Fluocinolone acetonide F 891 H3C-CO-NH-Br. HCIO, b N-bromoacetamide 1 0 CH, 0 Se02, (H3C)3C-OH selenium fluoride i fluocinolone (IV) - - Fiuacinolone acetonide US 3 014 938 (Syntex; 26.12.1961, appl. 23.8.1960; MEX-prior. 7.9.1959). US 3 124 571 (Syntex; 10.3.1964; appl. 19.5.1960; MEX-prior. 26.1.1960). Djerassi, C. et al.: 3. Am. Chem. Soc. (JACSAT) 82, 3399 (1960). starting material: Julian, P.L. et al.: J. Am. Chem. Soc. (JACSAT) 72, 5145 (1950). alternative syntheses: GB 933 867 (American Cyanamid; appl. 5.12.1959; USA-prior. 8.12.1958). US 3 197 469 (Pharmaceutical Research Prod.; 27.7.1965; appl. 6.8.1958). Formulation(s): cream 0.025 9%; ointment 0.025 %: topical sol. 0.01 % Trade Name(s): D: Flucinar (medphano) Jellin (Griinenthal) Jellisoft (Griinenthal) Procto-Jellin (Griinentha1)- comb. 892 F Fluocinonide F: Antibio-Synalar (Cassennc)-comb. Synalar (Cassenne) Synalar Neomycin (Cassenne)-comb. GB: Synalar (Zeneca) I: Alfabios (Biotekfarma) Alfafluorone (Biotekfarma) Boniderma (Boniscontro & Gazzonc) Coramide (Ottolenghi) Cortanest Plus (Piam)- comb. with lidocaine Dermobeta (Terapeutico M.R.) Dermolin (Lafare) Doricum (Farmila)-comb. with neomycinc Doricum Semplice (Farmila) Esacinone (Lisapharma) Fluocit (CT) Fluomicetina (Zoja)-comb. with kanamycin Fluomix Same (Savoma) Fluovitef (Italfarmaco) Lauromicina Pomata (Lafare)-comb. with eritromycin Localyn (Recordati) Mccloderm (Schwa@- comb. with meclocycline Meclutin (ABC-Torino)- comb. with meclocycline Nefluan (Mo1teni)-comb. Neoderm (Crosara) Omniderm (Face) Proctolin (Recordati)- comb. with lctocaine Sterolone (Francia Farm.) Ultraderm (Ecobi) J: Benamizol (Mohan Yakuhin) Biscosal (Ohta Seiyaku) Cortiphate (Tokyo Tanabe) Flucort (Syntex-Tanabe) Fluvean (Kowa) Fluzon (Taisho Seiyaku) USA: Derma-Smoothe (Hill) Fluonid (Allergan) FS Shampoo (Hill) Synalar (Medicis) Synemol (Medicis) Fluocinonide ATC: COSAAI 1; D07AC08 Use: glucocorticoid, anti-inflammatory RN: 356-1 2-7 MF: C,,H,,F,O, MW: 494.53 EINECS: 206-597-6 LD,,: >6 glkg (M, p.0.); 14 mgkg (R, p.0.) CN: (6a,11~,16a)-21-(acetyloxy)-6,9-difluoro-l 1-hydroxy-16,17-[(l-~ethylethylidene)bis(oxy)]pregna-l,4- diene-3.20-dione Reference(s1: GB 916 996 (Olin Mathieson; appl. 21.7.1959; USA-prior. 6.8.1958). US 3 124 571 (Syntex; 10.3.1964; appl. 19.5.1960; MEX-prior. 