Systemic Approaches in Teaching Courses of Pharmaceutical Chemistry

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Systemic Approaches in Teaching Courses of
Pharmaceutical Chemistry Pharmaceutical Sciences

• By
• Mohamed Abdel Hamid Ismail
• Prof. Organic Pharmaceutical Chemistry
• DEAN
• OF FACULTY OF PHARMASCTAIN SHAMS UNIVERSITY

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Department of pharmaceutical Chemistry

• This department teach
• 1) Organic Chemistry
• 2) Pharmaceutical
• (Medicinal) Chemistry

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• Organic Chemistry courses deals with teaching the
  students
• 1) Naming structure
• 2) Predicting method of synthesis
• 3) Predicting chemical and Physical
• properties of chemical structures.

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• Pharmaceutical Chemistry courses deals with
  teaching the students
• Predicting Biological Activity of any molecules
  (if any)
• Predict chemical and biological incompatibility
  of drugs combinations.

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• Teaching methodologies
• 1) Linear approach
• 2) Systemic approach
• 3) New E-learning, Self-Learning, etc.

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• Linear Approach
• In studying classes of organic chemistry,
• if we do the study for each of the function
  groups separately without making the relation
  between them, this will be the linear approach of
  teaching.
• Examples
• RH ? -CC- ? C?C
• R-X ? R-NH2
• R-OH ? R-O-R
• R-CHO (or R-CO-R) gt R-COOH
• R-COX ? R-COOR ?

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• Systemic Approach
• It is the reversible relationship of each concept
  with other related concepts.

Nitrile
Amides
Acids
Esters
Acid Halides
Acid anhydrides
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• Organic Chemistry courses deals with teaching the
  students
• 1) Naming structure
• 2) Predicting method of synthesis
• 3) Predicting chemical and Physical properties of
  chemical structures.
• The best systemic way is through the reported
  systemic approach by clusters of combined
  information

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Systemic Aproach for alkanes (reaction
synthesis)
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SYSTEMIC APPROACH FOR STUDYING ALKENES IN
RELATION TO ALKANES
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• SYNTHESIS IMPORTANT REACTIONS
• Alkynes From alkene by halogenation by Cl2,
  followed by double dehydrohaogenation with strong
  base (Na NH2)
• N. B To convert alkyne into alkene, we make
  partial hydrogenation of alkyne using Li
  /Ethylamine.

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• Alkyl halides (R-X)
• Prepared by either halogenation of alkane,
  hydrohalogenation of alkene, or substitution of
  alcoholic OH by halogens.

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• SN reactions

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• Alcohols ( R-OH ) Amines ( R-NH2 )
• Alcohols are preparedFrom alkene by hydration,
  2) From alkyl halide by SN using aqueous NaOH,
  3) From aldehydes or ketones by reduction using
  NaBH4 or Li Al H4. 4) From Acids or esters
  by reduction using Li Al H4.
• Amines are prepared from alkyl halides using
  NH3 or NaNH2.
• Amines could be converted to alcohols by
  nitrous acid (HNO2)

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• Aldehyde (R-CHO) , Ketones (R-CO-R
• Aldehydes are prepared by oxidation of 1ry
  alcohol using selective weak oxidizing agent
  (Cr2O3 in the presence of pyridine (Cr2O3 / Py).
• Aldehydes can undergo further oxidization by
  KMnO4 into Carboxylic acid. The reverse pass
  ways is by lithium tritertbutoxyaluminium hydride

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• Acids Synthesis

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• Acids derivatives
• Best wishes from Dr Mohamed. A. H. Ismail

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Systemic Approach in Aromatic Chemistry
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• Pharmaceutical Chemistry courses deals with
  teaching the students
• Predicting Biological Activity of any molecules
  (if any)
• Predict chemical and biological incompatibility
  of drugs combinations.
• The best systemic way is through
• Structure Activity Relation-ship
• (SAR)

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• Summary of SAR for NALIDIXIC ACID other
  quinolones as anti-infective TOPOISOMERASE ENZYME
  INHIBITION

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5) OFLOXACIN (Tarivid)6) Levofloxacin (Tavanic)

• Tarivid is racemic Tavanic is levo

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Other recently introduced quinolones (novel
ME-TOO DRUGS)

• SPARFLOXACIN (Zagam), MOXIFLOXACIN (Avelox)
  GATIFLOXACIN (Tequin)

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Chemical Incompatabilities to quinolones

• The quinolones chelate with heavy metals like
  (Ca2, Mg2, Al, and Fe2 to form less
  water-soluble complexes and thereby lose
  considerable potency.
• So, these drugs are contra-indicated with Ca, Mg,
  Fe nutitions

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• The Metal Chelates

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SARs for the substituted barbiturates CNS
depressants

• 1) At C-5 both hydrogen must be substituted
• 2) Introduction of polar groups (like OH, NH2,
  CO, COOH, SO3H, etc., at the alkyl substituents
  destroy potency.
• 3) Replacement of one oxygen by sulfur increases
  lipid solubility and increase rate of reaching to
  the brain

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THE VITAMIN Ks

• Naphtho-quinones
• The term vitamin K (Koagulation-Vitamin)

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SAR for Antihemorrhagic activity of Vitamin Ks

• .

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NICOTINAMID

• .
• Biologically, nicotinamide is present in the
  building block of the coenzyme II (called
  Nicotinamide-Adenine Dinucleotide-Phosphate
  (NADP) which is responsible for biological REDOX
  system.

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• NADP / NADPH system

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• Biological REDOX reactions.
• NADP NADPH

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Nicotinic acid, ( Vitamine B3)

• 3-pyridine carboxylic acid
• Serious deficiency of niacin or tryptophan may
  lead to pellagra (from the Italian, pelle agra,
  for rough skin).

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6) Pyridoxine Hydrochloride vitamin B6

• .

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RIBOFLAVIN (VITAMIN B2)

• .
• It Accelerate REDOX reactions of NAD/NADH

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Anti-oxidants are those molecules which can
quench free radical in the body and thus stop
AGING
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Mechanism of quenching Free Radicals by
conjugated systems
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• Electron rich molecules like
• 1) Phenols, 2) Amines,
• 3) Alcohols or 4) Thiols
• They can trap and detoxify the free radicals by
  supplying electrons and forming stable radicals.

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IMPORTANT EXAMPLES OF ANTIOXIDANT THERAPIES
Vitamine E
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• Computer Aided Drug Design
• Molecular Modeling
• As a systemic method of drug discovery

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Hypothesis Generation of the binding sites of
Receptorsand use for compare fit with data base
molecules to predict their activity
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Comparison of the hypothesis with the following
Data Base spreadsheet
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Results of COMPARE / FIT searching of the
hypothesis of methotrexate with the data base.
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Displaying the fitting
Compare fitting of data base compounds with
methotrexate hypothesis
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If the features of a Molecule could fit part of
the cavity of these meshes (hypothesis), it will
be considered as a biologically ACTIVE HIT
molecule for drug discovery.
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Binding site
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Then Draw the New molecule inside the cavity
based on complementarily
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• Systemic Approach
• Between other
• PHARMACEUTICAL SCIENCES
• For drug discovery

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Drug Discovery Team-work
Isolation of Natural Products
Synthesis
Molecular Modeling
Bio-Technology
Analysis Quality control
Pharmacology Toxicology
X-Ray Crystallography
Clinical Studies Stages
Pharmaceutics Technology
To the Market
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THANK YOU For Your Interest
Best wishes from Mohamed Abdel Hamid
Ismail 16/4/2008