Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medicinal Chemistry > Lead to drugs > Flashcards

Lead to drugs Flashcards

You may prefer our related Brainscape-certified flashcards:
Periodic Table flashcards Chemistry 101 flashcards AP® Chemistry flashcards Organic Chemistry 101 flashcards
1
Q

What is a pyridine type nitrogen?

A

A benzene core in which one -CH group is replaced by a N atom. Also Next to a double bond.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a pyrrole type nitrogen?

A

Pyrrole, any of a class of organic compounds of the heterocyclic series characterized by a ring structure composed of four carbon atoms andone N atom. The simplest member of the pyrrole family is pyrrole itself, a compound with molecular formula C4H5N.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which is more basic pyrrole or pyridine type nitrogen?

A

Pyridine consists of a stable conjugated system of 3 double bonds in the aromatic ring. Hence, the lone pair of electrons present on the nitrogen atom in pyridine has the ability to donate a hydrogen ion easily or a Lewis acid. Thus, pyridine is a stronger base than pyrrole.
Pyrrole, any of a class of organic compounds of the heterocyclic series characterized by a ring structure composed of four carbon atoms and one nitrogen atom.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What types of bonding are involved in drug-receptor interactions?

A
  • Covalent bonds
  • Ionic bonds
  • Hydrogen bonds
  • Hydrophobic or Van der Waal Forces
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are things to note about covalent bonds?

A
  • Rarely seen in pharmacodynamic receptors.
  • Lead to receptor block through irreversible bonding.
  • Important in Drug-DNA interactions eg Alkyl halides.
  • Very Strong - 40-110 kcal/mol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are some amino acids that interact with covalent bonds?

A
  • Cysteine (has SH so can form )
  • Serine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

When can disulphide (bridges) bonds form?

A

It can only happen between thiols so SH to SH.
Sulphur on its own/next to carbons can’t form it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are things to note about ionic bonds?

A
  • Important in drug-receptor interactions.
  • Allow the drug to bind but also to dissociate.
  • Mutual attraction between the receptor and drug based on opposing charges.
  • Medium strength - 5-10 kcal/mol
  • Occurs between acids and bases.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the amino acids that interact with ionic bonds?

A
  • Glutamic acid
  • Lysine (primary amine)
  • Arginine (Guanine type base)
  • Histidine (pyridine type nitrogen)
  • Aspartic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are things to note about hydrogen bonds?

A
  • Essential in drug-receptor interactions.
  • Dipole interactions.
  • Exchange oxygen for sulphur - weaken drug interactions.
  • Important to be additive - too weak alone - 2-5 kcal/mol.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What amino acids interact with hydrogen bonds?

A
  • Serine
  • Threonine
  • Cysteine
  • Tyrosine
  • Aspartamine
  • Glutamine
  • Histidine
  • Tryptophan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are things to note about hydrophobic or Van der Waals forces?

A
  • Occurs w/ neutral hydrocarbons.
  • Fluxional changes in electron distribution - temporary interaction of dipoles.
  • Require considerable complementarily.
  • Aromatic residues - pi-pi interactions between faces.
  • Alkyl residues - fit into hydrophobic pockets formed by aromatic residues.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What amino acids interact with hydrophobic or Van der Waals forces?

A
  • Glycine
  • Alanine
  • Valine
  • Leucine
  • Isoleucine
  • Phenylalanine
  • Proline
  • Methionine (can’t disulphide bridge)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which amino acids overlap in the interactions?

A
  • Cysteine & serine –> In both covalent and H-bonds.
  • Histidine –> Ionic and H-bonds
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why might an ionic bond (electrostatic)?

A

Receptor may have an acid near the binding site. Protonated will interact with acid as its negative.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What can form H-bonds?

A

Lone pairs eg OH, COOH

17
Q

Which type of nitrogen is basic?

A

Pyridine

18
Q

What does Huckel’s rule mean?

A

if a cyclic, planar molecule has 4n+2 π electrons, it is considered aromatic

19
Q

When do Van der Waals interactions happen?

A

Btwn induced dipole and induced dipole.
Very weal
Contribute to binding

20
Q

How is Structure-Activity relationships (SAR) studies?

A

Synthesis of analogues.

21
Q

What things can you do to study SAR?

A

Chemical modification of groups in lead structure.
Alternative - synthesis of full structure.

22
Q

What sort of modifications could be done to study SAR?

A

Steric Effects
Aromatic substitution
Extension of the structure
Ring variations
Ring fusions
Isosteres
Simplification of the structure
Rigidification of the structure
Conformation blockers (Stop free rotation)

23
Q

What can alcohol do?

A

Changes H-bonding and steric effect.
Change to an ester.
Alcohol can fit in binding site and H-bonds but when it becomes an ester it no longer fits.

24
Q

What does an amine do?

A

Change a primary or secondary amine to amide.
Changes H-bonding, pKa (no longer basic) and steric effects.
(possible to covert tertiary amine to secondary (changes steric effect but not pKa))

25
Q

What is the role of carbonyl?

A

May change to an alcohol (goes from potential to H-bond to tetrahedral and have poor interactions).
May change dipole shape.

26
Q

What is the role of an aromatic ring?

A

Replace w/ cyclohexyl group (not very feasible through reduction, probably requires full synthesis).
Could go from being able to aromatic stack to having poor interactions.

27
Q

What could the role of alkenes be?

A

Similar to aromatic rings. Reduction in lead compound more feasible. Reducing could be done to find importance of the rigidity.
Could go from pi-stacking and planar double bond to being tetrahedral with poor interactions.

28
Q

What can a simple alkyl-group variation do?

A

Changing the group could prevent them from binding in a receptor. Eg adding an extra CH3 could do this.

29
Q

What could happen if an aromatic substitution is made?

A

Substituent position is easily varied.
Leads to changes in activity.
Also can have an electronic effect. Eg meta position - inductive e- w/drawing effect and para position -> resonance effect as well inductive effect & stronger (though weaker base)

30
Q

What are isosteres?

A

Atoms or groups of atoms with same valency electrons but diff properties.

31
Q

What are the isosteres of OH?

A

SH, NH2, CH3

32
Q

What are isosteres of O?

A

S, NH, CH2

33
Q

What could be done to confirmation block?

A

Could add CH3 which stops rotation

Medicinal Chemistry (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions