Flugestone acetate F 88 1 Felunamin (Hokuriku) Nichisedan (Nissin) Ristogen (Kowa Yakuhin) Flufacid (Wakamoto) Paraflu (Dainippon) Romazal (Tobishi) Lanceat (Maruko) Reumajust A (Horita) Saal-F (Towa) Flugestone acetate (Hurogestone acetate) ATC: GO3 Use: progcstone RN: 2529-45-5 MF: C2,H3,FOs MW: 406.49 EINECS: 219-776-9 CN: (1 I P)-17-(acety1oxy)-9-fluoro-11 -hydroxypregn-4-ene-3,20-dione 1. Raney-Ni HI, CH,COOH rr hydrogen 2. acetic anhydride, iodide p-toluenesulfonic acid (n) ( Flugestone ocetote 1. HOBr 2. NO~CO~, H~O, THF -b 1. hypobromous acid 0 &OH Me H FH. 0 ' & H3 i i 0 2. HCI. CH,OH + 1 1, p-toluenesulfonic ocid Rejerence(s): a Bergstrom, C.G. et a].: J. Am. Chem. Soc. (JACSAT) 81,4432 (1959). b US 2 892 851 (Searle; 30.6.1959; prior. 19.5.1958). US 2963 498 (Searle; 6.12.1 960; prior. 11.5.1959). Trade Narners): USA: Cronolone (Searlc); wfm 882 F Flumazenil Flumazenil (Ro-15-1788) ATC: V03AB25 Use: henzodiazepine antagonist, treatment of benzodiazepine intoxication RN: 78755-81-4 MF: CL5HI4FN3O3 MW: 303.29 LD5,,: 4000 mg/kg (M, i.p.); 143 mglkg (M, i.v.); 1300 mglkg (M, p.0.); 85 mgkg (R, i.v.); 4200 mg/kg (R, p.0.) CN: 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[l,5-a][1,4]be1uodiazepine-3-carhoxylic acid ethyl ester 1. Hz. Pd-C KMnO 2. COC12 F CH3 potassium F COOH 2. phosgene n 2-nitro-5- per- 2-nitro-5-fluoro- mongonote fluorotoluene benzoic acid HOOC ethyl isocyanate- 0 CH3 ocetote potossium tert-butylate N-methyl- 7-fluoro-4-methyl- glycine 3,4-dihydro-2H-1.4- benzodiazepin-2,5(1H)- dione " 5-fluoroisatoic anhydride (I) Heference(s): EP 27 214 (Hoffmann-La Roche; appl. 10.2.1980; CH-prior. 4.10.1979,30.11.1979,25.7.1980). US 4 3 16 839 (Hoffmann-La Roche; 23.2.1982; appl. 3.10.1980; CH-prior. 4.10.1979, 30.11.1979, 25.7.1980). US 4 346 030 (Hoffmann-La Roche; 24.8.1982; appl. 16.1 1.1981; CH-prior. 4.10.1979, 30.1 l.l979,25.7.l98O). Hunkeler, W. et al.: Nature (London) (NATUAS) 290,5 14 (198 1). Formulation(s): amp. 0.5 mg/5 ml, 1 mg/lO ml Trade Narne(s): D: Anexate (Roche; 1989) GB: Anexate (Roche) J: Anexate (Yamanouchi) F: Anexate (Roche) I: Anexate (Roche; 1989) USA: Romazicon (Roche) Flumedroxone acetate ATC: N02CROI Use: antimigraine agent, progestogen RN: 987- 18-8 MF: C,,H,,F,O, MW: 440.50 EINECS: 213-577-0 CN: (6a)- 17-(acetyloxy)-6-(trifluoromethyl)pregn-4-ene-3,2O-dione 17-ocetoxyprogesterone triethyl orthoformote Flumequine F 883 trifluorornethyl iodide ' Reference(s): GB 905 694 (Lovens Kemiske Fa., valid from 14.3.1961; prior. 18.3.1960, 8.6.1960). Godfredsen, W.O.; Vangedal, S.: Acta Chem. Scand. (ACHSE7) 15, 1786 (1961). Fomulation(s): drg. 1 mg in comb. Trade Name(s): D: Praemenstron (Nordmark)- F: Precyclan (Leo)-comb. comb.; wfm Flumequine ATC: G04AB06 Use: chemotherapeutic, antibacterial RN: 42835-25-6 MF: CL4H12FN03 MW: 261.25 EINECS: 255-9626 CN: 9-fluoro-6,7-dihydro-5-methyl-] -oxo- 1 H,SH-benzo[ij]quinolizine-2-carboxylic acid 1. polyphosphoric acid 2. NaOH. H20 6-fiuoro-2-methyl- diethyl 1.2.3.4-telrohydro- ethaxymethylene- qulnolins maionate Reference(s): DOS 2 264 163 (Riker; appl. 29.12.1972; USA-prior. 