-a broad-spectrum antibiotics.
-It is commonly used to treat acne, infection, and other infections caused by bacteria.
-The first of these compounds was chlortetracycline followed by oxytetracycline and tetracycline.
Tetracycline is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and, more recently, rosacea, and is historically important in reducing the number of deaths from cholera. Tetracycline is marketed under the brand names Sumycin, Tetracyn, and Panmycin, among others. Actisite is a thread-like fiber formulation used in dental applications. It is also used to produce several semisynthetic derivatives, which together are known as the tetracycline antibiotics. The term "tetracycline" is also used to denote the four-ring system of this compound; "tetracyclines" are related substances that contain the same four-ring system.
2. Tetracyclines:
-a broad-spectrum antibiotics.
-It is commonly used to treat acne, infection, and
other infections caused by bacteria.
-The first of these compounds was chlortetracycline
followed by oxytetracycline and tetracycline.
AZEEZ. MYMOONA.NASEEFA
6. R5 R4 R3 R2 R1.
Chlortetracycline H H OH CH3 Cl
Oxytetracycline H OH OH CH3 H
Tetracycline H H OH CH3 H
Demethylchlortetracycline H H OR H CI
Rolitetracycline + H OH CH3 H
Metacycline H OH CH2 H
Doxycycline H OH H CH3 H
Minocycline H H H N(CH3)2
AZEEZ. MYMOONA.NASEEFA
7. All derivatives containing less than four rings are inactive
Substitution at 1,2,3,4,10,11,11a, and 12 represent hydrophillic
property that cannot be charged drastically.
Replacement of amide at c-2 with aldehyde or nitrile abolishes
activity
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
AZEEZ. MYMOONA.NASEEFA
8. A slight modification of ring A can be done without much loss
of activity
Aromatisation of ring C gives in hydro tetracycline which is
loess active than natural one.
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
ABCD
AZEEZ. MYMOONA.NASEEFA
9. The hydrophobic part of the molecule from C-5 to C-9
may be altered in various ways:
modifications at C-6 and C-7 in particular afford products having
greater chemical stability.
increased antibiotic activity and more favourable pharmacokinetics
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
ABCD
AZEEZ. MYMOONA.NASEEFA
10. Dehydrogenation to form a double bond between C-
5a and C-11a markedly decreases activity
Polar substituents at C-5 and C-6 contribute
decreased lipid versus water solubility to the
tetracycline
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
ABCD
AZEEZ. MYMOONA.NASEEFA
11. Retention of the configuration of the asymmetric centres C-4,
C-4a and C-12a is essential, whereas the configurations at C-5,
C-5a and C-6 may be altered:
1) The amide hydrogen may be replaced with a methyl group,
but larger groups have a deleterious effect except for those
which are eliIminated spontaneously in water .
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
ABCD
AZEEZ. MYMOONA.NASEEFA
12. 2)The dimethyl amino group may be replaced by a primary amino
group without loss of in vitro activity but all other changes so
far lead to decreased bacteriostatic action .
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
ABCD
AZEEZ. MYMOONA.NASEEFA
13. Mono alkylation of amide group result in loss of activity
Presence of electron withdrawing group (cl- or Na+) and
electron donating group (dimethylamine) at c7 increaes
activity.
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
ABCD
AZEEZ. MYMOONA.NASEEFA
14. Epimerization at C-5a gives or dehydrogenation and double
bond formation between 5a and 11a markedly decreases
activity.
Alkyl substitution at c-11a leads to inactive compound because
inolisable β-diketone at c-11a and 12 is essential for activity.
CONH21
2
3
4
4a
5
5a6a
67
8
9
10
10a 11a
11 12 12a
R1
R2
R3
R4
ABCD
AZEEZ. MYMOONA.NASEEFA
15. An introduction to medicinal chemistry by Graham . L . Patrick.
Medicinal chemistry by Ashuthosh kar.
AZEEZ. MYMOONA.NASEEFA