Fluazacort F 87 1 1. HBr, AcOH 2. BrZ. CHCI, :: :' Br2, diomne e NYCHz 3. DMF. LiBr. Li2c03 b H O H (3~.5a.5'p)-2l-acetoxy-3- hydroxy-2'-methyl-5H- pregn-9(11)-eno[l7,16-dl- oxozol-20-one (N) (5'8)-21 -ocetoxy-2'-methyl- S'H-pregna-1.4,9(11)-trieno[l7,16-dl- oxazole-$20-diane (VI) 1. H3C-CO-NU-Br, HCIO, 2. NoOH 3. H2FZ. THF 1. N-bromoacetarnide Fluazocort L 1. Ac,O, pyridine I. KOH 2. I,. NCXC~~N,~ H3C NH CN 3. H~C-COOH !N(c~H~)~ y+ 111 , N 2. rnesyl chlorrde 2. iodine, ozoisobutyronitrile 3. triethylommon~um acetate (5a,5'@)-3@,1 Ig-dihydroxy- 2'-methyl-SH-pregnano- [17,16-d]oxozol-20-one (cf. Deflozacort) 0 1. H3C.!-+Br , HCIO, 1. Cr03 2. NoOH 2. Br2 3. HF 3. LizC03 4. Ac20. pyridine N -b VI , 1. N-brornoocetamide Reference(s): a DOS 1 618 613 (Lepetit; appl. 7.1.1967; GB-prior. 11.1.1966, 11.7.1966,29.9.1966). US 3 461 119 (Lepetit; 12.8.1969; appl. 1967; GB-prior. 1.1 1.1966). 872 F Flubendazole sytlthesis of starting compound: DE 1 568 971 (Gruppo Lepetit; appl. 23.12.1966; GB-prior. 11.1 .l966, 11.7.1966,29.9.1966). US 3 624 077 (Gruppo Lepetit; 30.1 1.1971; GB-prior. 11.1.1966). Nathansohn, G. et al.: J. Med. Chem. (JMCMAR) 10,799 (1967). Nathansohn, G. et al.: Gazz. Chim. Ital. (GCITA9) 95, 1338 (1965). review: Nathanson, G. et al.: Steroids (STEDAM) 13,365 (1969). alternative synthesis of VI: DOS 1 568 071 (Lepetit; appl. 23.12.1966; GB-prior. 11.1.1966, 11.7.1966,29.9.1966). DOS 1 568 972 (Lepetit; appl. 23.12.1966; GB-prior. 11.1.1966, 1 1.7.1966, 29.9.1966). b Nathansohn, G. et al.: J. Med. Chem. (JMCMAR) 10,799 (1967). Nathansohn, G. et al.: Steroids (STEDAM) 13, 383 (1969). Formulatior2(s): cream 0.025 % Trade Name(s): I: Azacortid crema (Lepetit) Flubendazole ATC: PO2CA05 Use: anthelmintic RN: 31430-15-6 MF: C,,H,,FN,O, MW: 3 13.29 EINECS: 250-624-4 LD,,,: ~2560 mg/kg (M, p.0.); 2560 mgkg (R, p.0.) CN: [5-(4-fluorobenzoy1)-IH-benzimidazol-2-yl]cbamic acid methyl ester 1. NH3, CH30H, sulfolone.125 OC 2. HZ. Pd-C. HCL 0 chloride 0 fluorobenzene 3-chloro-4-nitro- 3-chloro-4-nitro- benzoyl chloride 4'-fluorobenrophenone Refererlce(s): DOS 2 029 637 (Janssen; appl. 16.6.1970; USA-prior. 20.6.1969). US 3 657 267 (Janssen; 18.4.1972; appl. 20.6.1969). Raymaekers, A.H.M. et al.: Arzneim Forsch. (ARZNAD) 28,586 (1978). 3,4-diomino-4'- S-methyl- methyl Formulation(s): susp. 100 mglml; tabl. 100 mg Flubendazole Trade Name(s): D: Flubenol (Janssen); wfm F: Fluvermal (Janssen-Cilag) lluorobenzophenone (1) isothioureo chloroformate P" Fluclorolone acetonide F 873 Fluclorolone acetonide (Flucloronide) ATC: H02AB Use: topical glucocorticoid RN: 3693-39-8 MF: C2,H,yC12FOs MW: 487.40 EINECS: 223-010-9 CN: (6a,l 1 P,16a)-9,l I-dichloro-6-fluoro-2l-hydroxy-16,17-[(I-methylethylidene)bis(oxy)]pregna- 1 ,4-diene- 3,20-dione d HJC-SOzCI. pyridine. DMF 21-0-acetyl-6 fluoro- 16a-hydmxyhydrocortisone ocetonide 1. CIZ. CHCI3 2. SeOz, (CH3)3COH, pyridine 3. KOH b 1. chlorine 2, selenium dioxide 3. potassium hydroxide ( Fluclarolone occtonide I Reference(s): US 3 201 391 (Syntex; 17.8.1965; MEX-prior. 