4-Substituted piperidine analogs and their use as subtype selective NMDA receptor antagonists

Disclosed are 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs as selective active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, psychosis, anxiety, migraine headaches, glaucoma, CMV retinitis, aminoglycoside antibiotics-induced hearing loss, convulsions, chronic pain, opioid tolerance or withdrawal, urinary incontinence or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. The compounds are generally represented by the formula (I) where Ar and Ar' each are optionally substituted aryl or heteroaryl; z is a single or double bond; X is (CHR)m, O, S or NR (where m is 0, 1 or 2 and R is H, OH or alkyl); R1 is H or OH; each R2 is H, OH or alkyl; n is 0, 1, 2, 3 or 4; Y is O, S, NR4 or a bond; and R5 is H or OH.