Desoxycortone acetate D 601 CH 0 H3 H3cG"-cH3 + 80 OC & H3 + HCOOH -b b TosOH 11 isopropenyl acetate H H H H HO ' OHC-0 ' 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 CH30H. THF H3C-CO-CH3 Oesoxycortone acetate iodine progesterone pregnenolone diethyl oxolote NaOCH3 iodine 602 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); Diamant) wfm wfm Percorten (Ciba); wfrn Detajmium bitartrate ATC: COlB Use: antiarrhythmic RN: 53862-8 1-0 MF: C27H,2N30, . C,H606 . H20 MW: 624.75 LDs,,: 6000 pg/kg (R, i.v.) CN: (17R,21a)-4-[3-(diethylamino)-2-hydroxypropyl]-17,21-dihydroxyajrnalaniurn salt with [R(R*,R*)]-2,3- 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 hydrin 1 -diethylomino- 2.3-epoxypropane (I) Dexamethasone 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 iodide bromide HO,.,, 604 D Dexamethasone 1. (H3C-CO)20. Tos-OH 0-OH 1. bromine OK , & - - :H3 2. sodium iodide HO.%'' H H CrO,, pyridine I1 chrorn~um(Vl) oxide 1. bromine 3. sernicarbozide 3. pyruvic ocid 2. NoBH, 3. H+ CH3 H3C-SO2-Cl, pyridine - rnethonesulfonyl 2. sodium chloride boranote NaOBr IVsodium hypobrornite H2F2. CHCly THF - rnicrobiologicol dehydration [Schizornycetes (ATCC-7063)] or Se02 I Dexamethosone I Reference(s): a Arth, G.E. et a].: J. Am. Chern. Soc. (JACSAT) 80,3 160 (1958). DE 1 113 690 (Merck & Co.; appl. 22.2.1958; USA-prior. 27.2.1957). Applezweig, N.: Steroid Drugs, Vol. 1,72 (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) 1,420 (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; USA-~~~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. 606 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: ~alaione (Forest; as acetate) Decadron (Merck) Decadron (Merck; as acetate) Decaspray (Merck) TobraDex (Alcon) several combmation preparations and generics Dexamethasone tert-butylacetate ATC: AOIAC; D07AB; ROl AD 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 (4. v.) onhydride 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 comb.; wfm wfm Sharp & Dohme); wfm Dexamethasone 21-isonicotinate D 607 Dexamethasone 214sonicotinate ATC: DO~AB; SOI BA 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.) I%.) comb. . GB: Dexa-Rhinaspray Corti Biciron (S & K Dexa Loscon (Galderma) (Boehringcr 1ng.)-comb. Pharma)-comb. Dexa-Rhinospray I: Desalfa (1ntes)-comb. (Boehringer Ing.)-comb. Dexamethasone 21-linolate ATC: D07AB Use: glucocorticoid RN: 39026-39-6 MF: C,H,,FO, MW: 654.90 EINECS: 254-254-4 CN: [ll ~,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 608 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 Dexamethasone phosphate ATC: H02AB; SOlBA; S03BA; D07AB 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 mgkg (M, p.0.) dexarnethasone dirnorpholino- (9. v.) phosphinic chloride 1 ion exchonge 2. NaHCOJ I Dexomethosone phosphate Dexamethasone pivalate D 609 Referencefs): DE 1 134 075 (Merck AG, appl. 26.11.1959). alternative synthesis: US 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. Dexamethasone pivalate ATC: DO~AB (Dexamethasone trimethylacetate) Use: glucocorticoid 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 ~arh. Polfa; appl. 10.4.1973; PL-prior. 21.4.1972). Formulation(s): ointment 0.02 % 6 10 D Dexamethasone valerate Trade Name(s); D: Millicorten-Vioform (Ciba) Dexamethasone valerate ATC: D07AB Use: glucocorticoid RN: 33755-46-3 MF: C,H,,FO, MW: 476.59 EINECS: 25 1-669-2 LD,,: >3 gkg (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) Beecham) Zaluks (Hokuriku) Dexbrompheniramine ATC: R06AB06 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 mgkg (M, i.v.); 176 mglkg (M, p.0.); 191 mglkg (R, p.0.) . 20 6-2 3 2-0 CN: (1 1 P, l6a)-Y-fluoro-l l , 17-dihydroxy- 16-methy 1-2 1-( phosphonooxy)pregna-1,4-diene-3,20-dione disodium salt RN: 239 2-3 9-4 MF: C,,H,,FNa20,P MW: 516.41 EINECS: 21 9-2 4 3-0 . tert-butylacetate ATC: AOIAC; D07AB; ROl AD Use: glucocorticoid RN: 2466 8-7 5-5 MF: C,,H,,FO, MW: 490 .61 EINECS: 24 6-3 8 9-2 CN: (1 10,16a )-2 1-( 3,3-dimethyl-1 -oxobutoxy )-9 -fluoro-11,17-dihydroxy-. glucocorticoid RN: 5 0-0 2-2 MF: CzzHz,F05 MW: 392.47 EINECS: 20 0-0 0 3-9 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