12
11
1
2
HH
9
10
5
3
H
13
14
8
H
H
4
17
H
16
15
7
6
21
18
18
18
12
13
11
1
H
2
10
3
5
4
9
CH3
H
6
7
17
19
16
14
8
H
12
H
15
1
2
9
10
3
5
4
13
11
CH3
CH3
H
6
7
17
19
16
14
8
H
12
H
15
1
CH3
2
10
3
5
4
11
9
CH3
13
H
14
6
7
H
15
18
CH3
12
H
19
16
8
H
21
20
17
H3C
1
2
10
3
5
4
13
11
CH3
9
CH3
H
8
H
6
7
23
17
H
16
14
H
24
22
20
15
26
25
27
•
•
!
"
#
• $
!
%
• $
%
%
! &
'
()
!
%
!
! "
%
% *
! %
!
#
$ %% %
&
$
()
!
'
()
%
! % &
!
+
$
!
'
%
"
& &
,
%
%
!"
!
!
• $
!
•
&
• $&
-
!!
! "
'
• .
- / "
!
"
!!
!!
"
&
OH
O
OH
H3C
H
CH3
H
OH
CH3 H
H
H
HO
H
%-(.%'/
%- '
'1'
H
O
'
2
0
OH
H
H
O
'%()(!*%+,'
)(%- '
H3C
O
H3C
')'
0
)(%%(.+'
'1'
'
0*
,
3
H3C
OH
H3C
17-beta hydroxyl oxidn.
H
H
0
O
H
H
H
16-alpha hydroxylation
H
Estradiol
Estrone
Most potent
OH
OH
H
reduction of C17 keto
HO
HO
H3C
H
H
HO
Estriol
Most abundant in serum
Synthesized mostly by ovaries and adrenal gland
least potent, Most abundant in urine
synthesized mostly by placenta
All are excreted as their sulfate (3-OH) or glucouronides (3, 17-OH) conjugates
'%()(!*%+,'
)(%- '
'
)'
0
'%()(!*%+,'
'%-'
'%()(!*%+,'
')(%4 (%- '
%
'0
!
0
! %
! %
#
!
#
! 1 2'
!
#
!
!
$
,
!!
%
2 7 '
!
345 2
!
64
! 1 2" %
/ !!
%
'
#
%
&
5
'
66
OH
CH3
OH
CH3
CH
H
H
HO
H
H
Ethinyl estradiol
%- '
'%()(!*%+,
')(%- '
CH
O
CH3
H
H
Mestranol
%- '
')'
%()(!*%+,
0
'%- '
'
• 8
#
4# !
/ !!
!
! 295 :
#
'
12
"
&
&
#
9 52
72
#
%
%
7
H3C
H
H
OR
Estradiol benzoate (Menovis)
R = H; R` = -CO-Ph
Estradiol dipropionate
R = R`= -CO-CH2-CH3
Estradiol cypionate
R`=H, R = -COH 2CH 2C
Estradiol hexahydrobenzoate
R` =H, R =
H
R`O
R`= H, R= -CO-(CH2)3-CH3
Estradiol valerate (progynova)
4 ":"; <
.
" #
0. *
#
#
8
%
4:"
34
,"
"
-OC
4
4
8
*
H3C
,
H3C
O
O
%
NaO3SO
NaO3SO
Estrone sodium sulfate
Equilin sodium sulfate
sodium 17-Oxo-estra
-1,3,5(10),7 tetraene-3- sulfate
=
#
H3C
H
H
+
N
N
H
O
O
OS
H
O
H
O
5
*
4 4
4 ":"; < 4
4:4 4 !
&
.
2 %
%
%
'
%
%
%
&
'
H3C
H3C
H3C
Na2O3PO
HO
Diethylstilbsterol
%
1 !
,
#
HO
Fosfosterol
Dienesterol
<>
%
%
!
CH3
CH3
CH3
,
OH
OPO 3Na2
OH
%
%
#
!%
#
%
% !
%
%
6666
9
* 9 ,
2
N-desmethyl metabolite
contribute to the
antiestrogenic activity
N
CH3
N
O
CH3
O
CH3
N
CH3
O
CH3
CH3
H 3C
Cl
Cl
Clomiphene
Tamoxiphene
Toremiphene
(Nolvadex)
(Fareston)
(Clomid)
:
0
;*
,
,
<
(
"
(
2
9 =
"
9
0
*
,
O
N
O
HO
S
OH
11.8 oA
?
!
$
&
$
A 54 !
" @@@@''
52
&
"
!!
B
%
@@@@@''
? ' '
" C '
• 0
! % &
• 0
!
!
%
9
@@@
%
'
!