30.12.1971). US 3 896 131 (Riker; 22.7.1975; prior. 2.1 1.1972, 30.12.1971). Formulation(s): tabl. 400 mg Trade Name(s): F: Apurone (3M Santt) I: Flumural (SPA) Flumetasone (Flumethasone) ATC: D07AB03; D07BBO1; D07CB05; D07XB01; S02CA02 Use: glucocorticoid, anti-inflammatory RN: 2135-17-3 MF: C,,H2.F,0s MW: 410.46 EINECS: 218-370-9 CN: (6a,l lp,l6a)-6,9-difluoro- 1 l,17,21 -trihydroxy-16-methylpregna- 1,4-diene-3,20-dione pivalate RN: 2002-29- 1 MF: C2,H,,F20, MW: 494.58 EINECS: 21 7-901 - 1 LD,,: >5 g/kg (M, p.0.); 884 F Flumetasone 16-dehydropregnenolone methylrnognesium 16o-methylpregnenolone acetate bromide 3pacetote peroxyocetic 1. HZFZ 2. O 1 1 . pyridine H3c~cl , n3c o cH3 , HC OF K 2. Nol 0 H,C+ II2 perocetic 0 acid H3CK0 H3Cy0 F 1. CrO,, CH3COOH 2. CH COOK. C,H,OH L 1. KOH, CZH50H 2. Curvulorio lunoto (micro- biological hydroxylation) 3. 1 1 . pyridine H,C 0 CH, b HCI, CH3COOH b 1. CH,SO,CI, pyridine 2. CH,COONa , v Flunarizine F 885 2. KHCO, ' VI hydrogen 1 selenium(N) fluoride oxide 0 - t Flumetasone Flumetasone pivalate (from 3,11.20-trioxo-4,16-pregnadiene) Reference(s): a US 2 671 752 (Syntex; 1954; appl. 1951). Djerassi, C. et a].: J. Am. Chem. Soc. (JACSAT) 81, 3156 (1959); 82, 2318 (1961). b FR 1 374 591 (Ciba; appl. 8.10.1963; CH-prior. 12.10.1962). synthesis of 21-(2,2-dimethylpropionyloxy)-3,20-dioxo-6a-fluoro-17-hydroxy-16a-methyl- I ,4,9(11) pregnat~ iene: US3 557 158 (Upjohn; 19.1.1971; prior. 18.3.1959). alternative syntheses: US 3 557 158 (Upjohn; 19.1.1971; appl. 22.1.1962; prior. 18.3.1959). Schneider, P. et a].: J. Am. Chem. Soc. (JACSAT) 81, 3167 (1959). GB 902 292 (Upjohn; appl. 27.7.1959; USA-prior. 14.8.1958). US 4041 055 (Upjohn; 9.8.1977; appl. 17.11.1975). Formulation(s): sol. 0.02 gI100 g (0.02 %); cream 0.02 g1100 g (0.02 %); lotion 0.02 gI100 g (0.02 %); ointhent 0.02 g1100 g (0.02 %) Trade Name(s): D: Cerson (LAW) Psocorthe (Ciba-Geigy)- Neolog (Zyma)-comb. Locacorten (Novartis comb.; wfm several combination Pharma) GB: Locorten Vioform preparations F: Locacortkne (Ciba-Geigy)- (Novartis)-comb. J: Locorten (Ciba-Geigy) comb.; wfm I: Locorten (Zyma) Testohgen (Teisan) Locasalkne (Ciba-Geigy)- Locorten (Zy ma)-comb. USA: Locorten (Ciba); wfm comb.; wfm Losalen (Zyma) Flunarizine ATC: N07CA03 Use: cerebral and peripheral vasodilator, antivertigo RN: 52468-60-7 MF: C2,H2,F2N2 MW: 404.50 EINECS: 257-937-5 LD,,: 960 mglkg (M, p.0.) CN: (E)-1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine 886 F Flunisolide dihydrochloride RN: 30484-77-6 MF: Cz6Hz6FzNz. 2HC1 MW: 477.43 EINECS: 250-216-6 LD,,,: 27 mglkg (M, i.v.); 285 mglkg (M, p.0.); 35 mglkg (R, i.v.); 503 mg/kg (R, p.0.); >2 g/kg (dog, p.0.) 