Theme 1 Lecture 2 Flashcards
Elucidation of morphine structure
30 years
What developments were there?
IR, NMR and MS allowed smaller quantities of material to determine F groups, molecular masses and connectivity.
X-rays allowed complex compounds to be fully elucidated and well understood.
Gemtuzumab ozogamicin
Use is myeloid leukemia by targeting the protein CD33 (transmembrane protein on leukemic cells)
Advances in Total Synthesis
Biological natural products: synthesis and analogues (structural variation) became possible.
Access to materials may be restricted due to climatic or political conditions.
Isolation= time consuming
Large material in kg to produce mg
Synthesis provides reliable access to new and unnatural analogues
Galantamine
Indication: Treatment Alzheimer’s disease.
Mode of Action: Inhibits acetylcholinesterase, increasing acetylcholine in the brain.
Natural Origin: Derived from plants in the Amaryllidaceae family (e.g., snowdrops).
Industrial Synthesis: Multi-step chemical synthesis from starting materials like narwedine, for large-scale production.
Syntheses of Ephedrine, what form is at the end
No control of the chirality therefore at the end you get a racemic mix.
Halichondrin B to Eribulin
Isolated from the marine sponge and has powerful anti-tumour activity (mitosis inhibitor)
Was inexpensive and many chiral centers which was good for research.
Research behind Halichondrin to Eribulin
SAR studies
RHS of HB showed activity and this was called Eribulin
Rifamycin B
Origin: Isolated from Nocardia mediterranei.
Activity: Potent against gram-positive bacteria
tuberculosis (tuberculosis).
Development: Original Rifamycin B modestly effective.
Improvement: Enhanced potency through semi-synthetic derivatives.
How does this structural change improve the activity of this analogue?
Would appear to be mainly a PK enhancement of activity (solubilising group) and potential structural
importance as well.
Witchcraft to Molecular Medicine
Historical Beliefs: Diseases caused by witchcraft
Scientific Progression: Proof now shows diseases result from infectious agents or physiological abnormalities.
Germ Theory: Accepted in the 1800s; revolutionized understanding of disease causation.
Physiology: 20th-century studies of human physiology enhanced knowledge of various conditions.
Genomics: Advances in DNA technology and the human genome project allow for precise identification of disease-related genomic alterations and their protein-level impacts.
Macromolecular targets
Paul Ehrlich=Side chain Theory 1897
“specific chemical entity which could interact with drugs”
Chemical entity=enzyme, receptors, nucleic acids
Magic bullet to target bacteria
Selective toxicity
Salvarsan was the first anti-syphilitic.
John Langley
Jaborandi=decrease HR and atropine=increase HR
Nicotine discovery
Nicotine and curare were discovered by Langley
And atropine was found out to be a muscarinic antagonist
Receptor Theory
1930s was when it was fully accepted
1940s more understanding of receptor subtypes and selectivity
1970s=isolation
