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Development of Novel Building Blocks
to Accelerate Drug Discovery
(Enamine Ltd, Kyiv, Ukraine)
Dr. Pavel Mykhailiuk
Kyiv
www.enamine.net
World's largestproducer of building blocks
Founded in 1991
www.enamine.net
100.000 building blocksin stock
It will take 300 years to test the whole collection,
when using 1 building block a day.
Founded in 1991
www.enamine.net
> 95% of all medicinal projects fail
activity,selectivity,solubility,toxicity
Chemical problems
P. Morgan et al. Drug Discov. Today 2012, 419,I. Kola et al. Nature Rev. Drug Discov. 2004, 711
Industrial challenge:
www.enamine.net
Why we still have chemical problems
in medicinal chemistry?
www.enamine.net
Becausewe have low diversity of
building blocks
www.enamine.net
1. Fluorinated amines
2010-2014
www.enamine.net
used in 50 patents unknown compounds
2010
www.enamine.net
shape
2010-2014
Tetrahedron 2011, 803.Synthesis 2012, 2739.
Synthesis 2011, 119.EurJOC 2011, 1782.
Synthesis 2012, 1152.Synthesis 2013, 225.
EurJOC 2013, 3086.EurJOC 2014, 3592.
Library of >100 fluorinated amines
www.enamine.net
shape
↑ metabolic stability
~ shape ↓ basicity2010-2014
(↓ toxicity)~ lipophilicity
Tetrahedron 2011, 803.Synthesis 2012, 2739.
Synthesis 2011, 119.EurJOC 2011, 1782.
Synthesis 2012, 1152.Synthesis 2013, 225.
EurJOC 2013, 3086.EurJOC 2014, 3592.
www.enamine.net
www.enamine.net
Poster (synthesis) Catalogue
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2. Analogues of morpholine
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ligand ligand
receptor receptor
Morpholine Morpholine analogue2010
unknown20 FDA-approved drugs
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Bicyclic morpholine analogues
fused spiro bridged
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O
NH
NH
ONH
O NH
O
NH
O
NH
O
NH
O
NH
O
NH
O
NH
O
O
NH
NH
O
NH
O
NH
O
NH
O
H HH
H
H
H
H
H
NH
O
NH
O
H HNH
O
H H
NH
OH H N
H
O
O
H H
H
H
H H
H
H
NH
OH
H
Library of >100 morpholine analogues2010 2014
↑ metabolic stability
~ shape
~ basicity
~ lipophilicity
www.enamine.net
2014
www.enamine.net
Poster (synthesis) Catalogue
www.enamine.net
3. Advanced piperidine linkers
www.enamine.net
1,4-Disubstituted piperidine drugs
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Piperidine
Piperidine analogue
Conformational analysis
Org Lett 2010, 4372.
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Advanced building blocksCommon building block2010 2014
JOC 2014, in press.Synthesis 2010, 493.
Org Lett 2010, 4372.Tetr Lett 2010, 1790.
www.enamine.net
Poster (synthesis)
www.enamine.net
50 papers
www.enamine.netP. Morgan et al. Drug Discov. Today 2012, 419,I. Kola et al. Nature Rev. Drug Discov. 2004, 711
> 95% of all medicinal projects fail
Industrial challenge:
www.enamine.net
becausewe have low diversity of
building blocks..
www.enamine.net
if your medicinal projectis really important
to you
www.enamine.net
then you really need diverse advancedbuilding blocks
www.enamine.net
2010
2014
www.enamine.net
500 chemists
Matvienko V.
Mituk A.
Mikhalchuk V.
Nikitin K.
Gryshuk S.
Iminov R.
Komarov I.
Klukovsky D.
Karpus V.
Kondratov V.
Kubyshkin V.
Levchenko K.
Logvinenko V.
Martirosov R.
Ostapchuk E.
Plaskon A.
Parhomenko L.
Pervak I.
Pustovit U.
Radchenko D.
Savich V.
Scherbatiuk A.
Shyshlik O.
Slobodianuk E.
Tarasenko K.
Tkachenko A.
Tkachuk G.
Tolmacheva N.
Tolmachev A.
Trofimchuk S.
Tymzunik A.
Tverdochlebov A.
Volochnyuk D.
Yakovenko N.
Yarmolchuk V.
Yarmoluk D.
Zherz S. and others
Alekseenko A.
Artamonov O.
Artemenko A.
Andrushko O.
Arkhipov V.
Bezdudny A.
Bilenko V.
Chekotilo O.
Chalyk B.
Datcenko O.
Denisenko O.
Druzhenko T.
Granat D.
Gorulia O.
Garbuz P.
Gavrilenko K.
Grygorenko O.
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Contact us forspecific structures
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Development of Novel Building Blocks
to Accelerate Drug Discovery