26.1.1960). fluocinolone ocetonide Forrnulation(s): cream 0.5 mglg; ointment 0.5 mglg, sol. 0.5 mg/g Trade Narne(s): D: Topsym (Grunenthal) Topsyne nkomycine J: Bestasone (Kodama) Topsym (Grunentha1)- (Cassenne)-comb. Topsym (Syntex-Tanabe) comb. with neomycin GB: Metosyn (Zeneca) USA: Dermacin (Pedinol) F: Topsync (Cassenne) I: Flu 21 (Select Pharma) Lidex (Medicis) Topsyn (Recordati) Lidex E Cream (Medicis) Fluocinonide 1 Fluocortin butyl F 893 Fluocortin butyl (Fluocortin butyl ester) ATC: D07AB04 Use: glucocorticoid RN: 41767-29-7 MF: C2,H3,F05 MW: 446.56 EINECS: 255-543-8 LD,: >5 g/kg (M, p.o.1; >4 g/kg (R, p.0.); >I &/kg (dog, p.0.) CN: (6a,11 P, 16a)-6-fluoro- 1 1 -hydroxy-16-methyl-3,20-dioxopregna-l,4-dien-21 -oic acid butyl ester fluocortin RN: 33124-50-4 MF: C22H27FOs MW: 390.45 EINECS: 251-383-8 F fluocortolone (9. v.) MnOZ. CW2CIZ I b manganese dioxide Fluocortin butyl DOS 2 150 268 (Schering AG; appl. 4.10.1971). DOS 2 204 361 (Schering AG; appl. 27.1.1972). DOS 2 260 303 (Schering AG; appl. 6.12.1972). GB 1 387 91 1 (Schering AG; valid from 19.3.1975; D-prior. 4.10.1971,27.1.1972). Laurent, H. et al.: Arzneim Forsch. (ARZNAD) 27 (II), 2187 (1977) (also other methods). DOS 2 441 284 (Schering AG; appl. 27.8.1974). BE 823 682 (Schering AG; appl. 20.12.1974; D-prior. 21.12.1973, 27.8.1974, 16.9.1974). Formulation(s): cream 7.5 mglg; ointment 7.5 mglg; powder 100 mgl4 g Trade Narnefs): D: Bi Vaspit (Asche)-comb. Lenen (Alk-Scherax; Vaspit (Asche) Schering) I: Vaspit (Schering) Fluocortolone ATC: C05AA08; D07AC05; D07BC03; H02AB03; S01CA04 Use: glucocorticoid RN: 152-97-6 MF: CZ2H2,FO4 MW: 376.47 EINECS: 205-811-5 CN: (6a,11~,16a)-6-fl~oro-11,21-dihydroxy-l6-methylpregna-l,4-diene-3,20-dione 894 F Fluocortolone 1. BrZ 2. Nal 3. KOwCH3 b I N-bromo- succinimide. 16a rnethylpregnenolone 21 -0cetoxy-3p-hydraxy-16-a- 3@-ocetote methyl-20-axo-5-pregnene fluoride (cf. flumetasone synthesis) OH microbiological dehydrogenation ,,,CHJ [Corynebacterium simplex or Bacillus lentus] + Fluocortolone Referetrce(s): DE 1 135 899 (Schering AG; appl. 20.5.1960). BE 614 196 (Schering AG; appl. 21.2.1962; D-prior. 22.2.1961). Domenico, A. et al.: Arzneh-Forsch. (ARZNAD) 15,46 (1965). Dl3 1 169 444 (Schering AG; appl. 22.2.1961). synthesis of starting cotnpound: Petrov, V.; Williamson, D.M.: J. Chem. Soc. (JCSOA9) 1959, 3595. alternative synthesis: Kieslich, K. ct a].: Justus Liebigs Ann. Chem. (JLACBF) 726, 168 (1969). DOS 1 909 152 (Schering AG; appl. 19.2.1969). review: Akhrem, A.A. et al.: Russ. Chem. Rev. (Engl. Trans].) (RCRVAB) 34,926 (1965). Formulation(s): cream 2.5 mglg; lotion 2.5 mglg; ointment 2.5 mglg; tabl. 5 mg, 20 mg, 50 mg Trade Name(s): D: Ultralan (Schering) Ultralanum (Schering). Ultralanum oint. Ultrasine (Schering) comb.; wfm (Schering)-comb,; wfm CB: Ullradil (Schering); wfm Fluocortolone caproate