Neuroprotective 2-pyridinamine compositions and related methods for reducing ischemic death of cells or neuronal cell death

摘要

Neuroprotective pharmaceutical compositions comprising 2-pyridinaminesor their salts of formula (I) and methods of using these compositions to prevent ischemic cell death, particularly neuronal cell death, and reduce the likelihood of neuronal cell death in a subject due to a traumatic event are disclosed, wherein: (a) R1 is H or a substituent bound at either the 5 or 6 ring position and selected from the group consisting of alkyl, alkenyl, alkynyl, thienyl, furanyl, pyrrolyl, phenyl, pyrimidinyl, substituted pyrimidinyl, pyridinyl, substituted pyridinyl, phenyl alkenyl, substituted phenyl alkenyl, benzo[b] thien-2-yl, 2-benzofuranyl and substituted phenyl, said substituted phenyl having the formula as described in the specification; wherein (i) R6 is selected from the group consisting of H, OH, halogen, alkylamino, dialkylamino, hydroxy-substituted dialkyl amino, lower alkyl, acidic lower alkyl, alkoxy, halogen-substituted lower alkoxy, phenyl and morpholinyl, and (ii) R7 represents between one and four substituents which may be the same or different and are selected from the group consisting of H, halogen, amino, alkyl, lower alkyl, halogen substituted lower alkyl, alkylamino, dialkylamino, acidic lower alkoxy, alkoxy, halogen-substituted lower alkoxy, alkoxy and phenylalkoxy, with the proviso that R6 and R7 may be fused to form 2-naphthyl or 1,3, benzodioxolyl; (b) Each R2 is independently H or lower alkyl ; (c) Each R3 is independently selected from the group consisting of H, lower alkyl, amino, alkylamino, dialkylamino and lower alkoxy; (d) R4 is H, alkoxy or morpholinyl, with the proviso that R4 may be fused with R3 to form 2,3-dihydro-1,4-benzodioxinyl or 9-alkyl 9H carbazolyl; and (e) R5 is H or lower alkyl. Also disclosed is an apparatus such as a pre filled syringe for administering to a subject the instant pharmaceutical compositions.