QSAR in Development of Antidepressants
QSAR in Development of Antidepressants QSAR in Development of Antidepressants
Treatment Past and Present • First generation – Monoamine oxidase inhibitors(MAOIs) • mechanism-based irreversible inhibitors – Tricyclic antidepressants(TCAs) • three ring molecular core • Second generation – Selective serotonin (5-HT) reuptake inhibitors(SSRIs) – Selective norepinephrine(NE) reuptake inhibitors (SNRIs) N Imipramine NH 2 Cl Cl sertaline N O N N N H H N phenelzine amoxapine NH 2
Serotonin Hypothesis • serotonergic neurotransmission in forebrain – key determinant of mood • euphoria-high activity • dyphoria-low activity • depression response to low levels • Serotonin inhibitors interfere with 5-HT activity – removes serotonin from synapse – elevating low levels of synaptic serotonin
- Page 1 and 2: The Next Generation of Antidepressa
- Page 3: Depression as a Disease • 1 out 5
- Page 7 and 8: Serotonin effect Phil Skolnick, P.
- Page 9 and 10: Project Aim • explore a faster ac
- Page 11 and 12: QSAR Design • Create training set
- Page 13 and 14: Why use GFA • builds multiple mod
- Page 15 and 16: • r 2 =.87 QSAR results • valid
- Page 17 and 18: Strategy Nh 2 fluoxetine F Cl O H N
- Page 19 and 20: Synthetic scheme S antidepressants
- Page 21 and 22: Synthetic scheme
- Page 23: References • Phil Skolnick, P. P.
Treatment Past and Present<br />
• First generation<br />
– Monoam<strong>in</strong>e oxidase<br />
<strong>in</strong>hibitors(MAOIs)<br />
• mechanism-based irreversible<br />
<strong>in</strong>hibitors<br />
– Tricyclic<br />
antidepressants(TCAs)<br />
• three r<strong>in</strong>g molecular core<br />
• Second generation<br />
– Selective seroton<strong>in</strong> (5-HT)<br />
reuptake <strong>in</strong>hibitors(SSRIs)<br />
– Selective<br />
norep<strong>in</strong>ephr<strong>in</strong>e(NE)<br />
reuptake <strong>in</strong>hibitors (SNRIs)<br />
N<br />
Imipram<strong>in</strong>e<br />
NH 2<br />
Cl<br />
Cl<br />
sertal<strong>in</strong>e<br />
N<br />
O<br />
N<br />
N<br />
N<br />
H<br />
H<br />
N<br />
phenelz<strong>in</strong>e<br />
amoxap<strong>in</strong>e<br />
NH 2
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