1 -cinnornyl- piperozine bis(4-fluoropheny1)- chlorornethone Flunerizine Reference(s): DAS 1 929 330 (Janssen; appl. 10.6.1969; USA-prior. 2.7.1968). ilS 3 773 939 (Janssen; 20.1 1.1973; prior. 2.7.1968, 24.1 1.1971). inhibiting effect to complementary activity: DOS 2 254 893 (Janssen; appl. 9.1 1.1972; GB-prior. 9.11.1971; USA-prior. 17.10.1972).' Formulation(s): cps. 5.9 mg, 11.8 mg (as dihydrochloride) Trade Name(s): D: Flunarizin (ct-Arzne~mittel) I: Flugerd (Italfarmaco; Issium (Lifepharma) Flunarizin-ratiopharm 1981) Sibelium (Janssen) (ratiopharm) Flugeral mite (Italfarmaco) Vasculene (Leben's) Sibelium (Janssen-Cilag; Flunagen (Gentili) J: Flunarl (Kyowa Hakko; 1977) Fluxarten (SmithKline 1984) F: SibClium (Janssen-Cilag; Beecham) USA: Sibelium (Janssen); wfm 1986) Gradient (Polifarma) Flunisolide ATC: ROlAD04; R03BA03 Use: glucocorticoid, antiasthmatic RN: 3385-03-3 MF: Cz4H,,F06 MW: 434.50 EINECS: 222-193-2 LD,,,: >76 pglkg (M, i.v.); >500 pglkg (M, p.0.); >5 1 mglkg (R, i.v.); >500 pglkg (R, p.0.) CN: (6a, 11 P,16a)-6-fluoro- 1 1,21-dihydroxy- 16,17-[(I-methylethylidene)bis(oxy)]pregna- 1,4-diene-3,20- dione hydrate (2:l) RN: 77326-96-6 MF: CZ4H3,F0,. 1/2Hz0 MW: 887.02 c Flunisolide F 887 rnicrobiolog~cal hydroxylotion [Cunnighomella blokesleeano (ATCC 8688b)I 0 : F F I Flunisolide rnicrobiologicol dehydrogenation [Corynebocterium simplex (ATCC 4964)] rnicrobiologicai hydroxylotion [Streptomyces roseochrornogenea] . I acetone a - US 3 124 571 (Syntex; 10.3.1964; MEX-prior. 26.1 .l96O). b US 3 126 375 (Syntex; 24.3.1964; MEX-prior. 13.6.1958). c GB 933 867 (American Cyanamid; appl. 5.12.1959; USA-prior. 8.12.1958). Formulatinn(s): nasal spray 25 mglmetered dose inhaler with 0.25 mglspray Trade Name(s1: D: lnhacort (Boehringer Ing.) F: Bronilide (Cassenne) GB: Syntaris (Roche) Syntaris (Roche; Syntex) Nasalide (Cassenne) 888 F Flunitrazepam I: Gibiflu (Metapharma) Syntaris (Recordati) Lunibron-a (Valeas) J: Synaclyn (Otsuka) Lunis (Valeas) USA: Aerobid (Forest) Nasalide (Dura) Nasarel (Dura) Flunitrazepam ATC: N05CD03 Use: anticonvulsant, hypnotic, muscle relaxant RN: 1622-62-4 MF: Ci6HI2FN1O3 MW: 313.29 EINECS: 216-597-8 LD,,: 1200 mglkg (M, p.0.); 4 15 mg/kg (R, p.0.) CN: 5-(2-fluoropheny1)-1,3-dihydro- 1-methyl-7-nitro-2H- 1,4-benzodiazepin-2-one 4-chloroaniline 2-fluorobenzoyl chloride bromoocetyl brorn~de 2-amina-2'-fluaro- benzophenone (1) KN03. H2S04 NaH, DMF 11 , ."Xg + 17 / \ - 5-(2-fluoropheny1)-7- methyl Flunitrozeparn nitro-1.3-dihydro-2H-1.4- iodide benzodlazepin-2-one Reference(s); US 3 116 203 (Hoffmann-La Roche; 31.12.1963; appl. 14.3.1962). US 3 123 529 (Hoffmann-La Roche; 3.3.1964; appl. 9.3.1962). US 3 203 990 (Hoffmann-La Roche; 31.8.1965: prior. 