| Stereochemistry | ABSOLUTE |
| Molecular Formula | C11H11Cl2N |
| Molecular Weight | 228.118 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12C[C@@]1(CNC2)C3=CC(Cl)=C(Cl)C=C3
InChI
InChIKey=BSMNRYCSBFHEMQ-GZMMTYOYSA-N
InChI=1S/C11H11Cl2N/c12-9-2-1-7(3-10(9)13)11-4-8(11)5-14-6-11/h1-3,8,14H,4-6H2/t8-,11+/m0/s1
| Molecular Formula | C11H11Cl2N |
| Molecular Weight | 228.118 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DOV-102,677 is a “Triple” Monoamine Neurotransmitter Uptake Inhibitor being developed by Merck for treating the major depressive disorder. In preclinical studies, DOV 102,677 increased extracellular levels of DA and 5-HT in the prefrontal cortex at 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 240 min post-dosing. Consistent with these increases in NE levels, the density of β-adrenoceptors was selectively decreased in the cortex of rats treated with DOV 102,677. DOV 102,677 dose-dependently reduced the amount of time spent immobile by rats in the forced swim test, a model predictive of antidepressant activity, with a minimum effective dose (MED) of 20 mg/kg and a maximal efficacy comparable to imipramine. However, phase I clinical trials for treatment Depression in the USA was discontinued. Instead of being developed for depression, DOV-102,677 is being developed for the treatment of alcoholism.
CNS Activity
Originator
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
HEK-hDAT and HEK-hSERT cells were incubated in modified Eagle’s medium supplemented with 5% fetal bovine serum, 5% calf bovine serum, 0.05 U penicillin/streptomycin and puromycin (2 μg/mL). HEK-hNET cells were incubated in Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum, 0.05 U penicillin/streptomycin and geneticin (300 μg/mL). Cells were grown until confluent on 150 mm diameter tissue culture dishes in a humidified 10% CO2 environment at 37◦C. [125I]RTI-55 (Perkin Elmer Life Sciences, Boston, MA) was used in competition binding assays characterizing DOV 102,677 affinity for the three monoamine neurotransmitter transporters. Aliquots (50 μL) of the suspended cells were added to assay tubes containing drugs and Krebs-HEPES assay buffer in a final assay volume of 0.5 mL. Uptake inhibition studies were conducted using triplicate determinations for each test substance. [3H]DA, [3H]5-HT, or [3H]NE (Perkin Elmer Life Sciences, Boston, MA, 56, 26.9, 60 Ci/mmol, respectively, 20 nM final concentration) was added after a 10 min pre-incubation of the isolated cells in a 25◦C water bath, and the assay incubated an additional 10 min. The reaction was terminated by vacuum filtration over Whatman GF/C filters using a 96-well Tomtec cell harvester (Hamden, CT). Specific uptake was defined as the difference in uptake observed in the absence and presence of 5 μM mazindol (hDAT and hNET) or 5 μM imipramine (hSERT).
