Flurbiprofen F 91 1 Flurazeporn Reference(s): US 3 567 710 (Hoffmann-La Roche; 2.3.1971; prior. 3.6.1968). alternative synthesis by reaction of 2-diethylan~inoethyl chloridc with 7-chloro-5-(2-fluoropheny1)-2-oxo-2,3- dihydro-1 H- l,4-benzodiazepine: GB 1 O4O 548 (Roche; appl. 1.3.1963; USA-prior. 2.3.1962). Formulation(s): cps. 10 mg, 15 mg; tabl. 27.42 mg (as base); cps. 15 mg, 30 mg; tabl. 30 mg (as monohydrochloride); cps. 15 mg, 30 mg; s. r. cps. 20 mg (as dihydrochloride) Trade Narne(s): D: Dalmadorm (Roche) Felison (~a~ro~h&n) J: Benozil (Kyowa) Flurazepam 15130 Riker Flunox (Boehringcr Dalmate (Nippon Roche) (3M Medica) Mannh.) Insumin (Kyorin) Staurodorm Neu Mldorm A.R. (Piarn) USA: Dalmane (Rochc) (Dolorgiet) Remdue (Biornedica GB: Dalrnane (Roche) Foscarna) I: Dalmadorm (Roche) Valdorm (Valeas) Flurbiprofen ATC: M01AE09; M02AA19; S01BC04 Use: anti-inflammatory, analgesic RN: 5104-49-4 MF: ClsH13F0, MW: 244.27 EINECS: 225-827-6 LDsU: >385 mg/kg (M, i.v.); 640 mgkg (M, p.0.); 117 rngkg (R, p.0.); 10 mglkg (dog, p.0.) CN: 2-fluoro-a-methyl[l , 1'-biphenyl]-4-acetic acid sodium salt RN: 56767-76-1 MF: C,,H,,FNaO, MW: 266.25 bromobenzene 4'-brorno-3'- 4-acetyl-2-nitra- 4-ocetyC2-ornino- nitroacetaphenone biphenyl biphenyl 912 F Flurbiprofen A HO''CH~ HzS04 . COOH 0-CH, 0 4-ocetyl-2-fluoro- biphenyl (1) 2-fluoro-4-biphe- nylylocetic ocid ethyl 2-fluoro-4- biphenylylocetote (U) 1. NoOC,H, 2. H~c'O\ o o"Sb,~~3 " + A - COOH H3C O O CH3 2. dimethyl sulfotc CH3 diethyl corbonote I Flurbiprofen 4-bromo-2- fluorobiphenyl 2-(2-fluoro-4-biphenylyl)- 2-hydroxypropionic acid (111) polyphosphoric acid 111 - Flurbiprofen CH2 2-(2-fluoro-4-bi- phenylyl)ocrylic acid Reference (s): a DAS 1 518 528 (Boots; appl. 19.1.1965; GB-prior. 24.1.1964). US 3 755 427 (Boots; 28.8.1973; GB-prior. 24.1.1964). US 3 793 457 (Adams Sectal; 19.2.1974; GB-prior. 24.1.1964). b GB 1 5 14 8 12 (Boots; appl. 4.4.1975; valid from 31.3.1976). similar method: US 3 959 364 (Boots; 25.5.1976; GB-prior. 24.5.1973). alternative syntheses: DOS 2 646 792 (Mitsubishi Petrochemical; appl. 16.10.1976; J-prior. 23.10.1975, 31.7.1976). racemate resolution: DOS 2 809 794 (Boots; appl. 7.3.1978; GB-prior. 8.3.1977, 18.1.1978). Formulation(s): amp. 50 mg; cps. 200 mg; drg. 50 mg, 100 mg; eye drops 0.3 mglml (as sodium salt dihydrate); plaster 40 mg; s. r. cps. 200 mg; suppos. 100 mg; tabl. 50 mg, 100 mg Trade Name(s): D: Froben (Kanoldt; 1980) Ocufen (Allergan) J: Froben (Kakenyaku) Ocuflur (Pharm-Allergan) GB: Froben (Knoll; 1977) USA: Ocufen (Allergan; 1987). F: Antadys (Theramex) Ocufen (Allergan) Cebutid (Knoll; 1979) I: Froben (Boots Italia) Flurotyl F 913 Flurotyl (Flurothyl) RN: 333-36-8 MF: C4H,F,0 MW: 182.06 LDs0: 46 mgkg (M, i.v.) CN: 1,l'-oxybis[2,2,2-trifluoroethane] No F~'OH -+ F~C-ON~ 2,2,2-trifluoro- (n) ethanol (I) Use: CNS stimulant. convulsant Tos-CI Flurotyl I Reference(s): US 3 363 006 (Pennwalt; 9.1 .l968; prior. 