Phosphono-hydroisoquinoline compounds useful in reducing...

C - Chemistry – Metallurgy – 07 – F

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167/226, 260/461

C07F 9/18 (2006.01) A61K 31/675 (2006.01) C07F 9/40 (2006.01) C07F 9/60 (2006.01) C07F 9/62 (2006.01)

Patent

CA 2000901

PHOSPHONO-HYDROISOQUINOLINE COMPOUNDS USEFUL IN REDUCING NEUROTOXIC INJURY ABSTRACT A class of phosphono-hydroisoquinoline compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes admini- stration of a phosphono-hydroisoquinoline compound alone or in a composition in an amount effective as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of Formula I: (I) Image wherein each of R1 through R4 is hydrido, wherein each of Z1 and Z2 is hydroxyl, wherein W is a single bond connecting the phosphorus atom with the aromatic ring and wherein the A ring is aromatic. Also disclosed are two classes of intermediate compounds having a fully unsaturated A ring, which intermediate compounds are useful in methods to make product compounds of Formula I.

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