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Use of estrogen receptor-beta selective agonists for radiation-or chemotherapy-induced mucositis and radiation cystitis

A selective, mucositis technology that can be applied to medical preparations containing active ingredients, digestive system, organic active ingredients, etc., and can solve problems such as large differences in effects

Inactive Publication Date: 2008-02-06
WYETH LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The effects of these treatments vary widely

Method used

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  • Use of estrogen receptor-beta selective agonists for radiation-or chemotherapy-induced mucositis and radiation cystitis
  • Use of estrogen receptor-beta selective agonists for radiation-or chemotherapy-induced mucositis and radiation cystitis
  • Use of estrogen receptor-beta selective agonists for radiation-or chemotherapy-induced mucositis and radiation cystitis

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0076] The preparation of compounds of Formulas III, IV and V is described in US Published Application 2003 / 0181519, US Patent No. 6,914,074, and PCT US 02 / 39883 filed December 2, 2002, each of which is incorporated herein in its entirety Reference.

[0077] In some further embodiments of the above methods, the ERβ selective ligand has formula VII:

[0078]

[0079] in:

[0080] A and A' are each independently OH or OP;

[0081] P is alkyl, alkenyl, benzyl, acyl, aroyl, alkoxycarbonyl, sulfonyl or phosphoryl;

[0082] R 1 and R 2 Each independently is H, halogen, C 1 -C 6 Alkyl, C 2 -C 7 Alkenyl, or C 1 -C 6 alkoxy;

[0083] R 3 is H, halogen, or C 1 -C 6 alkyl;

[0084] R 4 is H, halogen, C 1 -C 6 Alkyl, C 2 -C 7 Alkenyl, C 2 -C 7 Alkynyl, C 3 -C 7 Cycloalkyl, C 1 -C 6 Alkoxy, -CN, -CHO, acyl, or heteroaryl;

[0085] R 5 and R 6 Each independently is H, halogen, C 1 -C 6 Alkyl, C 2 -C 7 Alkenyl, C 2 -C 7 Alkynyl, C 3 -C 7 Cycloalkyl, C ...

Embodiment 1

[0166] Example 1: Evaluation of Erβ and Erα affinity

[0167] The ability of compounds to compete with 17[beta]-estradiol can be assessed using Er[beta] and Er[alpha]. This assay provides a means for determining the relative affinity to ER[beta] or ER[alpha]. The method used was as described in Harris HA et al., Steroids 2002;67(5):379-384.

Embodiment 2

[0168] Example 2: Evaluation of uterotropism

[0169] Uterotropic effects of test compounds can be determined according to standard pharmacological assays as disclosed in Harris HA et al., Endocrinology 2002;143(11):4172-4177. For the sake of brevity, the standard pharmacological assay disclosed by Harris et al. will be referred to as the "uterotropic assay".

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PUM

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Abstract

The present invention provides a method of treating or inhibiting mucositis or radiation cystitis using an ERss selective ligand. The present invention also provides compositions, including pharmaceutical compositions, containing the ERss selective ligand and a traditional medicament for mucositis or radiation cystitis.

Description

technical field [0001] The present invention relates in part to a method of treating mucositis and radiation cystitis or symptoms thereof caused by radiation or cytotoxic agents comprising administering to the patient an effective amount of an ER[beta] selective ligand. In some embodiments, the ERβ selective ligand is administered topically. In some further embodiments, the ERβ selective ligand is auterotropic, amammotrophic, or auterotrophic and amammatropic. The present invention further relates to a kit for treating mucositis and radiation cystitis caused by radiation or cytotoxic agents or their symptoms and the like. Background technique [0002] The use of X-rays and / or chemotherapy for diagnostic and therapeutic purposes is common in medicine today. While this can be used for beneficial medical purposes, X-rays and cytotoxic agents such as chemotherapy are also harmful to the patients the X-rays and chemotherapy are intended for, the medical staff who must administe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/415A61K31/277A61K31/47A61K31/353A61P17/16A61P13/10
CPCA61K31/353A61K31/47A61K31/423A61K31/428A61K31/4184A61K31/277A61K31/56A61K31/415A61P1/00A61P1/02A61P1/04A61P13/02A61P13/10A61P17/16A61P43/00A61P7/10
Inventor W·雅各布森H·A·哈里斯
Owner WYETH LLC
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