29.12.1955,20.6.1960). Formulation(s): 2 ml in special inhalation device Tmde Name(s): USA: Indoklon (Ohio Med.); wfm Fluroxene ATC: NOlAA Use: inhalation anesthetic RN: 406-90-6 MF: C4H5F30 MW: 126.08 EINECS: 206-977-1 LD,,: 5600 mgkg (R, i.p.) CN: (2,2,24rifluoroethoxy)ethene K HCGCH HO"CF~ -+ KO"CF~ . acetylene 2,2,2-triflu~ro- Fluroxene ethanol (I) montmorillonite. 240-280 OC H3C-CHO + 1 r ocetoldehyde Reference(s): a US 2 830 007 (Air Reduction Cornp.; 1958; appl. 1953). b US 2 870 21 8 (Air Reduction Cornp.; 1959; appl. 1955). Fonnulation(s): liquid for inhalation 125 rnl 914 F Fluspirilene Trade Name(s): USA: Fluorornar (Ohio Med.); wfm Fluspirilene ATC: NOSAGO1 Use: neuroleptic KN: 1841 -19-6 MF: C,,H,,F,N,O MW: 475.58 EINECS: 217-418-6 LD,,: 106 mg/kg (M, i.m.); >I46 mg/kg (R, i.m.) CN: 8-[4,4-bis(4-fluorophenyl)butyl]-l-phenyl-l,3,8-triazaspiro[4.5]decan-4-one aN9O+ 4 + KCN b NH2 1 -benzyl- aniline potassium 4-piperidone cyanide 4-onilino- 1 -benzyl- 4-corbomoylpiperidine (I) spiro[4.5]decane (11) 4,4-bis-(4-fiuaro- phenyl)butyl bromide Reference(s): Fluspirilene BE 633 914 (Janssen; appl. 20.6.1963; USA-prior. 22.6.1962). US 3 238 216 (Jansscn; 1.3.1966; prior. 22.6.1962, 20.6.1963). DAS 1 470 125 (Janssen; appl. 21.6.1963; USA-prior. 22.6.1962). Formulation(s): amp. 1.5 mg10.75 ml, 2 mgl ml, 12 mg16 ml; vial 12 mg (2 mglml) Trade Name(sJ: D: Fluspi (Neuro Hexal) GR: Redeptin (Smith Klinc & Imap (Janssen) French); wfm Kivat (Honnosan) USA: Imap (McNeil); wfm Flutamide F 915 Flutamide ATC: L02BB01 Use: antiandrogen, antineoplastic (hormonal) RN: 133 11-84-7 MF: CllHl1F3N2O3 MW: 276.21 EINECS: 236-341-9 LD,,: 787 mgkg (R, p.0.); >2 glkg (dog, p.0.) CN: 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide Qc, HNO,, H2S0, H2. Pd-C w OpN ncF3 - HzN trifluoro- msthylbenzene 1-nitro-3-tri- fluoromethyl- benzene 3-trifluoromethyl- aniline (I) 3'-trifluoromethyl- acetonilide 4-nitro-3-trilluoro. methylaniline (11) isobutyryl chloride (Ill) Flutornide pyridine 1 + UI d H3C')(40CF3 CH,~ 3'-Lrifluorornethyl- isobutyronilide Reference(s): J. Med. Chem. (JMCMAR) 10,93 (1967). a DOS 2 130 450 (Scherico; appl. 19.6.1971). US 4 144 270 (Scherico; 13.3.1979; appl. 26.6.1974). b US 4 302 599 (Schering Co.; 24.11.1981; prior. 