Transcript Reactor - ChemAxon

Scientific & technical presentation
Virtual Synthesis - Reactor
Elements of the Virtual Synthesis Technology
• Chemical properties predictions
– Calculator Plugins
• A language for describing chemical rules
–
Chemical Terms
• A library of selective reactions „knowing”
chemistry
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Chemaxon Reaction Library
• A reaction engine with high capacity and
performance
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Reactor
• Virtual synthesis applications
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Synthesizer (combinatorial, random, exhaustive)
Chemical Terms, a Language for
Cheminformatics
Elements of the language
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structure matching functions (describing functional groups, reaction sites, similarity…)
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property calculations (partial charge distribution, pKa, logP, localization energy…)
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arithmetic and logic-operators
Chemical Terms examples
structure search
match("olefine.mol") and !match("c1ccncc1") and (atomCount("16")
== 0) or (mass() < 300);
goal function
inhibitor = inhibitor.mol;
similarity(inhibitor, chemical_tanimoto) - similarity(inhibitor,
pharmacophore_tanimoto);
drug likeness filter
(mass() <= 500) and
(logP() <= 5) and
(donorCount() <= 5) and
(acceptorCount() <= 10);
Calculator Plugins
acceptor acceptorCount acceptorSiteCount acidicpKa acidicpKaLargeModel
aliphaticAtom aliphaticAtomCount aliphaticBondCount aliphaticRingCount
angle
aromaticAtom
aromaticAtomCount
aromaticBondCount
aromaticElectrophilicityOrder
aromaticNucleophilicityOrder
aromaticRingCount array asymmetricAtom asymmetricAtomCount atno
atomCount atomicPolarizability averagePolarizability balabanIndex basicpKa
basicpKaLargeModel BCUT bond bondCount bondType canonicalResonant
canonicalTautomer carboaromaticRingCount carboRingCount chainAtom
chainAtomCount
chainBond
chainBondCount
charge
chiralCenter
chiralCenterCount composition conformer conformerCount conformers
connected connectedGraph connections count cxsmarts cxsmiles
cyclomaticNumber dihedral dissimilarity distance distanceDegree donor
donorCount
donorSiteCount
dotDisconnectedFormula
doubleBondStereoisomer
doubleBondStereoisomerCount
doubleBondStereoisomers
dreidingEnergy
eccentricity
electrophilicLocalizationEnergy
enumeration
enumerationCount
enumerations
exactMass
field
filter
formalCharge
formula
fusedAliphaticRingCount
fusedAromaticRingCount
fusedRingCount
hararyIndex
hasValidConformer
hydrogenCount
heavy
heteroaromaticRingCount
heteroRingCount
hyperWienerIndex
isoelectricPoint isotopeComposition isotopeFormula largestAtomRingSize
largestRingSize logD logP logPIncrement logS logSMicro logSNeutral
logSTrue lowestEnergyConformer majorMicrospecies majorMs map mass
match
matchCount
max
maxAtom
maxValue
microspecies
microspeciesCount microspeciesDistribution min minAtom minValue
molBinFormat
molecularPolarizability
molFormat
molImage
name
nucleophilicLocalizationEnergy
pair
piChargeDensity
piEnergy
piOrbitalElctronegativity pKa plattIndex polarizability property randicIndex
refractivity refractivityIncrements resonant resonantCount resonants
ringAtom
ringAtomCount
ringBond
ringBondCount
ringCount
ringCountOfAtom
rotatableBond
rotatableBondCount
shortestPath
sigmaOrbitalElectronegativity
smallestAtomRingSize
smallestRingSize
smarts smiles solubility solubilityAtIsoelectricPoint solubilityOfMicroSpecies
solubilityOfNeutral
solventAccessibleSurfaceArea
sortAsc
sortDesc
stereoisomer
stereoisomerCount
stereoisomers
stericEffectIndex
stericHindrance sum szegedIndex tautomer tautomerCount tautomers
tetrahedralStereoisomer
tetrahedralStereoisomerCount
tetrahedralStereoisomers topologicalPolarSurfaceArea totalChargeDensity
traditionalName uniqueSmiles valence vanDerWaalsSurfaceArea wienerIndex
wienerPolarity
Applications of Chemical Terms
virtual synthesis
reaction and synthesis rules
pharmacophore analysis
pharmacophore definitions
CT
drug design
goal functions
structure searching
advanced query expressions
Encoding Synthetic Knowledge in Reactions
The Friedel-Crafts acylation
Charles Friedel
1832-1899
James Mason Crafts
1839-1917
Encoding Synthetic Knowledge in Reactions
The Friedel-Crafts acylation: generic scheme
The hydrogen of an aromatic carbon atom is substituted with an acyl group of an acid
halide during hydrogen halide elimination.