18.2.1959, 20.10.1959). starting material: Mills, J.S. et al.: J. Am. Chem. Soc. (JACSAT) 81, 1264 (1959). Formulation(s): cream 0.025 %, 0.25 % Trade Name(s): F: Topilar (Syntex-Daltan); GB: Topilar (Syntex); wfm wfm Flucloxacillin (J3oxacillin) ATC: JOlCA 1Jse: antibiotic RN: 5250-39-5 MF: CIyH,,C1FN3OSS MW: 453.88 EINECS: 226-051-0 CN: [2S-(2a,5a,6~)]-6-[[[3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl]carbonyl]amin]-3,3-dimethyl- 7-oxo-4-thia-l-azabicyclo[3.2.0]heptane-2-carboxylic acid monosodium salt RN: 1847-24-1 MF: C,,H16ClFN3NaOSS MW: 475.86 EINECS: 217-428-0 LD,,: 1360 mglkg (M, i.v.); 7600 mgkg (M, p.0.); 680 mglkg (R, i.v.); 1 1 glkg (R, p.0.); 670 mg/kg (dog, i.v.); >10 glkg (dog, p.0.) 874 F Fluconazole CHO %OH CIAN-OH 2-chloro-6-fluoro- benzaldehyde 0 0 I + 4 NaOH F21 , CooH d soclz I1 H3C /CH3 CH, CH3 methyl ocetoacetate GB 987 299 (Beecharn; appl. 17.10.1962; addition to GB 905 778 from 14.3.1961). US 3 239 507 (Beecham: 8.3.1966; GB-prior. 17.10.1962). (11) 6-aminopenicillanic For~nulation(s): cps. 272 mg, 544 mg; vial 272 mg, 544 mg, 1088 mg, 2176 mg (as sodium salt hydrate) Flucloxacillin Trade Narne(s): D: Flanomox (Wolfo-comb. GB: Floxapen (SmithKline I: Infectrin (Pierrel)-comb. Fluxapril (Leder1e)-comb. Beecham). with ampicillin Staphylex (SmithKline Magnapen (SmithKline J: Culpen (Fujisawa) Beecham) Beecham)-comb. Floxapen (Beecham) Stafoxil (Yamanouchi) acid Fluconazole (UK-49858) ATC: J02ACOI; J02AX Use: antifungal (treatment of vaginal, oropharyngeal and atrophic oral candidiasis) RN: 86386-73-4 MF: C,,H,,F,N,O MW: 306.28 LD,,,: >200 mg/kg (M, i.v.); 1408 mglkg (M, p.o.1; >200 mg/kg (R, i.v.); 1271 mg/kg (R, p.0.); >I00 mglkg (dog, i.v.); >300 mglkg (dog, p.0.) CN: a-(2,4-difluoropheny l)-a-(IN-1,2,4-triazol-l-ylmethyl)-1H-1,2,4-triazole- 1-ethanol Fluconazole F 875 c4H9Li 6 butyllithium CI~CI 0 ______, 1 -3-dichloro- ocetone 1 H-1.2.4- triozole (111) F Fluconazole 1,3-difluoro- 2.4-difluoro- 1 -3-dichloro-2-(2,4-difluoro- benzene (I) phenyllithium phenyl)-2-proponol (11) chloroacetyl a-chloro-2.4-difluoro- a-(1 H-l,2.4-triozol-1 -yl)- chloride acetophenone 2,4-difluc~oacetophenone (N) trirnethylsulfoxonium 1 -[2-(2.4-difluorophenyl)- iodide 2,3-epoxypropyll- 1 H- 1.2.4-triozole Reference(s): GB 2 099 818 (Pfizer; appl. 22.4.1982; prior. 6.6.1981,4.3.1982). EP 96 569 (Pfizer; appl: 6.6.1983; GB-prior. 