A seminar on

Adrenal cortex hormones

Presented by:
Jignesh Patel
1st year M. pharm
A.B.M.R.C.P
Banglore-90
(A)
It was observed that the 1-dehydroderivatives of
cortisone and hydrocortisone namely prednisone
and prednisolone which are more potent
antirheumatic and anti-allergic agent
(B)
Between 1953 to 1960, many derivatives of Δ-
corticoids and the halogen containing analogues
were synthesized.
(C)
During some period, in 1956 methyl prednisolone
was synthesized and introduce into clinical practice,
having same activity as of triamcinolone
(D)
To stabilize the 17β-keton side chain, research with
16-methyl substituted corticoids lead to
development of dexamethasone is 1957
(E)
Slightly modified analog of dexamethasone
synthesized in 1960, was peramethasone.
(E)
The newer analogs, fluprednisolone and flucinolone
were synthesized and are found to be potent anti-
inflammatory agents.
 SAR
The adrenal cortex synthesizes two classes of steroids
(a)glucocorticoids: regulate carbohydrate, protein
& fat metabolism
(b)mineralocorticoids: influence mainly salt and
water balance
In hope to develop a compound with high
glucocorticoid activity, the following major features
were recognized
(1)substituents which significantly increase anti-
inflammatory and glucocorticoid activity are
1-dehydro
6α-fluoro
(2)substituents which significantly decrease
mineralocorticoid activity are
16α-hydroxy
16α and 16β-methyl
16α,17β-ketons
(3) Substituents which markedly increase both
glucocorticoid and mineralocorticoid activities are
9α-fluoro
21-hydroxy
2α-methyl
9α-chloro
mineralocorticoids:
(1) naturally occurring, highly active
mineralocorticoids have no OH function at positions
11 & 17
 (2) According to the hormone-receptor binding
studies, the C and D rings involving positions
11,12,13,16,17,20 and 21 are more important for
binding than the rings A and B.
(3) Generally 9α-f, 9α-cl and 9α-Br substituents
cause increased mineralocorticoid activity.
(4)Insertion of a 16α-OH group results in reverse
effect
(5) A double bond between positions 1 and 2, also
decreases the activity
(6) 12α-f, 2α-CH3 and21-Ohgroups moderately
elevate the mineralocorticoid activity.
REFERENCE
Kadam SS, principles of medicinal chemistry, nirali
prakashan august 2004.
THANK
YOU