as phenylpropionatc- Ciba; as pivalate; wfm comb.; wfm comb.; wfrn I: Cortiron Schering; wfrn J: Syncorta Takeda F: Syncortyl Rousscl Neodin Lusofarrnaco; USA: Doca Acetate Organon; Perc
Trang 1Desoxycortone acetate D 601
CH 0 H3 H 3 c G " - c H 3 +
8 0 OC
isopropenyl acetate
3$-hydroxy-20-0x0-5,16- formic
pregnodiene (1) acid
(fmm diosgenin)
K
0 CH,
@ A1[OCH(CH3)zl3 cyclo- aluminum hexonone triisopropylate
Desoxycortone acetate
Oesoxycortone acetate iodine
progesterone
pregnenolone diethyl oxolote
NaOCH3
Trang 2602 D Detajmium bitartrate
CH,COOH
H,C-CO-CH, Go A1[oCH(CH&
VI + N -+
cyclo- olurninurn hexanone triisopropylate
Reference(s):
a Sondheimer, F et al.: J Am Chern Soc (JACSAT) 79,5034 (1957)
synthesis of I:
Wall, M.E.: J Am Chem Soc (JACSAT) 77,5665 (1955)
b Ringold, H.J.; Stork, G.: J Am Chem Soc (JACSAT) 80, 250 (1958)
c Ruschig, H.: Angew Chem (ANCEAD) 60,247 (1948)
Ruschig, H.: Chem Ber (CHBEAM) 88, 878 (1955)
alternative syntheses:
DE 871 153 (Hoechst; appl 1937)
DE 875 353 (Schering AG; appl 1938)
US 2 3 12 480 (Roche-Organon; 1943, CH-prior 1937)
US 2 409 043 (Schering Corp.; 1946, D-prior 1939)
US 2 470 903 (W C Ross; 1949; GB-prior 1945)
Serini, A et al.: Ber Dtsch Chern Ges (BDCGAS) 72,391 (1939)
Wilds, A.L.; Shunk, C.H.: J Am Chem Soc (JACSAT) 70, 2427 (1948)
review:
Ullrnanns Encykl Tech Chern., 4 Aufl., Vol 13, 52
Formulation(s): amp 10 mglml
Trade Name(s):
D: Docabolin (Nourypharrna; GB: Percorten M Crystals Sinsurrene (Parke Davis)
as phenylpropionatc- (Ciba; as pivalate); wfm comb.; wfm
comb.); wfrn I: Cortiron (Schering); wfrn J: Syncorta (Takeda) F: Syncortyl (Rousscl Neodin (Lusofarrnaco); USA: Doca Acetate (Organon);
Percorten (Ciba); wfrn
Use: antiarrhythmic RN: 53862-8 1-0 MF: C27H,2N30, C,H606 H 2 0 MW: 624.75
LDs,,: 6000 pg/kg (R, i.v.)
dihydroxybutanedioic acid (1:l) rnonohydrate
tartrate (1:l)
RN: 33774-52-6 MF: C27H,,N,0, C,H,O, MW: 606.74
LD,,,: 10 rnglkg (R, i.v.); 290 mglkg (R, p.0.)
epichloro- diethylamine 1 -diethylomino-
Trang 3Dexamethasone D 603
H
ajmaline
L-tartaric acid
HO,
H
Oetajmiurn bitartrate
DE 2 025 286 (VEB Arzneimittelwerk Dresden; appl 23.5.1970; DDR-prior 28.7.1969)
GB 1 244 597 (VEB Arzneimittelwerk Dresden; appl 5.7.1970; DDR-prior 28.7.1969)
Formulation(s): sugar coated tabl 25 mg
Trade Name(s):
D: Tachmalcor (ASTA Medica
AWD)
Dexamethasone
(Dexametasone)
ATC: AOlAC02; C05AA09; D07AB 19; D07XB05; DlOAA03; H02AB02; ROlAD03; SOIBAOI; SOICBOI; S02BA06; S03BA01
Use: glucocorticoid
RN: 50-02-2 MF: CzzHz,F05 MW: 392.47 EINECS: 200-003-9
LD,,: >3 g/kg (R, p.0.)
