enamine drug discovery 2014
TRANSCRIPT
![Page 1: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/1.jpg)
Development of Novel Building Blocks
to Accelerate Drug Discovery
(Enamine Ltd, Kyiv, Ukraine)
Dr. Pavel Mykhailiuk
![Page 2: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/2.jpg)
Kyiv
![Page 3: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/3.jpg)
www.enamine.net
World's largestproducer of building blocks
Founded in 1991
![Page 4: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/4.jpg)
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
![Page 5: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/5.jpg)
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:
![Page 6: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/6.jpg)
www.enamine.net
Why we still have chemical problems
in medicinal chemistry?
![Page 7: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/7.jpg)
www.enamine.net
Becausewe have low diversity of
building blocks
![Page 8: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/8.jpg)
www.enamine.net
1. Fluorinated amines
2010-2014
![Page 9: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/9.jpg)
www.enamine.net
used in 50 patents unknown compounds
2010
![Page 10: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/10.jpg)
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
![Page 11: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/11.jpg)
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.
![Page 12: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/12.jpg)
www.enamine.net
![Page 13: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/13.jpg)
www.enamine.net
Poster (synthesis) Catalogue
![Page 14: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/14.jpg)
www.enamine.net
2. Analogues of morpholine
![Page 15: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/15.jpg)
www.enamine.net
ligand ligand
receptor receptor
Morpholine Morpholine analogue2010
unknown20 FDA-approved drugs
![Page 16: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/16.jpg)
www.enamine.net
Bicyclic morpholine analogues
fused spiro bridged
![Page 17: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/17.jpg)
www.enamine.net
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
![Page 18: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/18.jpg)
www.enamine.net
2014
![Page 19: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/19.jpg)
www.enamine.net
Poster (synthesis) Catalogue
![Page 20: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/20.jpg)
www.enamine.net
3. Advanced piperidine linkers
![Page 21: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/21.jpg)
www.enamine.net
1,4-Disubstituted piperidine drugs
![Page 22: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/22.jpg)
www.enamine.net
Piperidine
Piperidine analogue
Conformational analysis
Org Lett 2010, 4372.
![Page 23: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/23.jpg)
www.enamine.net
Advanced building blocksCommon building block2010 2014
JOC 2014, in press.Synthesis 2010, 493.
Org Lett 2010, 4372.Tetr Lett 2010, 1790.
![Page 24: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/24.jpg)
www.enamine.net
Poster (synthesis)
![Page 25: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/25.jpg)
www.enamine.net
50 papers
![Page 26: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/26.jpg)
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:
![Page 27: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/27.jpg)
www.enamine.net
becausewe have low diversity of
building blocks..
![Page 28: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/28.jpg)
www.enamine.net
if your medicinal projectis really important
to you
![Page 29: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/29.jpg)
www.enamine.net
then you really need diverse advancedbuilding blocks
![Page 30: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/30.jpg)
www.enamine.net
2010
2014
![Page 31: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/31.jpg)
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.
![Page 32: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/32.jpg)
www.enamine.net
Contact us forspecific structures
![Page 33: Enamine drug discovery 2014](https://reader037.vdocuments.net/reader037/viewer/2022100307/5871155a1a28abac6d8b6ea5/html5/thumbnails/33.jpg)
www.enamine.net
Development of Novel Building Blocks
to Accelerate Drug Discovery