selected organic reactions database (sord)
DESCRIPTION
An introduction to the SOR Database, an essential supplement to other reaction databasesTRANSCRIPT
SORD and Lost Chemistry
Dick WifeSORD BV
SORD Objectives
It is not our job to discover new drugs
It is our job to make this process easier
ChemistryScheikunde (Dutch): the ability to cut
Sensible questions:Is this product new?Is this reaction new?Is there a related precedent?What sort of reagent(s) and
reaction conditions?
Choices
PublicationNote, Letter,
Communication
PublicationNote, Letter,
Communication
Publication/Thesis
ThesisThesis
PublicationFull paper
PublicationFull paper
? ?
Thesis/Dissertation
AbbreviationsIntroductionResults & DiscussionExperimental +/- 95 reactionsReferences/NotesSupporting Data
“Lost Chemistry”
Only published as a Note, Communication, Letter, etc.Unpublished = Unpublishable? Not enough story for a publication…Reputation: ABCZ/loose endsNot written in English
It really depends on who you are and what you are looking for…
Source Languages
Analysis: country of origin of 300k “drug-like” compounds
SOR Database
Reaction Scheme (RS) Experimental (EX)
Fields:Reagent(s)Solvents(s)YieldMPOptical Rotation
PDF-EX
Spectral data
Excerption Rules
Reaction Scheme: only reactants and productsReagent: needed for the reaction but does not show up in the productSteps: 1,2, etc. if no intermediate is isolatedProduct: if isolated and characterizedNo failed reactions
Time Line 05/2011
Hard copy Digital/E-born E-born
0.2% 14.9% 48.8% 35.1%
Source Reaction Data
15 May 2011 Theses Groups Univ.1941 368 138
Europe 73% North America 21% Asia 5%
SOR Database
Selected Life Science ChemistryRS & EX fully searchablePDF-EX (>90% with spectral data)French/German English EX translationCharacterized reaction products onlyFree access to academic collaborators
Databases and Content
de Laet, A.; Hehenkamp, J. J.; Wife, R. L. Finding Drug Candidates in Lost/Emerging Chemistry. J. Heterocycl. Chem. 2000, 37, 669–674. (SORT&gen)
G.W. Bemis and M.A. Murko J. Med. Chem. 42 (1999), : 50 scaffolds account for 50% of known drug molecules
Commercial Database with 9 million organic compounds
450k (5%) “drug-like” organic compounds
Drug Discovery & Chemical Space (1)
It may be comforting to know that for every possible disease, now and in the future,
a drug exists in Chemical Space
Real/Virtual Chemistry!
Drug Discovery & Chemical Space (2)Intuition
• Rational Design• High Throughput Screening (HTS)• Combinatorial Chemistry (CC)• Targeted Libraries
Kalliokoski, Tuomo. Accelerating Three-Dimensional Virtual Screening: NewSoftware and Approaches for Computer-Aided Drug Discovery. Publicationsof the University of Eastern Finland. Dissertations in Health Sciences, 22. 2010
Drug Discovery in silico tools
• Compound selection• Compound solubility• ADME tox• Further chemistry
What does a drug look like?