"
'0
% '
! &
/
* $ %>,
N
N
N
N N
N
N
H3C
CH3 H3C
N
CH3
Anstrozole
(Femara)
!
D
# EE
!
N
Letrozole
(Arimidex)
8
N
%
@@@@@
# EE
%
!
% '
O
CH3
C 2H 5
O
N
H
CH3
O
CH3
CH3
O
NH2
O
O
OH
Aminoglutethimide
Formestane
(Cytadren)
(Lentaron)
8
%
!
3
-0.
2
D
'H #
G
(Teslac)
!
%
!
#
'
% '
F
&
"
I %
/
4
%
Testolactone
/"
4
/
!
!
"
O
estrone-3-sulfate sodium salt
NaOH
CH3O
OH
CH3
H
estopiperate
piperazine O
O
H
OH
S
H
O
HO
H
H
K/ HC=CH/liquid NH3
SO3/pyridine
H3C
O
H3C
H
H
HO
Estrone
H
NaBH4
H
H
CH
benzoyl chloride/K2CO3/RT
estradiol-3-benzoate
OH
less liable to esterication
less liable to hydrolysis
H
HO
exclusive esterification
R-CO-Cl/pyridine/heat
estradiol 3,17-diesters
mild hydrolysis
1. acid chloride/pyridine
2. K2CO3/methanol
K2CO3/methanol
estradiol 17 esters
CH3
N
OH
O
H3C
Cl
N
CH3
H
CH3
O
CH3
OH
N
MgCl
O
O
CH3
HCl
-H2O
O
O
CH3
N
Cl
CH3
N
CH3
Cl
O
N
CH3
O
?
N
BrH2C
N
N
NH
N
N
N
N
K t-butoxide/DMF/0 oC
CH2Cl2/RT
N
N
N
N
F
N
N
(
H3C
H3C
O
CH3
'1'
')(.+'
O
H3C
H3C
H3C
OH
H3C
CH3
HO
;34
H
4:6" <64
H3C
O
H3C
CH3
CH3
O
O
OH
J642
<6(342
OH
H3C
CH3
O
H3C
O
H3C
H3C
H
CH3 H
H
NHNH2
O
+
NH
N
N
H
O
N
'.
'
8C
K ;:;'
%
"
'
I
&
09 2
%"
!
#
O
@
1
"
'
%
!
G#
%
!
%
# "
%
%
%
&
#
%
,'
%-' '
!
!
!
,
A 54 !
0
0
64
!
A 54 ! %
%
#
. /
)
/
'
!
A5 2
J !
)&
! %
)
"
(
!
%
"
'
H3C
H3C
CH3 H
H
H
H3C
O
O
CH3
O
CH3 H
H11C5
H
H
H3C
O
O
H3C
H3C
O
4I4
!
"
42
# :%
%
&
42
%
Megesterol actate
(Depo-Provera)
42
G
CH3
Medroxyprogesterone acetate
(Primolut-depot)
!
"
&
/
'
4I4
4:" <4
" G
%
% '?
7
4J4%
(Megace)
4:" <4
4J64%
"
H3C
O
CH3
Hydroxyprogesterone caproate
O
H
H
O
O
O
H
H3C
O
%
%
!
4 G
'
4I"J4
%
4:" <4
% '
"
"
H3C
H3C
O
CH3 O
O
CH3 H
H
O
H3C
CH3
H3C
H
H
O
H
O
Cl
Cyproterone acteate
Dydrogesterone
(Androcur)
J4
4
(Duphaston)
4
4 46" 464%
"
"
43" <64
4I"J4
4I"J4
4:" <4
!
"
"
?
%
!
"
'
<
(
4:" <4
"
(
%- '
'%>'&
OH
H3C
OH
H3C
CH
H
H
H
H
O
H
O
Norethindrone = Norethisterone
H
Norethynodrel
esters: norethisterone acetate
Norethisteronenanthate
64
4
4
4I
H3C
H
H
H
OH
CH
4:4
OH
CH3
H
H
H
Lynesternol
Allylsternol
CH2
CH
H3C
H
OH
metabolism
H
H
HO
N
Norelgestromin (R = H)
D(-) Levonorgestrel
Norgestimate (R = -COCH3)
OH CH
H2C
H
H2C
H
#
%
9
,
"
A
4! #
&
'
'
%
"
CH
Etonogestrel
<<>
7 #
OH
O
Desogestrel
7 #
H3C
metabolism
H
H
#
H
(+) Norgestrel
H3C
&
CH
H
H
H
H
O
OR
H3C
CH
(
"
*
!
,"
9
&
%
'
&
%
#
%
'
%
!
0
!
64
# '
!
&
$
!
08
64
#
# '
345 2
&
<>
#
! %
%
!
'
9
&
#
"
'
• 7
#
*
##
I4
A 5
4:4
%'
•
#
%
&
'
• 2 & # " #
%
#
•
%
%
%
08 ,'
:
CH3
H3C
N
CH3 OH
CH3
H
H
O
. !
34MI4 , %
. !
%
N4
34
4:4
I" 4
%
IL
$
%
!
4
4 4
4
#
!
%
'
!!
%
! %
"
*
#
CH3
OH
CH3
H
O
H
H
OH
H
aromatase
H
H
CH3
CH3 H
5alpha-reductase
CH3 H
OH
H
HO
O
H
5-alpha-Dihydrotestosterone
Testosterone
(active)
Estradiol
(active)
(active)
17beta-Hydroxyandrost-4-ene-3-one
dehydrogenase
CH3
O
CH3
5alpha-reductase
O
H
H
CH3
aromatase
H
H
H
O
H
HO
O
H
5-alpha-Androstenedione
Androstendione
(inactive)
CH3
CH3
O
H
O
O
CH3
dehydrogenase
CH3 H
H
H
(active)
5beta-reductase
CH3 H
H
Estrone
(inactive)
dehydrogenase
HO
O
CH3 H
CH3 H
H
dehydrogenase
dehydrogenase
H
H
Androsterone
5beta-Androstenedione
(inactive)
(inactive)
CH3 H
H
HO
O
H
H
Etiocholanolone
(inactive)
$
!
%
(
'
"
"
!
,
#
/
!
#
2
?
-C2H5
Testosterone propionate
O
CH3
O
-
R
Testosterone phenylpropionat
CH3
CH3 H
H
Testosterone isocaproate
H
-
CH3
O
Testosterone heptanoate (enanthate)
.
*
%
'H #
0.
G
!
?"
-
CH3
@
,
&
0%
%
5
%
%
%
! %
,
%
5
*
A
,
! %- '
0
0
# '
!
/ &
#
! %- B
0
/
!
0
" "
! I3
(
&
3A
(
%
B
#
'
!1
!
4
OH
H3C
H3C
CH3
H
H
H
O
O
Mesterolone
(Hormo-Gerobion)
(proviron)
4
4I4
4%
4:4
342
OH
CH3
CH3
HO
CH3 CH3
CH3 H
H
HO
CH3 H
H
O
H
Oxymestrone
H
F
O
4 64%
4:4
H H3C OH
CH3
H3C
H
H
O
OH
Fluoxymestrone
Methandrostenolone
(oranabol)
34,
H
Methyltestosterone
342
I"
CH3OH
CH3
CH3
(Ultandren)
(Dianabol)
4 4%
4I4 4:4
41
32
4
"I4
4%
4:4
4
3"
4
34
4I4
<>
4 4%
4:4
<>
%
CH3
CH3
OCOR
H3C
OH
H3C
H3C
HO
H
H
O
O
H
Methenolone (primoblan)
4:4
4 34
H
H
Oxymetholone (Anabolon)
Methonolone acetate (Primoblan depot)
4.
4 4
CH3
4
342
4 4
%
4:4
4
H C OH
H3C3
CH3 H
N
H
HN
H
H
Stanozolol (Stromba)
64.
4 F 4
4
M:" 4 N4
* 4
4
4
#
C
%>DD
5
4%
R-OCO
H3C
H
H
O
H
H
H
R = H Nandrolone (Durabolin)
R = C9H19 = Nandrolone decanoate (Decadurabolin)
342
N
O
4I4
4:4
OH
CH3
CH
CH3 H
H
H
Danazol
(Danatrol)
64
4 "I4
4 <4
":4
* 4
34
! B
@
"
E
!
"
%
!
"
%
%
' '
9
4
' ' %
"!
%
# #
H3C
H
H3C
O
F
F
NH
NO2
Flutamide
(Flutamex)
:O4 !
%
(
K
! '9
F
4IF4
H3C
H
N
O
F
F
N
H3C
F
O
NO2
Nilutamide
(Nilandron)
4 :O4$ !
%
4I"I4 %
(
4IO4
K ;<
$ %- E
O
CH3
NH
H3C
CH3
N
CH3
CH3 H
H
O
N
H H
H
HO
Finasteride
(Prostide)
P
CH3
O
1. CH3MgCl
CH3 H
H
CH3
CH3 H
2.Oppenour oxidation
H
H
H
O
HO
Dehydroepiandrosterone
5
K
!
! %
&
!4I4
4:4
/
G
%'
OH
CH3
O
CH3
OH
CH3 H
H
' D
' D
HO
)
)
OH
H
H3C
H
H
O
H
O
Deoxycorticosterone
42
O
O
4I4
Aldosterone
41 % 4 3" 4
4
4I4
4:" <4
4:" <4
)
%
$2"
00
9
QR
R" 2
5
% QR
"
HO
O
H3C
HO
OH
H
H3C
H
F
O
1
1
41
64 1
>
.