CN: (1 1 P,16n)-9-fluoro-11,17,21-trihydroxy- 16-methylpregna-1,4-diene-3,20-dione
H3C-MgI, LiBr
methylmagnesium lithium
Trang 4604 D Dexamethasone
1 (H3C-CO)20 Tos-OH
0-OH
1 bromine OK , & - - 3 H :
2 sodium iodide HO.%'' H H
CrO,, pyridine
oxide
1 bromine
3 sernicarbozide
3 pyruvic ocid
2 NoBH,
3 H+ CH3 - H3C-SO2-Cl, rnethonesulfonyl pyridine
boranote
NaOBr
IVsodium
hypobrornite
H2F2 CHCly THF
-
rnicrobiologicol dehydration
[Schizornycetes (ATCC-7063)] or Se02
I Dexamethosone I
Trang 5Reference(s):
a Arth, G.E et a].: J Am Chern Soc (JACSAT) 8 0 , 3 160 (1958)
DE 1 113 690 (Merck & Co.; appl 22.2.1958; USA-prior 27.2.1957)
Applezweig, N.: Steroid Drugs, Vol 1 , 7 2 (New York, Toronto, London 1962)
b Oliveto, E.P et al.: J Am Chern Soc (JACSAT) 80,4431 (1958)
US 2 852 51 1 (Olin Mathieson; 1958; prior 1953)
US 3 007 923 (Lab Franq de ChirniothCrapie, 7.1 1.1961; appl 12.1.1960; F-pr~or 22.1.1959)
Applezweig, N.: Steroid Drugs, Vol 1, 74 (New York, Toronto, London 1962)
' synthesis from tigogenin:
Ohta, T et al.: Org Process Res Dev (OPRDFK) 1 , 4 2 0 (1997)
synthesis of VII:
Oliveto, E.P et al.: J Am Chem Soc (JACSAT) 80, 4431 (1958)
Marker, R.E.; Crooks, H.: J Am Chern Soc (JACSAT) 64, 1280 (1942)
GB 869 511 (Upjohn; appl 24.4.1959; U S A - ~ ~ ~ O ~ : 26.5.1958)
alternative synthesis:
US4041 055 (Upjohn; 9.8.1977; appl 17.1 1.1975)
review:
Ullmanns Encykl Tech Chem., 4 Aufl., Vol 13, 57
Formulation(sJ: aerosol 0.075 mglper pump; amp 5 mglrnl; eye drops 1 rnglrnl; f c tabl 0.5 rng, 0.75 mg,
1.5 mg; ointment 0.1 %; sol 0.03 %; suppos 2.2 rng
Trade Name(s):
D: afpred forte Dexa (Hefa-
Frenon)
Anernul (Medopharm)
Baycuten (Bayropharm; as
acetate)-comb
Chibro-Cadou (Chibret)
Cortidexason Crinale,
Salbe (Dermapharn1)-
comb
Cortisumman (Dr Winzer)
Corto-Tavegil (Novartis
Pharma)-comb
Dexa-Allvoran (TAD)
Dexa Biciron (A1con)-
comb
Dexagel (Mann)
Dexa Loscon (Galderma)
Dexamonozon (Medice)
Dexamytex (Mann)-comb
Dexa-Philogout (Azupharma) Dexa Polyspectral (Alcon) Dexa-Rhinospray (Boehringer Ing.) Dexa-sine (Thilo) Duodexa N Salbe (Kade) Fortecortin (Merck) Isopto-Dex (Alcon)-comb
Lipotalan (Merckle) F:
Localison (Dorsch)-comb
Millicorten (Novartis Pharma)-comb
Nystalocal (Nourypharrna)- comb
Otobacid (Axhe)-comb
Predni (Sanirania) GR:
Predni-F-Tablinen (Sanorania)
Predni-F-Tablinen (Sanorania) Sokaral (Pharma-Allergan) Solutio Cordes (lchthyol) Spersadex (CIBA Vision) Tuttozem (S trathrnann) Tuttozem N (Mayo) various combination preparations and generics DCcadron (Merck Sharp &
Dohrne-Chibret) Dectancyl (Roussel Diarnant; as acetate) Maxidex (Alcon) numerous combination preparations
Decadron (Merck Sharp &
Dohrne) Maxidex (A1con)-comb
Trang 6606 D Dexamethasone tert-butylacetate
Eurason D (Ciba-Geigy) Metasolon (Shionogi) Mitasone (Toyo Pharmar) Orgadron (Organon- Sankyo)
Rheumadex (Nakataki) comb
Rheumatol (Sankyo)-comb Santeson (Santa) Sawasone (Sawai) Sunia-D Comp (Zeria Shinyaku)
Maxitrol (Aleon)-comb
Otomize (Stafford-Miller)
Sofradex (Florize1)-conlb
1: Antimicotico liquid01
pomata (1FI)-comb
Aurizone (SIF1)-comb
