USE OF ETODOLAC TO TREAT HYPERPLASIA

摘要

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, (omega-(4-pyridyl)(C₂-C₄ alkoxy), (omega-((R⁸)(R⁹) amino)(C₂-C₄ alkoxy), an amino acid ester of (omega-(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.