4
3" " 4
4I4
4:" <4
%
#
!
4
;<<>
#
'
!!
' '
O
@
0% %
/"
%
%
#
'
<
&
! ! %%
% "
'7 / %
&
'
#
" %
"&
!
' '
%
"
% B
"
%
"
!
% "
"
#
"
&
'
9
S$
# #
S0
&
!
!
'
&
S1
# '
%
34
!
!
#
S$
64 !
"
&
!
34
&
!
S
*
2
&
J6
6!
!
#
'2 & # "
# '
%
!
&
%
!
S
# "
%
!
!
'
"
!
O
H3C
O
OH
OH
HO
metabolism
H3C
O
H3C
OH
OH
H3C
11beta-HSD
O
O
Cortisone ...inactive
Hydrocortisone .....active
Hydrocortisone acetate, hydrocortisone sodium succinate (Solu-cortef)
O
O
OH
CH3 OH metabolism
O
CH3
CH3
HO
11beta-HSD
Prednisone .....inactive
(Hostacortin)
OH
CH3 OH
HO
CH3
CH3
O
O
O
O
OH
OH
CH3
Prednisolone ......active
(Hostacortin-H)
Methylprednisolone
(Solu-medrol)
metabolism
6beta; 16 alpha; 20 hydroxyl
derivative
F%
%
G1'! H
I
I4
! %
4:4
!
@ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ''
"I4
!
4:4
HO
O
CH3 OH
HO
H3C
CH3
CH3 H
F
H3C
HO
H
OH
CH3
H
F
OH
OH
O
HO
H3C
H3C
H
OH
H
F
H
O
OH
O
O
O
Betamethasone
Dexamethasone
Triamcinolone
stabilize 17 ketol towards metabolism by 16 alpha or beta substituent
triamcinolone, highest hydrophilicity, lowest oral bioavailability and glucocorticoid
activity but all are of better glucorticoid and lower mineralocorticoid activity relative to
hydrocortisone
641
4 J 34%
4
3" " 4
4
4 "I4
4:" <4
641
" J64.
4
34 " 4
4 "I4
4:" <4
1+0
#
641
:" <4
?
%
4
3" J46" "
4 "I4
4
4
single bond
OR
O
double bond
HO
O
H3C
HO
H3C
OH
H3C
H3C
OH
CH3
H
F
OPO 3Na2
H
O
O
Dexamethasone sodium phosphate
Hydrocortisone sodium phospahte
R = -PO3Na2
Hydrocortisone sodium succinate
R = -CO-(CH2)2-COONa
Prednisone sodium phosphate
=
Prednisone sodium succinate
=
G
5
"
K %
"
%
## "
!
#
!EEE
(
A
OH
single or double
O
CH3
HO
OCOCH 3
OH
HO
H3C
H3C
H
CH3 H
H
F
H
O
O
O
CH3
CH3
H
O
O
Triamcinolone acetonide (Kenacort A)
Hydrocortisone acetate
Ointments, creams, long acting injections
Prednisolone acetate
Injections, 2 injections/week
O
H3C
HO
H3C
OCOCH 3
H3C
HO
H3C
OH
CH3
H
F
O
OR`
CH3
H
F
OR
H
O
H
O
Dexamthasone acetate (Fortecortin)
Betamethasone dipropionate (Deprisone) R =R`= -COC2H5
Betamethasone valerate (Betnovate) R = H, R`= -COC4H9
Long acting injection twice weekly
for chronic treatment of pain and other conditions
Ointments, creams, gels,...........etc
2
,
"
4
"
7
TI'; " & 2 5
".
%
F
OH
H3C
H
(Beclonase)
F
H
H
F
)
Fluticasone propionate
(Synalar)
8
(Flexotide)
Oint, cream
glucocoticoid
CH3
CH3
H
Fluocinolone acetonide
Inhaler
OCOC2H5
O
F
Beclomethasone dipropionate
O
CH3
HO
CH3
O
O
5000 X as
hydrocortisone
O
H
F
CH3
O
H
CH3 H
Cl
H3C
HO
CH3 OCOC2H5
CH3
HO
S
O
H5C2OCO
O
0
Oint., cream, inhaler
!
! 8
%
#
as
500 x as betamethasone
O
bexlomethasone
monopropionate
(17) is more active
HO
CH3
CH3
O
OCOC 4H9
HO
CH3
CH3
F
O
CH3
Cl
OCOC 2H5
CH3
F
O
F
Diflucortolone valerate
Clobetasol propionate
(Nerisone)
(Dermovate)
Cream, oint
Cream, oint