F 895 Ultraproct (Schering)- I: Ultralan (Schering)-comb. Ultraproct (Schering)- comb.; wfm Ultralan orale (Schering) comb. - F~uoco~~o~o~~ caproate ATC: C05AA08; D07AC05; H02AR03 Use: glucocorticoid RN: 303-40-2 MF: C2,H,,FOs MW: 474.61 EINECS: 206-140-0 CN: (6a,ll P, 16a)-6-fluoro-1 l-hydroxy-l6-methyl-21-[(1-oxohexyl)oxy]pregna-1,4-diene-3,20-dione fluocortolone caproic anhydride Fluocortolone coproate Referencefs): FR 1 561 884 (Schering AG; appl. 10.5.1968; D-prior. 13.5.1967). Forrnulation(s): cream; lotion; ointment 2.5 mglg in comb. with fluocortolone Trade Narnefs): D: Ultralan Creme (Schering)- comb. Ultralan Salbe (Schering)- comb. GB : Ultraproct (Schering)- comb. F: Myco-Ultralan (Schering)- comb. Ultralan (Schering)-comb. Ultralanum (Schering Ultraproct (Schering)- Chemicals)-comb.; wfm comb. Ultraproct (Schering Ficoid (F1sons)-comb.; Chemicals)-comb.; wfm wfm I: Ultralan (Schering)-comb. Ultradil (Schering Ultraproct (Schering). Chemicals)-comb.; wfm comb. Fluocortolone trimethylacetate (Fluocortolone 2 1 -pivalate) ATC: C05AA08; D07AC05; H02AB03 Use: glucocorticoid RN: 20380-10-3 MF: C2,H3,FO5 MW: 460.59 CN: 6a-fluoro-17,21-dihydroxy-l6a-methyl-pregna-l,4-diene-3,20-dione 21-pivalate tl~ocortol~ne pivolic anhydride F Fluocortolone trimethylacetote Referencefs): FR 1561 884 (Schering AG; appl. 10.5.1968; D-prior. 13.5.1967). 896 F Fluorescein Formulatio~z(s): cream 20 mg/g; cream 2.5 mglg in comb. with fluocortolone; emulsion 2.5 mglg in comb. with fluocortolone/-caproate; suppos. 40 mg in comb. with lidocain hydrochloride Trade Name(s): D: Doloproct (Schering)- Ultraproct (Schering)- Ultraproct (Schering comb. with lidocaine comb. Chemicals) hydrochloride F: Ultraproct (Schering)- I: Ultralan (Schering)-comb. Ultralan Creme (Schering)- 'jmb. Ultraproct (Schering)- comb. GB: U tralanum (Schering)- comb. comb. Fluorescein ATC: SOlJAOl Use: diagnostic RN: 2321-07-5 MF: CZoHj2O5 MW: 332.31 EINECS: 219-03 1-8 LD,,,: 300 mg/kg (M, i.v.) CN: 3',6'-dihydroxyspiro[isobenzofuran-1(3H),9'-[9H]xanthen]-3-one disodium salt RN: 518-47-8 MF: C20H,oNa20S MW: 376.28 EINECS: 208-253-0 ' LD,,,: 1 glkg (M, i.v.); 4738 mglkg (M, p.0.); 1 glkg (R, i.v.); 6721 mglkg (R, p.0.); 1 glkg (dog, i.v.) phthalic resorcinol anhydride Fluorescein Reference (s): Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 23,414. Formulation(s): amp. 113.2 mglml (as disodium salt); eye drops 1.7 mg/ml Trade Name(s): D: Fluorescein-Losung 1 0 % Thilorbin (Alcon) I: Pancreolauryl Test intravenos 1nj Losung GB: Minims Fluorescein (Geymonat; as laurate) (Alcon) Sodium (Chauvin) J: Fluor (Tobishi-Santen) Fluoreszein 0,15 % Thilo Minims lignocaine and Fluores (Showa Yakuhin) Augentropfen (Thilo) fluorescein (Chauvin)- Fluorescein sodium Pancreolauryl-Test comb. (Kobay ashi) (Temmler) Fluorescite (Alcon) Fluorometholone ATC: C05AA06; D07AB06; D07XB04; DlOAAOl; SOlBA07; SOlCBO5 Use: glucocorticoid RN: 426-13-1 MF: Cz2H2,F0, MW: 376.47 EINECS: 207-041 -5 LD,,,: 443 mglkg (R, i.p.) CN: (6a, 1 1 P)-9-fluoro- 1 1,17-dihydroxy-6-methylpregna-1,4-diene-3,20-dione Fluorometholone F 897 Ob ,CH3 pyridine + ___* CH, CH, 9-fluoro-6a-methyl- methane- (1) hydrocortisone sulfonyl chloride Zn, CH3COOH I rnicrobiologicol dehydration [Ssptomym offinis (ATCC 6737)] I1 CH3 Fluorometholone Referencets): US 2 867 638 (Upjohn; 6.1.1959; appl. 17.5.1967; prior. 10.9.1956). DE 1056 605 (Upjohn; appl. 6.5.1959; USA-prior. 10.9.1956). starting material: Spero, G.B. el al.: J. Am. Chem. Soc. (JACSAT) 79, 1515 (1957). Formulation(s): eye drops 1 mglml Trade Namets): D: Efflumidex (Pharm- Allergan) F: Efflumycin (Pharm- I: Allergan)-comb. Ehrtolan (Albert-Rousse1)- comb. Ejemolin (CIBA Vision)- J: comb. Fluoropos (Ursapharm) Isoptotlucon (Alcon) Ursnon (Nihon Yakuhin Flucon collyre (Alcon) Kog~o) Efemoline (CIBA Vision). USA: FML Liquifilm (Allergan); comb. wfm Fluaton (Allergan) Neo-Oxylone (Upjohn). Flumetol (Farmila)-comb. comb.; wfm Flu-Base (Kowa) Oxylone (Upjohn); wfm Flumetholon (Santen) Okilon (Sumitorno) 898 F Fluorouracil Pluorouracil (Fluracilum) ATC: LOlBC02 Use: antineoplastic RN: 51-21-8 MF: C4H,FN202 MW: 130.08 EINECS: 200-085-6 LD,,,: 81 mgkg (M, i.v.); 115 mglkg (M, p.0.); ! 245 mglkg (R, i.v.); 230 mgkg (R, p.0.); 30 mglkg (dog, p.0.) CN: 5-fluoro-2,4-pyrimidinediol or 5-fluoro-2,4(1H,3H)-pyrimidinedione ethylate H 0' ethyl fluoroocetote ethyl formate (1) S-methylthiouronium sulfote 5-fluoro- fluorourocil 2-methyl- thiouracil F2 or CF30F b fluorine H trifluoromethyl urocil hypofluorite Refewnce(s): a US 2 802 005 (C. Heidelberger, R. Duschinsky; 6.8.1957; prior. 26.9.1956). Duschinsky, R et al.: J. Am. Chem. Soc. (JACSAT) 79,4559 (1957). b US 3 682 917 (I. L. Knuniants et al.; 8.8.1972; appl. 25.3.1970). US 3 846 429 (S. A. Giller et al.; 5.1 1.1974; appl. 22.9.1971). US 3 954758 (PCR, Inc.; 4.5.1976; prior. 7.8.1967, 1.3.1968,27.5.1970,4.10.1971). DOS 2 149 504 (Research Inst. f. Med. and Chem.; appl. 4.10.1971; USA-prior. 5.10.1970). DOS 2 719 245 (Daikin Kogyo; appl. 29.4.1977; J-prior. 29.4.1976). DOS 2 726 258 (Daikin Kogyo; appl. 10.6.1977; J-prior. 11.6.1976). synthesisfiom orotic acid by fluorination and following decarboxylation: DOS 2 826 496 (Asahi Glass; appl. 16.6.1978; J-prior. 