Decadron (Merck Sharp &
Dohme)
Desalark (Farmacologico
Milanese)
Desamix-neomicina
(Savoma)-comb
Deseronil (Sea)
Fluorobioptal (Farmila)-
comb
Lasoproct (Bayer)-comb
Luxazone (Allergan)
Nasicort~n (Bracco)-con&
Neocortofcn (Ripari-Gero)-
comb
Rinedrone (Deca)-comb
Tobradere (Aleon)-comb
Visumetazone (Merck
Sharp & Dohme)
various combination preparations J: Alpermell (Nippon Shinyaku) Amumetazon (Choseido) Aphtasolon (Showa Yakka) Bisno-DS (Ohta)
Carulon (Yamanouchi) Corson (Takeda) Dab M (Zenyaku) Decaderm (Banyu) Decadron (Banyu) Dectan (Nippon Roussel- Chugai)
Dekisachosei (Choseido) Delenar (Schering- Shionogi)-comb
Dersene (Ikeda) Dethamedin (Oh ta) Dexa A (Shinsei Sawai) Dexaltin (Nippon Kayaku) Dexamamalet (Showa) Dexame (Dojin) Dexasone (Hokuriku)
USA: ~ a l a i o n e (Forest; as
acetate) Decadron (Merck) Decadron (Merck; as acetate)
Decaspray (Merck) TobraDex (Alcon) several combmation preparations and generics
Use: glucocorticoid RN: 24668-75-5 MF: C,,H,,FO, MW: 490.61 EINECS: 246-389-2
CN: (1 10,16a)-21-(3,3-dimethyl-1 -oxobutoxy)-9-fluoro-11,17-dihydroxy- 16-methylpregna- 14-diene-3,20- dione
dexornethosone tert-butylacetic
Dexarnethosone tert-butylocetate
R<ference(s):
DOS 2 317 954 (Jelen Zaklady Farm Polfa; appl 10.4.1973; PL-prior 21.4.1972)
uerosol:
US 3 282 78 1 (Merck & Co 1.11.1966; prior 25.11.1960)
Formulution(s): nasal drops 0.2 mg
Trade Nume(s):
D: Dissiden (Al1egopharma)- Nasicortin (Merck)-comb.; USA: Decadron T.B.A (Merck
Trang 7Dexamethasone 21-isonicotinate D 607
Use: glucocorticoid RN: 2265-64-7 MF: C28H32FN0, MW: 497.56 EINECS: 218-866-5
LD,,: 3470 mgkg (M, p.0.);
3562 mglkg (R, p.0.)
CN: (1 1 P,16a)-9-fluoro- 1 1,17-dihydroxy- 16-methyl-21 -[(4-pyridinylcarbonyl)oxy]pregna-1,4-diene-3,20-
dione
dexamethasane isonicotinoyl Dexarnethasone 21 -isonicotinate
(9 v.1 chloride
Reference(s):
ZA 623 489 (Thomae; appl 1.8.1962; D-prior 19.8.1961)
Formulation(s): aerosol 0.125 mglpuff, 0.02 mg; eye drops 0.25 mglml; sol 0.025 %
Trade Narne(s):
D: Auxiloson (Boehringer Dexa Biciron (A1con)- F: Auxisone (Boehringer Ing.)
Corti Biciron (S & K Dexa Loscon (Galderma) (Boehringcr 1ng.)-comb
(Boehringer Ing.)-comb
Use: glucocorticoid RN: 39026-39-6 MF: C,H,,FO, MW: 654.90 EINECS: 254-254-4
CN: [ l l ~,16a,21-(Z,Z)]-9-fluoro-l1,17-dihydroxy- 16-methyl-2l-[(l-oxo-9,12-octadecadienyl)oxy]-pregna-
1,4-diene-3,20-dione
dexamethasane
(9 v.)
rnethanesulfonyl chloride
Trang 8608 D Dexarnethasone ohosohate
potossium lhnolote I Dexornethosone 21 -linolo(e I
Reference(s):
GB 1 292 785 (ISF; valid from 19.4.1971; I-prior 17.10.1970)
Formulation(s): cream 0.2 %; lotion 0.15 %
Trade Name(s):
I : Kanaderm 200 (Firma)- Situalin Antibiotic0
comb with kanamycine (Puropharma)-comb with
Situalin (Puropharma) bekanamy cinc
Use: glucocorticoid RN: 3 12-93-6 MF: C,,H,,FO,P MW: 472.45 EINECS: 206-232-0
CN: (1 1 P, l6a)-Y-fluoro-l l , 17-dihydroxy- 16-methy1-21-(phosphonooxy)pregna-1,4-diene-3,20-dione
disodium salt
RN: 2392-39-4 MF: C,,H,,FNa20,P MW: 516.41 EINECS: 219-243-0
LD,,,: 1800 m g k g (M, p.0.)