10.9.1979). synthesis of 4-nitro-3-trifluoromethylaniline: Jones, R.G.: J. Am. Chem. Soc. (JACSAT) 69,2346 (1947). medical use: US 3 995 060 (Scherico; 30.11.1976; appl. 11.9.1974). US 4 139 638 (Schcring Corp.; 13.2.1979; appl. 3.10.1977). US 4 161 540 (Schering Corp.; 13.2.1979; appl. 3.10.1977). US 4 329 364 (Schering Corp.; 11.5.1982; appl. 23.9.1976). US 4 474 813 (Schering Corp. 2.10.1984; appl. 24.5.1982). Formulation{s): cps. 125 mg; tabl. 250 mg 916 F Flutazolam Trade Name(s): D: Apimid (Apogepha) Cytamid (esparma) Flumid (Hexal) Fluta GRY (GRY-Pharma) Flutarnex (Sanofi F: Winthrop) Fugerel (Essex Pharma; GR: 1984) Flutazolam Prostica (TAD) Drogenil (Schering- Prostogenat (Azupharma) Plough) Testac (medac) I: Eulexin (Schering-Plough; Testotard (Chephasaar) 1986) Eulexine (Schering-Plough; J: Odyne (Nippon Kayaku) 1987) USA: Eulexin (Schering) Chimax (Chiron) ATC: NOSBA Use: benzodiazepine anxiolytic, tranquilizer RN: 27060-91-9 MF: CI9HIRC1FN2O3 MW: 376.82 LD,,,: 19 10 mgkg (M, p.0.); >6 @kg (R, p.o.1 CN: 10-chloro- l l b-(2-fluoropheny1)-2,3,7,1 1b-tetrahydro-7-(2-h~droxyethyl)oxazolo[3,2- d][l,4]benzodiazepin-6(5H)-one 2-amino-5-chloro- glycine ethyl estel 2'-fluorobenzo- hydrochloride phenone (cf. flunitrozepom synthesis) U ol~rnin~m chloride ethylene oxide Flutozolorn u 7-chloro-5-(2- f1uorophenyl)- 1.3-dihydro-2H- 1,4-benzodioze- pin-2-one (I) Rcference(s): DOS 1 952 486 (Hoffmann-La Roche; appl. 17.10.1969; USA-prior. 18.10.1968). synthesis of 7-chloro-5-(2-fluoropheny1)- 1,3-dihydro-2H- 1,4-henzodiazepin-2-one: US 3 109 843 (Hoffinann-La Roche; 5.1 1.1963; prior. 21.6.1962). Formulation(s): tabl. 4 mg Trade Name(s): J: Coreminal (Mitsui) Fluticasone propionate F 9 17 Fluticasone propionate ATC: ROlAD08; R03BA05; D07AC 17 Use: locally active glucocorticosteroid RN: 80474-14-2 MF: C,,H,,F,O,S MW: 500.58 LDS,: >2 glkg (R, p. 0.); >1 glkg (R, s. c.) CN: (6a,1 1j3,16a,17a)-6,9-Difluoro- l l-hydroxy-l6-methyl-3-oxo-l7-(1-oxopropoxy)androsta-1,4-diene-17- carbothioic acid S-(fluoromethyl) ester 0 H,IO,, THF , 1 periodic acid propionyl chloride F F (cf. diflucortolone volerate) 2. H,S, DMF q0*cH3 3. HCI. H20 Me I n2 ~~~CH, H0v-4 b - Me or 1, arcl. DMA, NaHC03 2. AgF. CH&N I1 , F Fluticasone propionate I Reference(s): BE 887 518 (Glaxo Group; appl. 13.2.1981; GB-prior. 15.2.1980). L 109 656 (Chemagis LTD.;IL-prior. 15.5.1994). Phillipps, G.H. et al.: 5. Med. Chem. (JMCMAR) 37,3717 (1994). Formulation(s): aerosol for inh. 44 pg, 110 pg, 220 pg; cream 0.05%; ointment 0.005%; nasal spray 0.05% Trade Name(s): D: Atemur (ASTA Medica Viani (Cascan; Glaxo I: Flixotide (Glaxo AWD; Glaxo Wellcome) Wellcome) comb. with Wellcome) Flutide (Cascan; Glaxo Salmeterol Fluspiral (Menarini) Wellcome) GB: Cutivate (Glaxo Wellcome) USA: Cutivate (Glaxn Wellcome) Flutivate (Cascan; Glaxo Flixonase (Allen & Flonase (Glaxo Wellcome) Wellcome) Hanburys) Flovent (Glaxo Wellcomc) Flixotide (Allen & Hanburys) 918 F Flutoprazepam Flutoprazepam ATC; NOSBA Use: long acting benzodiazepine anxiolytic RN: 25967-29-7 MF: C,,H,,CIFN,O MW: 342.80 LD,,,: 21 10 mglkg (M, i.p.); 2430 mgkg (M, p.0.); 2230 mglkg (R, i.p.); 10.06 g/kg (R, p.0.); I000 mgkg (rabbit, p.0.); >I0 glkg (dog, p.0.) CN: 7-chloro-l -(cyclopropylmethyl)-5-(2-fluoropheny1)- 1.3-dihydro-2H- l,4-benzodiazepin-2-one 1. Brz *. 