o-Phosphono(alkyl)-N-sulfonyl-phenyl-alanine derivatives useful

Details o-Phosphono(alkyl)-N-sulfonyl-phenyl-alanine derivatives useful o-Phosphono(alkyl)-N-sulfonyl-phenyl-alanine derivatives useful

1990-12-31

1993-01-05

Lee, Mary C.

Organic compounds -- part of the class 532-570 series

Organic compounds

Phosphorus esters

558191, 562 9, 562 10, 562 11, 546 23, C07F 940, C07F 938

Patent

active

051772400

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 administration 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: ##STR1## wherein each of R.sup.1 through R.sup.4 is hydrido, wherein each of Z.sup.1 and Z.sup.2 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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patent: 4918064 (1990-04-01), Cordi
Greene, T. W. Protective Groups in Organic Synthesis; John Wiley and Sons: New York, 1981; pp. 284-287.
S. M. Rothman et al, Annals of Neurology, vol. 19, No. 2, 105-111 (1986).
M. N. Perkins et al, Neuroscience Lett., 23, 333-336 (1981).
J. Davies et al, Neuroscience Lett., 21, 77-81 (1981).
K. Matoba et al, Chem. Pharm. Bull., 32 (10)3918-3925 (1984).
J. W. Olney et al, Neuroscience Letters, 68, 29-34 (1986).

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