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24 Cards in this Set
- Front
- Back
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ligand-receptor complex
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structural complimentarity
consider biological response |
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Therapeutic Index
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LD/EC
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Drug Recep Theories
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Hemoglobin Cooperativity Model (ligand bonding shifts equilibrium)
Receptor Dimerization (ligand binding leads to enzyme dimerization) |
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Acceptor
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any protein that participates in any nonspecific interaction
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measurement of pharmacologcial activity
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acetylcholine
can act on nicotine and muscarine receps because of difference in distances between acceptors and donors for H bonding |
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In vitro
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cell based
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in vivo
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animal model
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potency
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strength of the effect
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Clinical Feedback/Observation
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drug repositioning or repurposing that occurs during in vivo testing or clinical trials
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Minoxidil
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vasodialator-- hair regrowth
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Dramamine
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antihistamine-- motion sickness
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Slidenafil
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vasodilator-- viagra
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Lead modification/optimization
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minimize side effects
maximize therapeutic index |
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The larger the therapeutic index...
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the greater the safety of the drug
oral contraceptives have agonist... turn into antagonist on purpose |
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Pharmacophore
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refers to functional groups and spacial relationships
1. systematically alter or remove portions of the molecule 2. identify essential regions for activity |
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antihypertensive medications
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chlorothiazide-- strong diuretic side effect
diazoxide |
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functional group modifications
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homologation
chain branching |
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homologation
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can have max potency...
but what about solubility? long C chains are not soluble |
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chain branching
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placement of chains can alter function of molecule
ring chain transformations: replace branching with cyclic |
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Isosteres
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functional groups with similar props: structural or chemical (hydrogen bonding ability)
used to modify lead compound activity: minimize toxicity, alter metabolism, max bioavailability |
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Classical Isosteres
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groups that have the same number of valence electrons... but diff numbers of atoms
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Examples of classical isosteres
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ch3, nh2, oh, f, cl
ch2, nh, o, s, se ch, n |
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Bioiososteres
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not included with classical
contain at least one similar physical property Props: size, shape, hydrophobicity, pka, chemical reactivity, hydrogen bonding capacity |
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Use of Bioisosteres
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structural: change size/shape but retain functionality?
receptor interactions: max/remove recept interactions pharmacokinetics: change completely hydrophobicity, pka, etc metabolism |
