抑制物氯萘帕林-RS43-179在银屑病中的药学和临床效果；Journal of Investigative Dermatology 95(1)：50-4，1990Jul)。已经报导了多种5-脂肪氧化酶抑制物。其中大多数似乎是部分氧化的亲脂性还原剂，包括酚。
芳族化合物与含有杂原子-杂原子键的化合物相同。其中的多种化合物不是选择性5-脂肪氧化酶抑制物。
一般来说，这些化合物中许多种的体内全身活性不佳，可能是因为其亲脂性和代谢不稳定性(酚化合物的氧化和共轭)引起的生物相容性不良。但是，多种药剂在局部使用时显示有望治疗皮肤炎症，其中效果最好的是氯萘帕林(Batt DG.，5-脂肪氧化酶抑制物及其抗炎活性，Progress in Medicinal Chemistry，29：1-63，1992)。
然而，氯萘帕林的临床使用并不成功，这可能是由于其副作用明显。人们已经尝试寻找类似于氯萘帕林的其他局部使用的非甾族抗银屑病化合物，但未能成功(Venuti MC.，Loe BE.，Jones GH.，Young Gm.，局部使用的非甾族抗银屑病药剂氯萘帕林类似物2.2，3-亚烷基二氧萘，Journal ofMedicinal Chemistry，31(11)：2132-6，1988 Nov.)(Jone GH.，Venuti MC.，Young JM.，Murthy DV.，Loe BE.，Simpson RA.，Berks AH.，Spires DA.，Malonej PJ.，Kruseman M.，et al.，局部使用的非甾族抗银屑病药剂.1.1，2，3，4，-四氧化萘衍生物，J.Med.Chem.，29(8)1504-11，1986 Aug.)。
发明内容
考虑到以上所述，发明人的注意力转移到寻找同氯萘帕林一样有效但没有副作用的分子上。初步筛选后，发明人选择了没有卤素的分子，寻找到的分子为2，6或2，7-二甲氧基萘，在申请专利时命名为ENDIPALENE。
Endipalene似乎具有与氯萘帕林同样的作用，但没有明显的副作用。
附图简述
附图显示氯萘帕林(图1)和endipalene(图2)的结构式。
实施本发明的最佳方式
发明人认为，endipalene应当以1％到2％的浓度局部使用。我们需要进一步的研究，以证实选择性作用机制(5-脂肪氧化酶抑制物)，检查皮肤吸附，药物动力学和代谢。我们也应当证实不存在副作用，确证其长期疗效。
工业实用性
考虑到银屑病在北欧人和美国人的发病率为2％，且91％的患者其近亲和远亲也患有此病，如果研究证实了疗效，在本领域成功的可能性是显而易见的。

Claims (2)

  1. 在银屑病和炎症皮肤疾病的治疗中endipalene是全新的。在各种病毒性和推测的病毒性皮肤病中，所谓的萘类化合物，包括单环和双环氧基和氧代化合物进行临床试验。类似物或衍生物(氯萘帕林)在银屑病生物测定筛选中已进行了试验。Endipalene在本领域中是全新的。
    本申请的权利要求为：
    1.Endipalene以任何浓度在任何溶剂中局部或以其他方式应用，用以治疗炎症性皮肤病，特别是银屑病。
  2. 2.Endipalene以任何浓度在任何溶剂中局部或以其他方式应用，用以治疗不同于上述权利要求1中所述的疾病。
CN98808689A 1997-08-29 1998-08-27 治疗银屑病的新化合物 Pending CN1268887A (zh)

Applications Claiming Priority (2)

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IT1997TN000008A IT1304595B1 (it) 1997-08-29 1997-08-29 Inibitore della 5-lipoossigenasi
ITTN97A000008 1997-08-29

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CN1268887A true CN1268887A (zh) 2000-10-04

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US (1) US6291534B1 (zh)
EP (1) EP1011649B1 (zh)
JP (1) JP2001514214A (zh)
CN (1) CN1268887A (zh)
AT (1) ATE209033T1 (zh)
AU (1) AU9183698A (zh)
BR (1) BR9811402A (zh)
CA (1) CA2302241A1 (zh)
DE (1) DE69803303T2 (zh)
DK (1) DK1011649T3 (zh)
ES (1) ES2165701T3 (zh)
HK (1) HK1029058A1 (zh)
IT (1) IT1304595B1 (zh)
PT (1) PT1011649E (zh)
WO (1) WO1999011249A2 (zh)

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* Cited by examiner, † Cited by third party
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WO1993010154A1 (en) * 1991-11-12 1993-05-27 Protein Polymer Technologies, Inc. High molecular weight collagen-like protein polymers
ES2391326T3 (es) * 2008-05-23 2012-11-23 Novaera S.R.L. Formulaciones de endipaleno en el tratamiento de la psoriasis
NZ720946A (en) 2009-04-29 2017-09-29 Amarin Pharmaceuticals Ie Ltd Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same

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FR2732964B1 (fr) * 1995-04-14 1997-05-16 Adir Nouveaux amides tricycliques, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
US6156790A (en) * 1997-12-30 2000-12-05 Hauser, Inc. C-10 carbon-substituted artemisinin-like trioxane compounds having antimalarial, antiproliferative and antitumor activities
US6160004A (en) * 1997-12-30 2000-12-12 Hauser, Inc. C-10 carbon-substituted artemisinin-like trioxane compounds having antimalarial, antiproliferative and antitumor activities

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ITTN970008A1 (it) 1999-03-01
HK1029058A1 (en) 2001-03-23
IT1304595B1 (it) 2001-03-19
WO1999011249A3 (en) 1999-09-16
EP1011649A2 (en) 2000-06-28
JP2001514214A (ja) 2001-09-11
ATE209033T1 (de) 2001-12-15
US6291534B1 (en) 2001-09-18
DE69803303T2 (de) 2002-05-02
PT1011649E (pt) 2002-05-31
CA2302241A1 (en) 1999-03-11
ES2165701T3 (es) 2002-03-16
DK1011649T3 (da) 2002-05-21
WO1999011249A2 (en) 1999-03-11
EP1011649B1 (en) 2001-11-21
AU9183698A (en) 1999-03-22
DE69803303D1 (de) 2002-02-21
BR9811402A (pt) 2000-08-29

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