MOLECULAR MODIFICATIONS Special Processes

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MOLECULAR MODIFICATIONSSpecial Processes

• ALTERATION OF PHYSICOCHEMICAL PROPERTIES BY
  INTRODUCTION OR REPLACEMENT OF GROUPS

• Bioisosteres

• Change of
• position or
• orientation

• Modification
• of electronic
• states

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ALTERATION OF PHYSICOCHEMICAL PROPERTIES BY
INTRODUCTION OR REPLACEMENT OF GROUPS
Isosteres

• DEFINITION Compounds or groups of atoms that
  have the same number and arrangement of electrons
  Langmuir 1919

• Similar physical properties
• are anticipated

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ALTERATION OF PHYSICOCHEMICAL PROPERTIES BY
INTRODUCTION OR REPLACEMENT OF GROUPS
Isosteres
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ALTERATION OF PHYSICOCHEMICAL PROPERTIES BY
INTRODUCTION OR REPLACEMENT OF GROUPS
Isosteres

• REFINED DEFINITION Atoms, ions or molecules
  in which the peripheral layer of electrons can be
  considered to be identical

• See periodic table

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ALTERATION OF PHYSICOCHEMICAL PROPERTIES BY
INTRODUCTION OR REPLACEMENT OF GROUPS
Bioisosteres Grimms Hydride Displacements (
and arrangement of es)
6 7 8 9
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ALTERATION OF PHYSICOCHEMICAL PROPERTIES BY
INTRODUCTION OR REPLACEMENT OF GROUPS
Bioisosteres

• FINALIZED DEFINITION Compounds which fit the
  broadest definition of isosteres and have the
  same type of biological acitivity

• Are of two types classical and nonclassical

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CLASSICAL BIOISOSTERES
Five Classes According to es
(in rings)
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CLASSICAL BIOISOSTERES
Procaine (Novocain)

Procainamide (Pronestyl)
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CLASSICAL BIOISOSTERES
Carbutamide
Tolbutamide
10
CLASSICAL BIOISOSTERES
Hypoxanthine
6-Mercaptopurine (Purinethol)
11
CLASSICAL BIOISOSTERES
Dopamine
p-Hydroxybenzylhydrazine
12
CLASSICAL BIOISOSTERES
Cholesterol
Diazacholesterol
13
CLASSICAL BIOISOSTERES
Meprobamate
Silameprobamate
14
CLASSICAL BIOISOSTERES
Androstenol
Thiaandrostanol
15
CLASSICAL BIOISOSTERES

Amiloride (Midamor)

1,2,4-Oxadiazole
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NONCLASSICAL BIOISOSTERES
Steric arrangement and electronic configuration
of substitute are similar to those of the parent

• exchangeable groups

• cyclic/acyclic

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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Testosteroxytrimethyl silane
Testosterone
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Chloramphenicol
Chloramphenicol silyl ether
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Phenylephrine
Alkylsulfonamidophenethanolamine
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Diphenydramine
d-Carbinoxamine
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Uracil
5-Fluorouracil
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Carbonyl
Carboxylic Acid
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Catechol
Halogen
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Thiourea
Thioether
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NONCLASSICAL BIOISOSTERES
Exchangeable Groups
Pyridine
Hydrogen
Spacer
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CARBOXYLIC ACID BIOISOSTERES
Indomethacin
Oxamethacin
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UREA, THIOUREA BIOISOSTERES
Cimetidine
Ranitidine
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NONCLASSICAL BIOISOSTERES
Cyclic/Acyclic
Diethylstilbestrol
Estradiol
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NONCLASSICAL BIOISOSTERES
Cyclic/Acyclic
Noncyclic Analogs of Estradiol
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NONCLASSICAL BIOISOSTERES
Cyclic/Acyclic
Amopyroquine
Amodiaquine
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NONCLASSICAL BIOISOSTERES
Cyclic/Acyclic
Cyclobarbital
Hexethal
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NONCLASSICAL BIOISOSTERES
Cyclic/Acyclic
L-()-Muscarine
Choline ethyl ether