27.6.1960.20.4.1961, 21.3.1962). Fortnzilation(s): amp. 2 mg; f. c. tabl. 1 mg; tabl. 1 mg, 2 mg Trade Name(s): D: Flunimerck (Merck) GB: Rohypnol (Roche) J: Rohypnol (Roche) Fluninoc (Neuro Hexal) , I: Darkene (Bayropharm) Silece (Eisai) Rohypnol (Roche) Roipnol (Rochc) F: Rohypnol (Roche) Valsera (Polifarma) Flunoxaprofen F 889 Flunoxaprofen ATC: G02CC04; MO1 AEI 5; M02AA Use: non-steroidal anti-inflammatory, cyclooxygenase and lipoxygenase inhibitor RN: 66934-18-7 MF: CI,Hl,FNO, MW: 285.27 LD,: 1275 mgkg (M, p.0.); 521 mglkg (R, p.0.) CN: (S)-2-(4-fluorophenyl)-a-methyl-5-benzoxazoleacetic acid DL-~YS~~ salt (1:l) RN: 124816-13-3 MF: CI6Hl2FNO3 . C,H,,N202 MW: 43 1.46 LD,,: 723.5 mgkg (M, p.0.) L-lysine salt (1: 1) RN: 124816-14-4 MF: C,,H12FN03 . C,HI4N2O2 MW: 43 1.46 D-lysine salt (1:l) RN: 124816-15-5 MF: C1,Hl2FNO3 . C6HL4N2O2 MW: 431.46 2-(4-amino- 2-(4-hydroxy phenyl)- phenyl). propionitrile propionitrile H3C COOH Q. + NH2 F OH 2-(3-amino- 4-fluoro- 4-hydroxypheny1)- benzoyl propionic acid (11) chloride (111) HNOJ, HOAc 0 H 2-(3-nitro- 4-hydroxypheny1)- propionitrile (I) H3C COOH Y 1. HCI 2. HZ, Pd-C - I1 H3P0.3 , phosphoric N OH 2-[3-(4-fluorobenz- ornido)-4-hydroxy- phenyllpropionic acid resolution with H3C&ieF N-methyl-0-qluwninc _____+ H3C$QO~ COOH ( Flunoxaprofen I 1. resolution with I-ephedrine 2. H*. Pd-C 3. nI , pyridine. 200 OC 4. HCI I 890 F Fluocinolone acetonide w 1. resolution with I-ephedrine 2. CH,COOH. 70 "C 3. Hz. Pd-C. NoHC03, H20 4. 111 5. H3P0,, 120 OC 1 Reference(s): a,c DE 2 931 255 (Ravizza; appl. 1.8.1979; I-prior. 4.8.1978). a Dunwell, D.W. et al.: J. Med. Chem. (JMCMAR) 18,53 (1957). synthesis of2-(4-aminopheny1)propionitrile: GB 1 198 212 (J. Borck et al.; appl. 1968). Iysine salt: EP 324 402 (Euroresearch; appl. 9.1.1989; I-prior. 3.1 1.1988). US 4 897 408 (Euroresearch; 30.1.1990; appl. 5.1.1989; I-prior. 3.1 I. 1988). b DE 2 728 323 (Ravizza; appl. 23.6.1977; GB-prior. 23.6.1976). c DOS 3 325 672 (Ravizza; appl. 15.7.1983; I-prior. 19.7.1982). Formulation(s): gel 5 %; tabl. 50 mg, 100 mg, 200 mg Trade Name(s): I: Priaxim (Ravizza) Fluocinolone acetonide ATC: CO~AA lo; DO~ACO~ Use: glucocorticoid, anti-inflammatory RN: 67-73-2 MF: C24H30F206 MW: 452.49 EINECS: 200-668-5 LD,,,: >4 g/kg (M, p.0.); >4 glkg (R, p.0.) CN: (6a,11 P,16a)-6,9-d~fluoro-1 l,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20- dione F 3.20-diouo-6a-fluoro- 11~.16a.17.21-tetro- hydroxy-4-pregnene (cf. Fludroxycortide synthesis) H3C-SO2-CI pyridine DMF, pyridine .I oceiic anhydride kCH3 methonesulfonyl chlor~de . per- 2-nitro-5-fluoro- mongonote fluorotoluene benzoic acid HOOC ethyl isocyanate- 0 CH3 ocetote potossium tert-butylate N-methyl- 7-fluoro-4-methyl- glycine 3,4-dihydro-2H-1. 4- benzodiazepin-2,5(1H )-. 162 2-6 2-4 MF: Ci6HI2FN1O3 MW: 313.29 EINECS: 21 6-5 9 7-8 LD,,: 1200 mglkg (M, p.0.); 4 15 mg/kg (R, p.0.) CN: 5-( 2-fluoropheny1 )-1 ,3-dihydro- 1-methyl-7-nitro-2H- 1,4-benzodiazepin-2-one. anti-inflammatory RN: 213 5-1 7-3 MF: C,,H2.F,0s MW: 410.46 EINECS: 21 8-3 7 0-9 CN: (6a,l lp,l6a )-6 ,9-difluoro- 1 l,17,21 -trihydroxy-16-methylpregna- 1,4-diene-3,20-dione pivalate RN: 200 2-2 9-