Patrick An Introduction to Medicinal Chemistry 3/e Chapter 9 DRUG DISCOVERY: FINDING A LEAD
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1 © Patrick Patrick An Introduction to Medicinal Chemistry An Introduction to Medicinal Chemistry 3/e 3/e Chapter 9 Chapter 9 DRUG DISCOVERY: DRUG DISCOVERY: FINDING A LEAD FINDING A LEAD Part 4: (Lead compounds - Impact of the human Part 4: (Lead compounds - Impact of the human genome project) genome project)
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Patrick An Introduction to Medicinal Chemistry 3/e Chapter 9 DRUG DISCOVERY: FINDING A LEAD Part 4: (Lead compounds - Impact of the human genome project). Contents Part 4: Lead compounds - Impact of the human genome project 4.5. Lead Compounds - PowerPoint PPT Presentation
Transcript of Patrick An Introduction to Medicinal Chemistry 3/e Chapter 9 DRUG DISCOVERY: FINDING A LEAD
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Patrick Patrick An Introduction to Medicinal An Introduction to Medicinal
ChemistryChemistry 3/e 3/e
Chapter 9Chapter 9
DRUG DISCOVERY: DRUG DISCOVERY: FINDING A LEADFINDING A LEAD
Part 4: (Lead compounds - Impact of the human Part 4: (Lead compounds - Impact of the human genome project)genome project)
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ContentsContents
Part 4: Lead compounds - Impact of the human genome project
4.5. Lead Compounds - Impact of the human genome project (6 slides)
4.6. Lead Compounds - de novo design (6 slides)4.7. Design of Lead Compounds using NMR
Spectroscopy (11 slides)
[24 slides]
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The PastThe Past
Lead CompoundLead Compound
TargetsTargets
TargetsTargets
Lead compoundsLead compounds
The FutureThe Future
4.5 Lead Compounds4.5 Lead Compounds - Impact of the human genome project- Impact of the human genome project
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4.5 Lead Compounds4.5 Lead Compounds - Impact of the human genome project- Impact of the human genome project
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4.5 Lead Compounds 4.5 Lead Compounds - Impact of the human genome project- Impact of the human genome project
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4.5 Lead Compounds4.5 Lead Compounds - Impact of the human genome project- Impact of the human genome project
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4.5 Lead Compounds4.5 Lead Compounds - Impact of the human genome project- Impact of the human genome project
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4.5 Lead Compounds 4.5 Lead Compounds - Impact of the human genome project- Impact of the human genome project
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4.6 Lead Compounds - 4.6 Lead Compounds - de novode novo design design
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4.6 Lead Compounds - 4.6 Lead Compounds - de novode novo design design
X-RAY CRYSTALLOGRAPHYX-RAY CRYSTALLOGRAPHY
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4.6 Lead Compounds - 4.6 Lead Compounds - de novode novo design design
PROTEIN STRUCTURE
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Receptor
4.6 Lead Compounds - 4.6 Lead Compounds - de novode novo design design
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Scaffold
CO2-
HOIONICIONICBONDBOND
H-H-BONBONDD
VDWVDWBONDBOND
ScaffoldScaffold
Scaffold
ScaffoldH3N+ O
CH3
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NNHNHN
OO
SSOO
OO
NHNH
NN
NN NN
HH22NN
SSOO
OO
OO
NN
THYMIDYLATE KINASE INHIBITORTHYMIDYLATE KINASE INHIBITOR
ANTICANCER AGENTANTICANCER AGENT
LEADCOMPOUND
Optimisation
4.6 Lead Compounds - 4.6 Lead Compounds - de novode novo design design
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4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
NMR SPECTROSCOPYNMR SPECTROSCOPY
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Binding Site
ProteinProtein
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
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ProteinProtein
NO OBSERVABLE BIOLOGICAL EFFECT
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
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1313C NMRC NMR
CCCC
CHCHCHCH
CHCH
CHCH22
CHCH22
CHCH33
CHCH33
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
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CHCH22
CHCH33
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
1313C NMRC NMR
CCCC
CHCHCHCH
CHCH
CHCH22
CHCH33
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ProteinProtein
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
Optimise Optimise epitopeepitope
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ProteinProtein
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR Spectroscopy NMR Spectroscopy
Optimise Optimise epitopeepitope
Optimise Optimise epitopeepitope
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ProteinProtein
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
Optimise Optimise epitopeepitope
Optimise Optimise epitopeepitope
LinkLink
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LEAD COMPOUNDLEAD COMPOUND
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
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HN
HO
OOH
NO
O
OMeOMe
MeO
O
O
Me
Design of a lead compound as an immunosuppressantDesign of a lead compound as an immunosuppressant
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
Epitope AEpitope A
Epitope BEpitope B
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HN
HO
OOH
NO
O
OMeOMe
MeO
O
O
Me
Design of a lead compound as an immunosuppressantDesign of a lead compound as an immunosuppressant
4.7 Design of Lead Compounds using 4.7 Design of Lead Compounds using NMR SpectroscopyNMR Spectroscopy
Lead compoundLead compound