NH
NH
OH
O
NH
O
NH
O
NH
OHO
NH
NH2
O
NH O
NH
NH
O
OOH
S
S
NHO
NH
O
NH
O NH
ONH2
OH
O
NH2
O
NHO
NH2
Somatostatin, Octreotide ($ 1 billion 2009)
NH2
Amphetamine ($ 1 billion 2009)
Top 200 drugs 2006
Discrete organic structures 162
Antibodies, vaccines, etc. 38
MW < 200
N
OH
O
N NH NH2
NH NH NH2
NO
O
NH2OH
O
OH
NH
O
OH
O
OH
NH2
OH
O OH
NH2
OH
NH2
H ONO
H
NH2
O
N
N
OH
N+ O
-
O NH2
OH
O
OHNH2
OH
O
O
OO
OH
H OH
ON+
O
O- N
NN
NN
O
ONH2
Top drugs
Atovastatin (Lipitor, Pfizer $ 13.3 billion 2006)
N OH
OOHOH
F
O
NH
Statins (1)
Atovastatin (Lipitor, Pfizer $ 13.3 billion 2006)N OH
OOHOH
F
O
NH
N
N
F
N
S OO
OH OH
OH
O
Rosuvastatin (Crestor, AZ $ 2.1 billion 2006)
O
OH
H
OOH
OH
OHO
Pravastatin (Pravachol, BMS $ 1.2 billion 2006)
Carreira & Seebach (2003)
O
OOOH H
H
OO
O
OHB
H
H
H HO
O
OHOHNa
+
+
Indole chemistry
N
H
H
H
N
H
H
Reactant 523 Product 112
Product 126
N
H
HN
H
H
H
N
H
H
H
N
H
H
NH
+
O
N
NH
OH
N
NH
+ N
O
O
NH
O
O
NH
NH
+I O
F F
F NH
F
F
F
Ley
Joule
Togni
Ley
Joule
Dumy
N
H
HN
H
H
H
N
O
O
O
O
+NH
O
NH
NH
O
O
O
OO
+
NH
NH
O O
O
OO
NH
+ OH +O
O
Cl
Cl NH
O
O
O
N+
N+
O-
O
O-
O
O NHO
O
+ NH
Br
N+
NH
N
NH
O-
O
O
O
OHO
O
Br
Marcantoni
Echavarren
N
H
HN
H
H
H
NH
+N
+
O-
O
NN
+
NH
O-
O
N
NH
+OH
NH
O
BMS/HIV 2011
N
N
N
O
O
O
BMS-216
N N
N
N
O
O
O
O
BMS-378806
N N
N
N
O
O
O
O
O
N N
N
N
O
O
O
O
N
N
NO P
O
O
O
O O
O
N+
BMS-488043 BMS-663068
Indole chemistry/BMS/HIV
NH
+ OH +O
O
Cl
Cl NH
O
O
O
N
N
N
O
O
O
BMS-216
Joule
BMS/HIV
N N
N
N
O
O
O
O
O BMS-488043
N+
NO
-
O
Cl
+NO
O+ H H N
NH
Cl
NH
+ OH +O
O
Cl
Cl NH
O
O
O
Joule
Joule
Tetrazoles
NN
NNH
N
N
Cl
OH
NN
NNH
N
N
O
N
OHO
O
N
NNH
N
N
NNH
NN
N
OH
O
O N
N
O
O
O
O
O
OH
N
NNH
N
N
S
O OH
S
N N
NN
NHO
O
S
S
NH2
O
OOH
O
Hypertension 2009 $ billion
2.135 0.767 3.912
1.705 1.533
Tetrazoles
N
NNH
N
NN
N NH
NS
N+
N N
NN
N
NNH
N
N
NH
S
Al+
+Neier
Benzimidazoles
NH
N
A
S
N
NH
NH
O
O
NH
NO
N
NH
O
NH
N
O
S
O
N O
N
NH
S
O
N
O
O
NH
NS
O
N
O
F
F
F
N
NH
S
OOF
F
N
O O
N
NNH
NN
N
OH
O
O
N
N OH
OO
N
NNH
NH2
NH
O
OH
NN
N
N
Benzimidazole
Buschauer
Batey
Black
N
NH
S
O
Cl
O
N
N
S
O
O
+
N N
NH
O
O
I
O
N
N
N
O
O
O
N+
NH
O
O
O
O
O
NH2 NH2N
NH
O
O
+
Reagent DB (2764)
Reaction Reagent (Similar) reactions
Hermann-Beller palladacycle
O O
P Pd+
OO
PPd+
Inspiration!
Hermann-Beller palladacycle
Tietze
N
O
O
O
N
IN
O
O
N
O
+
O O
P Pd+
OO
PPd+
O
Br
OO
O
O O O
O
OO
O
Br
O
H
H
O
O
H
HH
Greaney
More inspiration!
Hermann-Beller palladacycle
Tietze
O O
P Pd+
OO
PPd+
N
O
O
O
Br
N
O
O O
H
N
O
O
Br
N
O
O
H
O O
Br BrH H
H H
O O
H H
HH
HH
Grubbs 2 catalystO
O+Blechert
N
O O
N
O
OCraig
O
I
O
I
Lautens
Conclusions
• All-thesis excerpted so surprises too• Will contain trivial reactions• Intelligent queries deliver results• Graphics driven (needs improvement)• As diverse as possible• A supplement to bigger databases
For Licensing and Sales information please contact ACD/Labs
To become an academic collaborator please contact SORD