9.6.1982, 30.7.1982). tablet formulation: EP 178 682 (Schering Corp.; appl. 23.4.1986; USA-prior. 19.10.1984). alternative synthesis: ES 549 684 (Lazlo Int.; appl. 6.12.1985). ES 5 490 202 (Inke S. A.; appl. 19.1 1.1985). US 5 710 280 (Dev. Center Biotech. Taiwan; 20.1.1998; appl. 9.7.1996). WO 9 703 971 (Apotex; appl. 17.7.1996; NZ-prior. 17.7.1995). Formulation(s): cps. 50 mg, 100 mg, 150 mg, 200 mg; susp. 50 mg/5 ml; syrup 50 mgIl0ml; tabl. 50 mg, 100 mg, 150 mg, 200 mg; vial 100 mg, 200 mg, 400 mg Trade Name(s): D: Diflucan (Pfizer) I: Biozolene (Bioindustria; Elazor (Sigma-Tau) F: Triflucan (Pfizer; 1989) 1989) J: Diflucan (Pfizer Taito) GB: Diflucan (Pfizer; 1988) Diflucan (Roerig) USA: Diflucan (Pfizer; 1990) 876 F Flucytosine Flucytosine ATC: DOlAE21; J02AXO 1 Use: fungicide RN: 2022-85-7 MF: C4H4FN30 MW: 129.09 EINECS: 217-968-7 LD,,: 500 mg/kg (M, i.v.); >I5 g/kg (M, p.0.); >600 mgkg (R, i.v.); >I5 g/kg (R, p.0.) CN: 4-amino-5-fluoropyrimidin-2(IH)-one H POCIJ. dimethylaniline F F 0 CI 2.4-dichloro- 5-fluoro- pyrimidine 5-fluoro-2- 4-chloro-5-fluoro- methylthiourocii 2-methylthio- (cf. fiuorouracil pyrimidine synthesis) 4-omino-2- chloro-5-fluoro- pyrimidine a Duschinsky, R. et al.: J. Am. Chem. Soc. (JACSAT) 79,4559 (1957). Undheim, K.; Gacek, M.: Acta Chem. Scand. (ACHSE7) 23, (I), 294 (1969). US 3 040 026 (Roche; 19.6.1962; appl. 3.6.1959). US 3 185 690 (Roche; 25.5.1965; prior. 3.6.1959, 14.9.1961). b US 2 945 038 (Roche; 12.7.1960; prior. 26.9.1956). US 2 802 005 (Roche; 6.8.1957; prior. 26.9.1956). medical use: US 3 368 938 (Roche; 13.2.1968; prior. 2.3.1962). Formulation(s): cps. 250 mg, 500 mg; tabl. 500 mg; vial 2.5 g1250 rnl Trade Name(s): D: Ancotil Roche (ICN) GB: Alcobon (Roche); wfm J: Ancotil (Roche) F: Ancotil (Roche) I: Ancotil (Roche) USA: Ancobon (Roche) Fludarabine phosphate (2-fluoro-ara-AMP) ATC: LOlBB05 Use: antineoplastic, antimetabolite, treatment of chronic lymphocytic leucemia RN: 75607-67-9 MF: C,,H,,FN,O,P MW: 365.21 LD,,,: 375 mglkg (M, i.p.); 1236 mgkg (M, i.v.) CN: 2-fluoro-9-(5-O-phosphono-~-~-arabinofuranosyl)-9H-purin-6-amine fludarabine RN: 21679-14-1 MF: C,,H,,FNSO4 MW: 285.24 EINECS: 244-525-5 Fludarabine phosphate F 877 + OHC-NH2 4 k H2N N 2,4,5,6-tetroornino- forrnornide 2-omino- pyrimidine 2, Bz-ogL , HCI orobinofuronose adenine (I) 1. NoOCH,, CH,OH 1. BCI* CH,CI, 2. HBF,. NoNO 2. POCIJ. PO(OC2H5)3 If Z 2. tetrofluaroboric acid 1. boron trichloride sodium nitrite 2. phosphorus oxychloride, triethyl phosphate 0-02 OH 9-(2,3,5-tri-0-benzyl- Fludorobine 8-D-orobinofuronosyl)- phosphate 2-fluoroodenine Reference(s): US4 357 324 (Department of Health of USA; 2.1 1.1982; appl. 24.2.1981). synthesis of 9-P-D-arabinofuranosyl-2-fluoroadenine: US 4 210 745 (Department of Health of USA; 1.7.1980; appl. 20.1 1.1978; prior. 