C(a)
aromatic carbon atom
L[O, S]
oxygen or sulfur atom
L[Cl, Br, I]
chlorine, bromine or iodine atom
Encoding Synthetic Knowledge in Reactions
The Friedel-Crafts acylation: finding reactive sites
REACTIVITY:
charge(ratom(1), "aromaticsystem") < -0.2
Friedel-Crafts acylation occurs only if the aromatic system is at least as activated as
monohalobenzenes.
Encoding Synthetic Knowledge in Reactions
The Friedel-Crafts acylation: finding the most reactive sites
SELECTIVITY:
-energyE(ratom(1))
TOLERANCE:
0.02
Directing rule: the electrophilic substitution takes place on the aromatic carbon atom
with the lowest localization energy having an attached electrophile in the transition
state. Aromatic carbons having the lowest localization energies provide the main
product.
Aromatic carbons having similar localization energies to the lowest one (within 0.02
tolerance range) are included.
Encoding Synthetic Knowledge in Reactions
The Friedel-Crafts acylation: excluding compounds giving side
reactions, destroying the catalyst
EXCLUDE:
match(reactant(1), "[Cl,Br,I]C(=[O,S])C=C") or
match(reactant(0), "[H][O,S]C=[O,S]") or
match(reactant(0), "[P][H]") or
(max(pka(reactant(0), filter(reactant(0),
"match('[O,S;H1]')"), "acidic")) > 14.5) or
(max(pka(reactant(0), filter(reactant(0),
"match('[#7:1][H]', 1)"), "basic")) > 0)
Exclude aromatic compounds containing nucleophilic groups and acrylic halides. For
example, phenols and indols are processed, but benzylalcohols or anilines are not.
Encoding Synthetic Knowledge in Reactions
The Friedel-Crafts acylation as a smart reaction
REACTIVITY:
charge(ratom(1), "aromaticsystem") < -0.2
SELECTIVITY:
-energyE(ratom(1))
TOLERANCE:
0.02
EXCLUDE:
match(reactant(1), "[Cl,Br,I]C(=[O,S])C=C") or
match(reactant(0), "[H][O,S]C=[O,S]") or
match(reactant(0), "[P][H]") or
(max(pka(reactant(0), filter(reactant(0),
"match('[O,S;H1]')"), "acidic")) > 14.5) or
(max(pka(reactant(0), filter(reactant(0),
"match('[#7:1][H]', 1)"), "basic")) > 0
Reactor, the engine
ChemAxon Reaction Library
Reactants
Baeyer-Villiger ketone oxidation
Baylis-Hillman vinyl alkylation
Beckmann rearrangement
Bischler-Napieralski isoquinoline synthesis
Friedel-Crafts reaction
Friedlander quinoline synthesis
Gabriel synthesis
Grignard reaction
Hell-Volhardt-Zelinski halogenation
REACTOR
Products
Reactor the Application
The Reaction Editor
Reactor, key features
Effective
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millions of compounds in a combinatorial reaction
up to 500,000 compounds / hour (P4 1.8 GHz)
Compatible
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reactions: MRV, RXN, RDF, SMARTS/SMIRKS
compounds: MRV, MOL, SDF, SMILES
mapping: MDL, Daylight, automapper
Flexible
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memory, file and database operations (via Oracle Cartridge)
sequential or combinatorial mode
compound or reaction output type
reverse direction
Smart
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chemo-, regio- and stereospecific
customizable
Available
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Java API, command line tool, JSP, GUI
premade reaction library
documentation and examples
free for the Academic community
Visit other technical presentations
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http://www.chemaxon.com/MarvinSketch_View.ppt
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http://www.chemaxon.com/MarvinSpace.ppt
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http://www.chemaxon.com/Calculator_Plugins.ppt
JChem Base
http://www.chemaxon.com/JChem_Base.ppt
JChem Cartridge
http://www.chemaxon.com/JChem_Cartridge.ppt
Standardizer
http://www.chemaxon.com/Standardizer.ppt
Screen
http://www.chemaxon.com/Screen.ppt
JKlustor
http://www.chemaxon.com/JKlustor.ppt
Fragmenter
http://www.chemaxon.com/Fragmenter.ppt
Reactor
http://www.chemaxon.com/Reactor.ppt