17.6.1977). Formulation(s): cream 5 %; ointment 50 mglml, 1 g/20 g; plaster 96 ~gll .l3 cm2; vial 50 mglml, 250 mg15 ml, 500 mg/lO ml, 1000 mg120 ml Trade Name(s): D: Actino-Hermal Pflaster Verrumal (Herma1)-comb. GB: Accusite (Matrix) (Hermal) numerous generics and I: Efudlx (Roche) Efudix Roche (ICN) combination preparations Fluoro-Urac~le (Roche) Fluroblastin (Pharmacia & F: Efudix (Roche) generic Upjohn) Fluoro-uracile (Roche) J: 5-FU (Kyowa) Ribofluor (ribosepharm) generic Arumel (SS Seiyaku) Fluoxetine F 899 Benton (Toyo Jozo) Lifril (Kissei) Ulup (Maruko) Carzonal (Tobishi) Timadin (Torii) USA: Efudex (Roche) Efudix (Roche) Ulosagen (Kyowa Yakuhin Fluoroplex (Allergan) Flacule (Nippon Kayaku) Osaka) generic Fluoxetine ATC: NO~ABO~ &illy 1 10140) Use: antidepressant, serotonin-uptake inhibitor f RN: 54910-89-3 MF: C,,HlnF3NO MW: 309.33 LD,: 464 mgkg (M, p.o.1; 825 mgkg (R, p.0.) CN: (~)-N-methyl-y-[4-(trifluoromethyl)phenoxy]benzenepropanamine monohydrochloride RN: 59333-67-4 MF: C17HlnF3N0 . HC1 MW: 345.79 LD,: 100 mgkg (M, i.p.1 acelophenone paraform- dimethyl- 3-dimethylamino- aldehyde amine propiophenone (1) 1. B,H, 2. S0Cl2 F3c~0H, NaOH I 11 1. diborone I CH3 4-trifluoromethyl- 2. thionyl chloride phenol 1.BrCN 2. KOH NNCH3 1. cyanagen bromide (*)-N,N-dirnethyl-3-phenyl-3- (4-trifluoromethylphenoxy)- pmpylamine (11) NaOH, DMF Fluoxetine (*)-I -phenyl-3-(methyl- 1 -chloro-4-(tri- omino)propan- 1-01 (111) fluoromethyl)- benzene (1V) 900 F Fluoxetine bentyl 4-(tri- fluoromethyl)- phenyl ether 1. o3 2. H2N-CH, 3. NaCNBH3 _____* 3. sodium cyano- Fluoxetine borohydride N-methyl- hydroxyl- omine N-methyl- nitrone 2-methyl-5- . phenylisoxo- zolidine (VI) H . Pd-C N VI 2. 111 - ( Fluoxetine ( 1. NoBH,, THF 1. N 2. NaH, OMS0 NH, - VII cyanomethyl phenyl ketone (?)'-3-phenyl-3- hydroxy-l- proponarnine 0 LIAIH,, THF + CI,kOP'3 diborone I + methyl chloroformoie Fluoxetine El 1. CIC02C2H5 2. NaOH -b Ill 1. ethyl chloroformote . (*)-I -phenyl- 3-( methyl- 1 -chloro- 4-( tri- omino)propan- 1-0 1 (111) fluoromethyl )- benzene (1V) 900 F Fluoxetine bentyl 4-( tri- fluoromethyl )- phenyl ether 1. o3 2. H2N-CH,. S01CA04 Use: glucocorticoid RN: 15 2-9 7-6 MF: CZ2H2,FO4 MW: 376.47 EINECS: 20 5-8 1 1-5 CN: (6a,11~,16a )-6 -fl~oro-11,21-dihydroxy-l6-methylpregna-l,4-diene-3,20-dione 894 F Fluocortolone 1 2 1 -pivalate) ATC: C05AA08; D07AC05; H02AB03 Use: glucocorticoid RN: 2038 0-1 0-3 MF: C2,H3,FO5 MW: 460.59 CN: 6a-fluoro-17,21-dihydroxy-l6a-methyl-pregna-l,4-diene-3,20-dione 21-pivalate