Use of etodolac to treat hyperplasia

Abstract

The present invention provides a therapeutic method to treat non-malignant diseases characterized by the excessive tissue growth, e.g., hyperplastic diseases, comprising administering to a mammal (e.g., human) afflicted with excessive tissue growth, an effective amount of a derivative of an indole compound of formula (I):formula (I): wherein R1 is lower alkyl, (hydroxy)lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, phenyl, benzyl or 2-thienyl; R2, R3, R4 and R5 are the same or different and are each hydrogen or lower alkyl; each R6 is individually hydrogen, lower alkyl, hydroxy, (hydroxy)lower alkyl, lower alkoxy, benzyloxy, lower alkanoyloxy, nitro or halo, R7 is hydrogen, lower alkyl or lower alkenyl, X is oxy and thio, Y is carbonyl, —(CH2)1-3—, —(C1-C3)alkyl(CO)—, or —(CH2)1-3SO2—; Z is hydroxy, lower alkoxy, (C2-C4)acyloxy, —N(R8)(R9), phenylamino, (ω-(4-pyridyl)(C2-C4 alkoxy), (ω-((R8)(R9) amino)(C2-C4 alkoxy), an amino acid ester of (ω-(HO)(C2-C4))alkoxy, —N(R8)CH(R8)CO2H, 1′-D-glucuronyloxy, —SO3H, —PO4H2, —N(NO)(OH), —SO2NH2, —PO(OH)(NH2), —OCH2CH2N(CH3)3+, or tetrazolyl; wherein R8 and R9 are each H, (C1-C3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R8), S or nonperoxide O; n is 0, 1, 2, or 3; wherein R8 and R9 are each H, (C1-C3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R8), S or nonperoxide O; each alkyl or phenyl group of R1, R2, R3, R4,R5, R6, R7 and Z is optionally substituted with 1, 2, or 3 (C1-C4)alkyl groups; or a pharmaceutically acceptable salt thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority of U.S. provisional patent application Ser. No. 60 / 412,193, filed Sep. 19, 2002, which is incorporated by reference herein.GOVERNMENT FUNDING [0002] This invention was made with the assistance of the National Institutes of Health under Grant Nos. AR47360 and GM23200. The U.S. Government has certain rights in this invention.BACKGROUND OF THE INVENTION [0003] Hyperplastic diseases are non-malignant conditions that represent an unmet medical need. Typically, these diseases are characterized by the uncontrolled growth of cells. In many patients these cells are not malignant and the hyperplastic cells do not lead to the development of cancer. Thus, the hyperplastic cells are not treated with the conventional chemotherapeutic agents useful against malignant diseases. [0004] One example of a hyperplastic disease is benign prostatic hypertrophy (BPH). This disease is characterized by the abnormal growth of the p...

AI Technical Summary

Benefits of technology

The use of etodolac or its analog effectively reduces the size of hyperplastic tissues, such as the prostate, and synergistically enhances the effectiveness of chemotherapeutic agents, inhibiting the growth of hyperplastic cells without harming normal cells, as demonstrated in animal models.

Problems solved by technology

Thus, the hyperplastic cells are not treated with the conventional chemotherapeutic agents useful against malignant diseases.

In many patients, hyperplastic diseases do not lead to the development of cancer, and are not treated with the conventional chemotherapeutic agents used against malignant diseases.

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