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Neuromuscular Blocking Agents 225
14.9 NEWER AGENTS
1. Atracurium Besylate: 2,2’-(3,11-dioxo-4,10-dioxatridecylene)-bis-[6,7-dimethoxy-benzyl)-2-
methyl-1,2,3,4 tetra hydro Isoquinolinum]. Dibenzene sulfonate is the new series of competitive
neuromuscular blocking agents. Atracurium besylate is used in anaesthesiology for muscle relaxants.
N
H
N
HCO
3
OCH
3
+
CH
3
OCH
3
OCH
3
OCH
3
OCH
3
+
OCH
3
HCO
3
O
(CH )
25
O
O
O
HC
3
Fig. 14.20
2. Mivacurium:
Mivacurium is a short acting non-depolarizing muscle relaxant (NDPMR) with benzyl-isoquinoline
structure. Neuromuscular blocking activity may be prolonged due to low plasma choline sterase
activity.
HCO
3
N
+
HCO
3
H
(CH ) — OC(CH ) — CH CH (CH ) — CO — O — (CH )
23 22 2 22 23
HCO
3
HCO
3
OCH
3
CH
3
+
N
OCH
3
OCH
3
OCH
3
OCH
3
OCH
3
HC
3
Fig. 14.21
2, 2-(1,8–dioxo-4-dtene 1,8-diyl)-bis-(oxy-3,1-Propanediyl)-bis (1,2,3,4-tetrahydro-6,7-dimethoxy-
2-methyl-1-(3,4,5-trimethoxyphenyl)-methyl] isoquinoinium) dichloride.
C. Lee (2001) “British-J. of Anaesthesia, 87(5): 755-69(2001) Structure, conformation and action of neuromuscular
blocking drugs.
226 A Textbook of Medicinal Chemistry
EXERCISE
1. Define neuromuscular blocking agents.
2. Explain non-depolarizing and depolarizing muscle relaxant with their structures.
3. Classify NMB agents and give their mechanism of action.
4. Explain aminosteroids derivatives. Give the SAR of aminosteroids agents.
5. Write the synthesis of the following drugs with MOA and uses
1. Pancuronium
2. Gallamine
3. Hexa fluorinium
4. Succinyl choline
6. Write the SAR on depolarizing muscles relaxants.
7. Explain 10 atoms roles in NMB agents.
8. Write in details of tetrahydro isoquino lines derivatives.
General Considerations of Heterocyclic Chemistry Concept 227
15
General Considerations of
Heterocyclic Chemistry Concept
15.1 INTRODUCTION
Concept of heterocyclic chemistry in medicinal csompounds is that which possesses the cyclic
ring structure, having at least two different kinds of atoms in the ring. The most common type of
atoms include nitrogen, oxygen and sulphur heteroatoms that contains largely carbon atoms. Apart
from that, many atom elements including even bromine also is part of heterocyclic chemistry.
Heterocyclic compounds are widely arranged in nature and are essential for life in various ways.
They can be aliphatic or aromatic in nature depending upon the distribution of electronic constitution.
In this chapter a brief introduction is detailed to the simple types of three-, five- and six-
membered heterocyclic system and their naming.
15.2 NOMENCLATURE OF HETEROCYCLIC COMPOUNDS
According to Systemic Nomenclature System (Hantzsch-Widman System)
According to this system, heterocyclic compounds are recognized by their trival names.
