Alkoxy-substituted compounds, methods, and compositions for inhibiting PARP activity

US6197785A · kind A · utility

Assignee

• Guilford Pharmaceuticals, Inc. · US

Inventors

• Paul F. Jackson · Bel Air, US
• Keith M. Maclin · Baltimore, US
• Jie Zhang · Beijing, CN

Key dates

• Filing date: Sep 1, 1998
• Grant date: Mar 6, 2001
• Expiry date: Sep 1, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F9/6561
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A compound, compositions, methods of use, and processes of making formula I: ##STR1## or a pharmaceutically acceptable salt, hydrate, ester, solvate, prodrug, metabolite, stereoisomer, or mixtures thereof, wherein: PA1 R.sup.1, when present, is hydrogen or lower alkyl; PA1 R.sup.2 is lower alkyl, aryl, aralkyl, lower alkanoyl, or --(CH.sub.2).sub.n --(CHOH).sub.y (CH.sub.2).sub.m A, wherein n is 1-4, y is 0 or 1, m is 0-5, and A is cycloalkyl, cycloalkenyl, lower alkanoyl, aryl, aralkyl, --NH.sub.2, --NH--(lower alkyl), ##STR2## PA1 Y represents the atoms necessary to form a fused 5- to 6-membered ring that is aromatic or nonaromatic and carbocyclic or heterocyclic; PA1 Z is (i) --CHR.sup.2 CHR.sup.3 -- where R.sup.2 and R.sup.3 are independently hydrogen, alkyl, aryl or aralkyl; PA2 (ii) --R.sup.6 C.dbd.CR.sup.3 -- where R.sup.6 and R.sup.3 are independently hydrogen, lower alkyl, aryl, aralkyl, chlorine, bromine or --NR.sup.7 R.sup.8, where R.sup.7 and R.sup.8 are independently hydrogen or lower alkyl, or, R.sup.6 and R.sup.3, taken together, form a fused 5- to 6-membered ring that is aromatic or nonaromatic and carbocyclic or heterocyclic; PA2 (iii) --R.sup.2 C.dbd.N--; PA2 (iv)…