0 0 H3CFH3 CI DNHz , NoN02 tic1 r 2. ethyl ocetoocetote F 2-fluoro- toluene ethyl a-(2-fluoro- benzyl)ocetoocetate 2. KOH 3. S0Cl2 HCI. C2H,0H 4. NH, + CI + N 1 cyclopropylmethyl bromide -, LI ethyl a-(2-fluoro- benzy1)-a-(4-chloro- phenyloza)oceto- ethyl 5-chloro-3- (2-fluoropheny1)- indole-2-corbo~ylote (11) acetate (I) 5-chlaro-1 -cycle- ('0 propylrnethyl-3- (2-fluoropheny1)- indole-2-corbou- ornide (N) I Flutoprozeporn Flutrimazole F 919 1. KOH 1. NH, 1. 111 CN 2. LiAIH, CI - CI -v \ / 5-chloro-3- (2-fluoropheny1)- indole-2- carbonyl chloride Referencefs): DE 1 795 372 (Sumitomo; appl. 20.9.1968; J-prior. 22.9.1967). DE 1 795 771 (Sumitomo; appl. 20.9.1968; J-prior. 2.1 1.1967). US 3 925 364 (Sumitomo; 6.8.1974; appl. 16.9.1968; J-prior. 22.9.1967). additional synthesis: DOS 2 151 540 (Sumitomo; appl. 15.10.1971; J-prior. 17.10.1970). DOS 2 113 122 (Sumitomo; appl. 18.3.1971; J-prior. 19.3.1970). Formulation(s): tabl. 2 mg Trade Narnefs): J: Restas (Banyu; 1985) Flutrimazole (UR-4056) ATC: DOlA Use: topical antifungal RN: 119006-77-8 MF: C,,H,,F,N, MW: 346.38 CN: l-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole 920 F Flutropium bromide 2.4'-difluoro- benzophenone (2-fluorophenyl)- Flutrimazole (4-fluoropheny1)- phenylchloro- methane Refewnce(s): EP 352 352 (J. Uriach &Cia.; appl. 31.1.1990; prior. 28.7.1988). Formulation(s): cream 1 % Trade Name(s): E: Micetal (Uriach) Flutropium bromide (BA-598 BR) ATC: R03BB Use: anticholinergic, bronchodilator RN: 635 16-07-4 MF: C,H,,BrFNO, MW: 478.40 LD,,: 53 mgkg (M, i.p.1; 11 mgkg (M, i.v.); 760 mgikg (M, p.0.); 228 mglkg (M, LC.); 77 mglkg (R, i.p.); 12.5 mglkg (R, i.v.); 740 mgkg (R, p.0.); 615 mgikg (R, s.c.) CN: (endo,syn)-8-(2-fluoroethyl)-3-[(hydroxydiphenylacetyl)oxy]-8-methyl-8-azoniabicyclo[3.2.l]octane bromide 1. PCI, H / \ 2. N-carbobenzyloxynortropine - benzilic acid (I) N-carbobenzyloxynortropine benzilate (Il) H H I. . NapJ 2. H3C-Br I1 b ______* H OH 1. 1 -bromo-2- fluoroethane (IU) / \ 2. methyl Br- - nortropine benzilote bromide (N) 1 Flulropium bramide . phenyloza)oceto- ethyl 5-chloro- 3- (2-fluoropheny1 )- indole-2-corbo~ylote (11) acetate (I) 5-chlaro-1 -cycle- ('0 propylrnethyl- 3- (2-fluoropheny1 )- indole-2-corbou- ornide (N) I. 2-fluoro-a-methyl[l , 1'-biphenyl ]-4 -acetic acid sodium salt RN: 5676 7-7 6-1 MF: C,,H,,FNaO, MW: 266.25 bromobenzene 4'-brorno-3&apos ;- 4-acetyl-2-nitra- 4-ocetyC2-ornino- nitroacetaphenone. 7-chloro- 5-( 2- f1uorophenyl )- 1.3-dihydro-2H- 1,4-benzodioze- pin-2-one (I) Rcference(s): DOS 1 952 486 (Hoffmann-La Roche; appl. 17.10.1969; USA-prior. 18.10.1968). synthesis of 7-chloro- 5-( 2-fluoropheny1)-