The Full Wiki

More info on DOV-102,677

DOV-102,677: Wikis


Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

DOV-102,677
Systematic (IUPAC) name
(5R)-5-(3,4-dichlorophenyl)bicyclo[3.1.0]hexane
Identifiers
CAS number  ?
ATC code  ?
PubChem  ?
Chemical data
Formula  ?
Mol. mass  ?
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes  ?

DOV 102,677 is a psychoactive drug being developed by Merck as an antidepressant and is currently in clinical trials.[1] It is a so-called triple (re)uptake inhibitor (TUI), or serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).[1] Instead of being developed for depression, DOV-102,677 is being developed for the treatment of alcoholism.

IC50 values for the SERT, NET and DAT are 129 nM, 103 nM, and 133 nM.[1]

DOV.gif
Com Uptake Binding
5-HT NE DA SERT NET DAT
216303 14 20 78 190 380 190
21947 12 23 96 100 260 210
102677 130 100 130 740 1000 220

The discrepancy between binding to the NET and the IC50 for [3H]NE is remarkable.

"DOV 102,677 (20 mg/kg IP) increased extracellular levels of DA and 5-HT in the prefrontal cortex to 320 and 280% above baseline 100 min after administration. DA levels were stably increased for the duration (240 min) of the study, but serotonin levels declined to baseline by 200 min after administration. NE levels increased linearly to a maximum of 348% at 240 min post-dosing."[1]

Chemistry

DOV scientists and their collaborators have developed an efficient, asymmetric synthesis of 102,677.[2] This economical and robust new route uses phenylacetonitrile and (R)-epichlorohydrin as starting materials to synthesize 102,677 in 3 steps:

  1. Phenylacetonitrile is reacted with (R)-epichlorohydrin in the presence of base to give the cyclopropyl compounds.
  2. The nitrile group is then hydrogenated into the amino alcohol compounds. These are cyclized with SOCl2 under acidic conditions and subsequently neutralized with base.

References

  1. ^ a b c d PMID 16636898 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  2. ^ Skolnick P, Basile A, Chen Z (2006) WO patent 2006096810







Got something to say? Make a comment.
Your name
Your email address
Message