10.3.1978,4.1 .l978). Montgomery, J.A. et al.: J. Heterocycl. Chem. (JHTCAD) 16, 157 (1979). Montgomery, J.A.; Hewson, K.: J. Med. Chem. (JMCMAR) 12,498 (1961). synthesis of Zaminoadenine: Robins, R.K. et al.: J. Am. Chem. Soc. (JACSAT) 75,263 (1953). Formulation(s): vial (lyo.) 5 mg, 50 mg Trade Name(s): D: Fludara (rneda; Schering) 'GR: Fludara (Schering) F: Fludara (Schering) USA: Fludara (Berlex; 1991) 878 F Fludrocortisone Fludrocortisone ATC: H02AA02; SOlCA06; S02CA07; S03CA05 Use: glucocorticoid IRN: 127-31-1 MF: C2,H2,FOs MW: 380.46 EINECS: 204-833-2 LD,,: 170 mglkg (M, i.p.) CN: (1 1 P)-9-fluoro-ll,l7.21-trihydroxypregn-4-ene-3,20-dione acetate RN: 514-36-3 MF: C,,H,,FO, MW: 422.49 EINECS: 208-180-4 LD,,: >I glkg (R, p.0.) 3 sr '.H$ N' POC13, pyridine 2. CHJCOONa . I ' , r 1. N-bromo- ocetamide . / hydrocortisone 21-ocetote H2F2. & ICH3 onhydrous ;130,b or HCIJ/THFc or CHCI~/H~O/HCIO~~ + I1 me^ H o/ 21-ocetoxy-3.20-dioxo-98.118- epoxy-17-hydroxy-4-pregnene (I) ( fludrocortisone ocetote (11) Fludrocortisone Refennce(s): a Fried, J.; Sabo, E.F.: J. Am. Chem. Soc. (JACSAT) 76, 1455 (1954). b GB 792 224 (Oh Mathieson; appl. 1954; USA-prior. 1954). c DE 1 035 133 (Merck & Co.; appl. 1956; USA-prior. 1955). Hirschmann, R.F. et al.: J. Am. Chem. Soc. (JACSAT) 78,4956 (1956). d US 2 894 007 (Merck & Co.; 7.7.1959). e DE 1 028 572 (Schering AG; appl. 2 1.1.1 957). synthesis of hydrocortisone acetate: Fried, J.; Sabo, E.F.: J. Am. Chem. Soc. (JACSAT) 75,2273 (1953). US 2 771 475 (Upjohn; 1956, appl. 1953). GB 792 224 (Olin Mathieson; appl. 1954; USA-prior. 1954). alternative syntheses: US 2 771 475 (Upjohn; 1956; appl. 1953). US 2 799 688 (Upjohn; 1957; appl. 1954). US 2 852 51 1 (Olin Mathieson; 1958; prior. 1953). US 4 041 055 (Upjohn; 9.8.1977; appl. 17.1 1 .l975). Fludroxycortide F 879 Formulation(s): ear drops 8 mgI8 ml in comb. with polymyxin B; ointment 0.001 %; tabl. 0.1 mg (as acetate) Trade Name(s): D: Astonin H (Merck) F: Panotile (Zambon)-comb. USA: Florinef (Apothecon) Fludrocortison (Bristol- GB: Florinef (Bristol-Myers Myers Squibb) Squibb; as acetate) Panotile (Zambon)-comb. J: Florinef (Bristol Squibb) Fludroxycortide (Flurandrenolide) ATC: D07AC07 Use: glucocorticoid, anti-inflammatory RN: 1524-88-5 MF: C24H33FOh MW: 436.52 EINECS: 216-196-8 CN: (6a,11 ~,16a)-6-fluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]pregn-4-ene-3,20-dione 21-acetoxy-16a.17-epoxy- 3P-hydroxy-20-0x0-5-pregnene (from pregnenolone) 0 , CH2C12, - 80 "C b &FH3 hydrogen N-bromo- fluoride ocetamide H ti H0 Br F 1 Cr03 2. HBr, CH3COOH 1 CH3COOK. CH3COOH 2 No2C05. CH30H I , 11 1, chromium(VI) oxide 2. acetic anhydride microbiological hydroxylation [Arthrobotrys superb0 vor. oligospora (ATCC 11572)] or [Cunninghamello blakesleeana (ATCC 8688b)I 0 z F F o=tcH3 CH3 ocetone HCIO, 880 F Flufenamic acid Reference(s): a US 3 014 938 (Syntex; 26.12.1961; appl. 23.8.1960; MEX-prior. 