dexarnethasone dirnorpholino-
(9 v.) phosphinic
chloride
1 ion exchonge
2 NaHCOJ
I
Trang 9Dexamethasone pivalate D 609
Referencefs):
DE 1 134 075 (Merck AG, appl 26.11.1959)
alternative synthesis:
U S 2 939 873 (Merck & Co.; 7.6.1960; appl 26.1.1959; prior 20.1 1.1957)
Jrmscher, K.: Chem Ind (London) (CHINAG) 1961, 1035
Forrnulation(s): amp 5 mglml, 48 mgl2 ml, 20 mgl5 ml, 8 mgl2 ml, 120 mgl5 ml; eye drops 1.1 mglml;
ointment 0.2 %
Trade Name(s):
D: Dexabene (Merckle)
Dexa-Brachialin
(Steigerwald)
Dexa-Effekton (Brenner-
Efeka)
Spersadexolin (Dispersa)-
comb
Totocortin (Winzer)
various combination
preparations and generics
F: CCbCdex (Chauvin; as
disodium salt)
Ctbtdexacol (Chauvin; as
disodium salt)-comb
Chibro-Cardon (Merck Sharp & Dohme-Chibret;
as monosodium salt)-comb
Corticttine (Chauvin; as monosodium salt)-comb
Dexagrane (Leurquin; as monosodium salt) J:
Frakidex (Chauvin; as monosodium salt)-comb
Soludtcadron (Merck Sharp & Dohme-Chibret;
as monosodium salt) I: Decadron Fosfato (Merck USA:
Sharp & Dohme) Desalark (Farm Mil.)
Eta-Biocortilen (SIF1)- comb with neomycine Eta-Cortilen (SIFI) Kanazone (SIT)-comb
with kanamycine Soldesam (Farm Mil.) Corson (Takeda) Decadron (Banyu) Donray (Kodama) Orgadrone (Sanky o) Solcort (Fuji) Teikason (Teika) Decadron Phosphate (Merck)
Neo-Decadron Phosphate (Merck)-comb
RN: 1926-94-9 MF: C2,H3,FO6 MW: 476.59 EINECS: 217-659-7
CN: (1 1~,16a)-21-(2,2-dimethyl-l-oxopropoxy)-9-fluoro-11,17-dihydroxy-l6-methylpregna-l,4-diene-3,20-
dione
dexarnethosone pivaloyl
1 Dexomethosane pivalate (9, v.) chloride
Reference (s):
US 3 033 881 (Ciba; 8.5.1962; CH-prior 4.7.1958)
CH 398 585 (Ciba; appl 1956)
alternative syntheses:
ES 320 497 (Lab M Cuatrecasas; appl 30.11.1965)
DOS 2 3 17 954 (Jelen Zaklady ~ a r h Polfa; appl 10.4.1973; PL-prior 21.4.1972)
Formulation(s): ointment 0.02 %
Trang 106 10 D Dexamethasone valerate
Trade Name(s);
D: Millicorten-Vioform (Ciba)
Use: glucocorticoid RN: 33755-46-3 MF: C,H,,FO, MW: 476.59 EINECS: 25 1-669-2
LD,,: >3 g k g (M, p.0.);
>3 glkg (R, p.0.)
CN: (1 1 P, 16a)-9-fluoro- 11,21-dihydroxy- 16-methyl- 17-[( 1-oxopentyl)oxy]pregna- 1,4-diene-3,20-dione
(cf betornethasone volerate)
17,21-(1 -butyl-1-methoxyrnethylene-
dioxy)-3.20-dioxo-9-fluoro-1 lp-hydroxy-
Reference(s):
DOS 2.1 11 114 (Inst Luso Farmaco; appl 9.3.1971 ; I-prior 14.3.1970)
Dexornethosone volerote
alternative syntheses:
DOS 2 055 221 (Lab Chim Farm Blasina; appl 10.1 1.1970)
16a-methyl-1.4-pregnodiene
Fnrmulation(s): cream 0 l %
Trade Narnefs):
I: Dermadex (SmithKline J: Voalla (Maruho)
Use: antihistaminic RN: 132-21 -8 MF: C1,Hl,BrN2 MW: 3 19.25 EINECS: 205-053-5
CN: (S)-y-(4-bromophenyl)-N,N-dimethyl-2-pyridinepropanamine
maleate (1:l)
RN: 2391-03-9 MF: C,,H,,BrN, C,H,O, MW: 435.32 EINECS: 219-236-2
LD,,,: 25 m g k g (M, i.v.); 176 mglkg (M, p.0.);
191 mglkg (R, p.0.)