178375-00-3

Upstream product

• 178374-99-7 6-fluoro-7-benzyloxychroman-4-one 
• 178374-98-6 6-fluoro-7-hydroxy-2,3-dihydro-4H-chromen-4-one 
• 151-10-0 1,3-Dimethoxybenzene 
• 7789-45-9 copper(II)bromide 
• 103068-41-3 4-fluororesorcinol 
• 17715-70-7 1,3-dimethoxy-4-fluorobenzene 

Downstream Products

• 178375-65-0 7-benzyloxy-6-fluoro-3-(4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl)-chromen-4-one 

Relevant academic research and scientific papers

COMBINATIONS FOR THE TREATMENT OF PARKINSONISM CONTAINING SELECTIVE NMDA ANTAGONISTS

This invention relates to a method of treating Parkinson's Disease whereby a mammal suffering from Parkinson's Disease is treated with a combination of a forebrain selective NMDA antagonist and a compound which is capable of increasing the excitatory feedback from the ventral lateral nucleus of the thalamus into the cortex. This invention also relates to pharmaceutical compositions containing the synergistic combination.

Neuroprotective 3-(piperidinyl-1)-chroman-4,7-diol and 1-(4-hydroxyphenyl)-2-(piperidinyl-1)-alkanol derivatives

PCT No. PCT/IB95/00380 Sec. 371 Date Feb. 13, 1996 Sec. 102(e) Date Feb. 13, 1996 PCT Filed May 18, 1995 PCT Pub. No. WO96/06081 PCT Pub. Date Feb. 29, 1996This invention relates to compounds of formula (I), or pharmaceutically acceptable acid addition salts thereof, wherein: (a) R2 and R5 are taken separately and R1, R2, R3 and R4 are each independently hydrogen, (C1-C6) alkyl, halo, CF3, OH or OR7 and R5 is methyl or ethyl; or (b) R2 and R5 are taken together, forming a chroman-4-ol ring, and R1, R3 and R4 are each independently hydrogen, (C1-C6) alkyl, halo, CF3, OH or OR7; and R6 is a substituted piperidinyl, pyrrolidinyl or 8-azabicyclo(3.2.1)octanyl derivative; provided that (a) when R2 and R5 are taken separately, at least one of R1, R2, R3 and R4 is not hydrogen; and (b) when R2 and R5 are taken together, at least one of R1, R3 and R4 is not hydrogen; pharmaceutical compositions thereof; and methods of treating mammals suffering from stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised with a compound of formula (I) hereinabove or a pharmaceutically acceptable salt thereof.

(3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol: A conformationally restricted analogue of the NRr2B subtype-selective NMDA antagonist (1S,2S)-1-(4-hydroxyphenyl)-2(4-hydroxy-4-phenylpiperidino)-1- propanol

(1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606, 1)is a recently described antagonist of N-methyl-D-aspartate (NUDA) receptors containing the NR2B subunit. In the present study, the optimal orientation of compounds of this structural type for their receptor was explored. Tethering of the pendent methyl group of 1 to the phenolic aromatic ring via an oxygen atom prevents rotation about the central portion of the molecule. Several of the new chromanol compounds have high affinity for the racemic [3H]CP-101,606 binding site on the NUDA receptor and protect against glutamate toxicity in cultured hippocampal neurons. The new ring caused a change in the stereochemical preference of the receptor - cis (erythro) compounds had better affinity for the receptor than the trans isomers. Computational studies suggest that steric interactions between the pendent methyl group and the phenol ring in the acyclic series determine which structures can best fit the receptor. The chromanol analogue, (3R,4S)- 3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol (12a, CP- 283,097), was found to possess potency and selectivity comparable to CP- 101,606. Thus 12a is a new tool to explore the function of the NR2B- containing NUDA receptors.