7.9.1959). US 3 119 749 (Syntex; 28.1.1964; appl. 17.1 1.1961; MEX prior. 7.6.1961). US 3 124 571 (Syntex; 10.3.1964; MEX-prior. 26.1.3960). starting material: Julian, P.L.: J. Am. Chem. Soc. (JACSAT) 72,5145 (1950). US 2 678 932 (Sterling Drug; 1954; prior. 1951). b US 3 126 375 (Syntex; 24.3.1964; appl. 11.6.1959; MEX-prior. 13.6.1958). DE 1 131 213 (Syntex; appl. 6.6.1959; MEX-prior. 13.6.1958). alternative syntheses: Mills, J.S. et al.: J. Am. Chem. Soc. (JACSAT) 82, 3399 (1960); 81, 1264 (1959). [JS 3 203 869 (Syntex; 31.8.1965; MEX-prior. 11.10.1962). Formulation(s): lotion 0.05 % (15 ml, 60 ml); tape 4pg/cm2 Trade Name(s): D: Sermaka (Lilly) I: Drenison (Lilly); wfm J: Drenison Q (Lilly- GB: Drenison (Lilly); wfm Drenison Neomicina Dainippon) Haclan (Dista); wfm (Li1ly)-comb.; wfm USA: Cordran (Oclassen) Flufenamic acid ATC: MOIAGO~ (Acide flufenamique) Use: anti-inflammatory, antirheumatic RN: 530-78-9 MF: C14HloF1N02 MW: 281.23 EINECS: 208-494-1 LD,,: 158mg/kg(M,i.v.);490mglkg(M,p.o.): 98 mgkg (R, i.v.); 249 mglkg (R, p.0.) CN: 2-[[3-(trifluoromethyl)phenylJamino]benzoic acid aluminum salt RN: 16449-54-0 MF: C4,H,AIF9N306 MW: 867.66 EINECS: 240-498-9 LD,,,: 1460 mglkg (M, p.0.); 550 mglkg (R, p.0.) 2-chloro- 3-trifluoro- benzoic methylonilhe ocid COOH Flufenornic ocid I Reference (s): FR 1 341 M (Parke Davis; appl. 1 1.8.1961). Moffett, R.B.; Aspergen, B.D.: J. Am. Chem. Soc. (JACSAT) 82, 1605 (1960). salts with amines: DOS 2 758 787 (T. Eckert; appl. 29.12.1977). Formulation(s): ointment 3 g/100 g (3 %); sol. 25 mglg Trade Name(s): D: Algesalona (Sohay)-comb. Rheuma Lindofluid Meralen (Merrell); wfm Dignodolin (Sankyo) (Lindopharm) I: Mobilisin (Luitpold)-comb. Mobilisin (Sankyo)-comb. F: Arlef (Parke Davis); wfrn J: Achless (Tatsumi) GB: Arlef (Parke Davis); wfm Arlef (Parke Davis-Sankyo) . (3~.5a.5'p )-2 l-acetoxy- 3- hydroxy-2'-methyl-5H- pregn-9(11)-eno[l7,16-dl- oxozol-20-one (N) (5'8 )-2 1 -ocetoxy-2'-methyl- S'H-pregna-1.4,9(11)-trieno[l7,16-dl- oxazole-$20-diane. [2S-(2a,5a,6~) ]-6 -[ [[ 3-( 2-chloro-6-fluorophenyl )-5 -methyl-4-isoxazolyl]carbonyl]amin ]-3 ,3-dimethyl- 7-oxo-4-thia-l-azabicyclo[3.2.0]heptane-2-carboxylic acid monosodium salt RN: 184 7-2 4-1 MF:. Fluconazole 1,3-difluoro- 2.4-difluoro- 1 -3 -dichloro- 2-( 2,4-difluoro- benzene (I) phenyllithium phenyl )-2 -proponol (11) chloroacetyl a-chloro-2.4-difluoro- a-(1 H-l,2.4-triozol-1 -yl )- chloride