Examples:
N
O
S
N
H
N
N
N
N
O
N
N
Pyrrole Furan Thiophene Pyrazole Imidazole Furazan
a
a a
228 A Textbook of Medicinal Chemistry
Symbols represents
a → 1H Tautomer
b → 2H Tautomer
c → 9H Tautomer
d → 4H Tautomer
e → 10H Tautomer
f → Saturated heterocyclic rings
Fig. 15.1
15.3 NAMING OF HETEROCYCLIC RINGS
Prefix
+
Stem
Heteroatoms
Number
Position
Ring size
Saturation
1
2
3
2
1
Fig. 15.2
Table 15.1: Common prefixes
Element Prefix
Oxygen Oxa
Sulphur Thia
N
H
Carbazole
Phenazine
Phenothiazine
Phenenthridine
Pyrrolidine
f
Piperidine
Piperazine
Chroman
e
O
H
N
Morpholine
O
f
f
f
f
N
H
NH
N
H
N
N
H
N
Indole Isoindole Indazole Purin Indolizine
Quinoline Isoquinoline Quinazoline Pteridine Quinalizine
b
a
a
c
d
N
N
N
N
N
N
N
N
N N
N
N
N
N
N
H
S
N
H
N
N
H
N
H
N
H
General Considerations of Heterocyclic Chemistry Concept 229
Selenium Selena
Nitrogen Az a
Tellurium Tellura
Phosphorus Phospha
Arsenic Arsa
Silicon Sila
Germanium Germa
Boron Bora
Table 2:
Stem Ring Size Unsaturated Ring Saturated Ring
3 irene
(a)
irane
(b)
4 ete etane
(b)
5 ole olane
(b)
6 ine© inane
(d)
7 epine epane
8 ocine ocane
9 onine onane
10 ecine ecane
SYMBOLS REPRESENT:-
a → Three-member ring contain nitrogen
b → Saturated ring containing nitrogen
c → ‘inine’ used with some Phosphorous, arsenic and boron heterocycles
d → ‘ane’ is used if immediately preceded by the Prefixes ‘ox’, ‘thi’, selen.
Examples:
O
O
N
N
ON
Thirene
Oxirane
1, 3-diazete
1, 2-Oxazetidine
O
O
S
1, 3-Dioxolane 1,2,4 Triazine
Thiepene
Azocine
N
N
N
N
H
Fig. 15.3
230 A Textbook of Medicinal Chemistry
15.4 NOMENCLATURE OF FUSED RING SYSTEM
Fused ring system involving the benzene ring may be fused on to the carbon atoms of each of these
three heterocyclic compounds in two different positions. Six possible structures are illustrated
below:
N
X
X
Indole X = NH Isoindole Indolizine
Benzofuran X = O Isobenzofuran
Benzo[b] thiophene X= S Benzo[c]thiophene
Fig. 15.4
15.5 RULES OF NOMENCLATURE OF FUSED RING SYSTEM:
(1) Select prefix (O)
(2) Select base component
Example
Benzoxazole
O
N
Fig. 15.5
Base Component:
1. Choose, one ring containing ‘N’
Example
Benzoxazole
O
N
Fig. 15.6
2. Prefer than oxa, thia, aza
S
O
Thieno [ ] furane
Fig. 15.7
General Considerations of Heterocyclic Chemistry Concept 231
3. Select one consisting two or more rings
N
H
NH
Pyrrolo [ ] indole
4. Select the larger ring if two rings of different size
N
H
N
Pyrrolo [ ] Pyridine
5. Select the most heteroatom containing ring
Pyrrolo [ ] pyrrazole
H
N
N
H
N
6. If same number of heteroatoms are present, choose with priority oxa > thia > aza with
higher electronegativity
O
N
N
H
N
Imidazo [ ] oxazole
7. If the same number of heteroatoms are present of oxa, thia, aza then select with lower
numbering
Oxazola [ ] isoxazole
Imidazo [ ] Pyrrazola
O
N
N
O
N
N
N
H
H
N
232 A Textbook of Medicinal Chemistry
8. Another aspect to indicate the fusion by the given letter symbols to the base components and
numbers to the prefix (in same direction)
Example
O
N
d
c
b
a
O
O
1
2
3
4
5
Oxazolo[5,4-d]isoxazole
EXERCISE
1. Give a brief note on heterocyclic chemistry
2. Discuss nomenclature of heterocyclic compounds.
3. Write about Hantzsch-Widman system.
4. Write the name of tricyclic heterocyclic compounds
5. Discuss with examples of nomenclature of fused ring system.
General Considerations of Heterocyclic Chemistry Concept 233
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th
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