Posts Tagged ‘calcium channel inhibitor’

Mirogabalin for diabetic neuropathy

Larry H. Bernstein, MD, FCAP, Curator







Mirogabalin, A-2000700, DS-5565
1138245-13-2, C12H19NO2, 209.28
[(1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetic acid
2-[(1R,5S,6S)-6-(aminomethyl)-3-ethyl-6-bicyclo[3.2.0]hept-3-enyl]acetic acid
Daiichi Sankyo
Therapeutic Claim
Treatment of fibromyalgia

Phase III clinical trials at Daiichi Sankyo for the treatment of pain associated with fibromyalgia


Analgesic drugs (small molecules)
Mechanism of action
CACNA2D1 protein modulators


Mirogabalin (DS-5565) is a drug developed by Daiichi Sankyo and related to drugs such as gabapentin and pregabalin. Similarly to these drugs, mirogabalin binds to the α2δ calcium channels (1 and 2), but with significantly higher potency than pregabalin. It has shown promising results in Phase II clinical trials for the treatment of diabeticperipheral neuropathic pain,[1][2] and is currently in Phase III trials.

Mirogabalin, a voltage-dependent calcium channel subunit alpha-2/delta-1 ligand, is in phase III clinical trials at Daiichi Sankyo for the treatment of pain associated with fibromyalgia. The company is also conducting phase III clinical studies for the treatment of chronic pain and pain associated with diabetic peripheral neuropathy.


WO 2009041453


JP 2010241796

WO 2012169475

WO 2012169474




In the present invention, compounds having formula (IX) prepared via the process F from Step A (and / or its enantiomer) may be very produced as pure compounds. Compounds of formula (IX) which can be obtained by the present invention typically have a quality below.

The content of the diastereomer represented by the formula (X): 0.1% less than the content of the enantiomers represented by the formula (XI): 1.0% less than the formula (XII) and the double bond represented by the formula (XIII) The total content of regioisomers: less than 0.5% (Note that each content is calculated from the area percentage of the free form of formula (IX) (VII) in the by test High Performance Liquid Chromatography) [formula 23] [of 24]


 Next, the present invention is described by examples in detail, the present invention is, which however shall not be construed as limited thereto.
The internal standard substance in a magnetic resonance spectra (NMR), and using tetramethylsilane and abbreviations indicate the multiplicity, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, and brs = It shows a broad singlet.
In the name of the compound, “R” and “S” indicate the absolute configuration at the asymmetric carbon. Furthermore, “RS” and “SR” indicates that the asymmetric carbon atom is racemic. In addition, “(1RS, and 5SR) -” if such a can shows the relative arrangement of the 1-position and the 5-position, as well shows only one of the diastereomers, its diastereomers are racemic We show that.
In the name of the compound, “E” and “Z” indicates the arrangement of positional isomers in the structure of the compound having a position isomerism.
“EZ” and “ZE” indicates that it is a mixture of regioisomers. Way more notation, is in accordance with the conventions in this area of the normal.

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